Electrical stimulation of the ear, head, cranial nerve, or cortex for the treatment of tinnitus: a scoping review

Tinnitus is defined as the perception of sound in the absence of an external source. It is often associated with hearing loss and is thought to result from abnormal neural activity at some point or points in the auditory pathway, which is incorrectly interpreted by the brain as an actual sound. Neurostimulation therapies therefore, which interfere on some level with that abnormal activity, are a logical approach to treatment. For tinnitus, where the pathological neuronal activity might be associated with auditory and other areas of the brain, interventions using electromagnetic, electrical, or acoustic stimuli separately, or paired electrical and acoustic stimuli, have been proposed as treatments. Neurostimulation therapies should modulate neural activity to deliver a permanent reduction in tinnitus percept by driving the neuroplastic changes necessary to interrupt abnormal levels of oscillatory cortical activity and restore typical levels of activity. This change in activity should alter or interrupt the tinnitus percept (reduction or extinction) making it less bothersome. Here we review developments in therapies involving electrical stimulation of the ear, head, cranial nerve, or cortex in the treatment of tinnitus which demonstrably, or are hypothesised to, interrupt pathological neuronal activity in the cortex associated with tinnitus

Neuromodulation with Electromagnetic Stimulation for Seizure Suppression: From Electrode to Magnetic Coil

Non-invasive brain tissue stimulation with a magnetic coil provides several irreplaceable advantages over that with an implanted electrode, in altering neural activities under pathological situations. We reviewed clinical cases that utilized time-varying magnetic fields for the treatment of epilepsy, and the safety issues related to this practice. Animal models have been developed to foster understanding of the cellular/molecular mechanisms underlying magnetic control of epileptic activity. These mechanisms include (but are not limited to) (1) direct membrane polarization by the magnetic field, (2) depolarization blockade by the deactivation of ion channels, (3) alteration in synaptic transmission, and (4) interruption of ephaptic interaction and cellular synchronization. Clinical translation of this technology could be improved through the advancement of magnetic design, optimization of stimulation protocols, and evaluation of the long-term safety. Cellular and molecular studies focusing on the mechanisms of magnetic stimulation are of great value in facilitating this translation

Targeted vagus nerve stimulation for rehabilitation after stroke

No abstract available

Noninvasive Transcranial Focal Stimulation Via Tripolar Concentric Ring Electrodes Lessens Behavioral Seizure Activity of Recurrent Pentylenetetrazole Administrations in Rats

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We have been developing a noninvasive transcranial focal electrical stimulation with our novel tripolar concentric ring electrodes as an alternative/complementary therapy for seizure control. In this study we demonstrate the effect of focal stimulation on behavioral seizure activity induced by two successive pentylenetetrazole administrations in rats. Seizure onset latency, time of the first behavioral change, duration of seizure, and maximal seizure severity score were studied and compared for focal stimulation treated (n = 9) and control groups (n = 10). First, we demonstrate that no significant difference was found in behavioral activity for focal stimulation treated and control groups after the first pentylenetetrazole administration. Next, comparing first and second pentylenetetrazole administrations, we demonstrate there was a significant change in behavioral activity (time of the first behavioral change) in both groups that was not related to focal stimulation. Finally, we demonstrate focal stimulation provoking a significant change in seizure onset latency, duration of seizure, and maximal seizure severity score. We believe that these results, combined with our previous reports, suggest that transcranial focal stimulation may have an anticonvulsant effect

Neuromodulation of Thalamic Sensory Processing of Tactile Stimuli

Neuromodulatory systems, such as the locus coeruleus (LC) - norepinephrine (NE) system, are integral in the modulation of behavioral state, which in turn exerts a heavy influence on sensory processing, perception, and behavior. LC neurons project diffusely through the forebrain as the sole source of NE. LC tonic firing rate has been shown to correlate with arousal level and behavioral performance. As the LC-NE system innervates sensory pathways and NE has been shown to affect neuronal response, the LC-NE system could potentially allow for state-dependent modulation of sensory processing. However, the precise link between LC activation and sensory processing in the various stages of the sensory pathway that underly perception remained elusive. It is well established that thalamic relay nuclei play an essential role in gating the flow of sensory information to the neocortex, serving to establish cortical representation of sensory environment. Thalamocortical information transmission has been proposed to be strongly modulated by the dynamic interplay between the thalamic relay nuclei and the thalamic reticular nucleus (TRN). Neurons in the early stages of sensory pathways selectively respond to specific features of sensory stimuli. In the rodent vibrissa pathway, thalamocortical neurons in the ventral posteromedial nucleus (VPm) encode kinetic features of whisker movement, allowing stimuli to be encoded by distinctive, temporally precise firing patterns. Therefore, understanding feature selectivity is crucial to understanding sensory processing and perception. However, whether LC activation modulates this feature selectivity, and if it does, the mechanisms through which this modulation occurs, remained largely unknown. This work investigates LC modulation of thalamic feature selectivity through reverse correlation analysis of single-unit recordings from different stages of the rat vibrissa pathway. LC activation increased feature selectivity, drastically improving thalamic information transmission. This improvement was dependent on both local activation of α-adrenergic receptors and modulation of T-type calcium channels in the thalamus and was not due to LC modulation of trigeminothalamic feedforward or corticothalamic feedback inputs. LC activation reduced thalamic bursting, but this change in thalamic firing mode was not the primary cause of the improved information transmission as tonic spikes with LC stimulation carried three-times the information than tonic spikes without LC stimulation. Modelling confirmed NE regulation of intrathalamic circuit dynamics led to the improved information transmission as LC-NE modulation of either relay or reticular nucleus alone cannot account for the improvement. These results suggest a new sub-dimension within the tonic mode in which brain state can optimize thalamic sensory processing through modulation of intrathalamic circuit dynamics. Subsequent computational work was then performed to determine exactly how the encoding of sensory information by thalamic relay neurons was altered to allow for an increase in both information transmission efficiency and rate. The results show that LC-NE induced improvements in feature selectivity are not simply due to an increased signal-to-noise ratio, a shift from bursting to tonic firing, or improvements in reliability or precision. Rather, LC-NE-induced modulation of intrathalamic dynamics changed the temporal response structure thalamic neurons used to encode the same stimuli to a new structure that increased the information carried by both tonic and burst spikes. The shift in events times favors optimal encoding, as more events occur at ideal positions, i.e. when the stimulus most closely matches the neuron’s feature selectivity. Further, this work analyzed the ability to reconstruct the original stimulus using the evoked spike trains of multiple neurons and their recovered feature selectivity from an ideal observer point-of-view. The results showed that LC-activation improved the accuracy of this reconstruction, indicating it may improve the accuracy of perception of whisker stimuli. Finally, to make this work translatable, the use of vagus nerve stimulation (VNS) was investigated as a potential method for minimally invasive enhancement of thalamic sensory processing. The vagus nerve, which runs through the side of the neck, has long been known to have profound effects on brain-state and VNS has been shown to evoke LC firing. This work elucidates the previously uninvestigated short-term effects of VNS on thalamic sensory processing. Similar to direct LC stimulation, VNS enhanced the feature selectivity of thalamic neurons, resulting in a significant increase in the efficiency and rate of stimulus-related information conveyed by thalamic spikes. VNS-induced improvement in thalamic sensory processing also coincided with a decrease in thalamic burst firing, suggesting the same underlying mechanism as the improvements induced with direct LC stimulation

Effets de la stimulation cérébrale profonde dans l'épilepsie focale motrice

Epileptic seizures arise from pathological synchronization of neuronal ensemble.Seizures originating from primary motor cortex are often pharmacoresistant, and many times unsuitable for respective surgery because of location of epileptic focus in eloquent area. Basal ganglia play important role in seizure propagation. Micro electrode recordings performed during previous studies indicated that input structures of basal ganglia such as GPe, Putamen and Subthalamic nucleus (STN) are strongly modified during seizures. For example the mean firing rate of neurons of the STN and Putamen increased and the percentage of oscillatory neurons synchronized with the ictal EEG was higher during seizures as compared to interictal periods. Pilot studies in humans have shown the possible beneficial effect of chronic DBS applied to STN in treatment of pharmacoresistant motor seizures. Our study was aimed at studying the therapeutic effect of electrical stimulation of input structures of basal ganglia . We first developed a stable, predictable primate model of focal motor epilepsy by intracortical injection of penicillin and we documented it's pharmacoresistence. We then stereotactically implanted DBS electrodes in the STN and Putamen. The stimulator was embedded at the back of the animals. Subthreshold electrical stimulations at 130 Hz were applied to STN. Stimulator was turned ON when penicillin was injected. Sham stimulation at 0 volt was used as a control situation, each monkey being its own control. The time course, number and duration of seizures occurring in each epochs of 1 h were compared during ON and sham stimulation periods. Each experimental session lasted uptoo 6 hours,We also studied preventive high frequency stimulation of STN and subthershold low frequency stimulation of Putamen with 5 Hz and 20 Hz in the same model .Finally we studied combined effects of high frequency STN and low frequency Putamen stimulation in one monkey Results: Data was analysed from 1572 seizures in 30 experiments in three monkeys for chronic STN stimulation , 454 seizures in 10 experiments in one moneky during preventive STN stimulation ,289 seizures from 14 experiments in two monkeys during LFS putamen stimulation and 477 seizures from 10 sessions during combined STN and Putamen stimulation in one monkey The best results were observed during chronic STN stimulation The occurrence of first seizure was significantly delayed as compared to sham situation. Total time spent in focal seizures was significantly reduced by ≥69% on an average (p ≤0.05) after STN stimulation, due to a significant decrease in the number of seizures especially so during the first 3 hours after stimulation. The duration of individual seizures reduced moderately. Bipolar and monopolar stimulation modes were equally effective Preventive HFS STN (in one specimen) was not found to be superior to acute stimulation. LFS Putamen alone was effective but mainly in first two hours of stimulation .In a combined HFS STN and LFS Putamen stimulation the effect of stimulation in terms of seizure control was modest and poor compared to HFS STN alone or LFS Putamen alone. This study provides original data in primates showing the potential therapeutic effect of chronic HFS-STN DBS to treat focal motor seizures . A discussion explaining these results and comparison with STN DBS in human motor seizures as well as future translational perspective in human therapeutics is provided.Les crises d'épilepsie proviennent d'une synchronisation pathologique de réseaux neuronaux du cortex. Les crises motrices, générées à partir du cortex moteur primaire, sont souvent pharmaco-résistantes. La résection neurochirurgicale du foyer épileptique est rarement l'option thérapeutique de choix au regard des risques de deficits moteurs potentiellement induits par la résection. Les ganglions de la base ont un rôle important dans la propagation des crises. Des enregistrements par micro-électrode réalisés dans une précédente étude ont montré que les activités des structures d'entrée des ganglions de la base telles que le Putamen, le noyau caudé et le noyau sous-thalamique (NST) sont fortement modifiées pendant des crises motrices. Le taux de décharge moyen des neurones du NST et du Putamen augmente et le pourcentage de neurones oscillants synchronisés avec l'EEG durant la période ictale est plus élevé durant les crises que pendant la période inter-ictale. Des études pilotes chez l'humain ont montré un effet bénéfique potentiel de la stimulation cérébrale profonde (SCP) chronique du NST pour traiter les crises motrices pharmaco-résistantes. Le but de notre étude est d'évaluer les effets thérapeutiques de la SCP des structures d'entrée des ganglions de la base. Nous avons dans un premier temps développé un modèle primate de crise d'épilepsie motrice focale stable et reproductible par injection intra-corticale de pénicilline. Nous avons ensuite caractérisé la pharmaco-résistance du modèle. Nous avons implanté stéréotactiquement des électrodes de SCP dans le NST et le Putamen. Le stimulateur a été placé sous la peau dans le dos de l'animal. Un protocole de stimulation à 130 Hz à un voltage inférieur à l'apparition d'effets secondaires a été réalisé dans le NST. Le stimulateur était mis en marche au moment de l'injection de la pénicilline. Un protocole de stimulation à 0 volt a été réalisé comme condition contrôle. Chaque primate étant son propre contrôle. L'apparition des crises, leur nombre et leur durée ont été comparés par période de 1 heure entre la condition stimulée et non stimulée. Chaque session expérimentale a été menée sur une durée de plus de six heures. Nous avons évalué l'effet préventif de la SCP à haute fréquence (130 Hz) du NST sur les crises motrices. Nous avons également étudié l'effet préventif de la SCP à basse fréquence (5-20 Hz) du Putamen sur ce même modèle. Enfin, sur un autre primate, nous avons étudié l'effet combiné de la SCP du NST à haute fréquence et du Putamen à basse fréquence sur les crises motrices. Résultats : Les effets de la SCP chronique du NST à haute fréquence ont été analysés à partir de 1572 crises apparues au cours de 30 sessions expérimentales chez 3 primates. Les effets de la SCP préventive du NST ont été évalués sur 454 crises motrices durant 10 sessions expérimentales chez un primate. L'effet de la SCP du Putamen à basse fréquence a été analysé sur 289 crises durant 14 sessions chez 2 primates. Enfin l'effet combiné de la SCP du NST et du Putamen a été évalué sur 477 crises durant 10 sessions. Les meilleurs résultats ont été obtenus par SCP chronique du NST. L'apparition de la première crise était significativement retardée lorsque le primate était stimulé. Le temps total passé en situation de crise motrice était diminué en moyenne d'environ 69 % (p ≤0.05) par rapport à la condition non-stimulé au regard de la diminution significative du nombre de crises particulièrement durant les 3 heures après le début de la stimulation. La durée de chaque crise était modérément réduite. Les modes de stimulation mono-polaire ou bi-polaire avaient une efficacité similaire. La SCP préventive du NST n'a pas eu d'effet supérieur à la stimulation chronique du NST. La SCP chronique du Putamen à basse fréquence avait un effet positif mais principalement durant les deux premières heures de stimulation. L'effet combiné de la SCP du NST et du Putamen était inférieur à la SCP chronique du NST ou du Putamen

Transcranial focal electrical stimulation via concentric ring electrodes in freely moving cats: Antiepileptogenic and postictal effects

Transcranial focal electrical stimulation (TFS) via tripolar concentric ring electrodes (TCRE), tripolar TFS, is proposed to treat pharmacoresistant epilepsy. We determined the effect of tripolar TFS on electrical amygdaloid kindling (AK) in freely moving cats. Fifteen cats were bilaterally implanted with electrodes in the amygdala (AM) and prefrontal cortex and assigned to three groups: the control group, which only received AK; the tripolar TFS before AK group, in which TCREs were placed over the vertex and tripolar TFS (300 Hz, 200 μs biphasic equal charge, square pulses) was delivered for 40 min just prior to AK; and the tripolar TFS after AK group, in which the TCREs were placed over the temporal bone ipsilateral to the kindled AM, while tripolar TFS was administered for 2 min just after AK onset for 40 days, and, thereafter, only AK was applied. AK was applied daily until all animals reached kindling stage VI. A three concentric spheres finite element cat head model was developed to analyze the electric fields caused by tripolar TFS. Tripolar TFS after AK inhibited kindling development. Animals with tripolar TFS after AK remained at the focal seizure stages for 20 days after tripolar TFS cessation and required 80.0 ± 15.42 AK stimulations to reach stage VI, significantly higher than TFS before AK, and control (P \u3c .001). Tripolar TFS before AK did not show signs of protection against epileptogenesis. The finite modeling of tripolar TFS showed that the electric field is \u3e0.3 mV/mm at depths less than approximately 12.6 mm in the cat brain, which should be strong enough to alter brain activity. In conclusion, tripolar TFS applied via a TCRE over the ipsilateral temporal area significantly delayed AK. This taken together with other reports of tripolar TFS aborting seizures in acute seizure models suggests that tripolar TFS is a promising new modality that should be considered for further testing