Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/0404—Electrodes for external use
  • A61N1/0408—Use-related aspects
  • A61N1/0456—Specially adapted for transcutaneous electrical nerve stimulation [TENS]
• • 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
  • A61N1/36014—External stimulators, e.g. with patch electrodes
  • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition
• • 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
  • A61N1/36036—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of the outer, middle or inner ear

Definitions

• Stressors Events that trigger stress are generally called stressors; individuals react differently to similar as well as to dissimilar stressors.
• stressors can be divided into two main categories or types: physical and psychological.
• Physical stressors include a physical threat to bodily homeostasis; for example, bleeding profusely or having an infection.
• Psychological stressors include a perceived threat, which, as such, needs to be interpreted; for example, being in front of a hungry tiger, running late for a meeting, or feeling pressure to properly perform a task. Stress is part of normal life, and a healthy response to a stressor may be demonstrated by an anticipatory phase, a peak response during the event, and a return to baseline.
• Pressure-induced stress in some examples, may be experienced by professional athletes during competition, including those performing electronic sports (Esports), or by military operators, including those operating unmanned vehicles.
• Telomerase is an enzyme which activity counteracts telomere shortening. For instance, an autonomic overreaction has been correlated with an increased cortisol reactivity to stressors, with diminished immune cell function, and shorter TL. Perseverative cognition (e.g., rumination and concernedness), which can increase the stress reaction and prolong the recovery time to baseline has also been associated with shorter TL. An overreaction in the form of longer, or stronger/exaggerated anticipatory threat appraisals to acute stressors is one example of perseverance cognition.
• the two branches of the autonomic nervous system i.e., the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS) are in a dynamic balance.
• SNS sympathetic nervous system
• PNS parasympathetic nervous system
• SNS sympathetic nervous system
• PNS parasympathetic nervous system
• This stress-related autonomic imbalance is the result of a hyperactive SNS and a hypoactive PNS.
• the general response to both physical and psychological stress is activation of the sympathetic nervous system with inhibition of the parasympathetic nervous system.
• Fatigue can be said to be or to manifest as a lack of alertness.
• Wakefulness is a state in which an individual can perceive external stimuli and interact with their surroundings and their environment. The degree of vigilance and alertness during wakefulness is called arousal, and it corresponds to the level of: (a) responsiveness to sensory inputs, (b) emotional reactivity, and (c) cognitive processing.
• the present disclosure relates to increased activity in neural medullary structures such as, amongst others, the NTS.
• This activity increase in neural medullary structures triggers a cascade of neural activity in other brain areas which have direct and indirect connections to these neural medullary structures.
• the bleeding control method is described, for example, in U.S. Patent No. 8,729,129 to Tracey et al.; U.S. Patent No. 10,912,712 to Tracey et al.; U.S. Patent Application Publication No. 2020/0094055 to Manogue; and U.S. Patent Application Publication No. 2019/0321623 to Huston et al., hereby incorporated by reference in their entireties.
• the present disclosure relates to reducing likelihood of bleeding under stressful situations and/or speeding the stoppage of bleeding through vagal and/or trigeminal stimulation in combination with neurostimulation treatment to reduce stress reaction.
• FIG. 2A illustrates example connections of the Sympathetic-Adrenomedullary (SMA) Axis pathway
• FIG. 2B illustrates example connections of the Hypothalamic-Pituitary -Adrenal (HP A) Axis pathway
• FIG. 3A illustrates example connections of the main parasympathetic pathway
• FIG. 3B illustrates example connections of the central endorphin pathway
• FIG. 4A illustrates example connections of a stress reduction pathway
• FIG. 4B illustrates example connections of an arousal and alertness control pathway
• FIG. 4C illustrates example connections of an anti-inflammatory pathway
• FIG. 5 A illustrates example mechanisms for using electrical stimulation to control and/or decrease stress
• FIG. 5B illustrates example mechanisms for using electrical stimulation to promote wakefulness, increase arousal/alertness, and counteract fatigue
• FIG. 5C illustrates example mechanisms for using electrical stimulation to for decrease pro-inflammatory processes
• FIG. 6A and FIG. 6B illustrate an example electrode configuration and equivalent circuits for providing therapy
• FIG. 7 illustrates an example timing diagram for supplying stimulation pulses a an auricular therapeutic device
• FIGs. 8A-8B illustrate a first example auricular therapeutic device
• FIGs. 9A-9C illustrate a second example auricular therapeutic device
• FIGs. 10A-10C are drawings of example systems including an example treatment device in communication with remote systems through a computing cloud and/or a peripheral device;
• FIG. 11 is a block diagram of components of an example pulse generator in communication with an example auricular therapy device.
• treatment systems, devices, and methods for stimulation of neural structures on and surrounding a patient’s ear are designed for providing stimulation without piercing the dermal layers on or surrounding the ear (e.g., transcutaneous stimulation).
• Electrodes may be frictionally and/or adhesively retained against the skin on and surrounding the patient’s ear to target various nerve structures.
• the electrodes may have a substantial surface area in comparison to prior art systems relying upon dermal-piercing electrodes, such that multiple nerve terminals are stimulated by a single electrode during therapy.
• a number of nerve terminals may be situated directly beneath and/or beneath and closely adjacent to the skin upon which the electrode is positioned.
• a device enabling stimulation of one or more of the above-noted branches may be used to reduce bleed time and/or bleed volume when stimulating in a prophylactic fashion and/or after an injury that has caused bleeding to occur.
• a device such as the one described by Simon, et al, in U.S. Patent No. US 10,207, 106 could be utilized to trigger a vagal response.
• the device such as that described by Rigaux in U.S. Patent No. 8,914,123 can be used to trigger such responses.
• both devices could be used simultaneously or in an alternative manner to elicit a vagal, a trigeminal, or a trigeminal-vagal response.
• methods described herein for stimulation of neural structures on and surrounding a patient’s ear may be applied using devices designed for providing percutaneous stimulation.
• electrodes having tissue-penetrating portions and/or electrodes designed to penetrate tissue e.g., needle electrodes
• a minimally invasive manner e.g., through at least a top dermal layer of a patient’s skin.
• An example percutaneous auricular stimulation device is the P-STIM® device by Biegler GmbH, described, for example, in U.S. Patent No. 10,058,478 to Schnetz et al., incorporated herein by reference in its entirety.
• Percutaneous stimulation in other embodiments, may be performed at other locations on a subject’s skin, for example including the regions described above in relation to transcutaneous stimulation.
• the trigeminal and occipital fibers synapse, including the Auriculotemporal Nerve 130, the lesser occipital nerve 152, and the greater auricular nerve 154 (e.g., Cervical Spinal 148).
• the TCC 102 projects to multiple areas in the brain stem including, but not limited to parts of the Raphe nuclei (hereafter Raphe Nucleus (RN) 106), the Locus Coeruleus (LC) 108, Periaqueductal Gray (PAG) 110, Nucleus Basalis (NBM) 120, the Nucleus Ambiguus (NA) 122, the Ventral Tegmental Area (VTA) 124, the Nucleus Accumbens (NAc) 126, and Parabrachial nucleus (PbN) 114.
• Raphe Nucleus hereafter Raphe Nucleus (RN) 106
• LC Locus Coeruleus
• PEG Periaqueductal Gray
• NBM Nucleus Basalis
• NA Nucleus Ambiguus
• VTA Ventral Tegmental Area
• NAc Nucleus Accumbens
• PbN Parabrachial nucleus
• the NTS 104 among others, also projects to the RN 106 the LC 108, and the PAG 110 as well as to higher centers like the hypothalamus 132, including into the Arcuate Nucleus (ARC) 112 which receives its majority of non-intrahypothalamic afferents from the NTS 104.
• Cells in the ARC 112 are the main source of endorphins in the Central Nervous System (CNS).
• CNS Central Nervous System
• the medulla oblongata is the lower region of the brainstem containing important neuronal structures (nuclei) modulating, for example, several important involuntary actions such as respiration, heart rate, and blood pressure.
• the medulla contains several important nuclei (medullary nuclei) such as the NTS 104, the spinal trigeminal nucleus, the NA 122, and at least some of the RN 106.
• LC 108, PAG 110, and RN 106 project to the NA 122
• PPN 116 projects into the VTA 124
• the VTA 124 projects to the Prefrontal Cortex 136, being interconnected with the hypothalamus 132 and the hippocampus 138.
• the VTA 124 projects directly to the Hippocampus 138 as well.
• the Hippocampus 138 projects to the NAc 126 and interconnects with the hypothalamus 132.
• MOR/KOR/DOR p/K/6-opioid receptor
• NOP nociception/orphanin FQ receptor
• NAc nucleus accumbens
• PFC prefrontal cortex
• VTA ventral tegmental area. Affinity is presented in parenthesis.
• this neural circuit is crucial for learning and memory as well as for arousal and wakefulness.
• norepinephrine produced by activity in the Locus Coeruleus (LC) 108
• Serotonin (5-HT) produced by activity in the RN
• Acetylcholine (ACh) produced by activity in the Pedunculopontine Nucleus (PPN) 116 or NBM 120 is extremely important for memory and learning.
• Arousal and wakefulness are modulated, amongst others, by catecholamines in the brain, such as norepinephrine and dopamine.
• Indirect connections include connections where there is at least one synapse elsewhere before reaching the target. This means that modulating the activity of these neural circuits can affect the respective organs.
• heart rate can be modulated (e.g., heart rate can be decreased and heart rate variability can be increased); oxygen absorption can be increased at the lungs 142 by increasing the compliance of the bronchi tissue and thus increasing the oxygen transport availability therefore increasing the potential for more oxygen to be absorbed into the blood; gut motility can be increased by descending pathways originating in the dorsal motor nucleus of the vagus nerve (DMV) 304 of FIG. 3B; since DMV activity is modulated by NTS activity, motility in the gut 144 can be affected by modulating the activity in the NTS 104; and a decrease in circulating pro- inflammatory cytokines can be achieved by modulating spleen 146 activity via NTS 104 descending pathways.
• DMV dorsal motor nucleus of the vagus nerve
• the vagus nerve 156 is a cranial nerve that which on its path can be located adjacent to the carotid artery in the neck.
• Direct stimulation of the vagus nerve 156 activates the nucleus tractus solitarius (NTS) 104, which has projections to nucleus basalis (NBM) 120 and locus coeruleus (LC) 108.
• NBM 120 and LC 108 are deep brain structures that release acetylcholine and norepinephrine, respectively, which are pro-plasticity neurotransmitters important for learning and memory.
• Stimulation of the vagus nerve 156 using a chronically implanted electrode cuff is safely used in humans to treat epilepsy and depression and has shown success in clinical trials for tinnitus and motor impairments after stroke.
• the auricular branch of the vagus nerve 158 innervates the dermatome region of outer ear, being the region known as the cymba conchae one of the areas innervated by it.
• Non-invasive stimulation of the auricular branch of the vagus nerve 158 may drive activity in similar brain regions as invasive vagus nerve stimulation.
• Auricular neurostimulation has proven beneficial in treating a number of human disorders.
• the response to a stressor is carried out via two main pathways: the Sympathetic- Adrenomedullary (SMA) Axis 202 and the Hypothalamic-Pituitary-Adrenal (HP A) Axis 204.
• SMA Sympathetic- Adrenomedullary
• HP A Hypothalamic-Pituitary-Adrenal
• LC Locus Coeruleus
• PVN Paraventricular Hypothalamic Nucleus
• the LC 108 is the main producer of Norepinephrine (NE) in the Central Nervous System (CNS) and is one of the main drivers of the SNS. In response to a stressor, the LC 108 releases NE.
• NE Norepinephrine
• CNS Central Nervous System
• the PVN 206 In responding to a stressor, the PVN 206 produces, amongst others, Corticotropin (also written as Corticotrophin) Releasing Hormone (CRH), also known as Corticotropin Releasing Factor (CRF).
• Corticotropin also written as Corticotrophin
• CRF Corticotropin Releasing Factor
• CRH is delivered to several brain nuclei, including the LC 108, as well as to the pituitary gland 208 which consequently releases, amongst others, [3-endorphins 210 and adrenocorticotropic hormone (ACTH) 212 into the blood steam.
• Corticotropin also written as Corticotrophin
• CRF Corticotropin Releasing Factor
• the circulating ACTH 212 reaches the adrenal gland (adrenal cortex) 214 and triggers the release of Epinephrine (Epi), NE, and glucocorticoids into the blood stream, in particular cortisol 216 in humans.
• Epinephrine Epinephrine
• NE Epinephrine
• glucocorticoids glucocorticoids into the blood stream, in particular cortisol 216 in humans.
• the Epi/NE ratio released by the adrenals is 80/20.
• Epi and NE primarily elicit a sympathetic response (e.g., increase heart rate).
• Cortisol 216 has various physiologic effects, including catecholamine release (e.g., Epi, NE, etc.), suppression of insulin, mobilization of energy stores through gluconeogenesis and glycogenolysis, as well as the suppression of the immune-inflammatory response.
• cortisol 216 serves as a feedback molecule-signal to limit the further release of CRH, thus slowing down the stress response.
• the P-endorphins 210 are released from the pituitary gland 208 to opioid receptors primarily in the peripheral nervous system (but also to immune cells), where, amongst other effects, they produce analgesia.
• This analgesia is the result of a cascade of interactions resulting in inhibition of the release of tachykinins, particularly of substance P, which is involved in the transmission of pain.
• the PVN 206 receives stress-related ascending monosynaptic afferent signals from several areas/nuclei. These nuclei include the Nucleus of the Solitary Track (NTS) 104, the LC 108, the parabrachial nuclei (PbN) 114, the Periaqueductal Grey Area (PAG) 110, and the Raphe Nucleus (RN) 106. These ascending pathways carry information regarding the stressor or stressors encountered. In addition to these ascending afferent signals, intrahypothalamic as well as descending afferent signals modulate the PVN 206 response to stressors.
• NTS Nucleus of the Solitary Track
• PbN parabrachial nuclei
• PEG Periaqueductal Grey Area
• RN Raphe Nucleus
• signals from the Prefrontal cortex (PFC) 218, the Hippocampus (Hipp) 138, and the Amygdala 149 reach the PVN 206; in some cases, these signals are further integrated at the Bed Nucleus of the Stria Terminalis (BNST) before reaching the PVN 206. Together, these signals incorporate cognitive and memory information into the stress response.
• PFC Prefrontal cortex
• Hipp Hippocampus
• BNST Bed Nucleus of the Stria Terminalis
• FIG. 3A and FIG. 3B psychological stressors are perceived and interpreted in an anticipatory fashion, and the response can be heavily modulated by the reward circuit, which includes the PFC 218, the Amygdala 149, the Ventral Tegmental Area (VTA) 306, as well as the Nucleus Accumbens (NAc) 126 (dopaminergic pathways, which are highly modulated by the central endorphin pathway 302).
• the reward circuit which includes the PFC 218, the Amygdala 149, the Ventral Tegmental Area (VTA) 306, as well as the Nucleus Accumbens (NAc) 126 (dopaminergic pathways, which are highly modulated by the central endorphin pathway 302).
• the Pre- Limbic (PL) and Infra-Limbic (IL) areas of the PFC 218 coordinate a top-bottom control over the stress response to psychological stressors.
• the brain areas or nuclei forming the neural circuitry involved in the stress response are not only involved in depression but also are integral components of the Endogenous Opioid Circuit (EOC), which includes the Central Endorphin Pathway (FIG. 3B) as well as the secondary connections arising from it.
• EOC Endogenous Opioid Circuit
• FIG. 3B together with Figs 2A and 2B, the NTS 104, LC 108, PbN 114, PAG 110, RN 106, PFC 218, VTA 306, NAc 126 (as it receives afferents from the VTA 306), the Amygdala 149 are part of the EOC.
• the central endorphin pathway 302 interacts with several other brain regions or nuclei including with other hypothalamic areas such as the PVN 206. Stimulating afferent pathways to the central endorphin pathway 302 such as vagal and/or trigeminal structures activates this circuit and connected regions, including the VTA 306, which is one of the main producers of dopamine in the CNS. By activating the central endorphin pathway 302 and connected regions, systems and methods described herein are able to modulate stress and alertness levels.
• one of the characteristics of stress is a hyperactive SNS, and hypoactive PNS, or both; resulting in a high SNS/PNS activity ratio.
• An increase in the activity of the PNS leads to a faster return to baseline after a response to a stressor.
• One way to increase PNS activity is to increase vagal tone which can be achieved by increasing the activity of the Vagus nerve 156.
• Activation of The Main Parasympathetic Pathway 300 of FIG. 3A results in an increase in vagal tone and thus a better stress response.
• the main vagus nerve afferent pathways are those originating in the NTS 104, the NA 122, and the DMV 304. Activity in these regions generally results in an increase in vagal tone.
• Activation of the ABVN 118 and the ATN 130 directly and indirectly lead to increase activity in all three above mentioned pathways going from the NTS 104, the DMV 304, and the NA 122, to the Vagus nerve 156. As seen in FIG. 3A these pathways also involve other nuclei or regions such as LC 108, PAG 110, RN 106, and TCC 102.
• stimulation e.g., of the ABVN 118 and/or ATN 130
• NPS Neuropeptide S
• NE is primarily produced in the LC 108.
• NPS is produced in the LC 108, the trigeminal nucleus, and the Parabrachial Nucleus (PbN) 114.
• the NPS release 404 includes release via the TCC 102, the PbN 114, and the LC 108.
• LC 108 activity is key for arousal.
• Norepinephrine 408 and NPS which are produced in and around the LC 108, promote arousal and wakefulness.
• interventions that increase NE and NPS in the CNS 404 also increase arousal, mitigating the effects of fatigue.
• Descending pathways from the LC 108 directly activate sympathetic preganglionic neurons in the spinal cord (e.g., Coeruleo-Spinal Pathway). Activation of these sympathetic spinal neurons has a net sympathetic effect, such as for example an increase in heart rate. Many of the generalized sympathetic effects are a direct effect of the higher amount of circulating catecholamines, in particular epinephrine and norepinephrine.
• the main source of these catecholamines is the adrenal medulla 412, which is innervated by preganglionic sympathetic nerves 410.
• the adrenal medulla 412 releases a mix of approximately 80% epinephrine and 20% norepinephrine 408 into the blood stream when stimulated.
• Heart rate variability is a reflection of the state of the autonomic nervous system (ANS).
• the sympathetic branch of the ANS which is more active during stress situations tends to increase heart rate (HR) and decrease HRV; the opposite is true for the parasympathetic branch of the ANS, which tend to decrease HR and increase HRV.
• HRV heart rate variability
• an anti-inflammatory effect is provided via activation of an anti-inflammatory pathway 420 (e.g., the cholinergic anti-inflammatory pathway), as illustrated in FIG. 4C.
• the methods and devices described herein may activate the anti-inflammatory pathway by stimulating the ABVN 118 and/or the ATN 130 which, as stated before, have projections to the NTS 104. These projections elicit cholinergic antiinflammatory effects via efferent pathways, mostly via the vagus nerve 156. Systemic antiinflammatory effects occur when the vagus nerve 156 mediates spleen 146 function, thereby reducing the amount of circulating pro-inflammatory cytokines.
• a local anti- inflammatory effect occurs at organs reached by the efferent pathways; for example at the lungs
• Decreasing systemic pro-inflammatory processes and/or pro-inflammatory processes in one or more target organs 140, 142, 144, and/or 146 involves modulating at least a portion of the anti-inflammatory pathway 420 such that activity at the NTS 104 is modulated affecting activity in efferent pathways through the celiac ganglion 422 and/or the parasympathetic ganglion 424, which in turn modulate activity in the spleen 146, lungs 142, gut 144, and/or heart 140 such that an anti-inflammatory response is elicited.
• the anti-inflammatory pathway 420 may be activated to reduce bleeding.
• activation of a portion of the anti-inflammatory pathway 420, via stimulation of the vagus nerve 156, is discussed in U.S. Patent No. 8,729,129 to Tracey et al., incorporated by reference herein in its entirety.
• a stimulation flow diagram 500 illustrates stimulation mechanisms for controlling and/or decreasing stress 510 using a treatment device such as a treatment device 800 of FIG. 8A or a treatment device 900 of FIG. 9A.
• the stimulation mechanisms are produced by a first stimulation 502a and a second stimulation 502b.
• the first and second stimulations in some embodiments, are temporally separated (e.g., in overlapping or nonoverlapping stimulations). In some embodiments, the first and second stimulations are physically separated (e.g., using a different electrode or set of electrodes contacting a different location on the patient).
• the first and second stimulations for example, may be provided via the stress reduction pathways 400 discussed in relation to FIG. 4A.
• the first stimulation 502a and/or the second stimulation 502b may be configured to stimulate the AB VN 118 which projects to the prefrontal cortex and/or the ATN 130 which has a pathway to the prefrontal cortex 136 via the TCC 102.
• parasympathetic activity and/or vagal tone is increased (504).
• Enkephalins may increase BDNF mRNA expression in the hippocampus mediated by DOR and MOR mechanisms while [3-Endorphin, endomorphin- 1 and endomorphin-2 upregulate BDNF mRNA in the prefrontal cortex, hippocampus and amygdala.
• DA dopamine
• VTA Ventral Tegmental Area
• MOR agonist e.g., endorphins and enkephalins
• GABAergic interneurons which in turn inhibit dopaminergic neurons in the VTA.
• these DAergic VTA neurons project to Nucleus Accumbens (NAc) 126, the Prefrontal Cortex (PFC) 136, the Hippocampus (Hipp) 138, and the Amygdala (Amyg) 149.
• NAc Nucleus Accumbens
• PFC Prefrontal Cortex
• Hipp Hippocampus
• Amygdala Amygdala
• ADD attention deficit disorder
• ADHD attention deficit hyper-activity deficit disorder
• the first stimulation 502a increases activity in one or more neural medullary structures 506a, such as the NTS 104, the spinal trigeminal nucleus, the NA 122, and at least some of the RN 106.
• the first stimulation 502a may increase 5-HT availability 506b, leading to an increase in BDNF expression.
• the BDNF may function to protect monoamine neurotransmitter neurons and assist the monoamine neurotransmitter neurons to differentiate.
• the second stimulation 502b also increases 5-HT availability.
• NPS is mainly produced in three areas in the brain: LC 108, PbN 404b, and the trigeminal nucleus, the latter being the target of the ATN 130 and at least partially included in the TCC 102. Activity in any of these three areas is necessary for NPS expression 404.
• the second stimulation 502b increases activity in neural structures in the TCC 508a.
• the second stimulation 502b may increases NPS release 508b via the activation cascade that follows the stimulation of the ATN 130.
• providing the first stimulation 502a and providing the second stimulation 502b involves providing a series of simultaneous and/or synchronized stimulation pulses.
• the parameters may include pulse frequency (e.g., low, mid-range, or high) and/or pulse width. Further, the parameters may indicate electrode pairs for producing biphasic pulses.
• the first stimulation may be applied using a low frequency, while the second stimulation is applied using a mid-range frequency. Conversely, in a second illustrative example, the first stimulation may be applied using a mid-range frequency, while the second stimulation is applied using a low frequency.
• Other combinations of low, mid-range, and high frequency stimulations are possible depending upon the patient and the disorder being treated. Therapy may be optimized according to the needs of individual patients including custom stimulation frequency, custom pulse width, custom stimulation intensity (amplitude), and/or independently controlled stimulation channels.
• a stimulation flow diagram 520 illustrates stimulation mechanisms for promoting wakefulness and increasing arousal/alertness to counteract fatigue 528 using a treatment device such as a treatment device 800 of FIG. 8A or a treatment device 900 of FIG. 9 A.
• the stimulation mechanisms are produced by a first stimulation 522a and a second stimulation 522b.
• the first and second stimulations in some embodiments, are temporally separated (e.g., in overlapping or non-overlapping stimulations). In some embodiments, the first and second stimulations are physically separated (e.g., using a different electrode or set of electrodes contacting a different location on the patient).
• the first and second stimulations may be provided via the arousal alertness/control pathways 402 discussed in relation to FIG. 4B.
• the first stimulation 522a and/or the second stimulation 522b may be configured to stimulate the ABVN 118 which projects to the prefrontal cortex and/or the ATN 130 which has a pathway to the prefrontal cortex via the TCC 102.
• 5-HT and NE availability are increased (524), leading to an increase in BDNF expression.
• the BDNF may function to protect monoamine neurotransmitter neurons and assist the monoamine neurotransmitter neurons to differentiate.
• the second stimulation 522b also increases 5-HT and NE availability.
• NE and 5-HT are respectively produced in the Locus Coeruleus (LC) 108 and in the Raphe Nucleus (RN) 106.
• LC Locus Coeruleus
• RN Raphe Nucleus
• BDNF Brain-Derived Neurotrophic- Factor
• PFC prefrontal cortex
• vagal afferents through the synergetic action of ACh, 5-HT and BDNF.
• acute vagal stimulation has been shown to increase NE and 5-HT release in the PFC 136 and the amygdala 149 as well as to enhance synaptic transmission in the hippocampus 138.
• the cognitive improvement due to the increase in BDNF which leads to a faster reorganization of neural circuits, can be leveraged not only to learn new things faster, but also to eliminate/extinguish undesirable and/or maladaptive behavior such as, in some examples, PTSD, phobias, and addictive behavior such as drug-seeking or overeating.
• vagal activation produces pairing-specific plasticity, thus stimulation of vagal afferents, irrespective of what neuromodulator is produced, can be used to eliminate and/or extinguish undesirable and/or maladaptive behavior such as those described above.
• the cognitive enhancement provided by the systems and methods described herein can be used to overcome the cognitive problems that have been described to occur in people exposed to microgravity environments such as astronauts in the space station or on a long space travel such as visiting Mars.
• BDNF levels have been shown to have an inverse correlation with factors associated with cognitive decline and/or impediments, such as in Alzheimer’s patients.
• the second stimulation 522b increases NPS release 526. As discussed above, this increase in NPS production or expression is the result of the activation cascade that follows the stimulation of the ATN 130.
• providing the first stimulation 522a and providing the second stimulation 522b involves providing a series of simultaneous and/or synchronized stimulation pulses.
• the parameters may include pulse frequency (e.g., low, mid-range, or high) and/or pulse width. Further, the parameters may indicate electrode pairs for producing biphasic pulses.
• the first stimulation may be applied using a low frequency, while the second stimulation is applied using a mid-range frequency. Conversely, in a second illustrative example, the first stimulation may be applied using a mid-range frequency, while the second stimulation is applied using a low frequency.
• Other combinations of low, mid-range, and high frequency stimulations are possible depending upon the patient and the disorder being treated. Therapy may be optimized according to the needs of individual patients including custom stimulation frequency, custom pulse width, custom stimulation intensity (amplitude), and/or independently controlled stimulation channels.
• Decreasing systemic pro-inflammatory processes and/or pro-inflammatory processes in one or more target organs 536 involves modulating at least a portion of the anti-inflammatory pathway of FIG. 4C such that activity at the NTS 104 is modulated affecting activity in efferent pathways through the celiac ganglion 422 and/or the parasympathetic ganglion 424, which in turn modulate activity in the spleen 146, lungs 142, gut 144, and/or heart 140 such that an anti-inflammatory response is elicited.
• a second stimulation 534 is provided at a second tissue location configured to stimulate the anti-inflammatory pathway 420 for decreasing systemic pro-inflammatory processes and/or pro-inflammatory processes in one or more target organs 536.
• target pathways and structures for stimulation of the second tissue location include those modulating activity at and/or on the auriculotemporal nerve 130, the lesser occipital nerve 152, and/or the great auricular nerve 154.
• the pathways for example, may include a portion of the pathways illustrated in FIG. 5C.
• the first stimulation may be applied using a midrange frequency, while the second stimulation is applied using a low frequency.
• Other combinations of low, mid-range, and high frequency stimulations are possible depending upon the patient and the disorder being treated.
• the therapy provided by the stimulation 532 and/or the stimulation 534 of the stimulation flow diagram 530 includes automatically adjusting delivery of the therapy (e.g., adjusting one or more parameters) based on feedback received from the pulse generator or another computing device in communication with the pulse generator.
• the feedback may include a blood oxygen concentration, a breathing rate, a breathing variation, tidal volume, skin conductance, blood pressure, heart rate, heart rate variability, and/or EEG signal.
• combinations of the stimulations described in stimulation flow diagrams 500 and/or 520 with the stimulations described in stimulation flow diagram 530 may be used to enhance stress reduction through reducing the time and/or volume of the physical stressor of bleeding.
• activation of the anti-inflammatory pathway 420 in combination with activation of the stress reduction pathway 400 of FIG. 4A may mitigate stress reactions in subjects experiencing physical stress at least partially induced by bleeding.
• activating the anti-inflammatory pathway 420 prior to initiation of bleeding may decrease or minimize bleeding if it occurs and may be used in combination with activation of the arousal/alertness control pathway 402 to improve performance, reduce tunnel vision, and maintain focus of the subject during the activity.
• the first stimulation 532 of the stimulation flow diagram 530 may be delivered synchronously or simultaneously with the second stimulation 502b of the stimulation flow diagram 500 of FIG. 5 A for controlling and/or decreasing stress 510 or vice-versa.
• the first stimulation 532 of the stimulation flow diagram 530 may be delivered synchronously or simultaneously with the second stimulation 522b of the stimulation flow diagram 520 of FIG. 5B for promoting wakefulness, increasing arousal/alertness, and counteracting fatigue 528 or vice-versa.
• the therapy of the stimulation flow diagram 500 including both the first stimulation 502a and the second stimulation 502b may be delivered for a first period of time
• the therapy of the stimulation flow diagram 530 including both the first stimulation 532 and the second stimulation 534 may be delivered for a second period of time
• the therapy of the stimulation flow diagram 510 including both the first stimulation 522a and the second stimulation 522b may be delivered for a first period of time
• the therapy of the stimulation flow diagram 530, including both the first stimulation 532 and the second stimulation 534 may be delivered for a second period of time.
• the combined therapies in some embodiments, may be repeated for a number of cycles of the first period of time and the second period of time.
• the length of one or both of the first period of time and the second period of time may be adjusted to control/decrease stress 510 or promote wakefulness, increase arousal/alertness, and counteract fatigue 528 while decreasing systemic pro-inflammatory processes and/or pro-inflammatory processes in one or more target organs 536 in an efficient manner.
• FIG. 6A and FIG. 6B an example electrode configuration of an earpiece device 600 and example equivalent circuits 610a-b for providing therapy are shown.
• the earpiece device 600 in some implementations, includes inner ear component electrode 602, and auricular component electrodes 604, 606, and 608. Circuitry connecting between the electrodes 602, 604, 606, and 608 may be configured to form corresponding circuits 610a and 610b, as illustrated in FIG. 6B.
• an equivalent circuit 610a is formed by electrode 602 and electrode 606 which are configured to stimulate tissue portions 620.
• the inner ear component electrode 602 is configured to contact a tissue portion 620 in the cymba conchae region which is enervated by branches of the auricular branch of the vagus nerve.
• the auricular component electrode 606, in some implementations, is configured to contact a tissue portion 620 in the region behind the ear which is enervated by branches of the great auricular nerve and/or branches of the lesser occipital nerve.
• An equivalent circuit 610b is formed by electrode 604 and electrode 608 of the auricular component of the device 600 and configured to stimulate tissue portions 622.
• the tissue portions 622 are in the region rostral to the ear which is enervated by the auriculotemporal nerve as well as the region behind the ear which is enervated by branches of the great auricular nerve and branches of the lesser occipital nerve.
• the tissue portions include the concha which may be stimulated, for example, at approximately 5Hz or at approximately 15 Hz.
• the tissue portions include tissue enervated by the trigeminal nerve which may be stimulated, for example, at approximately 100Hz.
• the equivalent circuit 1210a is stimulated by a first channel and equivalent circuit 1210b is stimulated by a second channel.
• FIG. 7 pictures a timing diagram 700 illustrating the triggering of multiple channels 704 and 706 using a master clock 702 according to an example.
• the clock 702 triggers pulses 708 at a predetermined clock frequency.
• a first channel 704 can be configured to trigger stimulation of equivalent circuit 610a and a second channel 706 can be configured to trigger stimulation of equivalent circuit 610b of FIG. 6B.
• the triggering can be reversed, for example, where equivalent circuit 610b is triggered before equivalent circuit 610a.
• stimulation is configured to be triggered by every pulse of the master clock 702; i.e., at a 1-to-l ratio.
• stimulation by one channel 704, 706 is configured to be triggered following a specific time interval after the pulse triggered by the other channel 704, 706 ends.
• one of the channels 704, 706 is be configured to be triggered based on every other pulse of the master clock; i.e., at a 2-to-l ratio with the master clock. For example, the triggering by the second channel 706, as shown occurs every other clock cycle and after a specific time delay 714 from the master clock pulse 708.
• stimulation by the second channel 706 may be configured to be triggered following a specific time interval after the pulse triggered by the first channel 704 ends.
• stimulation from one channel 704, 706 is offset from stimulation by the other channel 704, 706 by a synchronous delay.
• the synchronous delay 714 is 2ms and can be as little as zero (making both channels to trigger simultaneously depending on the master clock ratio for each channel) and as much as the master clock period less the combined duration of the stimulations provided by channel 704 and 706 plus the time interval between them. In some embodiments, this delay can be about 10ms.
• the equivalent circuits 610a, 610b are synchronized using a master clock counter and a register per channel.
• each register By setting each register to a number of master clock pulses to trigger the respective channel, each channel may be configured to be triggered when the channel register value equals the master clock pulses. Subsequently, the counter for each channel may be reset after the channel is triggered.
• the trigger frequency can be as high as the master clock frequency (1:1) and as low as 1/64 of the clock frequency (64:1).
• Stimulation delivery may vary based upon the therapy provided by the treatment device.
• Frequency and/or pulse width parameters may be adjusted for one or more if not all electrodes delivering stimulation.
• frequency and/or pulse width parameters are adjusted during therapy, for example responsive to feedback received from monitoring the patient (e.g., using one or more sensors or other devices).
• the stimulation frequencies may include a first or low frequency within a range of about 1 to 30 Hz, a second or mid-range frequency within a range of about 30 to 70 Hz, and/or a third or high frequency within a range of about 70 to 150 Hz.
• Stimulation pulses in some embodiments, are delivered in patterns. Individual pulses in the pattern may vary in frequency and/or pulse width. Patterns may be repeated in stimulation cycles.
• the stimulation patterns are such that stimulating frequencies are not the same in all electrodes.
• a stimulation frequency is varied between 2 Hz and 100 Hz such that different endogenously produced opioid receptor agonist are released (e.g., Mu, Delta, Kappa, nociception opioid receptor agonist).
• the pulse width can be adjusted from between 20 and 1000 microseconds to further allow therapy customization.
• different stimulation frequencies are used at the different electrodes.
• different combinations of high, mid-range and low frequencies can be used at a cymba electrode (602), an auriculotemporal electrode (604), and/or a great auricular nerve and lesser occipital nerve electrode (606, 608).
• a first or low frequency of between 1 to 30 Hz, or in particular one or more of 1 to 5 Hz, 5 to 10 Hz, 10 to 15 Hz, 15 to 20 Hz, 20 to 25 Hz, 25 to 30 Hz may be used at an in-ear electrode
• a third or mid-range frequency of between 30 to 70 Hz, or in particular one or more of 30 to 35 Hz, 35 to 40 Hz, 40 to 45 Hz, 45 to 50 Hz, 50 to 55 Hz, or 55 to 60 Hz or 60 to 65 Hz or 65 to 70 Hz can be used at one or more of the electrodes.
• one or more low or mid-range frequencies can be used at an in-ear electrode such as the cymba electrode 602, while one or more high frequencies is used at an electrode contacting tissue surrounding the ear, such as the auriculotemporal electrode 604.
• a high frequency can be use at an in-ear electrode such as the cymba electrode 602 while a low frequency can be used at an electrode contacting tissue surrounding the ear, such as the auriculotemporal electrode 604.
• Pulse widths may range from one or more of the following: first or short pulse widths within a range of about 10 to 50 microseconds, or more particularly between 10 to 20 microseconds, 20 to 30 microseconds, 30 to 40 microseconds, 40 to 50 microseconds; second or low midrange pulse widths within a range of about 50 to 250 microseconds, or more particularly between 50 to 70 microseconds, 70 to 90 microseconds, 90 to 110 microseconds, 110 to 130 microseconds, 130 to 150 microseconds, 150 to 170 microseconds, 170 to 190 microseconds, 190 to 210 microseconds, 210 to 230 microseconds, or 230 to 250 microseconds; third or high mid-range pulse widths within a range of about 250 to 550 microseconds, or more particularly between 250 to 270 microseconds, 270 to 290 microseconds, 290 to 310 microseconds, 310 to 330 microseconds,
• a variable frequency i.e., stimulating a non-constant frequency
• the variable frequency can be a sweep, and/or a random/pseudo-random frequency variability around a central frequency (e.g., 5 Hz +/- 1.5 Hz, or 100 Hz +/- 10Hz).
• treatment devices may be designed for positioning against various surfaces on or surrounding a patient’s ear.
• an example treatment device 800 is shown including an auricular component 802 configured to contact skin behind and around a patient’s ear.
• the auricular component 802 may wrap around a back of an ear and include electrodes 804 for contacting skin surfaces in front of and behind the ear.
• the auricular component 802 is connected to an inner ear component 806 by a connector 808.
• a proximal (auricular component 802 side) end or at distal (inner ear component 806) end of the connector 808 may be designed for releasable connection.
• the connector 808 is integrated with the auricular component 802 and inner ear component 806, behaving as a conduit for bridging an electrical connection between the auricular component 802 and the inner ear component 806.
• the auricular component 802 includes a number of electrodes 804 that are configured to be in contact with the dermis on and around the outer ear.
• the auricular component 802 may include an electrode positioned for proximity to vagal-related neural structures, an electrode positioned for proximity to a neural structure related to the auriculotemporal nerve, an electrode positioned for proximity to neural structures related to the great auricular nerve or its branches, and/or an electrode positioned for proximity to the lesser occipital nerve or its branches.
• a pulse generator is connected to the auricular component 802 by a second connector.
• the second connector may be releasably connected between the auricular component 802 and the pulse generator.
• at least one of a proximal (auricular component 802) end or a distal (pulse generator) end of the second connector may be designed for releasable connection.
• the second connector is integrated with the auricular component 802 and the pulse generator, behaving as a conduit for bridging an electrical connection between the auricular component 802 and the pulse generator.
• a pulse generator is built into the auricular component 802.
• a treatment device such as the device 800 of FIGs. 8A and 8B may be donned as follows.
• an earpiece assembly 900 includes a printed circuit board (PCB) layer having electrodes.
• a flexible PCB can include electronic components to suppress electrical spikes as well as a component to identify and/or uniquely identify the PCB. Exposed conductive surfaces on the PCB can serve as contact point to connect hydrogels to the PCB.
• the PCB extends forming a cable-like structure (connector) 904 to integrate an inner ear component 906 and an auricular component 902 without the need for soldering and/or connecting during assembly.
• the earpiece assembly 900 in some embodiments, is extremely flexible, allowing it to easily conform to different shapes presented by the anatomic variability of users.
• the earpiece assembly 900 is at least partially custom printed to provide a fitted shape for the user.
• PCB may be at least partially covered with a closed cell foam.
• the skin-contacting electrodes of the earpiece assembly 900 are formed in layers.
• a first layer may include a medical-grade double-sided conducting adhesive tape
• the second layer may include a conductive flexible metallic and/or fabric mesh for mechanical robustness and homogenic electrical field distribution
• a third layer may include a self-adhesive hydrogel.
• a two-layer version may be provided having a first layer configured for mechanical robustness and homogenic electrical field distribution and a second layer including a self-adhesive hydrogel.
• the PCB electrodes may be formed such that they cover a similar surface area as the skin-contacting hydrogel electrodes. In this manner, homogenic electrical field distribution may be achieved at the hydrogels without the need of any additional conductive layer.
• the earpiece assembly 900 connects to a pulse generator via a slim keyed connector.
• the PCB layer includes controller circuitry for generating pulses.
• a software update to the pulse generator may be delivered via wireless communication.
• the wireless communication in some examples, can include radio frequency (RF) communication (e.g., Bluetooth) or near-field communication (NFC).
• RF radio frequency
• NFC near-field communication
• the wireless communication may be enabled via an application installed on the peripheral device.
• a therapeutic auricular device includes few or no inputs accessible to the wearer.
• the therapeutic auricular device may include a power control buton or switch.
• a disposable therapeutic auricular device may include a removable batery tab that, when removed, engages power to the device and initiates therapeutic delivery.
• a therapeutic auricular device includes circuitry and/or other components to integrate the therapeutic auricular device with other devices, such as communications devices.
• the therapeutic auricular device may include a wireless speaker component, wireless signal reception, and/or wireless signal transmission.
• a therapeutic auricular device may include a Bluetooth or other limited range wireless communication module for remote therapy initiation.
• the configuration illustrated in FIG. 10A enables automatic adjustment of therapy delivery by reviewing feedback provided by the treatment device and/or one or more peripheral devices 1010 (e.g., fitness monitors and/or health monitors used by the patient).
• a cloud platform accessible via the network 1020 may receive the feedback, review present metrics, and relay instructions to the pulse generator 1004 (e.g., via a Wi-Fi network or indirectly via a local portable device belonging to the patient such as a smart phone app in communication with the treatment device 1000).
• the pulse generator 1004 in a further example, may gather feedback from the one or more fitness monitor and/or health monitor devices 1010, analyze the feedback, and determine whether to adjust treatment accordingly.
• the auricular component 1002 of the treatment device 1000 may further be enabled for wireless transmission of information with one or more peripheral devices 1010.
• the auricular component 1002 may include a short-range radio frequency transmitter for sharing sensor data, alerts, error conditions, or other information with one or more peripheral devices 1010.
• the data for example, may be collected in a small non-transitory (e.g., non-volatile) memory region built into the auricular component 1002.
• the pulse generator 1004 is included in the auricular component 1002 that is, they are co-located thus the need for an extension cable to connect them is not necessary.
• an isolated port 1118 such as a USB is used to charge the battery, and to communicate with the microcontroller(s) 1110.
• the communication can be both ways, such that instructions or entire new code can be uploaded to the microcontroller(s) 1110 and to download information stored in the memory 1122.
• memory 1122 can be added to the circuit as an external CHIP, while in other embodiments, the memory 1122 can be internal to the microcontroller(s) 1110.
• the FPGA 1112 may also have internal memory.
• an external trigger circuit 1124 is included, such that the stimulation can be started and/or stopped via an external signal.
• the external trigger signal can be passed through the isolated port 1118; in yet other embodiments a modified USB configuration (i.e., not using the standard USB pin configuration) can be used to pass the trigger signal.
• a modified USB configuration i.e., not using the standard USB pin configuration
• Using a modified USB configuration will force a custom USB cable to be used, thus ensuring that an external trigger cannot be provided by mistake using an off-the-shelf USB cable.
• the sensors may monitor one or more of electrodermal activity (e.g., sweating), movement activity (e.g., tremors, physiologic movement), glucose level, neurological activity (e.g., via EEG), and/or cardio-pulmonary activity (e.g., EKG, heart rate, blood pressure (systolic, diastolic and mean)).
• electrodermal activity e.g., sweating
• movement activity e.g., tremors, physiologic movement
• glucose level e.g., neurological activity
• cardio-pulmonary activity e.g., EKG, heart rate, blood pressure (systolic, diastolic and mean)
• imaging techniques such as MRI and fMRI could be used to adjust the therapy in a clinical setting for a given user.
• imaging of pupillary changes e.g., pupillary dilation
• a common cellular phone and/or smart-glass glasses could be used to provide feedback to make therapy adjustments.
• one or more sensors are integrated into the earpiece and/or concha apparatus.
• One or more sensors are integrated into the pulse generator. For example, periodic monitoring may be achieved through prompting the wearer to touch one or more electrodes on the system (e.g., electrodes built into a surface of the pulse generator) or otherwise interact with the pulse generator (e.g., hold the pulse generator extended away from the body to monitor tremors using a motion detector in the pulse generator).
• one or more sensor outputs may be obtained from external devices, such as a fitness computer, smart watch, or wearable health monitor.
• the monitoring used may be based, in part, on a treatment setting.
• EEG monitoring is easier in a hospital setting
• heart rate monitoring may be achieved by a sensor such as a pulsometer built into the earpiece or another sensor built into a low budget health monitoring device such as a fitness monitoring device or smart watch.
• EKG can be used to assess heart rate and heart rate variability, to determine the activity of the autonomic nervous system in general and/or the relative activity of the sympathetic and parasympathetic branches of the autonomic nervous system, and to modulate the therapy.
• Autonomic nervous activity can be indicative of symptoms associated with substance withdrawal.
• the treatment device can be used to provide therapy for treating cardiac conditions such as atrial fibrillation and heart failure.
• therapy can be provided for modulation of the autonomic nervous system.
• the treatment device can be used to provide therapy to balance a ratio between any combinations of the autonomic nervous system, the parasympathetic nervous system, and the sympathetic nervous system.
• the system can monitor impedance measurements allowing closed-loop neurostimulation.
• monitoring feedback can be used to alert patient/ caregiver if therapy is not being adequately delivered and if the treatment device is removed.
• processors can be utilized to implement various functions and/or algorithms described herein. Additionally, any functions and/or algorithms described herein can be performed upon one or more virtual processors, for example on one or more physical computing systems such as a computer farm or a cloud drive.
• aspects of the present disclosure may be implemented by hardware logic (where hardware logic naturally also includes any necessary signal wiring, memory elements and such), with such hardware logic able to operate without active software involvement beyond initial system configuration and any subsequent system reconfigurations.
• the hardware logic may be synthesized on a reprogrammable computing chip such as a field programmable gate array (FPGA), programmable logic device (PLD), or other reconfigurable logic device.
• FPGA field programmable gate array
• PLD programmable logic device
• the hardware logic may be hard coded onto a custom microchip, such as an application-specific integrated circuit (ASIC).
• software stored as instructions to a non-transitory computer-readable medium such as a memory device, on-chip integrated memory unit, or other non-transitory computer-readable storage, may be used to perform at least portions of the herein described functionality.
• computing devices such as a laptop computer, tablet computer, mobile phone or other handheld computing device, or one or more servers.
• Such computing devices include processing circuitry embodied in one or more processors or logic chips, such as a central processing unit (CPU), graphics processing unit (GPU), field programmable gate array (FPGA), application-specific integrated circuit (ASIC), or programmable logic device (PLD).
• processors or logic chips such as a central processing unit (CPU), graphics processing unit (GPU), field programmable gate array (FPGA), application-specific integrated circuit (ASIC), or programmable logic device (PLD).
• the processing circuitry may be implemented as multiple processors cooperatively working in concert (e.g., in parallel) to perform the instructions of the inventive processes described above
• the process data and instructions used to perform various methods and algorithms derived herein may be stored in non-transitory (i.e., non-volatile) computer-readable medium or memory.
• the claimed advancements are not limited by the form of the computer-readable media on which the instructions of the inventive processes are stored.
• the instructions may be stored on CDs, DVDs, in FLASH memory, RAM, ROM, PROM, EPROM, EEPROM, hard disk or any other information processing device with which the computing device communicates, such as a server or computer.
• the processing circuitry and stored instructions may enable the pulse generator 1004 of FIG. 10A through FIG. 10C or the pulse generator 1150 of FIG. 11 to perform various methods and algorithms described above. Further, the processing circuitry and stored instructions may enable the peripheral device(s) 1010 of FIG. 10A through FIG. 10C to perform various methods and algorithms described above.
• These computer program instructions can direct a computing device or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable medium produce an article of manufacture including instruction means which implement the function/ operation specified in the illustrated process flows.
• the network can be a public network, such as the Internet, or a private network such as a local area network (LAN) or wide area network (WAN) network, or any combination thereof and can also include PSTN or ISDN sub-networks.
• the network can also be wired, such as an Ethernet network, and/or can be wireless such as a cellular network including EDGE, 3G, 4G, and 5G wireless cellular systems.
• the wireless network can also include Wi-Fi, Bluetooth, Zigbee, or another wireless form of communication.
• the network for example, may be the network 1020 as described in relation to FIG. 10A through FIG. 10C.
• the computing device such as the peripheral device(s) 1010 of FIG. 10 A- 10C, in some embodiments, further includes a display controller for interfacing with a display, such as a built-in display or LCD monitor.
• a display such as a built-in display or LCD monitor.
• a general purpose I/O interface of the computing device may interface with a keyboard, a hand-manipulated movement tracked I/O device (e.g., mouse, virtual reality glove, trackball, joystick, etc.), and/or touch screen panel or touch pad on or separate from the display.
• a sound controller in some embodiments, is also provided in the computing device, such as the peripheral device(s) 1010 of FIG. 10A through FIG. 10C, to interface with speakers/mi crophone thereby providing audio input and output.
• circuitry described herein may be adapted based on changes on battery sizing and chemistry or based on the requirements of the intended back-up load to be powered.
• Certain functions and features described herein may also be executed by various distributed components of a system.
• one or more processors may execute these system functions, where the processors are distributed across multiple components communicating in a network such as the network 1020 of FIG. 10A through FIG. 10C.
• the distributed components may include one or more client and server machines, which may share processing, in addition to various human interface and communication devices (e.g., display monitors, smart phones, tablets, personal digital assistants (PDAs)).
• the network may be a private network, such as a LAN or WAN, or may be a public network, such as the Internet. Input to the system may be received via direct user input and received remotely either in realtime or as a batch process.
• a cloud computing environment such as Google Cloud PlatformTM
• Google Cloud PlatformTM may be used perform at least portions of methods or algorithms detailed above.
• the processes associated with the methods described herein can be executed on a computation processor of a data center.
• the data center for example, can also include an application processor that can be used as the interface with the systems described herein to receive data and output corresponding information.
• the cloud computing environment may also include one or more databases or other data storage, such as cloud storage and a query database.
• the cloud storage database such as the Google Cloud Storage, may store processed and unprocessed data supplied by systems described herein.
• the systems described herein may communicate with the cloud computing environment through a secure gateway.
• the secure gateway includes a database querying interface, such as the Google BigQuery platform.

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