WO2011127917A2 - Dispositif et procédé de traitement de maladies du cerveau et/ou de la moelle épinière au moyen du neurofeedback - Google Patents

Dispositif et procédé de traitement de maladies du cerveau et/ou de la moelle épinière au moyen du neurofeedback Download PDF

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Publication number
WO2011127917A2
WO2011127917A2 PCT/DE2011/075022 DE2011075022W WO2011127917A2 WO 2011127917 A2 WO2011127917 A2 WO 2011127917A2 DE 2011075022 W DE2011075022 W DE 2011075022W WO 2011127917 A2 WO2011127917 A2 WO 2011127917A2
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Prior art keywords
stimuli
stimulation
patient
neurons
unit
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PCT/DE2011/075022
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German (de)
English (en)
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WO2011127917A3 (fr
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Peter Alexander Tass
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Forschungszentrum Jülich GmbH
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36135—Control systems using physiological parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36064—Epilepsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36067—Movement disorders, e.g. tremor or Parkinson disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/361—Phantom sensations, e.g. tinnitus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128—Control systems
    • A61N1/36146—Control systems specified by the stimulation parameters

Definitions

  • the invention relates to a device and a method for the treatment of diseases of the brain and / or spinal cord by means of neurofeedback.
  • neurological or psychiatric disorders such as Parkinson's disease, essential tremor, dystonia or obsessive-compulsive disorder
  • neuron clusters in umschrie ⁇ enclosed areas of the brain including the thalamus and the basal ⁇ ganglia, morbid, for example excessively synchronous, active.
  • a large number of neurons synchronously action potentials, ie the participating neurons fire excessively synchronous.
  • the neurons in these brain areas fire qualitatively differently, for example in an uncorrelated way.
  • pathologically synchronous activity alters neuronal activity in other brain areas, for example, in areas of the cerebral cortex, such as the primary motor cortex.
  • the pathologically synchronous activity in the area of the thalamus and the basal ganglia forces the cerebral cortical areas to become rhythmic so that finally the muscles controlled by these areas develop pathological activity, eg a rhythmic trembling (tremor).
  • tremor rhythmic trembling
  • Neurological and psychiatric disorders with excessively pronounced neuronal synchronization have so far been treated by electrical brain stimulation in the case of failure of drug therapy.
  • Elect be ⁇ clearing in the brain of the patient and implanted so implanted by a likewise control unit with corresponding electrical stimuli supplied.
  • An electrical stimulation of the brain can lead to side effects for several reasons. For example, nen caused by the spread of stimulation current on the eigentli ⁇ che target area also unwanted side effects with ⁇ irritation of neighboring areas. In addition, excessive stimulation, for example, can damage the tissue. Therefore, it is of great benefit to the patient with as little as possible
  • Figure 1 is a schematic representation of a device with a stimulation unit, a neuro-feedback unit, a measuring unit and a control unit ⁇ according ei ⁇ nem embodiment during loading ⁇ drive.
  • Fig. 2 to 5 are schematic representations of procedures during the operation of in
  • Fig. 1 illustrated device
  • FIGS. 6 and 7 are schematic representations of Ausgestal ⁇ lines of the device shown in Figure 1.
  • FIG. 8A is a schematic representation of a neuro-feedback unit according to an execution example ⁇
  • FIG. 9 is a schematic representation of a new rofeedback unit according to a further embodiment
  • Figure 10 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of electrical stimuli in accordance with an embodiment.
  • 11 to 15 are schematic representations of electrical stimulation methods;
  • Fig. 16 is a schematic representation of a Sti ⁇ mulationshim for the generation and application-of visual stimuli in accordance with a
  • Figure 17 is a schematic diagram of the Ge ⁇ field of view of a patient.
  • Figure 18 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of visual stimuli in accordance with another embodiment.
  • Figure 19 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of visual stimuli in accordance with another embodiment.
  • FIGS. 26 and 27 are schematic illustrations of eyeglasses
  • Fig. 28 is a schematic representation of generated by a light glasses optical
  • Fig. 29 is a schematic representation of a Sti ⁇ mulationshim for the generation and application-of acoustic stimuli in accordance with a
  • Fig. 30 is an illustration of sine waves having different frequencies
  • FIG. 31 shows a representation of a sine oscillation amplitude-modulated with a rectangular function
  • FIG. Figure 32 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of acoustic stimuli according to another embodiment.
  • Figure 33 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of acoustic stimuli according to another embodiment.
  • Fig. 34 to 38 are schematic representations of akusti ⁇ rule stimulation process;
  • Figs. 39A and 39B are schematic diagrams of the generation of modulation signals
  • Fig. 40 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli- cation of tactile, vibratory
  • FIG. 41 is a schematic representation of a tak ⁇ tilen, vibrational and / or thermal stimulation process
  • FIGS. 42A to 42D are schematic representations of vibratory stimuli
  • FIG. 43 is a schematic representation of a tak ⁇ tilen stimulus.
  • FIGS. 44A to 44C are schematic diagrams of thermal stimuli;
  • Figure 45 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of tactile, vibratory and / or thermal stimuli, according to another embodiment.
  • Figures 46 to 48 are schematic representations of tactile, vibratory and / or thermal stimulation methods
  • 49 is a schematic representation of a Sti ⁇ mulationshim for generating and Appli ⁇ cation of tactile, vibratory and / or thermal stimuli, according to another embodiment.
  • Fig 50A to 52C are schematic representations of a Stimula ⁇ tion elements for generating and Applika ⁇ tion of tactile and / or vibrational stimuli.
  • Fig 53A to 54C are schematic representations of a Stimula ⁇ tion elements for generating and Applika ⁇ tion of thermal stimuli.
  • Figures 55 and 56 are schematic representations of tactile, vibratory and / or thermal stimulation methods.
  • FIG. 1 an apparatus 100 is shown for the treatment of diseases of the brain and / or spinal cord of a Pati ⁇ ducks schematically.
  • the device 100 consists of a control unit 10, a stimulation unit 11, a neuro-feedback unit 12 and a measuring unit 15.
  • the stimulation unit 11 generates first stimuli 21 which, when administered to a patient, suppress a pathologically synchronous activity of neurons in the brain and / or spinal cord of the patient.
  • the stimulation unit 11 is surgically implanted in the body of the patien ⁇ th.
  • the first stimuli 21 are electrical stimuli that are applied to the brain and / or spinal cord of the patient.
  • the stimulation unit 11 can be configured according to another embodiment as a non-invasive ⁇ unit, ie during operation of the device 100, the stimulation unit 11 is located outside the patient's body and will not be surgically implanted in the patient's body.
  • the first stimuli 21 may be stimuli in this case, from the group of opti ⁇ rule, acoustic, tactile, vibratory and thermal Stimuli.
  • the control unit 10 controls the stimulation unit 11 with control signals 23.
  • the measuring unit 15 receives one or more measurement signals 25 measured on the patient, converts these if necessary into electrical signals 26 and supplies them to the control unit 10.
  • the measurement signals 25 reflect the pathologically synchronous sectioni ⁇ ty of neurons in the brain and / or spinal cord of the patient.
  • the neuro-feedback unit (or neuro-feedback unit or Neurofeedback- transmitter) 12 generates second stimuli 22, illustrate the patient the severity of the pathological synchronous Akti ⁇ tivity of the neurons.
  • the second stimuli 22 are consciously perceptible by the patient and are, for example, optical, acoustic, tactile, vibratory and / or thermal stimuli.
  • the neurofeedback unit 12 may be designed as a non-invasive unit and is accordingly not implanted in the body of the patient, but is located during the operation of the device 100 outside the Kör ⁇ pers of the patient.
  • the control unit 10 controls the neuro-feedback unit 12 with control signals 24.
  • the New ⁇ rofeedback unit 12 to the patient can sensory veran- illustrate the strength of the expression of the pathological neuronal activity
  • the control signals include 24 Informatio ⁇ nen from the obtained by the measurement unit 25 signals 26.
  • the signals 26 are any of the control unit 10 still processed or further processed and then fed to the neurofeedback unit 12.
  • the individual components of the device 100 in particular the control unit 10, the stimulation unit 11, the neurofeedback unit 12 and / or the measuring unit 15, are structurally separated from one another.
  • the device 100 can therefore also be understood as a system consisting of the components shown in FIG.
  • the device 100 can be used in particular for the treatment of neurological or psychiatric disorders, for example Parkinson's disease, essential tremor, dystonia, epilepsy, tremor as a result of multiple sclerosis and other pathological tremors, depression, movement disorders, cerebellar diseases, obsessive-compulsive disorders, Tourette's syndrome, functional disorders after stroke, Spasticity, tinnitus, sleep disorders, schizophrenia, irritable bowel syndrome, addictions, personality disorders, attention deficit syndrome, attention deficit hyperactivity disorder, gambling addiction, neurosis, craving, burnout syndrome, fibromyalgia, migraine, cluster disorders Headache, generalized headache, neuralgia, ataxia, tic disorder or hypertension, but also other diseases.
  • neurological or psychiatric disorders for example Parkinson's disease, essential tremor, dystonia, epilepsy, tremor as a result of multiple sclerosis and other pathological tremors, depression, movement disorders, cerebellar diseases, obsessive-
  • the above-mentioned diseases can be caused by a disturbance of the bioelectrical communication of neuron assemblies that are connected in specific circuits.
  • a neuron population generated persistently abnormal neuronal activity and possibly an associated abnormal connectivity (network structure ⁇ ).
  • a large number of neurons synchronously form action potentials, ie the participating neurons fire excessively synchronously.
  • the sick ⁇ New ronen population oscillatory neuronal activity ⁇ has, ie the neurons fire rhythmically.
  • the mean frequency of the pathological rhythmic activity of the affected neuronal units is approximately in the range of 1 to 30 Hz, but may also lie outside this range. In healthy humans, however, the neurons fire qualitatively differently, eg in an uncorrelated way.
  • the device 100 is provided during its operation ⁇ .
  • at least one neuron population 30 has an as described above. described pathologically synchronous neuronal activity.
  • the stimulation unit 11 administers the first stimuli 21 to the patient in such a way that the first stimuli 21 are received via the eyes, ears or skin of the patient, depending on the modality, and from there via the nervous system to the pathological active neuron population 30 in the brain 29 and / or spinal cord 29 are forwarded.
  • the first electrical stimuli 21 of Neuronenpo- concerned are 30 either directly administered or applied to areas of the brain or spinal cord 29 which nenpopulation with neuro 30 connected pulation and the first stimuli 21 are forwarded to the neuron population 30.
  • the first stimuli 21 are designed such that they suppress the pathologically synchronous Akti ⁇ tivity of the neuron population 30.
  • a suppression of synchronous activity can mean that the coincidence rate of the neurons is lowered or that the neuron population ⁇ 30 is not desynchronized.
  • a reduction in the coincidence rate of the neurons caused by the stimulation can lead to a lowering of the synaptic weights and thus to a loss of the tendency to produce morbidly synchronous activity.
  • the second stimuli 22 generated by the neurofeedback unit 12 are likewise received via the eyes, the ears or the skin as well as deeper tissue of the patient and forwarded from there to the nervous system.
  • the second stimuli 22 are not therapeutically effective and therefore have little or no desynchronizing or coincidence-rate-reducing effect on the pathologically synchronous neuronal activity of the neuron population 30.
  • the second stimuli 22 illustrate the patient only the severity of the severity the pathological neuronal activity of the neuron population 30.
  • optical (or visual) or acoustic (or auditory) first or second stimuli 21, 22 are applied, they are recorded via at least one eye or at least one ear of the patient.
  • the tactile, vibratory and thermal first or second stimuli 21, 22 are taken up by in or under the skin receptors and forwarded to the nervous system.
  • These receptors include, for example, Merkel cells, Ruffini bodies, Meissner bodies and hair follicle receptors, which act in particular as receptors for the tactile stimuli 21, 22.
  • the vibratory stimuli 21, 22 are primarily aimed at sensitivity to depth.
  • the vibratory stimuli 21, 22 may be received by receptors located in the skin, muscles, subcutaneous tissue, and / or tendons of the patient.
  • receptors for the vibratory stimuli 21, 22 may be mentioned by way of example the father-Pacini bodies, which convey vibration sensations and accelerations.
  • thermoreceptors The thermal stimuli 21, 22 are absorbed by the thermoreceptors of the skin. These are warm receptors (also called heat receptors, warm sensors or heat sensors) and cold sensors (also called cold sensors, cold receptors or cold receptors). In the human skin, the cold sensors are more superficial, the warm receptors a little deeper.
  • the measuring unit 15 receives one or more measuring signals 25 measured on the patient, optionally converts these into electrical signals 26 and supplies them to the control unit 10.
  • the measuring unit 15 may be implanted in the form of one or more sensors in the body of the patient.
  • invasive sensors can, for example, epicortical electrodes, tie-fenhirnelektroden serve sub- or epidural brain electrodes, subcutaneous EEG electrodes and sub-or epidural counselmarkselekt ⁇ clear. Furthermore, electrodes to be attached to peripheral nerves can be used as sensors.
  • the measurement signals 25 can be recorded in permanent or breaks Zvi ⁇ rule administration of the first stimuli 21, or at predefined time points. If the neuronal activity of the target population 30 is measured, the measuring unit 15 measures the abnormally exaggerated synchronous neuronal activity, eg the beta-band activity in Parkinson's disease.
  • the extent of this morbidly synchronous neuronal activity can be represented, for example, by the amplitude of the power averaged in a time window in the associated frequency range of the local field potentials, ie, for example, in a-kinetic Parkinson patients in the beta frequency range between 10 and 30 Hz.
  • This measured value 26 is forwarded to the control unit 10 or else directly to the neuro-feedback unit 12.
  • the transmission can take place, for example, wirelessly via corresponding transmitters and receivers.
  • Non-invasive sensors include electroencephalography (EEG) electrodes, magnetic zephalography (MEG) sensors, and electromyography (EMG) electrodes.
  • EEG electroencephalography
  • MEG magnetic zephalography
  • EMG electromyography
  • the pathological oscillatory activity in the tremor frequency range or the lack of movement can be measured, for example, via an accelerometer.
  • the device 100 can be operated in two different operating modes. The respective operating mode can be given for example before ⁇ or can be selected by the control unit 10.
  • the control unit 10 controls the two stimulation ⁇ units 11 and 12 according to the selected operating mode.
  • a learning phase the patient learns under medical supervision, exclusively by neurofeedback, ie without any form of an applied by the stimulation unit 11 electrical or sensory neurostimulation, reliable morbid synchronous neuronal activity in the brain or Stud - To counteract ckenmark and thus counter symptoms that may occur.
  • neuro-feedback unit 12 By feedback of the expression level of pathologically synchronous neuronal activity by means of neuro-feedback unit 12, the patient learns to suppress this R ⁇ ty. This can be done for example by a form of thought control or relaxation and is individually different.
  • an assistive depending on the embodiment, invasive or non-invasive neurostimulation by means of the stimulation unit 11 is performed during the learning phase.
  • the activation of the stimulation unit 11 is communicated to the patient, for example, with ⁇ means of neuro-feedback unit 12th
  • the activation of the stimulation unit 11, ie, the through ⁇ guide an electrical, optical, acoustic, tactile, vibratory and / or thermal neurostimulation ( "Neuro modulation”) is carried out, for example, as soon as the severity determined by means of the measuring unit 15 of the morbidly syn neuronal activity exceeds a predetermined threshold.
  • the threshold value, beyond which the stimulation unit 11 is activated for example, relatively high ⁇ is set to intercept only particularly pronounced Symptomschü ⁇ be, but give the patient enough opportunity to learn the Neurofeedback.
  • the stimulation unit 11 can be activated even if the patient does not feel treated suffi ⁇ accordingly and an activation button of a patient-programmer, which is verbun to the control unit 10 ⁇ expresses.
  • the stimulation unit 11 can be deactivated and the neuro-modulation can be stopped accordingly as soon as the manifestation of the pathologically synchronous neuronal activity ascertained with the aid of the measuring unit 15 is below the predefined value
  • Threshold or other predetermined threshold falls and / or if the patient again feels sufficiently treated and depresses a deactivation button present on the patient programmer and / or after the expiration of a constant stimulation time preset by the physician.
  • the learning phase is ended and the device 100 is operated in the second operating mode, the actual neurofeedback phase.
  • the actual Neurofeedbackphase is exploited that at least some of the patients have now safely learned the Neurofeedback.
  • the stimulation unit 11 may be open during the second operating mode
  • Stand-by ie in a standby service
  • the implant then only switches on in the (unlikely) case of need if, for example, the expression of the pathologically synchronous neuronal activity determined with the aid of the measuring unit 15 exceeds a predetermined threshold value, which may differ, for example, from the corresponding threshold value in the first operating mode, and / or the PA- tient by pressing the activation key initiated.
  • a predetermined threshold value which may differ, for example, from the corresponding threshold value in the first operating mode, and / or the PA- tient by pressing the activation key initiated.
  • the sensory stimulator is not carried on by the patient during the actual neurofeedback phase, but reapplied only in the (unlikely) case of need.
  • the neuro-feedback unit 12 can communicate to the patient by means of the second stimuli 22 the expression of the pathologically synchronous neuronal activity determined with the aid of the measuring unit 15 or else transmit a warning signal to the patient only when a predetermined threshold value is exceeded the patient can apply the learned neurofeedback to reliably counteract morbid synchronous neuronal activity in the brain or spinal cord without any form of electrical or sensory neurostimulation performed by the stimulation unit 11.
  • the control unit 10 can, for example together with the measuring unit 15, which may for example be designed as epicortical electrode or animal fenelektrode be implanted in the body of the Pati ⁇ ducks.
  • the control unit 10 measures the thera Guideic effect ⁇ basis of information provided by the measuring unit 15 available signals 26 and determines the extent of the disease specific for the respective pathologic activi- ty.
  • the amplitude of the oscillations ⁇ pathological conditions is determined in typical frequency ranges of the local field potentials, eg at akinetic Parkinsonpatien-
  • the integral power in the beta frequency between 10 Hz and 30 Hz. With an effective neurofeedback or an effective neurostimulation this amplitude decreases.
  • the critical value can be set by the doctor individually for each patient.
  • typical values can be selected as the default value for the critical value, eg, the mean of the amplitude plus twice the standard deviation in ranges of the frequency spectrum without frequency peaks and above, for example, 70 Hz.
  • the device 100 allows a much gentler treatment of severe neurological and psychiatric disorders compared to conventional neuro-stimulation devices. It is crucial that in one embodiment, the applied by the stimulation unit 11 electrical or sensory neurostimulation in the second mode, the actual Neurofeedbackphase completely avoided in favor of Neurofeedback treatment or in another embodiment, the electrical or sensory neuro ⁇ stimulation in the second mode of operation only is activated when the therapeutic success of neurofeedback is insufficient. This avoids side effects and involves the patient as a mature partner in the treatment.
  • a further advantage of the device 100 is that the patient always falls back on the safe Neu rostimulationsà in case of failure of the Neurofeedback and thus apply the necessary for the performance of the Neurofeedback trust, insbesonde ⁇ ⁇ even in difficult situations such as stress, much easier and more legitimate can.
  • the resulting serenity of the patient improves thera ⁇ Terminator success of neurofeedback significantly.
  • an electrical neurostimulation leads to Mauwir ⁇ fluctuations due to the current entry.
  • the current input and thus the side effects are reduced by the device 100.
  • the sensory neurostimulation is often uncomfortable due to the stimulators and can be disruptive or even dangerous in the performance of everyday tasks and in particular when driving a vehicle in traffic.
  • FIGS. 2 to 5 the mode of operation of the device 100 is summarized schematically.
  • Fig. 2 shows a ⁇ The rapieschema with an electrical, applied via the stimulation unit 11 neurostimulation.
  • learning phase Neuro ⁇ Feed back the first operating mode
  • the second operating mode "learned Neuro Feedback”
  • the neurostimulator 11 is only activated to the relevant extent when the pathological neuronal activity reoccurs.
  • Fig. 3 shows a therapy scheme with a non-invasive
  • Stimulation unit 11 which applies optical, acoustic, tactile, vibratory and / or thermal first stimuli 21. After learning the neurofeedback by the patient, the patient no longer wears the sensory neurostimulator 11 and restores it only when symptoms recur, are persistently disrupted, and are no longer controllable by neurofeedback.
  • FIGS. 4 and 5 show flowcharts of the treatment procedure of a patient with the device 100 if it has an electrical stimulation unit 11.
  • the implanted stimulation unit 11 automatically switched on inadequate effect of the neurofeedback therapy, ie when the expression of the pathological feature is exceeded by a threshold value.
  • the implanted stimulation unit 11 is deactivated fourth when the expression of the pathological feature un ⁇ ter falls the threshold.
  • the patient activates the implanted electrical stimulation unit 11 by pressing the activation button if the patient does not feel well treated.
  • the stimulation unit 11 is then - depending on the embodiment - active for a specified period of time or remain active until the patient tivated the stimulation unit 11 via the deactivation button Deak, or the stimulation unit 11 turns be ⁇ must controlled from, ie as soon as the pathological feature ei ⁇ falls below a predetermined threshold.
  • Fig. 6 shows schematically an embodiment of the device 100, wherein the stimulation unit 11 is not implanted, but non-invasive, ie, optical, acoustic, tactical tile, vibrational and / or thermal first stimuli 21 he witnesses ⁇ (not shown).
  • the measuring unit is realized by depths ⁇ electrodes 15, which are connected via cable 16 with a likewise implanted control unit 10th.
  • Control unit 10 reports back, the extent of measured on the Tiefenelekt ⁇ roden 15 pathological neuronal activity via the neuro-feedback unit 12 to the patient, so that it can act against corresponds neurofeedback the pathological activity.
  • the control unit 10 and the neurofeedback unit 12 are connected via radio.
  • FIG. 7 shows schematically a further embodiment of the device 100, in which the stimulation unit 11 is implanted and generates electrical first stimuli 21.
  • the depths ⁇ electrodes act in the present embodiment both as a stimulation unit 11 as well as a measuring unit 15th
  • the depth electrodes 11, 15 are connected to the control unit 10 via cables 16 and a connector 17, which is not necessary in the embodiment shown in FIG. 6.
  • the control unit 10 reports the extent of the pathological neuronal activity measured via the depth electrodes 11, 15 back to the patient via the neurofeedback unit 12 so that the latter can counteract the pathological activity by neurofeedback.
  • the control unit 10 controls the depth electrodes 10 so that they apply the electrical first stimuli 21.
  • the first stimuli 21 may be electrical, optical, acoustic, tactile, vibratory and / or thermal stimuli which have a desynchronizing effect or at least cause a reduction in the coincidence rate of the diseased neurons. Is described below that it is possible to stimulate by means of the stimulation unit 11 different areas of the Ge ⁇ brain 29 or spinal cord 29 separately by the applied first stimuli 21 via nerves leads to different target areas in the brain 29 and / or back ⁇ mark 29 are forwarded. The target areas can be stimulated with possibly different and / or time-shifted first stimuli 21.
  • the neuron population 30, which has a pathologically synchronous and oscillatory activity, is administered first stimuli 21, which in the neuron population 30 cause a reset, a so-called reset, of the phase of the neuronal activity of the stimulated neurons.
  • the phase of the stimulated neurons is set to a particular phase value, eg 0 °, independent of the current phase value.
  • the phase of neuronal activity of the diseased Neuronenpopu ⁇ lation 30 is controlled by a targeted stimulation. Since it is also possible, the morbid neuron population
  • the phase of neuronal activity of the diseased neuron popula- be reset at 30 at the different stimulation sites at different times.
  • the diseased neuron population 30, whose neurons were previously synchronous and active with the same frequency and phase is split into a number of subpopulations, which in
  • Fig. 1 are shown schematically and are identified by the reference numerals 31, 32, 33 and 34 (for example, four subpopulations are shown here).
  • the neurons are for a Zuschset- the phase zen continue synchronously and firing continues with the same pathological rate, but each of the subpopulations 31 to 34 has with respect to their activity, the neural phase on to it by the Stimulation stimulus was imposed. This means that the neuronal activities of the individual subpopulations 31 to 34 after the resetting of their phases continue to have an approximately sinusoidal course with the same pathological frequency, but different phases.
  • the state generated by the stimulation is unstable with at least two subpopulations, and the entire neuro ⁇ nenpopulation 30 quickly approaches ren a state of complete desynchronization, in which the neuron-dip uncorrelated.
  • the desired state that is the complete Desynch ⁇ ronisation is, therefore after the application of the first stimuli 21 are not immediately available, but usually sets in within a few periods or even in less than one period of the pathological frequency.
  • One theory for explaining the stimulation success is based on the fact that the ultimately desired desynchronization is made possible by the morbidly increased interaction between the neurons.
  • a self-organization process is used, which is responsible for the morbid synchronization.
  • the same causes a Auftei ⁇ averaging a total population of 30 in subpopulations 31 to 34 with different phases a desynchronization follows.
  • no desynchronization would occur.
  • the reorganization of the connectivity of neural networks ge ⁇ disrupted can be obtained, so that sustained therapeutic effects can be caused by long the stimulation with the stimulation unit. 11
  • the achieved synaptic remodeling is of great importance for the effective treatment of neurological or psychiatric disorders.
  • FIGS. 8A, 8B and 9 Embodiments of the neurofeedback unit 12 for generating the second stimuli 22 are shown in FIGS. 8A, 8B and 9.
  • the neurofeedback unit 12 is implemented as a so-called "neurofeedback clock" which is convenient for the patient to wear.
  • FIG. 8A shows the front view
  • FIG. 8B the rear view of the neurofeedback clock 12.
  • the neuro-feedback watch 12 consists of a middle part 40, bracelets 41, a closure part 42 and associated holes 43. Alternatively, a hook-and-loop fastener or any other equivalent closure may be used.
  • the middle part 40 contains a loudspeaker 44 for generating acoustic second stimuli 22, for example a melody or a humming, warning or whistling sound, and a display 45 for generating a non-glaring optical second stimulus 22, for example one more depending on the expression of the pathological feature or less-opening flower or a concentric red "warning" disc having a diameter that correlates with the expression of the pathological neuronal activity, or a beam that increases with the expression of the pathological neuronal activity.
  • the neurofeedback clock 12 may be equipped with one or more vibrators 46 that generate "warning" tactile and / or vibratory second stimuli 22.
  • thermostimulator is arranged on the back of the neuro-feedback clock 12, with which "warning" thermal second stimuli 22 of the skin of the patient can be administered.
  • warning second stimuli 22 can not be applied until the expression of the pathological feature has exceeded a predefined threshold value.
  • the neurofeedback clock 12 may also be configured to include only a second stimulus 22 of a sensory modality, e.g. only an optical stimulus, generated.
  • the power supply of the neurofeedback clock 12 is provided by a battery and / or solar cells and / or a mechanical flywheel inside the neurofeedback clock 12.
  • the neurofeedback can watch 12 additionally include an accelerometer, which can be measured ducks morbid oscillatory activity, for example by krankhaf ⁇ tem tremor, or the average activity level of the Pati-.
  • the mean activity level of the patien ⁇ th reflects the slowdown or impoverishment of the movement or the immobility of the patient resist (ie Brady, hypo- and akinesia).
  • FIG. 9 Another embodiment of the neurofeedback unit 12 is shown schematically in FIG. 9. This is an example mobile-shaped device, which for example can be worn in a shirt pocket ⁇ or pocket of the patient and the acoustic means of a loudspeaker 47 generates second tire ze 22nd
  • an external programmer to the physician may be pre see ⁇ , can be set with which the parameters of the control unit 10, the stimulating unit 11, neuro-feedback unit 12 and / or the measuring unit 15 °.
  • an external Pro ⁇ programming device to the patient also will be provided with which the Patient can issue the stimulation devices or can modify parameters of the stimulation unit 11 in narrow limits dictated by the physician.
  • the particular for the patient programming unit may contain the above already described bene functionality by means of which the patient can independently acti fours for example by pressing an activation or deactivation key ⁇ neurostimulation operation ⁇ or off.
  • the programming devices can, for example, communicate via radio links with the respective components of the stimulation device.
  • Stimulation units for producing electrical first Rei ⁇ ze The following describes embodiments of the stimulation unit 11 for generating electrical stimuli first 21st Such stimulation units can also be found in German Patent Application No. 10 2008 052 078.0 entitled “Apparatus and Method for Conditioned Desynchronizing Stimulation", filed on 17 October 2008 with the German Patent and Trademark Office. The entire disclosure content of German Patent Application No. 10 2008 052 078.0 is hereby included in the disclosure of the present application.
  • the electrical stimuli first 21 desynchronized electrical stimulation signals are used or electrical stimulation signals that cause at least a reduction in the Koinzi ⁇ denzrate the diseased neurons.
  • the stimulation unit is designed as Stimulati ⁇ onselektrode 11, by means of which are transmitted to the brain Ü 29 or spinal cord 29 of patient 21, the first Rei ⁇ ze.
  • the stimulation electrode 11 can play, have one or two or more surfaces in StimulationsAuth- ⁇ standing and after implantation with the tissue of the brain or spinal cord 29 via the contact 29 in the first electrical stimuli are applied 21st In Fig. 10 a Stimulati ⁇ onselektrode 11 is schematically and exemplarily shown.
  • the stimulation electrode 11 be ⁇ is of an insulated electrode shaft 50 and at least one, for example two or more StimulationsWalletflä ⁇ surfaces that have been introduced into the electrode shaft 50th
  • the stimulation electrode 14 contains four stimulation contact surfaces 51, 52, 53 and 54.
  • the electrode shaft 50 and the stimulation contact surfaces 51 to 54 may be made of a biocompatible material.
  • the stimulation contact surfaces 51 to 54 are electrically conductive, for example, they are made of a metal ge ⁇ , and are located after implantation in direct electrical contact with the nerve tissue.
  • each of StimulationsWalletflä ⁇ chen 51 to 54 controlled by a separate lead 55 ⁇ the or it can display the recorded measurement signals are removed 26 via the leads 55, provided that the stimulation ⁇ electrode used 11 simultaneously as a measuring unit 15 becomes.
  • two or more stimulation pads 51 to 54 may be connected to the same lead 55.
  • the E may include a reference electrode 56 lektrode 11 whose upper ⁇ surface may be larger than that of the stimulation contact surfaces 51 to 54.
  • the reference electrode 56 is used in the stimulation tion of the nerve tissue used to generate a reference potential.
  • one of the stimulation pads 51 to 54 may be used for this purpose. That is, it can either be stimulated in a unipolar manner between a single stimulation contact area 51 to 54 and the reference electrode 56 (or the housing of the control unit 10) or bipolarly between different stimulation contact areas 51 to 54.
  • the electrode 11 can also be used as a measuring unit 15 within the device 100. In this case, measurement signals 25 are recorded via at least one of the contact surfaces 51 to 54.
  • the stimulation pads 51 to 54 may be connected to the control unit 10 via cables or via telemetric connections.
  • the plurality of stimulation contact surfaces 51 to 54 enables light to 51 to 54 to stimulate different regions of the brain 29 or ⁇ Scotland ckenmarks 29 via the individual stimulation contact surfaces separately.
  • each of the stimulation contact surfaces 51 to 54 can be connected to the control unit 10 via its own connecting line 55. This allows the control unit 10 to generate specific first stimuli 21 for each of the stimulation contact surfaces 51 to 54.
  • the stimulation contact surfaces 51 to 54 may be implanted in the patient such that the first stimuli 21 applied to the tissue are transmitted via nerve leads to different target areas located in the brain 29 and / or spinal cord 29. Consequently, 100 different target areas in the brain 29 and / or spinal cord 29 can be stimulated with possibly different and / or delayed first stimuli 21 by means of the device.
  • the neuron population 30 which has a pathologically synchro ⁇ ne and oscillatory activity, by means of the Stimu ⁇ lationselektrode 11 first stimuli 21 administered, which in the neuron population 30 a reset, a so-called set, the phase of neuronal activity of cause stimulated neurons.
  • the phase of the stimulated neurons is set to a particular phase value, eg 0 °, independent of the current phase value.
  • the phase of neuronal activity of the diseased neuron population 30 is controlled by targeted stimulation. Furthermore, it is possible on the basis of the plurality of stimulation ⁇ contact surfaces 51 to 54 to stimulate the pathological Neuronenpo ⁇ pulation 30 at different locations. This allows you to reset the phase of the neuronal activity of the ill ⁇ liable neuron population 30 at different pacing sites at different times. As a result, thereby the pathological Neuronenpopula ⁇ tion 30, the neurons before frequency synchronously and with the same frequency and phase were active, split into several subpopulations, which are shown schematically in Fig. 1 and by the reference numerals 31, 32, 33 and 34 Marked are.
  • the stimulation contact surfaces 51 to 54 may be placed on or in the patient's brain or spinal cord tissue 29 such that the first stimuli 21 applied by the stimulation contact surface 51 irritate the subpopulation 31 and reset its neuronal phase and those applied by the stimulation contact surface 52 first stimuli 21 irritate the subpopulation 32 and reset its neuronal phase.
  • the stimulation contact surface 53 or 54 with respect to the subpopulation 33 or 34.
  • the condition created by the stimulation with at least two subpopulations is unstable, causing the entire neuron population 30 to rapidly approach a state of complete desynchronization in which the neurons fire uncorrected.
  • stimulation signals to cause ⁇ resetting the phase of neurons are submitted time offset the different types of stimulation contact surfaces 51 to 54 to each of stimulated nerve tissue.
  • out of phase with the stimulation signals for example, or applied with different polarity so that they perform as a result also to a time-shifted Zugurset ⁇ zen the phases of the different subpopulations 31 to 34.
  • the device 100 can be operated, for example, in a so-called "open loop” mode, in which the control unit 10 generates predetermined first stimuli 21 and these are delivered via the stimulation contact surfaces 51 to 54 to the nerve tissue. Furthermore, the device 100 can also be operated as a so-called "closed-loop" system this case, the measuring unit 15 placed on the patient ⁇ recessed measurement signals 26 provides and forwards them to the STEU ⁇ erritt 10 on. With the aid of the measurement signals 26 a demand-driven ⁇ Sti mulation can be performed. For this purpose, the control 10 detects ⁇ unit based on the power consumed by the measuring unit 15 measuring signals 26, the presence and / or the expression of one or more pathological features.
  • measuring signals 26 may be set to play, the thickness of the first stimuli 21 in the ⁇ ⁇ .
  • one or more threshold values can be specified, and when the amplitude or the magnitude of the measurement signals 26 exceeds a specific threshold value, a specific strength of the first stimuli 21 is set.
  • the measuring signals 26 recorded by the measuring unit 15 are used directly or optionally after one or more processing steps as first stimuli 21 and are fed by the control unit 10 into the stimulation electrode 11.
  • the measurement signals can be amplified 26 and, where ⁇ appropriate, according to mathematical clearing (for example, after mixing the measurement signals) having a time delay and linear and / or nonlinear combination steps and combinations of processed and concentrated be ⁇ supplied to the stimulation electrode.
  • the billing mode is chosen so that the pathological neuronal activity is counteracted and the stimulation signal also disappears with decreasing morbid neuronal activity or at least significantly reduced in its strength.
  • Stimulati ⁇ onsclar which can be carried out, for example, the device 100 is shown in Fig. 11 schematically. There are among each other via the stimulation tact surfaces 51 to 54 applied first stimuli 21 plotted against the time t.
  • each of the stimulation pads 51-54 periodically applies the first stimulus 21 to the respective area of tissue on which the stimulation pads 51-54 are placed.
  • the administration of the first stimuli 21 via the individual stimulation contact surfaces 51 to 54 takes place with a time delay between the individual stimulation contact surfaces 51 to 54. For example, the beginning of temporally successive and first applied by different stimulation contact surfaces 51 to 54 Stimuli 21 be shifted by a time ⁇ .
  • the frequency f st i m may for example be in the range of mittle ⁇ ren frequency of the pathological rhythmic activity of the target network.
  • ER- the average frequency is typically in the Be ⁇ rich 1-30 Hz, but can also be outside this range. It should be noted that the frequency, with which the affected neurons fire synchronously in neurological and psychiatric disorders, is usually not constant, but may well have variations and moreover shows individual deviations in each patient.
  • a first stimulus 21 may be a pulse train consisting of a plurality of individual pulses 60, as shown in FIG.
  • the pulse trains 21 may be made 60 each of 1 to 100, in particular 2 to 10, electrical charge-balanced ⁇ rule individual pulses.
  • the pulse trains 21 are applied, for example, as a sequence with up to 20 or more pulse trains. Within a sequence, the pulse trains 21 are repeated at the frequency f st m in the range of 1 to 30 Hz.
  • a pulse train 21 consisting of three individual pulses 60 is shown in FIG.
  • the individual pulses 60 are repeated at a frequency f eo in the range from 50 to 500 Hz, in particular in the range from 100 to 150 Hz.
  • the individual pulses 60 may be current- or voltage-controlled pulses which are composed of an initial pulse component 61 and a subsequent pulse component 62 flowing in the opposite direction, the polarity of the two pulse components 61 and 62 also being opposite to the polarity shown in FIG can be reversed.
  • the duration 63 of the pulse component 61 is in the range between 1 ⁇ and 450 3.
  • the Amp ⁇ litude 64 of the pulse component 61 in the case of stromkontrol- Herten pulses in the range between 0 mA and 25 mA, and in the case of voltage-gated pulses in the range 0 to 20 V.
  • the amplitude of the pulse portion 62 is less than the Ampli ⁇ tude 64 of the pulse portion 61.
  • the pulse components 61 and 62 are ideally sized such that the La ⁇ tion, which is transmitted by them, at both Pulsantei ⁇ len 61 and 62 is the same size, ie the in Fig. 13 Schraf- The marked areas are the same size.
  • the control unit can for example also produce differently configured Stimu ⁇ lationssignale 10, eg temporally continuous stimulus ⁇ pattern.
  • Stimu ⁇ lationssignale 10 eg temporally continuous stimulus ⁇ pattern.
  • the time delay ⁇ between two successive first stimuli 21 does not necessarily always have to be the same. It can certainly be provided that the time intervals between the individual first stimuli 21 are chosen differently. Furthermore, the delay times can also be varied during the treatment of a patient. The delay times with regard to the physiological signal propagation times can also be adjusted. Furthermore, during the application of the first stimuli 21
  • Breaks are provided during which there is no stimulation.
  • Such a pause is shown by way of example in FIG. 14.
  • the pauses can be maintained after any number of stimulations. For example, stimulation during N consecutive periods of ge Tgtim be performed and then currency ⁇ rend M periods of length T st i m are adhered without stimulation pause, where N and M are small integers, such as in the range of 1 to 10.
  • This scheme may be continued either periodically or stochastically and / or deterministically, eg chaotically, modified.
  • a further possibility to deviate from the one shown in Fig. 11 strictly periodic stimulation pattern is the time sequence of the individual first 21 stimuli sto ⁇ chastisch or deterministic or mixed stochastisch- to vary deterministic.
  • the order in which apply the stimulation ⁇ contact surfaces 51 to 54, the first stimuli 21 varies, as is exemplarily shown in Fig. 15.
  • This variation can be stochastic or deterministic or mixed stochastic-deterministic.
  • the randomization shown in FIG. 15 may be combined with the stimulation form shown in FIG.
  • a re-randomization may be performed or it is performed after each break, the length of M x T st i m randomization and within the following N stimulation periods remains the Erasmusnfol ⁇ ge, in which the stimulation contact surfaces 51 to 54 apply the first stimuli 21, constant.
  • the "closed loop" mode of the device 100 can be configured such that the measuring signals 26 received by the measuring unit 15 are converted by the control unit 10 directly or optionally after one or more processing steps into electrical first stimuli 21 and be applied by the stimulation electrode 11 appli ⁇ .
  • the device 100 does not necessarily have to contain at least two stimulation pads. This type of stimulation, in which the measured signals recorded on the patient are fed back into the body of the patient, could in principle also be carried out with only a single stimulation contact surface, however, it is also possible to provide any, larger number of stimulation contact surfaces.
  • the above-described "closed loop” mode can be used if just ⁇ tivity for desynchronizing a neuron population with a pathologically synchronous and oscillatory neural AK.
  • the measurement signals can 26, for example, amplified and optionally after mathematical ⁇ shear clearing (for example, after mixing the measurement signals) having a time delay and linear and / or non-linear
  • Allocation steps are used as first stimuli 21 for electrical stimulation.
  • the billing mode can be chosen so that the pathological neuronal activity is counteracted and the stimulation signal also disappears with decreasing morbid neuronal activity or at least significantly reduced in its strength.
  • Stimulation units for generating optical first stimuli :
  • Embodiments of the stimulation unit 11 for generating optical first stimuli 21 will be described below.
  • Such stimulation units can also be found in German patent application no. 10 2008 012 669.1 entitled “Device and method for visual stimulation", which was deposited with the German Patent and Trademark Office on March 5, 2008. The entire disclosure of the German patent application no. 10 2008 012 669.1 is incorporated into the ⁇ Of fenbarung the present application.
  • FIG. 16 schematically shows an embodiment of the stimulation unit 11, which contains a plurality of stimulation elements.
  • the stimulation unit 11 has two stimulation elements 112 and 113, which are actuated by the control unit 10.
  • FIG. 16 also shows an eye 114 of a patient.
  • the stimulation elements 112 and 113 During operation of the stimulation unit 11, the stimulation elements 112 and 113 generate optical first stimuli 115 and 116, respectively, which are received by the patient via one or both eyes 114 and transmitted via the optic nerves to neuron populations in the brain.
  • the control unit 10 controls the stimulation elements 112 and 113 in such a way that the optical first stimuli 115 and 116 are generated, for example, with a time delay. Instead of a time-shifted application of the optical first stimuli 115 and 116, these can also be applied with different phases or different polarities. Furthermore, mixed forms are also conceivable, ie the optical first stimuli 115 and 116 may, for example, be delayed in time and have different polarities.
  • the stimulation unit 11 can be designed such that it can be used to carry out, for example, only one of the above-mentioned stimulation variants, or the stimulation unit 11 can al ⁇ ternatively be designed so that more of the said stimulation variants can be performed with it.
  • the optical first stimuli 115 and 116 can be based on a luminance variation (or variation of the light intensity or light intensity), for example, they can be applied as pulses or as sequences of pulses with varying luminosity or brightness.
  • the optical first stimuli 115 and 116 may vary depending Ausgestal ⁇ tung the stimulation unit 11 as luminance modulation natural optical stimuli, for example by means of a homogeneous o- the segmented transmission glasses, as in addition to egg nem natural visual stimulus occurring, modulated visual stimulus, for example by means of a partially transparent light glasses, or as an artificial optical brightness stimulus, for example by means of an opaque spectacle, administered. If the patient receives the optical first stimuli 115, 116 over both eyes 114, the respective optical first stimuli 115, 116 of both eyes 114 may be correlated.
  • the optical first stimuli 115, 116 generated by the stimulation elements 112, 113 can be configured such that, when they are taken up by the retina and guided via the optic nerve to a neuron population with a pathologically synchronous and oscillatory activity, in FIG Neuron population to reset the phase of neuronal activity of the stimulated neurons.
  • the visual field 117 of a patient is shown schematically.
  • a visual field is the space that is surveyed by an eye without eye movements.
  • the field of view 117 is shown in a circle for simplicity.
  • the field of view has a more rounded oval shape.
  • the exact size and shape of the Ge ⁇ field of view is subject to individual variations and is also dependent on age.
  • Points in the visual field 117 can be described, for example, with the aid of their polar coordinates.
  • Fig. 17 are the spatial positions of the stimulation elements 112 and 113 are exemplified in the field of view Ge ⁇ 117th
  • one corner point of the stimulation elements 112 and 113 is marked with a vector 118 or 119.
  • the vectors 118 and 119 can be described in the polar coordinate system by their magnitude and the angle (us or (ng) they include with the x-axis.
  • Different points in the field of view 117 are ⁇ rank on the lens of the eye on different parts of the retina.
  • the different parts of the retina are in turn connected via the optic nerve with different neurons in the brain.
  • stimulation elements 112 and 113 each have different neurons are stimulated Kgs ⁇ NEN. Consequently, the stimulation elements can be 112 and 113 arranged so as ⁇ possibly more stimulation elements spatially in Ge ⁇ field of view 117 of the patient, that the recorded from the retina optical stimuli to different target regions in the brain.
  • ⁇ Ronen population with the stimulation elements 112 and 113 are specifically stimulated by different subpopulations of a pathological new, and it can be performed a time-shifted to ⁇ resetting the phases of these sub-population, as described above in connection with FIG. 1 described ,
  • the stimulation unit 11 can be operated, for example, in a so-called "open loop" mode, in which the
  • the stimulation unit 11 controls such that the stimulation elements 112, 113 predetermined optical generate first stimuli 115, 116. Furthermore, the Stimula ⁇ tion unit 11 may also be a schematically depicted in Fig 18 "closed ⁇ '' together with the control unit 10 and the measuring unit 15 - are trained system..
  • parameters of the optical first stimuli 115, 116 such as the strength (Ampli ⁇ tude) of the stimuli or the frequency of the stimulation or the intervals between the stimulation sequences set by the control unit 10 based on the severity of the pathological features.
  • the measurement signals recorded by the measuring unit 15 are converted directly or optionally after one or more processing steps into optical first stimuli and applied by the stimulation unit 11.
  • the measurement signals may be amplified and optionally after mathematical clearing (for example, after mixing the measurement signals) with a Zeitverzöge ⁇ tion and linear and / or nonlinear combination steps as control signals to the control inputs of the stimulation ⁇ elements 112, are fed 113th
  • the clearing mode is that the pathological neuronal Ak ⁇ tivity is counteracted and the stimulation signals also disappear with decreasing pathological neuronal activity or at least significantly reduced in their thickness so selected.
  • FIG. 19 schematically shows an embodiment of the stimulation unit 11 as transmission goggles, which consists of the following components: (i) two enclosure parts 121, each with one transmission-modulated lens 122 (for each eye individually), (ii) two earhooks 123, with which the goggles are mechanically held behind the patient's ear, and (iii) the control unit 10, which controls the transmission of the transmission modulated glasses 122 of the glasses controls.
  • the control unit 10 which controls the transmission of the transmission modulated glasses 122 of the glasses controls.
  • the control unit 10 which controls the transmission of the transmission modulated glasses 122 of the glasses controls.
  • the control unit 10 which controls the transmission of the transmission modulated glasses 122 of the glasses controls.
  • a battery or a battery for the power supply of the electrical components can be housed in the control unit 10 or structurally separate from the control unit 10 in or on the glasses.
  • the glasses can be switched on by the patient by means of a control unit 124 (eg button and / or knob).
  • the rotary control can be used, for example, to set the maximum stimulation intensity.
  • a control medium 125 may be provided, which is connected to the control unit 10, for example by telemetry or via a connection cable. In the case of a connection via a cable, connectors for connection or disconnection can be used.
  • physician control medium may be (not shown) provided wel ⁇ ches telemetrically or is connected via a connecting cable to the control unit 10th
  • plug connections can be used for connecting or disconnecting.
  • one or more sensors e.g. EEG electrodes or an accelerometer, for registration and / or documentation of the stimulation success and for examination by the physician.
  • Fig. 20 a as a stimulation unit ⁇ designed transmission glasses 11 is shown with homogeneous TRANSMISSI ⁇ onsgläsern 122 schematically.
  • the transmission glasses 11 environmentally further summarizes earhook 123 for mechanical attachment to the patent tientenkopf, a web 140, which connects the two TRANSMISSI ⁇ onsgläser 122 and enclosure portions 121, in which the transmission lenses are edged 122nd
  • the transmissi Onsgläser 122 are homogeneous, ie not divided into different segments.
  • the transmittance of the right and left transmission lens 122 may be controlled separately ⁇ to, ie, the transmission lenses 122 may onsetti as Stimulati- 112 and 113 are used in the sense of the embodiment shown in Fig. 16.
  • FIG. 21 shows a transmission goggle 11 with segmented transmission glasses.
  • the transmission glasses are each divided into different segments whose transmission can be controlled separately.
  • the Segmentie ⁇ tion may be, for example, radial and / or circular (the two is shown in Fig. 21).
  • the exporting ⁇ tion of a segmented transmission goggles 11 shown in Fig. 21 is only an example to understand. The number of segments as well as the geometric shapes of the individual segments can be chosen differently.
  • the segments of the transmission goggles 11 correspond to the stimulation elements shown in FIG. In FIG. 21, by way of example, four of the segments are designated by the reference symbols 141, 142, 143 and 144.
  • the segments 141 to 144 Based on the segments 141 to 144 will be explained below by way of example, as by a time-delayed resetting of the phases of subpopulations of a morbidly synchronous and oscillatory neuron population desynchronization of the entire population of neurons can be achieved.
  • the segments 141 to 144 have been selected such that the first optical stimuli they generate are each preferably taken up by a specific part of the retina of the patient, from where the stimuli are forwarded to specific areas of the brain, so that the above described splitting ⁇ tion of a diseased neuron population in subpopulations is made possible.
  • the optical first stimuli of the segments 141 to 144 can be generated, for example, with a time delay. Synonymous with the time-delayed generation of the stimuli is a phase-shifted generating the stimuli, which also leads to a delayed reset of the phases of the different subpopulations.
  • FIG. 22 A suitable for the purposes described above Stimulati ⁇ onsclar, which can be carried out for example with the above-described transmission eyeglasses 11 is illustrated in Fig. 22 schematically.
  • first stimuli 145 are mutually plotted against time t.
  • FIG. 22 it is assumed that only the segments 141 to 144 of the transmission goggles 11 generate optical first stimuli 145, ie only the transmission of these segments is modulated by the control unit 10.
  • segments 141 to 144 may be used to generate the optical stimuli. It is possible to use as in Fig. 22 only a selection of segments of the transmission 11 to the glasses Sti ⁇ mulation or all segments. In the example shown in FIG. 22 process each of the segments 141 to 144 periodically applied to the optical first stimulus 145. In each segment 141 to 144 of the stimulus is applied three times in the vorlie ⁇ constricting Example 145. Alternatively, the stimulus 145 per sequence could be repeated, for example, one to fifteen times.
  • the frequency f st i m may for example be in the range of mittle ⁇ ren frequency of the pathological rhythmic activity of the target network. In neurological and psychiatric disorders, the average frequency is typically in the loading ranging from 1 to 30 Hz, but may be outside this Be ⁇ kingdom. It should be noted that the frequency with which the diseased neurons fire synchronously is usually not constant, but may well have variations and, moreover, shows individual deviations for each patient.
  • the mean peak frequency of the pathological rhythmic activity of the patient can then be used as a stimulation frequency f st i m or even be va ⁇ riiert, for example, in a range of f st i m - 3 Hz to f st st m + 3 Hz.
  • a frequency f st i m in the range of 1 to 30 Hz can be used without previous measurement can be selected and these vari- example, during stimulation are ated until the frequency f st i m is found at which achieve the best stimulation success to let.
  • the stimulation frequency F St i m a Hérange for the disease known literature value ⁇ subjected. This value can possibly be varied until, for example, optimal stimulation results he is aiming ⁇ .
  • Segment 141 controlled by the control unit 10 such that the transmission, ie the light transmission of the segment 141 is minimal.
  • the control unit 10 switches the transmission of the segment 141 to the maximum value. In other words, this means that the segment 141 becomes less transparent when stimulated. Accordingly takes the patient perceives diminished brightness of ambient light in the region of segment 141 during stimulation.
  • the duration of a first optical stimulus 145 ie the time ⁇ margin between times ti and t2 can beispielswei ⁇ s T s tim / 2, respectively.
  • the time currency ⁇ rend is stimulated, and the subsequent stimulation break equal length.
  • Stimulati ⁇ onsdauern for example in the range of T st i m / 2 - Tstim / 10 to Tgtim / 2 + Tgtim / 10 min.
  • Other stimulation periods are possible and can be determined experimentally, for example.
  • the administration of the optical first stimuli 145 via the individual segments 141 to 144 of the transmission eyeglasses 11 takes place with a time delay between the individual segments 141 to 144.
  • the beginning of temporally successive and of different segments 141 until 144 applied stimuli 145 are shifted by a time ⁇ .
  • T st in / 4 The requirement that the time delay ⁇ between each two consecutive stimuli amounts to 145 T st m / N can be deviated to a certain extent.
  • the rectangular shape of the individual pulses 145 illustrated in FIG. 22 represents an ideal form. Depending on the quality of the individual pulse ⁇ 145 generating electronics and transmission glasses 122 is deviated from the ideal rectangular shape. However, it is also possible to use stimuli with less sharp edges, ie smoother progressions, for example depending on the underlying disease of the patient as well as on the individual psycho-physical nature, eg sensitivity to glare.
  • the control unit 10 may, for example, also produce differently configured optical first stimuli, as illustrated by way of example in FIGS. 23 to 25.
  • triangular optical first stimuli 146 are shown. At time ti, for example, is switched to minimum transmission and until the time t 2 , the transmission increases continuously to the maximum value. Alternatively it can be provided that the transmission at the beginning of the stimulus 146 is maximum and then falls to the minimum value.
  • triangular optical first stimuli 147 are shown with a rising and a falling edge. Beginning at time ti, the transmission is increased at ⁇ game as here and after reaching the maximum until the time t 2 is reduced again.
  • the rising and falling edges of the stimuli are "rounded off". This is shown in FIG. 25 on the basis of rounded rectangular optical first stimuli 148.
  • the stimuli can also be replaced by a simple sinusoidal shape.
  • the temporal Ver ⁇ delay ⁇ need not necessarily be always the same size between two consecutive stimuli 145, 146, 147 and 148th It can be provided that the time intervals between the individual stimuli 145, 146, 147 and 148 are selected differently. Furthermore, the delay times can also be varied during the treatment of a patient. The delay times with regard to the physiological signal propagation times can also be adjusted. Furthermore, pauses may be provided during the application of stimuli 145, 146, 147, and 148, respectively, during which no stimulation occurs. The pauses can be selected arbitrarily long and, in particular, be an integer multiple of the period T st m .
  • the breaks can be followed after any number of stimulations. For example, a stimulation during N consecutive periods of length T st i m are performed and then a Stimulation break during M periods of length T st i m Standing ⁇ th, where N and M are small integers, such as in the range of 1 to 15.
  • This scheme can either be continued periodically or stochastically and / or deterministic table, for example, chaotic to be modified.
  • a further possibility of deviating from the strictly periodic stimulation pattern shown in FIGS. 22 to 25 is to compare the time intervals between successive stimuli 145, 146, 147 and 148 per segment 141 to 144 stochastically or deterministically or mixed stochastically to vary deterministically.
  • the order in which the segments 141 to 144 apply the stimuli 145, 146, 147 and 148, respectively, can be varied per period T st m (or in other time steps).
  • This variation can be stochastic or deterministic or mixed stochastic-deterministic.
  • belonging together within N Sti ⁇ mulationsperioden the same order of the segments may in the stimulation pattern to be followed at the N stimulation periods of M periods break and as a cycle to be repeated, are 141 to 144 is selected, which, however, varies between different blocks with N stimulation periods.
  • This variation can be stochastic or deterministic or mixed stochastic-deterministic.
  • each of the segments 141 to 144 may generate a (eg, continuous) sinusoidal signal with the phases of the sinusoidal signals generated by different segments 141-144 shifted from one another.
  • the mean frequency of the sinusoidal signals can be the same.
  • the phase shifters ⁇ environments between the individual sine waves can be either predefined, such as may be the phase shift between any two of N stimulation signals 2 ⁇ / ⁇ , which corresponds to a time lag of T st i m / N, or the phase shifts may, for example, chaotic and / or stochastically be varied.
  • the optical stimuli may have different polarities.
  • the sinusoidal signal of two segments can be applied at the same time but with the opposite polarity (corresponds to a phase shift of ⁇ ).
  • one of the segments a sinusoidal ⁇ signal at 5 Hz and the other three segments can sine ⁇ signals 4 Hz, 3 Hz, or 2 Hz apply (ie, in the case of a transmission glasses, the transmission of the respective segment 141 is changed to 144 with corresponding frequency).
  • sinusoidal signals may also be other (oscillating) signal forms, for example square wave signals are used with the ent ⁇ speaking fundamental frequency.
  • the signals brewing chen not be applied time shift, but the Seg ⁇ elements 141 to 144, the optical stimuli can for example, also generate simultaneously.
  • the visual stimuli can be applied continuously over a longer period of time, but it is also possible to observe pauses during the application.
  • optical stimulation at different frequencies does not necessarily lead to a rapid To ⁇ resetting the phase of the neural activity in the stimulated subpopulations, but is mulation by the Stimulated with these signals to each stimulated subpopulations over a certain period of time, a certain, imposed by the respective stimulation frequency phase. Ultimately, this also leads to a desynchronization of the entire neuron population.
  • Fig. 26 is a partially see-through glasses light 11 is shown schematically ⁇ table as another embodiment of the stimulation ⁇ unit.
  • the partially transparent light glasses 11 no glass is used whose transmission can be varied. Rather, only a part 149 of each of the lenses is transparent, while the remaining part 150 of the glasses ⁇ glasses is opaque.
  • a light source is arranged.
  • the light source can be, for example, a light-emitting diode or a fiber optic cable, which, for example, forwards the light of a light-emitting diode or other light-emitting means fastened to another point to this point on the spectacle lens .
  • the eyeglasses 11 can also have any other number of light sources that can be arranged in any desired geometry.
  • the transparent part 149 may be configured differently than shown in Fig. 26. The patient can only through the transparent part 149 of the
  • the patient is forced to constantly positioned his eyes relative to the glasses to hal ⁇ th.
  • the light sources 151 to 154 only irritate the retina of the patient, while an observer on the other side of the eyeglass do not visually stimulate.
  • the different light sources 151 to 154 for example, stimulate certain Subareas of the patient's retina.
  • the space between the edge of the spectacle and the face can be closed in a light-tight manner (not shown).
  • an opaque light glasses 11 is schematically shown as another embodiment of the stimulation device is provided ⁇ ⁇ . In the case of the opaque light glasses 11, the spectacle lens 155 is completely opaque.
  • each of the lenses 155 is a light source accommodated arrival.
  • the light sources can be configured as the par ⁇ tially transparent light glasses as well, eg as light emitting diodes or fiber optic cable.
  • each of the lenses has nine light sources. Four of these light sources are provided with reference numerals 151 to 154.
  • the light glasses 11 may also have any other number of light sources, which may be arranged in any manner.
  • the patient can not look through the lenses, but is visually irritated only by the light sources.
  • the light sources irritate - as with partially transmissive spectacles - only the retina of the patient.
  • the different light sources irritate certain areas of the patient's retina.
  • the space between the edge of the spectacle and the face can be closed in a light-tight manner (not shown).
  • the opaque light goggles 11 may contain a fixation target, which the patient can comfortably fix (eg without glare effects). By the instruction to fix the fixation target during treatment, it is prevented that the patient eye movement follows the differing ⁇ Chen, flashing light sources. In the latter case would in particular the central part of the retina, the fovea, irritated, while using a fixation-target, the differing ⁇ chen parts of the retina can be stimulated.
  • a stimulation method that can be performed, for example, with the spectacles 11 shown in FIGS. 26 and 27 is shown schematically in FIG. In FIG. 28, the optical first stimuli 156 applied by the light sources 151 to 154 of the light glasses 11 are plotted against one another with respect to time t.
  • the method illustrated in Fig. 28 corresponds onsbrille in Wesentli ⁇ chen the method shown in Fig. 22 for the Transmissi-.
  • each of the light sources 151 to 154 periodically applies the stimulus 156.
  • the stimulation method is shown in FIG. 28 only for four light sources 151 to 154. However, this method can be similarly extended to any number of light sources.
  • the relevant light source is typically switched on at time ti and switched off at time t 2 .
  • the maxima ⁇ le amplitude (brightness) of the individual light stimuli is ⁇ play, in a range of 1 to 20 cd / m 2.
  • ⁇ play in a range of 1 to 20 cd / m 2.
  • Stimulation units for generating acoustic first stimuli Embodiments of the stimulation unit 11 for generating acoustic first stimuli 21 will be described below. Such stimulation units can also be found in the German patent application no. 10 2008 015 259.5 entitled “Device and method for auditory stimulation", which was deposited with the German Patent and Trademark Office on March 20, 2008. The entire Offenbarungsge ⁇ halt the German patent application no. 10 2008 015 259.5 is taken hereby listed in the disclosure of the present application.
  • FIG. 29 schematically shows an embodiment of the stimulation unit 11 for generating acoustic first stimuli 21.
  • the stimulation unit 11 is actuated by the control unit 10 with control signals 23.
  • Fig. 29 are further an ear
  • the frequency spectrum of the acoustic first stimuli 21 may be wholly or partly within the audible range for humans.
  • the acoustic first stimuli 21 are picked up by the patient via one or both ears 212 and relayed via the auditory nerve (s) 216 to neuronal populations in the brain.
  • the acoustic first stimuli 21 are designed such that they represent neuron populations in the auditory cortex
  • the acoustic stimuli 21 stimulate.
  • a first frequency fi and a two-th frequency ⁇ ⁇ 2 are available.
  • the first acoustic stimuli 21 may further still more frequencies or frequency mixtures contain, in the example shown in Fig. 30 embodiment, this is a third frequency f3 and a fourth frequency f 4.
  • the first acoustic stimuli 21 generated by the stimulation unit 11 are converted in the inner ear into nerve impulses and forwarded via the auditory nerve 216 to the auditory cortex 213.
  • the tonotopic arrangement of the auditory Cortex 213 activates a specific part of the auditory cortex 213 during the acoustic stimulation of the inner ear at a specific frequency.
  • the tonotopic arrangement of the auditory cortex is described, for example, in the following articles: "Tonotopic Organization of the human auditory cortex as detected by BOLD-FMRI" by D. Bilecen, K. Scheffler, N. Schmid, K. Tschopp and J.
  • the acoustic first stimuli 21 are designed in such a way that they stimulate a neuron population of the auditory cortex 213 with a pathologically synchronous and oscillatory activity.
  • This neuronal population can be before the start of the stimulation, at least conceptually in different subpopulations glie ⁇ countries, inter alia in those shown in Fig. 29 subpopulations 217, 218, 219 and 220.
  • the neurons of all subpopulations 217-220 fire substantially synchronous, and Means with the same pathological frequency. Due to the tonotopic organization of the auditory cortex 213, the fi rst frequency fi becomes the first subpopulation
  • the stimulation with the acoustic first stimuli 21 causes in the respective subpopulations 217 to 220 a reset, a so-called reset, the phase of the neuronal activity of the stimulated neurons.
  • a reset a so-called reset
  • the phase of the stimulated neurons is set to a particular phase value, eg 0 °, independent of the current phase value.
  • the phase of neuronal controlled activity of the morbid subpopulations 217 to 220 by means of a targeted stimulation.
  • the auditory cortex 213 Due to the tonotopic arrangement of the auditory cortex 213 as well as the plurality of frequencies fi to f 4 contained in the acoustic first stimuli 21, it is possible to purposefully stimulate the diseased neuron population at the different locations 217 to 220. This allows the phase of the neuronal activity of the pathological neuronal population at the different pacing sites 217-220 reset at different times by the frequencies fi are applied to f 4 at different times. As a result, the diseased neuron population whose neurons were previously synchronous and active at the same frequency and phase is split into the subpopulations 217 to 220.
  • each of the subpopulations 217 to 220 the neurons continue to be in sync and continue to fire on average at the same pathological frequency, but each of the subpopulations 217 to 220 has the phase of their neuronal activity given by the stimulation stimulus with the associated frequency fi to f 4 was imposed.
  • the state generated by the stimulation with min ⁇ least two subpopulations is unstable, and the entire neuro ⁇ nenpopulation rapidly approaches a state of complete desynchronization in which the neurons fire uncorrelated.
  • the desired state ie the complete desynchronization, is thus not immediately available after the application of the acoustic first stimuli 21, but usually occurs within a few periods or even less than one period of the pathological activity.
  • pure tones In order to focal-stimulate the auditory cortex 213 at different points, for example the points or sub-populations 217 to 220 shown in FIG. 29, pure tones must be added to the auditory cortex 213.
  • the Staer ⁇ ke the irritation produced by the respective sine wave of the respective area in the auditory cortex 213 corresponds to the amplitude of each sine wave.
  • the generation of the pulsed sinusoidal oscillations shown in FIG. 30 is shown by way of example in FIG. 31.
  • There is a sine wave 221 with a rectangular function 222 which may assume, for example, the values 0 or 1, multiply ⁇ liziert. At the times when the rectangular function 222 has the value 0, the associated stimulus is turned off, and during the time in which the rectangular function 222 is equal to 1, the stimulus is turned on.
  • the sine wave 221 may be multiplied by any other function. As a result, this multiplication corresponds to an amplitude modulation of the sine wave 221.
  • the square function 222 provides a smoother comparison run are selected, for example, by multiplying the sinusoidal wave 221 with a half sinewave of appropriate duration, eg the duration of a stimulus.
  • oscillating signals with another signal form, such as square-wave signals, which oscillate with the corresponding fundamental frequency to generate the acoustic first stimuli 21.
  • the larger parts of the audito- step Cortex enabled 213 so frequency mixtures are at ⁇ place of individual frequencies, for example pulsed applied.
  • frequency mixtures are at ⁇ place of individual frequencies, for example pulsed applied.
  • all the parts of the auditory cortex 213 stimulated by the frequencies between f down U nd f above due to the tonotopic arrangement are stimulated.
  • the stimulation unit 11 can be operated for example in a so- ⁇ called "open loop” mode in which the control unit 10, the stimulation unit 11 controls such that this predetermined acoustic first stimuli generated 21 during egg ⁇ ner specific stimulation time (eg, several hours) , Furthermore, the stimulation unit 11, together with the control unit 10 and the measuring unit 15, can also be further developed into a "closed loop" system shown schematically in FIG. 32.
  • control unit 10 With regard to the interaction of the control unit 10 with the measuring unit 15, various embodiments are conceivable.
  • the control unit 10 based on the expression of the pathological features parameters of the acoustic first stimuli 21, such as the amplitudes of the sinusoids jewei ⁇ time or the pause between stimulation sequences to be set.
  • the measurement signals recorded by the measuring unit 15 are converted directly or optionally after one or more processing steps into acoustic first stimuli 21 and are applied by the stimulation unit 11.
  • the measurement signals may be amplified and optionally after mathematical Ver ⁇ bill (for example, after mixing the measurement signals) having a time delay and linear and / or nonlinear combination steps are fed as control signals 23 to the control input of the stimulation unit.
  • the clearing mode is that the pathological neuronal Ak ⁇ tivity is counteracted and the acoustic stimuli first 21 also disappear with decreasing pathological neuronal activity or at least significantly reduced in their thickness so selected.
  • Fig. 33 an embodiment of the stimulation unit 11 is schematically shown, which uses a sound generator (loudspeaker ⁇ cher), which is enclosed in an earplug 230th
  • the earplug 230 is inserted into the external auditory canal of an ear 212 of the patient and attached with or without wire or egg ⁇ ner other suitable mechanical aid to the ear 212th
  • the control unit 10 which controls the sound generator to ⁇ , and a battery or a battery for Stromversor ⁇ supply of the electrical components may be housed in one or several separate units ren 231st
  • the unit 10 which controls the sound generator to ⁇ , and a battery or a battery for Stromversor ⁇ supply of the electrical components may be housed in one or several separate units ren 231st
  • connection ⁇ cable 232 connects the earplugs 230 to the control unit 10 or the battery.
  • a headset may be used including the control unit 10 and the battery contains.
  • the device shown in FIG. 33 can be switched on by the patient by means of a control unit (eg switch-on button and / or rotary control) which is attached either to the unit 231 or directly to the earplug 230. By turning the knob as the maximum stimulation intensity can be ⁇ provides.
  • a control medium 233 may be provided, which is connected, for example, by telemetry (eg, via radio) or via a connecting cable to the control unit 10. In the case of a connection via a cable plug connections can be used for the connection or disconnection.
  • doctor e.g. be provided by the doctor to be operated control medium (not shown), which telemetrisch or via a connecting cable with the
  • Control unit 10 is connected.
  • plug connections can be used for connecting or disconnecting.
  • the four frequencies fi to f 4 are merely exemplary to be understood, that it may be any other number of frequencies or frequency mixtures are used for stimulation purposes.
  • the frequencies fi to f 4 have been selected so that each specific areas 217 to 220 of the auditori ⁇ rule Cortex 213 stimulated with them.
  • the frequencies fi to f 4 can be applied, for example, with a time delay.
  • a suitable for the purposes described above Stimulati ⁇ ons vide is shown schematically in Fig. 34.
  • FIG. 34 four sinusoidal oscillations having the frequencies fi, f_ 2, f3 and f 4 , respectively, are plotted against time t in the upper four lines. From the sinusoids shown, the acoustic first stimuli 21 are formed. To generate pulsed sinusoids, the four sinusoids have been multiplied by rectangular functions.
  • Each sinusoidal pulse repeats periodically at a frequency f st i m -
  • Such sequences of pulsed sinusoids when applied as acoustic first stimuli 21, are capable of resetting the neuronal phase of the respectively stimulated, diseased neuron subpopulation 217, 218, 219 and 220, respectively.
  • phase reset is thus not based not ⁇ sarily already after one or a few pulses, but it may require a certain number of in Fig. Sinewave pulses shown 34
  • the frequency f st i m may for example be in the range of mittle ⁇ ren frequency of the pathological rhythmic activity of the target network.
  • ER- the average frequency is typically in the Be ⁇ rich 1-30 Hz, but can also be outside this range.
  • tinnitus for example excessively synchronous neural sectioni ⁇ ty place in Frequency Ranges ⁇ rich from 1.5 to 4 Hz.
  • the frequency with which the diseased neurons fire synchronously is usually not constant, but may well have variations and In addition, each patient shows individual deviations.
  • f st m it is possible, for example, to determine the mean peak frequency of the pathological rhythmic activity of the patient. This peak frequency can then be used as a stimulation frequency f st i m or else be va ⁇ riiert, for example in a range of f st i m - 3 Hz to fstim + 3 Hz. Alternatively, however, a frequency f st i m in the range of 1 to 30 Hz can also be selected and these are, for example, during stimulation vari ⁇ ated until the frequency f st i m is found at which achieve the best stimulation success without prior measurement to let.
  • the stimulation frequency F St i m a Hérange for the disease known literature value ⁇ subjected. Eventually, this value can still be varied until, for example, optimum stimulation results are achieved.
  • the duration of a sinusoidal oscillation pulse ie the period of time in which the rectangular function assumes the value 1 in the present embodiment, can be, for example, T st m / 2. In this case, the time span during which the respective frequency contributes to the stimulation and the subsequent stimulation pause are the same. However, it is also possible to choose other stimulation durations, for example in the range of Tstim / 2 - Tstim / 10 to Tgtim / 2 + Tgtim / 10.
  • the stimulation durations can be determined experimentally, for example.
  • the administration of the individual frequencies fi to f 4 takes place with a time delay between the individual frequencies fi to f 4 .
  • the beginning of temporally successive pulses having different frequencies can be shifted by a time ⁇ .
  • the time delay ⁇ is accordingly T st m / 4.
  • the time delay ⁇ between each two consecutive sinusoidal pulses T st m / N is, can be deviated to some extent. For example, it is possible to deviate from the value T st i m / N for the time delay ⁇ by up to ⁇ 3%, ⁇ 5%, ⁇ 10%, ⁇ 20% or ⁇ 30%. In the case of such a deviation, stimulation successes were still achieved, ie a desynchronizing effect could still be observed.
  • the first acoustic stimulus 21 is formed by superposition.
  • the individual sinusoidal oscillation pulses can be combined, for example, linearly or non-linearly with each other. This means that the sinusoids of the individual frequencies fi to f 4 need not necessarily be combined with the same amplitudes to the first acoustic stimulus 21.
  • the frequency spectrum of the acoustic first stimulus 21 is shown by way of example at four different times ti, t 2 , t3 and t 4 .
  • the frequency spectra shown there, insbesonde ⁇ re the height and shape of the frequency peaks are to be understood only in ⁇ way of example and can also completely different? ⁇ che shapes. In detail, the following statements can be taken from the illustrated frequency spectra:
  • the frequency fi occurs in the acoustically ⁇ tables first stimulus 21st At time t 2, these are the frequencies f3 and f4, to the time t3, the frequencies f 2 to f 4, and at time t 4, the frequencies f2 and f3.
  • ⁇ j may be mixed down to f 3 0ben any number of frequencies in the range of f. 3
  • other functions for amplitude modulation of the sinusoidal oscillations will be used instead of the rectangular features, such as half sine waves whose frequency is less than fi to f. 4
  • triangular pulses are used as modulation functions.
  • Such a pulse may have a jump-like onset (from 0 to 1) and then a drop to 0, wherein the drop in ⁇ example, may be given by a linear or exponential function.
  • the modulation function ultimately determines the shape of the envelope of the individual pulses.
  • FIG. 35 shows the stimulation already shown in FIG. 34 over an extended period of time.
  • FIG. 35 shows a measurement signal 26 recorded, for example, by the measuring unit 15, which represents the neuronal activity in the auditory cortex before and during the stimulation.
  • the stimulation is started at time t start .
  • the measuring ⁇ signal 26 which has been band-pass filtered in the present example is to be found that the neurons in the auditory cortex have a synchronous and oscillatory activity before the beginning of stimulation. Shortly after the beginning of the stimulation, the pathologically synchronous neuronal activity in the target area is already suppressed.
  • the time delay Ver ⁇ needs ⁇ between two successive sine wave pulses not necessarily always be the same. It can be provided that the time intervals between see the individual sinusoidal pulses are chosen differently. Furthermore, the delay times can also be varied during the treatment of a patient. The delay times with regard to the physiological signal propagation times can also be adjusted.
  • 21 pauses may be provided during the application of the acoustic first stimuli, during which no stimulation takes place.
  • the pauses can be chosen arbitrarily long and in particular amount to an integer multiple of the period Tgtim.
  • the pauses can be followed after any number of stimulations. For example, a stimulation during N consecutive periods of length gtim be performed and then a Stimulati ⁇ on break during M periods of length T st m m be observed, where N and M are small integers, eg in the range of 1 to 15
  • This scheme can either be continued periodically or modified stochastically and / or deterministically, eg chaotically.
  • the above-described stimulation signals cause the phase of neuronal activity of the diseased neuron population at the different stimulation sites to be reset at different times.
  • the diseased neuron population whose neurons were previously synchronous and active with the same frequency and phase, split into several subpopulations, which ultimately leads to desynchronization.
  • the measuring signal 26 recorded by the measuring unit 15 can be used to generate a control signal 23 with which the stimulation unit 11 is activated.
  • the measuring signal 26 can be implemented in the acoustic stimuli first 21 and are applied by the pacing unit 11 either directly or gege ⁇ appropriate, to one or more processing steps.
  • the Verticiansmo- dus can be selected here so that the morbid new ⁇ ronalen activity is counteracted and the acoustic stimuli first 21 with decreasing pathological neuronal activated They also disappear or are at least significantly reduced in their strength.
  • the measuring signal 26 can be processed linearly or non-linearly.
  • the measurement signal 26 can be filtered and / or amplified and / or acted upon by a time delay and / or mixed with another measurement signal 26.
  • the amplitude of a sinusoidal oscillation having a frequency in the audible range can be modulated with the measurement signal 26 or the processed measurement signal 26, and the amplitude-modulated sinusoidal oscillation can then be applied by means of the sound generator as an acoustic ers ⁇ ter stimulus 21 or as part thereof.
  • the complete measurement signal 26 does not necessarily have to be used. It can be provided for example, that, only a part of the measurement signal 26 or the processed measuring signal 26 is used in game ⁇ , the part that is above or below a ⁇ be agreed threshold.
  • Such Amplitudenmodula ⁇ tion is shown in Fig. 37 by way of example.
  • the band-pass filtered measurement signal 26 is plotted against time t, and the start time t start of the stimulation is also indicated.
  • the modulation signal 250 obtained from the measurement signal 26 is shown. To generate the modulation signal 250, the measurement signal 26 has been processed non-linearly and all negative values of the measurement signal 26 and the processed
  • the modulation signal 250 represents the envelope of the sine wave, as shown in the lowermost graph of FIG. 37 for a small time excerpt.
  • the thus obtained amplitude-modulated sine wave is in ⁇ closing in the stimulation unit 11 is fed back wor ⁇ , to be converted from the sound generator in the first acoustic stimuli 21st
  • the modulation signal 250 (or other vibration) may be multiplied in the audible frequency range and with an arbitrary Ge ⁇ mixture of sinusoids, depending on where in the auditory cortex, the Desynchronisati- is to take place on.
  • the course of the measurement signal 26 shown in FIG. 37 shows that the acoustic non-linear time-delayed half-wave stimulation leads to a robust suppression of the pathologically synchronous neuronal activity.
  • the Wirkme ⁇ mechanism of this stimulation is different from the operation of the example in Fig. 34 shown ⁇ stimulation procedure.
  • the phase of neuronal activity in the respective stimulated subpopulations is not reset but the synchronization in the diseased active neuron population is suppressed by affecting the saturation process of the synchronization.
  • Equation (1) K is a gain that can be suitably chosen, and z (t) is a mean state variable the measuring signal 26.
  • Z (t) is a complex variable and can be represented as follows:
  • the auditory cortex can also be selectively stimulated at various points.
  • such a stimulation is shown by way of example.
  • the modulation signals 251, 252, 253 and 254 have been obtained here by linear processing steps, with which amplitude modulations of the frequencies fi to f 4 have been performed.
  • the control signal 23 has been generated, which is generated by the
  • Sound generator 11 has been converted into the acoustic first stimuli 21.
  • certain delay times Xi, ⁇ 2 , X3 and X4 are calculated, for example, by the following equation:
  • the modulation signals 251 to 254 can be obtained, for example, from the measurement signal 26 by delaying the measurement signal 26 in each case by the delay times Xi, ⁇ 2 , X 3 or x 4 :
  • S i (t), S 2 (t), S 3 (t) and S 4 (t) represent the modulation signals 251 to 254 and Z (t) the measurement signal 26.
  • K is a gain factor that can be chosen appropriately. Further, all negative values are set to zero (or all values o- BER or below a certain threshold) of the modu ⁇ lationssignale Si (t) to S 4 (t).
  • the modulation signals Si (t) to S 4 (t) is calculated only from the delay times Xi and X2, the Modula ⁇ tion signals Si (t) and S2 (t) or S 3 (t) and S 4 (t) each have different polarities:
  • Stimulation units for producing tactile, vibratory and / or thermal first stimuli :
  • Such stimulation units can also be found in the German Patent Application No. 10 2010 000 390.5 entitled "Apparatus and method for treating a patient with vibration, tactile and / or Thermeizenizen", the February 11, 2010 at the German Patent and Trademark Office has been deposited.
  • the TOTAL ⁇ te disclosure of the German patent application no. 10 2010 000 390.5 is incorporated the registration in the disclosure of the present ⁇ .
  • FIG. 40 schematically shows an embodiment of the stimulation unit 11, which contains a plurality of stimulation elements.
  • the stimulation unit 11 four stimulation elements 311, 312, 313, 314, which controlled by the control unit 10 the ⁇ .
  • the embodiment shown in FIG. 40 is merely an example.
  • the stimulation elements 311 to 314 are manufactured ⁇ tet, that they can be placed on the skin of the patient. Depending on the disease or parts of the body affected the stimulation elements 311 to 314 fixed in a geeigne ⁇ th arrangement on the patient's skin, wherein ⁇ play as the arm, leg, hand and / or the patient's foot. Tactile, vibratory and thermal first stimuli 21 can be administered either individually or in combination on the skin depending on the clinical picture.
  • the plurality of stimulation elements 311 to 314 makes it possible to stimulate different receptive areas of the skin over the individual stimulation elements 311 to 314 in a temporally and spatially coordinated manner.
  • the stimulation elements 311 to 314 can be arranged on the skin of the patient in such a way that the stimuli applied to the skin tissue are transmitted via nerves. lines to different target areas, for example, in Rü ⁇ ckenmark and / or in the brain are forwarded. Consequently, different target areas in the spinal cord and / or brain can be stimulated with significantly different and / or delayed stimuli during the same stimulation period.
  • FIG. 41 A stimulation method that can be performed with the stimulation unit 11 shown in FIG. 40 is shown schematically in FIG. 41.
  • the first stimuli 21 applied via the stimulation elements 311 to 314 are plotted against the time t.
  • the duration D st i m a single first stimulus 21 may, in particular depend on the nature of the stimulus.
  • the ordinate shown in FIG. 41 also depends on the nature of the first stimuli 21.
  • a vibratory or tactile stimulus for example, the deflection of a 1 Stimulationsele ⁇ ments can be plotted against time t, at a thermal stimulus can be presented a temperature T.
  • the first stimuli 21 applied via the various stimulation elements 311 to 314 may be identical or different.
  • FIGS. 42A, 42B, 42C and 42D Various configurations of individual vibratory first stimuli 21 are shown in FIGS. 42A, 42B, 42C and 42D.
  • the deflection 1 of a stimulation element is plotted against the time t.
  • the stimulation element becomes at the time ti deflected from its rest position and pressed into the skin of the patient.
  • the location of the skin surface is shown by a dashed line 321.
  • the stimulating element can exert a force of about 2 N.
  • the duration D st i m of the vibration stimulus 21 may be in the range of 10 to 500 ms.
  • the Stimu ⁇ lationsdauer D is st in the range of where N is the number of stimulation elements.
  • N the number of stimulation elements.
  • temporally overlapping stimuli can also be used.
  • the stimulating element is moved back to its Ru ⁇ heposition where it has no contact with the skin. As shown in Fig.
  • the vibratory first stimulus 21 may be a rectangular or sinusoidal stimulus, but may have other shapes.
  • the deflection Ii shown in Fig. 42A for indenting the stimulation element into the skin may be in the range of 0.5 to 3 mm.
  • the deflection 1 2 of the stimulation element during the vibration can be between 0.1 and 0.5 mm.
  • Fig. 42B a variation of the vibratory first stimulus 21 shown in Fig. 42A is shown.
  • the stimulation element is always in contact with the skin of the patient.
  • Sti ⁇ mulationszeitraums Dgtim one as described above vibratory first stimulus 21 is applied.
  • Another variation of the vibratory first stimulus 21 is shown in FIG. 42C.
  • the Stimulationsele ⁇ ment has already been moved back again during the stimulation period D st i m, so that the vibrations with increasing duration less pressed into the skin and the stimulation element finally completely from the skin solves.
  • the retraction of the stimulation element may be along a linear or non-linear, such as exponential len, curve 322, which the vibrations V f i b of the stimulation element are superimposed.
  • the falling edge of each pulse until the cam 322 reaches down.
  • the subsequent pulse has a fixed height 1 2 , that is, the rising edge of each pulse has the height 1 2 .
  • FIG. 1 An embodiment of a tactile first stimulus 21 is shown in FIG.
  • the stimulation element is pressed at time t in the patient's skin, remains there for the duration of stimulation D st i m and at time t 2 again Retired ⁇ go.
  • the stimulation duration D st i m is in a tactile first stimulus 21 in the range of 10 to 500 ms.
  • the stimulus duration D st i m in the angege ⁇ surrounded above in (12) region but it can also be used temporally overlapping Stimulated muli.
  • FIGS. 44A, 44B, and 44C Various embodiments of individual thermal first stimuli 21 are shown in FIGS. 44A, 44B, and 44C.
  • a stimulation element is heated or cooled to a temperature T temp .
  • the temperature T temp can not be reached until shortly before the application of the thermal first stimulus 21. be witnesses.
  • the stimulating element has currency ⁇ rend the stimulation pause a temperature To, which for example corresponds to the room temperature.
  • the stimulation element can be kept at a constant temperature T te mp.
  • the heated or cooled stimulating element at the time is brought ti to the skin of Pa ⁇ tienten and remains there for the entire Stimula- tion duration D st i m -
  • the thermal first stimulus 21 shown in FIG. 44C substantially corresponds to the thermal stimulus 21 of FIG. 44B.
  • the thermal record 21 of FIG. 44C is generated without contact.
  • the stimulation temperature T te mp is generated by electromagnetic radiation, such as infrared light.
  • the stimulation duration Dgtim is in the range of 10 to 500 ms.
  • the stimulation duration D s tim is ⁇ rich in the above in (12) Be, but it can be turned comparable temporally overlapping stimuli.
  • the temperature T te mp can be from 22 to 42 ° C.
  • the temperature To is usually the body temperature of the patient ⁇ Tempe.
  • the frequency f t hermo can be between 1 and 10 Hz, but may lie ⁇ gene outside of this range.
  • first stimulus 21 comprises several types of stimuli.
  • the one shown in FIG. vibratory first stimulus 21 was at the same time a thermo-stimulus provided that the stimulation element exerting the stimulus was correspondingly heated or cooled.
  • the vibra ⁇ toric first stimulus 21 is shown in FIG. 42A at the same time (to the skin touch receptors are activated by the impact of the stimulating element) is a tactile stimulus.
  • the first stimuli 21 applied by the stimulation units 311 to 314 are received by in or under the skin receptors and forwarded to the nervous system.
  • These receptors include, for example, Merkel cells, Ruffini bodies, Meissner bodies and Haarfollikelrezeptoren, acting in particular as receptors for the tactile first stimuli 21.
  • the vibratory first stimuli 21 are aimed primarily at the depth sensitivity.
  • the vibratory first stimuli 21 may be received by receptors located in the skin, muscles, subcutaneous tissue, and / or tendons of the patient. Examples of the receptors for the vibratory first stimuli 21 are the Father Pacini bodies, which convey vibration sensations and accelerations.
  • the thermal first stimuli 21 are absorbed by the thermoreceptors of the skin. These are warm receptors (also called heat receptors, warm sensors or heat sensors) and cold sensors (also called cold sensors, cold receptors or cold receptors). In the human skin, the cold sensors are more superficial, the warm receptors a little deeper.
  • the first stimuli 21 generated by the stimulation elements 311 to 314 are designed in such a way that, if they are received by the corresponding receptors and are conducted via the nerve leads to a neuron population in the brain or spinal cord with a pathologically synchronous and oscillatory activity cause the neuron population to reset the phase of neuronal activity of the stimulated neurons.
  • the phase of the stimulated neurons becomes independent of the current one Phase value set to a specific phase value, eg 0 °.
  • the phase of neuronal activity of the diseased neuron population is controlled by targeted stimulation.
  • the diseased neuron population whose neurons were previously synchronous and active at the same frequency and phase, is split into several subpopulations. Within a subpopulation, the neurons continue to be in sync and continue to fire at the same pathological frequency, but each of the subpopulations has the phase imposed by the stimulus on their neuronal activity.
  • the state generated by the stimulation with min- least two subpopulations is unstable, and the entire neuro ⁇ nenpopulation rapidly approaches a state of complete desynchronization in which the neurons fire uncorrelated.
  • the desired state, ie the complete Desynchroni ⁇ sation is thus not immediately available after the application of the first stimuli 21, but usually sets in within a few periods or even in less than one period of the pathological activity one.
  • Stimulation unit 11 shown in Fig. 45.
  • About the Sti ⁇ mulations institute 311 to 314 of the stimulation unit 11 advertising at different points of the skin 315 stimulates the respective receptors with tactile and / or vibratory and / or thermal first stimuli 21.
  • the first stimuli 21 applied by the stimulation elements 311, 312, 313 and 314 are applied to different subpopulations 331, 332,
  • the neuron population 330 forwarded (stimuli of stimulating element 311 to sub-population of 331 stimuli stimulation element 312 to sub-population of 332 stimuli of Sti ⁇ mulationselement 313 to subpopulation 333 and stimuli of stimulating element 314 subpopulation 334) and reset the phases of these Subpopulations at different times, whereby a desynchronization of the entire neuron population 330 is achieved.
  • the targeted stimulation of certain areas of the brain or spinal cord is made possible by the somatotopic assignment ofreassurere ⁇ regions to these areas.
  • the stimulation elements 311 to 314 may be attached to the foot, lower leg and thigh or to the patient's hand, lower back and upper.
  • the first stimuli 21, which cause the phase of neurons to be reset can be transmitted to the respective receptive fields of the skin in a time-delayed manner via the different stimulation elements 311 to 314. are given.
  • the stimuli can be applied, for example, out of phase or with different polarity, so that, as a result, they also lead to a time-delayed resetting of the phases of the different subpopulations 331 to 334.
  • FIG. 46 A suitable for the purposes described above Stimulati ⁇ onsclar is shown schematically in Fig. 46.
  • the first stimuli 21 applied via the stimulation elements 311 to 314 are plotted against the time t.
  • first stimuli 21 for example, the vibration, tactile and thermal stimuli shown in FIGS. 42A to 44C can be used.
  • the diagram shown in FIG. 46 is divided into periodically repeating first time segments of length T st m .
  • the first time intervals of length T st i m are further divided into two ⁇ te periods of length T st i m / 4.
  • the first time periods could be divided into N second time periods of length T st i m / N.
  • each of the stimulation elements 311 to 314 applies a first stimulus 21 strictly periodically at the frequency f st i m - the administration
  • the first stimulus 21 via different stimulation elements 311 to 314 takes place with a time delay between the individual stimulation elements 311 to 314
  • the frequency f st in the example can be in the range of mittle ⁇ ren frequency of the pathological rhythmic activity of the target network.
  • the mean frequency is typically in the range of 1 to 30 Hz, but may be outside this range.
  • beach ⁇ th that the frequency at which fire up the neurons affected synchronously, usually is not constant, but may well have variations in each patient and shows individual deviations beyond.
  • the temporal delay T st m between successive first stimuli 21 generated by the same stimulation element need not always be the same, but may vary in the range of ⁇ 10% or ⁇ 5% or ⁇ 3% by T st .
  • the time interval between two consecutive first stimuli 21 generated by different stimulation elements may also vary in the range of + 10% or + 5% or + 3-6 ⁇ m gtim / N. It can certainly be provided that the time intervals between the individual first stimuli 21 are chosen differently.
  • the delay times can also be varied during the treatment of a patient. Also the delay times can be adjusted with regard to the physiological signal propagation times.
  • pauses can be provided during which no stimulation takes place.
  • Such a pause is exemplified ge ⁇ shows in Fig. 47.
  • the pauses can be selected arbitrarily long and, in particular, be an integer multiple of the period T st m .
  • the pauses can be maintained after any number of stimulations. For example, one can
  • a further possibility to deviate from the one shown in Fig. 46 strictly periodic stimulation pattern is the time sequence of the individual first 21 stimuli sto ⁇ chastisch or deterministic or mixed stochastisch- to vary deterministic.
  • the randomization shown in Fig. 48 may be combined with the stimulation form shown in Fig. 47.
  • a new randomization can be carried out in each of the N consecutive stimulation time segments of length T st i m , or else, after each pause Length M x T st i m randomization and remains within the following N stimulation periods the Erasmusnfol ⁇ ge in which the stimulation elements 311 to 314 apply the ers ⁇ th stimuli 21, constant.
  • stimulation elements 311 to 314 can be used only a specified number of stimulation elements 311 to 314 for the stimulation and the stimulation elements involved in the stimulation can be varied in each time interval per period T st i m (or in another Zeitin ⁇ interval). This variation can also be done stochastically or deterministically or mixed stochastically-deterministically.
  • the stimulation unit 11 can be operated, for example, in an "open loop” mode, in which the control unit 10 controls the stimulation elements 311 to 314 such that they generate predetermined first stimuli 21 which are delivered to the skin tissue. Furthermore, the stimulation unit 11, together with the control unit 10 and the measuring unit 15, can also be further developed into a "closed ⁇ " system shown schematically in FIG. 49.
  • control unit 10 With regard to the interaction of the control unit 10 with the measuring unit 15, various embodiments are conceivable.
  • a certain frequency f V i b or indentation depth 1 2 in the case of vibration stimuli are adjusted based on the severity of the pathological features of parameters of the first stimuli 21, for example by the control unit 10th
  • the measurement signals 26 recorded by the measuring unit 15 are converted directly into the tactile, vibratory and / or thermal first stimuli 21, and optionally after one or more processing steps, and are applied by the stimulation unit 11.
  • the measured signals can be amplified and, if necessary, mathematically calculated (eg according to tion of the measurement signals) with a time delay and linear and / or nonlinear computation steps as control signals 23 are fed into the control input of the stimulation unit 11.
  • the clearing mode is in this case selected so-that the abnormal neuronal activity
  • the tactile, vibratory and / or thermal first stimuli 21 also disappear with decreasing pathological neuronal activity or at least significantly reduced in strength.
  • FIG. 50A to 50C schematically illustrate various possible answer ⁇ th to implement a stimulation element to produce tactile and / or vibratory first stimuli 21, as shown in FIGS. 42A to 43.
  • the stimulating element may be a rod 340 (or other Kör ⁇ per) designed to be, with one end of the skin 315 of the patient is stimulated.
  • the Stimula ⁇ tion element 340 is driven by an electromechanical transducer 341 (or actuator or actuator), the electrical energy into a movement of the stimulation member 340 translates.
  • Suitable electromechanical converters 341 are, for example, direct current motors, voice coils, piezoelectric transducers or converters constructed from electroactive polymers (EAP) which change their shape when an electrical voltage is applied.
  • EAP electroactive polymers
  • the electromechanical transducers 341 may be designed so that the stimulation element 340 is deflected perpendicular to the skin surface (see Fig. 50A) or parallel thereto (see Fig. 50B). The movement of the stimulation element 340 can also take place on any other paths. As an example in Fig. 50C pendeiförmige a deflection of the Stimu ⁇ lationselements 340 is illustrated.
  • the end of the stimulation element 340 which comes into contact with the skin surface and ultimately generates the stimuli, can be essentially in the shape of a hemisphere have (see Fig. 51A) or have a knob-like surface (see Fig. 51B) or have another suitable shape.
  • 52A to 52C show an embodiment of a stimulation element for the application of tactile and / or vibratory first stimuli 21 (see FIG.
  • the present stimulation element contains a piezo actuator 341 as an electromechanical transducer. Since the deflection of the piezo actuator 341 for beab ⁇ schreibten purposes is not sufficient, a mechanism for amplifying the displacement of the piezo actuator can be provided 341st By way of example, a lever arm 342 is shown here, which amplifies the movement of the piezoactuator 341.
  • the lever arm is present an elongated bending spring 342, which is saturated with buildin ⁇ ih ⁇ rem one end to the housing 343 of the stimulation element and is attached to the other end of the stimulation element 340th
  • the piezoactuator 341 presses on the upper side of the bending spring 342 and the stimulation element 340 attached to the underside of the bending spring 342 follows the deflection of the piezoactuator 341 with an amplified amplitude due to the geo ⁇ metric arrangement and applies the vibration and / or tactile stimuli on the Skin of the patient.
  • the underside of the stimulation member 340 that comes in contact with skin may have various geometries and dimen ⁇ solutions.
  • the stimulation element 340 may be flat, round or non-uniform on its underside.
  • a space 344 may be further provided for electronics and connection terminals.
  • an adjusting ring 345 is attached to the underside of the housing 343, which is connected to the housing 343 via a thread and the adjustment of the
  • FIGS. 53A to 53C schematically show differently configured stimulation elements for generating thermal first stimuli 21, as shown in FIGS. 44A to 44C.
  • the stimulation unit shown in Fig. 53A operates without contact and causes heating of the skin by the light of an infrared LED 350.
  • Stimulation elements that apply by touching the skin surface thermal stimuli are shown in Figs. 53B and 53C ge shows ⁇ .
  • the stimulation element shown in FIG. 53B contains, with an electromechanical transducer 341 and a rod-shaped stimulation element 340, substantially the same components as the stimulation element from FIG. 53A. Zusharm ⁇ Lich, the stimulating element shown in Fig. 53B, a heating and / or cooling element (for example in the form of a heating loop) which heats the stimulation element or cools.
  • the thermi ⁇ 's first 21 stimuli are generated by the movements of the stimulation element 340, in which the Stimulationsele ⁇ element 340 repeatedly comes into contact with the skin 315 and is removed again.
  • the temperature of the stimulation element 340 may be constant throughout the stimulation.
  • the heatable or coolable Stimulationsele ⁇ ment can stand 340 as shown in Fig. 53C during the entire Stimu ⁇ lationszeitraums in contact with the skin 315 of the patient.
  • the thermoreize in this case are due to a temporal variation of the temperature of the stimulation element 340 generated.
  • An electromechanical transducer is not absolutely necessary in this embodiment.
  • FIGS. 54A to 54C show an embodiment of a stimulation element for applying thermal first stimuli 21 in a perspective view (see FIG. 54A), a top view from below (compare FIG. 54B) and in cross-section (compare FIGS ).
  • the stimulation element contains a rod-shaped stimulation element 340, the lower end of which can be heated and / or cooled. At its upper end, the stimulation element 340 is driven by a cam plate 351.
  • a DC motor 352 rotates the cam 351 in rotation.
  • the stimulation element 340 is deflected downwards.
  • a return spring 354 ensures that the stimulation element 340 then returns to its original position.
  • the rotating movement of the cam plate 351 in a linear BEWE ⁇ supply of the stimulation element 340 is converted.
  • the stimulation element 340 for a certain time with the patient's skin are either in contact o- but in which the stimulation member 340 is brought by rotation of the cam plate 351 cyclically to the skin and how ⁇ the center.
  • the components of the stimulation element can be introduced into a housing 355.
  • a space 356 may be provided for electronics and connection terminals.
  • an adjusting ring 357 may be attached, which is connected to the housing 355 via a thread and which allows an adjustment of the height by which the stimulation element 340 protrudes in its rest position ⁇ from the bottom of the stimulation unit ⁇ stands (the stimulation element 340 may also lie completely above the underside of the adjusting ring in its rest position due to the adjusting ring).
  • the stimulating element sits with its bottom on the skin of the patient and is attached, for example with a suitable cuff on the body of the patient.
  • the Stimu ⁇ lationselement could be still attached to a single- or double-sided adhesive tape medi- zinischen to the skin of the patient.
  • the housing 355 protects the patient from potential hazards, such as electrical voltage.
  • a module may include a cuff with a plurality of pacing elements attached thereto.
  • the cuff can then be attached to an arm or leg of the patient.
  • Fig. 55 shows stimulation methods described can be performed with a total of N modules, each containing for example, four stimulation elements by ⁇ .
  • all stimulation elements apply at the beginning of a stimulation period T st i m a tactical tilen, vibratory or thermal first stimulus 21.
  • T st i m a tactical tilen
  • vibratory or thermal first stimulus 21 In the example shown in the middle of FIG.
  • the first stimuli are 21 of the four different stimulation elements of a module in each case by T st i m / 4 against each other ver ⁇ pushed.
  • exactly one stimulation element of each module applies a first stimulus 21 in each time segment of the length T st m / 4.
  • the four stimulation elements of a module generate their first stimuli 21 at the same time, however first stimuli 21 different modules against each other.
  • any pauses during the pacing can also be maintained.
  • pacing pauses are the length of one or more stimulation periods T st i m - as shown in FIG. 56 by way of example.
  • Sti ⁇ mulations mentor stimulation while two will alsein- other following stimulation periods T st i m performed because ⁇ is adhered to a Stimu ⁇ lationspause during a stimulation period T st i m after. This pattern is repeated peri ⁇ dically.
  • a sequence is Festge sets ⁇ in which the stimulation elements, the first stimuli 21 overall nerieren (eg the order forehead. # 4, forehead. # 2, forehead. # 3, forehead. # 1) and this sequence applies for all modules for the stimulation block until the next break.
  • Randomization of the stimulus sequences varies not coherent across all modules, but only coherently over a subset of all Mo ⁇ modules, that is, only for a specific module (for example, the module # 2), a randomization according to the above numbers 1 or 2. performed the remaining modules behave as shown in FIG. 55.
  • Randomization of the stimulus sequences is not coherent across all modules, but coherent over more than one subset of all Modules varies, ie, only for two or more modules (for example, the Module # 2 and # 4) is 1. or 2. performed in accordance with the randomization vorste ⁇ Henden numerals, the remaining modules behave as shown in Fig. 55.
  • randomization of the stimulus sequences is uncorrelated between different modules, that is, for each stimulation period T st i m or for each block of consecutive stimulation periods T st i m between two breaks independently for each module a sequence of the other modules, in which Stimulation elements generate the first stimuli 21, Festge ⁇ sets.
  • FIG. 57 schematically shows the block diagram of a device for producing tactile, vibratory and / or thermal first stimuli 21.
  • the device contains n modules each with n stimulation elements and n sensors.
  • the modules and sensors are on kauslei ⁇ obligations or wireless (eg, WPAN (Wireless Personal Area Network) network) with a connecting module 360 in combination, which in turn can be connected to a computer 361, such as a laptop, and external devices 362 , It need not necessarily all modules and sensors are used simultaneously, it can also only a subset thereof are used depending on Stimulati ⁇ onsart.
  • the modules and / or sensors can be powered by batteries or rechargeable batteries so that they are independent of a central power supply.
  • the user for example a physician, can select a stimulation method by means of a suitable software stored on the computer 361 and set the parameters of this stimulation method.
  • control of the integrated into the modules stimulation units can be done via the computer 361.
  • a control unit 10 may be integrated into each module
  • Fig. 58A which is responsible for the control of the stimulation elements of the respective module. This makes possible a largely independent operation of the modules.
  • a separate control unit 10 may be provided for each stimulation element (see FIG. 58B). This allows the greatest versatility in the operation of the stimulation elements, but increases the weight and dimensions of the modules.
  • the control unit 10 may be placed centrally in the connection module 360 (see Fig. 58C). An advantage of this are the low weight and size of the modules and cost-effective production. However, in this embodiment, the modules can not be operated independently of the connection module 360.

Abstract

L'invention concerne un dispositif (100) doté d'une unité de stimulation (11) pour produire des premiers stimuli (21) qui, dans le cas d'une administration à un patient, suppriment une activité synchrone pathologique des neurones dans le cerveau et/ou la moelle épinière du patient, d'une unité de mesure (15) pour recevoir des signaux de mesure (25) qui restituent l'activité synchrone pathologique des neurones, et d'une unité de neurofeedback (12) pour produire des deuxièmes stimuli (22) qui montrent au patient le degré d'activité synchrone pathologique des neurones.
PCT/DE2011/075022 2010-04-15 2011-02-11 Dispositif et procédé de traitement de maladies du cerveau et/ou de la moelle épinière au moyen du neurofeedback WO2011127917A2 (fr)

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JP2016532494A (ja) * 2013-08-08 2016-10-20 フォースチュングスヌートラム ユーリッヒ ゲーエムベーハー 音響的脱同期化神経刺激を較正するための装置および方法
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