Using EMG to deliver lumbar dynamic electrical stimulation to facilitate cortico-spinal excitability

BackgroundPotentiation of synaptic activity in spinal networks is reflected in the magnitude of modulation of motor responses evoked by spinal and cortical input. After spinal cord injury, motor evoked responses can be facilitated by pairing cortical and peripheral nerve stimuli.ObjectiveTo facilitate synaptic potentiation of cortico-spinal input with epidural electrical stimulation, we designed a novel neuromodulation method called dynamic stimulation (DS), using patterns derived from hind limb EMG signal during stepping.MethodsDS was applied dorsally to the lumbar enlargement through a high-density epidural array composed of independent platinum-based micro-electrodes.ResultsIn fully anesthetized intact adult rats, at the interface array/spinal cord, the temporal and spatial features of DS neuromodulation affected the entire lumbosacral network, particularly the most rostral and caudal segments covered by the array. DS induced a transient (at least 1 min) increase in spinal cord excitability and, compared to tonic stimulation, generated a more robust potentiation of the motor output evoked by single pulses applied to the spinal cord. When sub-threshold pulses were selectively applied to a cortical motor area, EMG responses from the contralateral leg were facilitated by the delivery of DS to the lumbosacral cord. Finally, based on motor-evoked responses, DS was linked to a greater amplitude of motor output shortly after a calibrated spinal cord contusion.ConclusionCompared to traditional tonic waveforms, DS amplifies both spinal and cortico-spinal input aimed at spinal networks, thus significantly increasing the potential and accelerating the rate of functional recovery after a severe spinal lesion.     

Distinct perceptive pathways selected with tonic and bursting patterns of thalamic stimulation

BackgroundNovel patterns of electrical stimulation of the brain and spinal cord hold tremendous promise to improve neuromodulation therapies for diverse disorders, including tremor and pain. To date, there are limited numbers of experimental studies in human subjects to help explain how stimulation patterns impact the clinical response, especially with deep brain stimulation.We propose using novel stimulation patterns during electrical stimulation of somatosensory thalamus in awake deep brain stimulation surgeries and hypothesize that stimulation patterns will influence the sensory percept without moving the electrode.MethodsIn this study of 15 fully awake patients, the threshold of perception as well as perceptual characteristics were compared for tonic (trains of regularly-repeated pulses) and bursting stimulation patterns.ResultsIn a majority of subjects, tonic and burst percepts were located in separate, non-overlapping body regions (i.e., face vs. hand) without moving the stimulating electrode (p < 0.001; binomial test). The qualitative features of burst percepts also differed from those of tonic-evoked percepts as burst patterns were less likely to evoke percepts described as tingling (p = 0.013; Fisher’s exact test).ConclusionsBecause somatosensory thalamus is somatotopically organized, percept location can be related to anatomic thalamocortical pathways. Thus, stimulation pattern may provide a mechanism to select for different thalamocortical pathways. This added control could lead to improvements in neuromodulation - such as improved efficacy and side effect attenuation - and may also improve localization for sensory prostheses.     

Assessment of safety of self-controlled repetitive trans-vertebral magnetic stimulation

ObjectiveThe aim of this study was to assess safety issues of self-controlled repetitive trans-vertebral magnetic stimulation (rTVMS) in humans.MethodsWe investigated effects of self-controlled rTVMS (≤20 Hz, ≤90% intensity) on vital signs and subjective sensations in 1690 trials of 30 healthy volunteers and 12 patients with spinal cord disorders.ResultsHealthy volunteers and the patients received 4595 ± 2345, and 4450 ± 2304 pulses in one day, respectively. No serious adverse events were observed in any participants, and only minor events were seen as follows. While blood pressure was unaffected in the patients, the diastolic blood pressure increased slightly after rTVMS in healthy volunteers. The peripheral capillary oxygen saturation increased after rTVMS in healthy volunteers. “Pain” or “Discomfort” was reported in approximately 10% of trials in both participants groups. Degree of the evoked sensation positively correlated with stimulus intensity and was affected by the site of stimulation.ConclusionSelf-controlled rTVMS (≤20 Hz and ≤90% intensity) did not induce any serious adverse effects in healthy volunteers and patients with spinal cord disorders.SignificanceOur results indicate that rTVMS can be used safely in physiological investigations in healthy volunteers and also as treatment for neurological disorders.     

Altered supraspinal motor networks in survivors of poliomyelitis: A cortico-muscular coherence study

ObjectivePoliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio.MethodsSurface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of cortico-muscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task.ResultsA pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30–47 Hz) was observed in frontal and parietal regions.ConclusionThese findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network.SignificanceThis research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions.     

A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation

BackgroundDeep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimulation paradigms in existing or prospective indications.ObjectiveProvide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on neuronal activity.MethodsIn patients with movement disorders, single-neuron recordings were acquired from the subthalamic nucleus, substantia nigra pars reticulata, ventral intermediate nucleus, or reticular thalamus during microstimulation across various frequencies (1–100 Hz) to assess single-pulse and frequency-response functions. Moreover, a biophysically-realistic computational framework was developed which generated postsynaptic responses under the assumption that electrical stimuli simultaneously activated all convergent presynaptic inputs to stimulation target neurons. The framework took into consideration the relative distributions of excitatory/inhibitory afferent inputs to model site-specific responses, which were in turn embedded within a model of short-term synaptic plasticity to account for stimulation frequency-dependence.ResultsWe demonstrated microstimulation-evoked excitatory neuronal responses in thalamic structures (which have predominantly excitatory inputs) and inhibitory responses in basal ganglia structures (predominantly inhibitory inputs); however, higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression. The model confirmed that site-specific responses could be simulated by accounting for local neuroanatomical/microcircuit properties, while suppression of neuronal activity during high-frequency stimulation was mediated by short-term synaptic depression.ConclusionsBrain-region-specific and frequency-dependant neuronal responses could be simulated by considering neuroanatomical (local microcircuitry) and neurophysiological (short-term plasticity) properties.     

Muscle responses to radicular stimulation during lumbo-sacral dorsal rhizotomy for spastic diplegia: Insights to myotome innervation

ObjectiveMost of knowledge on muscle radicular innervation was from explorations in root/spinal cord pathologies. Direct and individual access to each of the lumbar-sacral -ventral and dorsal- nerve roots during dorsal rhizotomy for spastic diplegia allows precise study of the corresponding muscle innervation. Authors report the lumbo-sacral segmental myotomal organization obtained from recordings of muscle responses to root stimulation in a 20-children prospective series.MethodsSeven key-muscles in each lower limb and anal sphincter were Electromyography (EMG)-recorded and clinically observed by physiotherapist during L2-to-S2 dorsal rhizotomy. Ventral roots (VR), for topographical mapping, and dorsal roots (DR), for segmental excitability testing, were stimulated, just above threshold for eliciting muscular response.ResultsIn 70% of the muscles studied, VR innervation was pluri-radicular, from 2-to-4 roots, with 1 or 2 roots being dominant at each level. Overlapping was important. Muscle responses to DR stimulation were 1.75 times more extended compared to VR stimulation. Inter-individual variability was important.ConclusionsAccuracy of root identification and stimulation with the used method brings some more precise information to radicular functional anatomy.SignificanceThose neurophysiological findings plead for performing Intra-Operative Neuromonitoring when dealing with surgery in the lumbar-sacral roots.     

Visualization of electrical activity in the cervical spinal cord and nerve roots after ulnar nerve stimulation using magnetospinography

ObjectiveTo establish a method for magnetospinography (MSG) measurement after ulnar nerve stimulation and to clarify its characteristics.MethodsUsing a 132-channel magnetoneurography system with a superconducting quantum interference device, cervical MSG measurements were obtained for 10 healthy volunteers after stimulation of the ulnar nerve at the elbow and the wrist, and neural current distribution was calculated and superimposed on the cervical X-ray images.ResultsNeuromagnetic signals were obtained in all participants after applying the stimulus artifact removal algorithm. The measured magnetic field intensity after elbow stimulation was about twice that after wrist stimulation. Calculated neural currents flowed into the intervertebral foramina at C6/7 to T1/2 and propagated cranially along the spinal canal. The conduction velocity from the peak latency of inward currents at C5-C7 was 73.4 ± 19.6 m/s.ConclusionsWe successfully obtained MSG measurements after ulnar nerve stimulation. The neural currents flowed into the spinal canal from more caudal segments after ulnar nerve stimulation compared with median nerve stimulation, and these MSG measurements were effective in examining the spinal tracts at C5/6/7.SignificanceThis is the first report on the use of MSG to visualize electrical activity in the cervical spinal cord and nerve root after ulnar nerve stimulation.     

External trigeminal nerve stimulation for drug resistant epilepsy: A randomized controlled trial

BackgroundExternal trigeminal nerve stimulation (ETNS) is an emergent, non-invasive neurostimulation therapy delivered bilaterally with adhesive skin electrodes. In previous studies, ETNS was associated to a decrease in seizure frequency in patients with focal drug-resistant epilepsy (DRE).ObjectiveTo determine the long-term efficacy and tolerability of ETNS in patients with focal DRE. Moreover, to explore whether its efficacy depends on the epileptogenic zone (frontal or temporal), and its impact on mood, cognitive function, quality of life, and trigeminal nerve excitability.MethodsForty consecutive patients with frontal or temporal DRE, unsuitable for surgery, were randomized to ETNS or usual medical treatment. Participants were evaluated at 3, 6 and 12 months for efficacy, side effects, mood scales, neuropsychological tests and trigeminal nerve excitability.ResultsSubjects had a median of 15 seizures per month and had tried a median of 12.5 antiepileptic drugs. At 12 months, percentage of responders was 50% in ETNS group and 0% in control group. Seizure frequency in ETNS group decreased by −43.5% from baseline. Temporal epilepsy subgroup responded better than frontal epilepsy subgroup (55.56% vs. 45.45%, respectively). Median stimulation intensity was 6.2 mA. ETNS improved quality of life, but not anxiety or depression. Long-term ETNS affected neither neuropsychological function, nor trigeminal nerve excitability. No relevant adverse events were observed.ConclusionsETNS is an effective and well-tolerated therapy for focal DRE. Patients with temporal epilepsy showed a better response than those with frontal epilepsy. Future studies with larger populations may define its role compared to other neurostimulation techniques.Classification of evidenceThis study provides Class II evidence that ETNS reduces seizure frequency in patients with focal DRE.     

Improved object recognition memory using post-encoding repetitive transcranial magnetic stimulation

BackgroundBrain stimulation is known to affect canonical pathways and proteins involved in memory. However, there are conflicting results on the ability of brain stimulation to improve to memory, which may be due to variations in timing of stimulation.HypothesisWe hypothesized that repetitive transcranial magnetic stimulation (rTMS) given following a learning task and within the time period before retrieval could help improve memory.MethodsWe implanted male B6129SF2/J mice (n = 32) with a cranial attachment to secure the rTMS coil so that the mice could be given consistent stimulation to the frontal area whilst freely moving. Mice then underwent the object recognition test sampling phase and given treatment +3, +24, +48 h following the test. Treatment consisted of 10 min 10 Hz rTMS stimulation (TMS, n = 10), sham treatment (SHAM, n = 11) or a control group which did not do the behavior test or receive rTMS (CONTROL n = 11). At +72 h mice were tested for their exploration of the novel vs familiar object.ResultsAt 72-h's, only the mice which received rTMS had greater exploration of the novel object than the familiar object. We further show that promoting synaptic GluR2 and maintaining synaptic connections in the perirhinal cortex and hippocampal CA1 are important for this effect. In addition, we found evidence that these changes were linked to CAMKII and CREB pathways in hippocampal neurons.ConclusionBy linking the known biological effects of rTMS to memory pathways we provide evidence that rTMS is effective in improving memory when given during the consolidation and maintenance phases.     

Probing EEG activity in the targeted cortex after focal transcranial electrical stimulation

BackgroundRecording electroencephalography (EEG) from the targeted cortex immediately before and after focal transcranial electrical stimulation (TES) remains a challenge.MethodsWe introduce a hybrid stimulation-recording approach where a single EEG electrode is inserted into the inner electrode of a double-ring montage for focal TES. The new combined electrode was placed at the C3 position of the EEG 10–20 system. Neuronal activity was recorded in two volunteers before and after 20 Hz alternating-current TES at peak-to-peak intensities of 1 and 2 mA. TES-induced electric field distributions were simulated with SIMNIBS software.ResultsUsing the hybrid stimulation-recording set-up, EEG activity was successfully recorded directly before and after TES. Simulations revealed comparable electrical fields in the stimulated cortex for the pseudomonopolar montage with and without embedded EEG electrode.ConclusionThe hybrid TES-EEG approach can be used to probe after-effects of focal TES on neuronal activity in the targeted cortex.     

A ventromedial prefrontal dysrhythmia in obsessive-compulsive disorder is attenuated by nucleus accumbens deep brain stimulation

BackgroundObsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized.Objective/hypothesisThe primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc).MethodsWe compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 μs). In addition, intracranial EEG was recorded directly from depth macroelectrodes in the NAc in four OCD patients.ResultsCross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16–25 Hz) -gamma (110–166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported.ConclusionWe reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches.     

Matching stimulation paradigms resolve apparent differences between optogenetic and electrical VTA stimulation

BackgroundOptogenetic stimulation has grown into a popular brain stimulation method in basic neuroscience while electrical stimulation predominates in clinical applications. In order to explain the effects of electrical stimulation on a cellular level and evaluate potential advantages of optogenetic therapies, comparisons between the two stimulation modalities are necessary. This comparison is hindered, however, by the difficulty of effectively matching the two fundamentally different modalities.ObjectiveComparison of brain-wide activation patterns in response to intensity-matched electrical and optogenetic VTA stimulation.MethodsWe mapped optogenetic and electrical self-stimulation rates in the same mice over stimulation intensity and determined iso-behavioral intensities. Using functional ^99mTc-HMPAO SPECT imaging of cerebral blood flow in awake animals, we obtained brain-wide activation patterns for both modalities at these iso-behavioral intensities. We performed these experiments in two mouse lines commonly used for optogenetic VTA stimulation, DAT::Cre and TH::Cre mice.ResultsWe find iso-behavioral intensity matching of stimulation gives rise to similar brain activation patterns. Differences between mouse lines were more pronounced than differences between modalities.ConclusionsPreviously found large differences of electrical and optogenetic stimulation might be due to unmatched stimulation intensity, particularly relative electrical overstimulation. These findings imply that therapeutic electrical VTA stimulation might be relatively specific if employed with optimized parameters.     

High density microelectrode recording predicts span of therapeutic tissue activation volumes in subthalamic deep brain stimulation for Parkinson disease

BackgroundSubthalamic deep brain stimulation alleviates motor symptoms of Parkinson disease by activating precise volumes of neural tissue. While electrophysiological and anatomical correlates of clinically effective electrode sites have been described, therapeutic stimulation likely acts through multiple distinct neural populations, necessitating characterization of the full span of tissue activation. Microelectrode recordings have yet to be mapped to therapeutic tissue activation volumes and surveyed for predictive markers.ObjectiveCombine high-density, broadband microelectrode recordings with detailed computational models of tissue activation to describe and to predict regions of therapeutic tissue activation.MethodsElectrophysiological features were extracted from microelectrode recordings along 23 subthalamic deep brain stimulation implants in 16 Parkinson disease patients. These features were mapped in space against tissue activation volumes of therapeutic stimulation, modeled using clinically-determined stimulation programming parameters and fully individualized, atlas-independent anisotropic tissue properties derived from 3T diffusion tensor magnetic resonance images. Logistic LASSO was applied to a training set of 17 implants out of the 23 implants to identify predictors of therapeutic stimulation sites in the microelectrode recording. A support vector machine using these predictors was used to predict therapeutic activation. Performance was validated with a test set of six implants.ResultsAnalysis revealed wide variations in the distribution of therapeutic tissue activation across the microelectrode recording-defined subthalamic nucleus. Logistic LASSO applied to the training set identified six oscillatory predictors of therapeutic tissue activation: theta, alpha, beta, high gamma, high frequency oscillations (HFO, 200–400 Hz), and high frequency band (HFB, 500–2000 Hz), in addition to interaction terms: theta x HFB, alpha x beta, beta x HFB, and high gamma x HFO. A support vector classifier using these features predicted therapeutic sites of activation with 64% sensitivity and 82% specificity in the test set, outperforming a beta-only classifier. A probabilistic predictor achieved 0.87 area under the receiver-operator curve with test data.ConclusionsTogether, these results demonstrate the importance of personalized targeting and validate a set of microelectrode recording signatures to predict therapeutic activation volumes. These features may be used to improve the efficiency of deep brain stimulation programming and highlight specific neural oscillations of physiological importance.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Individualized beta-band oscillatory transcranial direct current stimulation over the primary motor cortex enhances corticomuscular coherence and corticospinal excitability in healthy individuals

BackgroundSimultaneously modulating individual neural oscillation and cortical excitability may be important for enhancing communication between the primary motor cortex and spinal motor neurons, which plays a key role in motor control. However, it is unknown whether individualized beta-band oscillatory transcranial direct current stimulation (otDCS) enhances corticospinal oscillation and excitability.ObjectiveThis study investigated the effects of individualized beta-band otDCS on corticomuscular coherence (CMC) and corticospinal excitability in healthy individuals.MethodsIn total, 29 healthy volunteers participated in separate experiments. They received the following stimuli for 10 min on different days: 1) 2-mA otDCS with individualized beta-band frequencies, 2) 2-mA transcranial alternating current stimulation (tACS) with individualized beta-band frequencies, and 3) 2-mA transcranial direct current stimulation (tDCS). The changes in CMC between the vertex and tibialis anterior (TA) muscle and TA muscle motor-evoked potentials (MEPs) were assessed before and after (immediately, 10 min, and 20 min after) stimulation on different days. Additionally, 20-Hz otDCS for 10 min was applied to investigate the effects of a fixed beta-band frequency on CMC.ResultsotDCS significantly increased CMC and MEPs immediately after stimulation, whereas tACS and tDCS had no effects. There was a significant negative correlation between normalized CMC changes in response to 20-Hz otDCS and the numerical difference between the 20-Hz and individualized CMC peak frequency before the stimulation.ConclusionsThese findings suggest that simultaneous modulation of neural oscillation and cortical excitability is critical for enhancing corticospinal communication. Individualized otDCS holds potential as a useful method in the field of neurorehabilitation.     

A systematic exploration of parameters affecting evoked intracranial potentials in patients with epilepsy

BackgroundBrain activity is constrained by and evolves over a network of structural and functional connections. Corticocortical evoked potentials (CCEPs) have been used to measure this connectivity and to discern brain areas involved in both brain function and disease. However, how varying stimulation parameters influences the measured CCEP across brain areas has not been well characterized.ObjectiveTo better understand the factors that influence the amplitude of the CCEPs as well as evoked gamma-band power (70–150 Hz) resulting from single-pulse stimulation via cortical surface and depth electrodes.MethodsCCEPs from 4370 stimulation-response channel pairs were recorded across a range of stimulation parameters and brain regions in 11 patients undergoing long-term monitoring for epilepsy. A generalized mixed-effects model was used to model cortical response amplitudes from 5 to 100 ms post-stimulation.ResultsStimulation levels <5.5 mA generated variable CCEPs with low amplitude and reduced spatial spread. Stimulation at ≥5.5 mA yielded a reliable and maximal CCEP across stimulation-response pairs over all regions. These findings were similar when examining the evoked gamma-band power. The amplitude of both measures was inversely correlated with distance. CCEPs and evoked gamma power were largest when measured in the hippocampus compared with other areas. Larger CCEP size and evoked gamma power were measured within the seizure onset zone compared with outside this zone.ConclusionThese results will help guide future stimulation protocols directed at quantifying network connectivity across cognitive and disease states.     

Comparison of fiber tract low frequency stimulation to focal and ANT stimulation in an acute rat model of focal cortical seizures

BackgroundCurrent implementations of direct brain stimulation for epilepsy in patients involve high-frequency (HFS) electrical current and targeting of grey matter. Studies have shown that low-frequency (LFS) fiber-tract stimulation may also prove effective. To compare the efficacy of high-frequency grey matter stimulation to the low-frequency fiber tract stimulation technique a well-controlled set of experiments using a single animal model of epilepsy is needed.ObjectiveThe goal of this study was to determine the relative efficacy of different direct brain stimulation techniques for suppressing seizures using an acute rat model of focal cortical seizures.Methods4-AP was injected into the S1 region of cortex in rodents over 3 h. LFPs were recorded from the seizure focus and mirror focus to monitor seizure frequency during the experiments. CC-LFS, HFS-ANT, Focal-HFS, or a transection of the CC was applied.ResultsStimulation of the CC yielded a 65% ±14% (p = 0.0014) reduction of seizures in the focus and a 97% ±15% (p = 0.0026) reduction in the mirror focus (n = 7). By comparison transection of the CC produced a 65% ±18% reduction in the focus and a non-statistically significant reduction of 57% ±18% (p = 0.1381) in the mirror focus (n = 5). All other methods of stimulation failed to have a statistically significant effect on seizure suppression.ConclusionsLFS of the CC is the only method of stimulation to significantly reduce seizure frequency in this model of focal cortical seizures. These results support the hypothesis that LFSof fiber tracts has significant potential for seizure control.     

Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI

ObjectiveSpinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI.MethodsWe used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation).ResultsSomatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants.ConclusionsOur results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI.SignificanceIdentifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity.     

Comparison of clinical outcomes with left unilateral and sequential bilateral Transcranial Magnetic Stimulation (TMS) treatment of major depressive disorder in a large patient registry

BackgroundIt has been suggested that sequential bilateral (SBL) TMS, combining high frequency, left dorsolateral prefrontal cortex (DLPFC) stimulation and low frequency, right DLPFC stimulation, is more effective than unilateral TMS.ObjectiveTo contrast treatment outcomes of left unilateral (LUL) and SBL protocols.MethodsRegistry data were collected at 111 practice sites. Of 10,099 patients, 3,871 comprised a modified intent-to-treat (mITT) sample, defined as a primary MDD diagnosis, age ≥18, and PHQ-9 completion before TMS and at least one PHQ-9 assessment after baseline. The mITT sample received high frequency (10 Hz) LUL TMS exclusively (N = 3,327) or SBL TMS in at least 90% of sessions (N = 544). Completers (N = 3,049) were responders or had received ≥20 sessions and had an end of acute treatment PHQ-9 assessment. To control for site effects, a Matched sample (N = 653) included Completers at sites that used both protocols. To control for selection bias, the SBL group was also compared to a Restricted LUL group, drawn from sites where no patient switched to SBL after substantial exposure to LUL TMS. Secondary analyses were conducted on CGI-S ratings.ResultsThe LUL group had superior outcomes compared to the SBL group for multiple PHQ-9 and CGI-S continuous and categorical measures in the mITT, Completer and Matched samples, including in the specified primary analyses. However, outcome differences were not observed when comparing the Restricted LUL and SBL groups. Within SBL protocols, the LUL-RUL order had superior outcomes compared to the RUL-LUL order in all CGI-S, but not PHQ-9, measures.ConclusionsWhile limited by the naturalistic design, there was no evidence that SBL TMS was superior to LUL TMS. The sequential order of RUL TMS followed by LUL TMS may have reduced efficacy compared to LUL TMS followed by RUL TMS.     

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies.MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS.ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events.ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction.SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.