A revised calcium-dependent model of transcranial magnetic theta-burst stimulation.

OBJECTIVE: Calcium dependency is presently an essential assumption in modelling the neuromodulatory effects of transcranial magnetic stimulation. Y.Z.Huang et al.developed the first neuromodulation model to explain the bidirectional effects of theta-burst stimulation (TBS) based on the postsynaptic intracellular calcium concentration elevation. However, we discover that the published computer code is not consistent with the model formulation, neither do the parameters and derived plots consequently match the formulations. Here we intend to fix the computer code and re-calibrate the model. METHODS: We corrected the affected difference equations and re-calibrated the revised model with experimental data using non-convex optimisation based on a L2 penalty. RESULTS: The revised model outperforms the initial model in characterising the relative motor-evoked potential levels of TBS-induced after-effects in various conditions. CONCLUSIONS: We corrected the inconsistencies in the previous model and computer code and provided a complete calibration to support the research that is based on it. SIGNIFICANCE: This work improves the accuracy and secures the scope of the model, which is necessary to retain a rich body of research resulting from the model. Furthermore, this model provides both a quantitative model for several parameters of TBS and a basic model foundation for future refinement.

TMS excitability study in essential tremor: Absence of gabaergic changes assessed by silent period recordings.

BACKGROUND: Essential tremor (ET) is thought to emerge from activity in a distributed cerebello-thalamo-cortical network. It has been proposed that the network goes into oscillation because of abnormal GABAergic inhibitory transmission. OBJECTIVE: To test this idea by investigating GABAergic circuitry in motor cortex using transcranial magnetic stimulation (TMS). METHODS: Motor cortex excitability was examined using TMS in 21 patients with essential tremor and in 20 control subjects. Resting and active motor threshold (RMT, AMT) and input-output curves examined corticospinal excitability. Contralateral silent period (cSP) at a different range of stimulation intensities, and the ipsilateral silent period (iSP) using a stimulus intensity of 150% RMT were used as measures of GABAergic function. RESULTS: RMT and AMT were significantly lower in patients than controls and patients had a steeper I/O curve. However, there were no significant differences in either cSP at different intensities or in iSP. CONCLUSION: We found no evidence in favour of the GABA hypothesis in ET.

The effect of salient stimuli on neural oscillations, isometric force, and their coupling.

Survival in a suddenly-changing environment requires animals not only to detect salient stimuli, but also to promptly respond to them by initiating or revising ongoing motor processes. We recently discovered that the large vertex brain potentials elicited by sudden supramodal stimuli are strongly coupled with a multiphasic modulation of isometric force, a phenomenon that we named cortico-muscular resonance (CMR). Here, we extend our investigation of the CMR to the time-frequency domain. We show that (i) both somatosensory and auditory stimuli evoke a number of phase-locked and non-phase-locked modulations of EEG spectral power. Remarkably, (ii) some of these phase-locked and non-phase-locked modulations are also present in the Force spectral power. Finally, (iii) EEG and Force time-frequency responses are correlated in two distinct regions of the power spectrum. An early, low-frequency region (∼4 Hz) reflects the previously-described coupling between the phase-locked EEG vertex potential and force modulations. A late, higher-frequency region (beta-band, ∼20 Hz) reflects a second coupling between the non-phase-locked increase of power observed in both EEG and Force. In both time-frequency regions, coupling was maximal over the sensorimotor cortex contralateral to the hand exerting the force, suggesting an effect of the stimuli on the tonic corticospinal drive. Thus, stimulus-induced CMR occurs across at least two different types of cortical activities, whose functional significance in relation to the motor system should be investigated further. We propose that these different types of corticomuscular coupling are important to alter motor behaviour in response to salient environmental events.

Cervical dystonia: Normal auditory mismatch negativity and abnormal somatosensory mismatch negativity.

OBJECTIVE: Previous electrophysiological and psychophysical tests have suggested that somatosensory integration is abnormal in dystonia. Here, we hypothesised that this abnormality could relate to a more general deficit in pre-attentive error/deviant detection in patients with dystonia. We therefore tested patients with dystonia and healthy subjects using a mismatch negativity paradigm (MMN), where evoked potentials generated in response to a standard repeated stimulus are subtracted from the responses to a rare "odd ball" stimulus. METHODS: We assessed MMN for somatosensory and auditory stimuli in patients with cervical dystonia and healthy age matched controls. RESULTS: We found a significant group ∗ oddball type interaction effect (F (1, 34) = 4.5, p = 0.04, ρI = 0.63). A follow up independent t-test for sMMN data, showed a smaller sMMN amplitude in dystonic patients compared to controls (mean difference control-dystonia: -1.0 µV ± 0.3, p < 0.00, t = -3.1). However the amplitude of aMMN did not differ between groups (mean difference control-dystonia: -0.2 µV ± 0.2, p = 0.24, t = -1.2). We found a positive correlation between somatosensory MMN and somatosensory temporal discrimination threshold. CONCLUSION: These results suggest that pre-attentive error/deviant detection, specifically in the somatosensory domain, is abnormal in dystonia. This could underlie some previously reported electrophysiological and psychophysical abnormalities of somatosensory integration in dystonia. SIGNIFICANCE: One could hypothesize a deficit in pre-conscious orientation towards potentially salient signals might lead to a more conservative threshold for decision-making in dystonia.

Impaired intracortical inhibition demonstrated in vivo in people with Dravet syndrome.

OBJECTIVE: Dravet syndrome is a rare neurodevelopmental disorder characterized by seizures and other neurologic problems. SCN1A mutations account for ∼80% of cases. Animal studies have implicated mutation-related dysregulated cortical inhibitory networks in its pathophysiology. We investigated such networks in people with the condition. METHODS: Transcranial magnetic stimulation using single and paired pulse paradigms was applied to people with Dravet syndrome and to 2 control groups to study motor cortex excitability. RESULTS: Short interval intracortical inhibition (SICI), which measures GABAergic inhibitory network behavior, was undetectable in Dravet syndrome, but detectable in all controls. Other paradigms, including those testing excitatory networks, showed no difference between Dravet and control groups. CONCLUSIONS: There were marked differences in inhibitory networks, detected using SICI paradigms, while other inhibitory and excitatory paradigms yielded normal results. These human data showing reduced GABAergic inhibition in vivo in people with Dravet syndrome support established animal models.

Stimulation of PPC Affects the Mapping between Motion and Force Signals for Stiffness Perception But Not Motion Control.

How motion and sensory inputs are combined to assess an object's stiffness is still unknown. Here, we provide evidence for the existence of a stiffness estimator in the human posterior parietal cortex (PPC). We showed previously that delaying force feedback with respect to motion when interacting with an object caused participants to underestimate its stiffness. We found that applying theta-burst transcranial magnetic stimulation (TMS) over the PPC, but not the dorsal premotor cortex, enhances this effect without affecting movement control. We explain this enhancement as an additional lag in force signals. This is the first causal evidence that the PPC is not only involved in motion control, but also has an important role in perception that is disassociated from action. We provide a computational model suggesting that the PPC integrates position and force signals for perception of stiffness and that TMS alters the synchronization between the two signals causing lasting consequences on perceptual behavior. SIGNIFICANCE STATEMENT: When selecting an object such as a ripe fruit or sofa, we need to assess the object's stiffness. Because we lack dedicated stiffness sensors, we rely on an as yet unknown mechanism that generates stiffness percepts by combining position and force signals. Here, we found that the posterior parietal cortex (PPC) contributes to combining position and force signals for stiffness estimation. This finding challenges the classical view about the role of the PPC in regulating position signals only for motion control because we highlight a key role of the PPC in perception that is disassociated from action. Altogether this sheds light on brain mechanisms underlying the interaction between action and perception and may help in the development of better teleoperation systems and rehabilitation of patients with sensory impairments.

Cerebellar tDCS dissociates the timing of perceptual decisions from perceptual change in speech.

Neuroimaging studies suggest that the cerebellum might play a role in both speech perception and speech perceptual learning. However, it remains unclear what this role is: does the cerebellum help shape the perceptual decision, or does it contribute to the timing of perceptual decisions? To test this, we used transcranial direct current stimulation (tDCS) in combination with a speech perception task. Participants experienced a series of speech perceptual tests designed to measure and then manipulate (via training) their perception of a phonetic contrast. One group received cerebellar tDCS during speech perceptual learning, and a different group received sham tDCS during the same task. Both groups showed similar learning-related changes in speech perception that transferred to a different phonetic contrast. For both trained and untrained speech perceptual decisions, cerebellar tDCS significantly increased the time it took participants to indicate their decisions with a keyboard press. By analyzing perceptual responses made by both hands, we present evidence that cerebellar tDCS disrupted the timing of perceptual decisions, while leaving the eventual decision unaltered. In support of this conclusion, we use the drift diffusion model to decompose the data into processes that determine the outcome of perceptual decision-making and those that do not. The modeling suggests that cerebellar tDCS disrupted processes unrelated to decision-making. Taken together, the empirical data and modeling demonstrate that right cerebellar tDCS dissociates the timing of perceptual decisions from perceptual change. The results provide initial evidence in healthy humans that the cerebellum critically contributes to speech timing in the perceptual domain.

Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: a proof-of-concept study.

Impaired neural plasticity has been proposed as an important pathophysiological feature underlying the neurobiology and symptomatology of schizophrenia. In this proof-of-concept study, we aimed to explore cortical plasticity in schizophrenia patients with two different transcranial theta-burst (TBS) paradigms. TBS induces Ca(2+)-dependent long-term-potentiation (LTP)-like and long-term-depression (LTP)-like plasticity in the human motor cortex. A total of 10 schizophrenia patients and 10 healthy controls were included in this study. Cortical excitability was investigated using transcranial magnetic stimulation in each study participant before and after TBS applied to the left primary motor-cortex on two different days. cTBS600 was used to induce LTD-like and cTBS300 was used to induce LTP-like plasticity in the absence of any prior motor-cortex activation. Repeated measures ANOVAs showed a significant interaction between the timecourse, the study group and the stimulation paradigm (cTBS600 vs. cTBS300) for the left, but not for the right hemisphere. Healthy controls showed an MEP amplitude decrease at a trend level following cTBS600 and a numeric, but not significant, increase in MEP amplitudes following cTBS300. Schizophrenia patients did not show an MEP amplitude decrease following cTBS600, but surprisingly a significant MEP decrease following cTBS300. The proportion of subjects showing the expected changes in motor-cortex excitability following both cTBS paradigms was higher in healthy controls. These preliminary results indicate differences in cortical plasticity following two different cTBS protocols in schizophrenia patients compared to healthy controls. However, the incomplete plasticity response in the healthy controls and the proof-of-concept nature of this study need to be considered as important limitations.

An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition.

Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

OBJECTIVE: To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. METHODS: Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. RESULTS: Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. CONCLUSIONS: The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. SIGNIFICANCE: Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients.

Inhibitory theta burst stimulation of affected hemisphere in chronic stroke: a proof of principle, sham-controlled study.

Non-invasive brain stimulation is presently being tested as a potential therapeutic intervention for stroke rehabilitation. Following a model of competitive interactions between the hemispheres, these interventions aim to increase the plasticity of stroke hemisphere by applying either excitatory protocols to the damaged hemisphere or inhibitory protocols to the non-stroke hemisphere. Here we test the safety and feasibility of using an inhibitory protocol on the stroke hemisphere to improve the response to conventional therapy via a homeostatic increase in learning capacity. Twelve chronic stroke patients received TBS to stroke hemisphere (6 patients inhibitory TBS and 6 sham TBS) followed by physical therapy daily for 10 working days. Patients and therapists were blinded to the type of TBS. Action Research Arm Test (ARAT), Nine-Hole Pegboard Test (NHPT) and Jebsen-Taylor Test (JTT) were the primary outcome measures, grip and pinch-grip dynamometry were the secondary outcome measures. All patients improved ARAT and JTT scores for up to 3 months post-treatment. ARAT scores improved significantly in both real and sham groups, but only patients receiving real TBS significantly improved on the JTT: 3 months post-treatment mean execution time was reduced compared to baseline by 141 s for real group and by 65s for the sham group. This small exploratory study suggests that ipsilesional inhibitory TBS is safe and that it has the potential to be used in a larger trial to enhance the gain from a late rehabilitation program in chronic stroke patients.

Effect of anodal versus cathodal transcranial direct current stimulation on stroke rehabilitation: a pilot randomized controlled trial.

OBJECTIVE: We compared the long-term effect of anodal versus cathodal transcranial direct current stimulation (tDCS) on motor recovery in patients after subacute stroke. METHODS: Forty patients with ischemic stroke undergoing rehabilitation were randomly assigned to 1 of 3 groups: Anodal, Cathodal (over-affected and unaffected hemisphere, respectively), and Sham. Each group received tDCS at an intensity of 2 mA for 25 minutes daily for 6 consecutive days over of the motor cortex hand area. Patients were assessed with the National Institutes of Health Stroke Scale (NIHSS), Orgogozo's MCA scale (OMCASS), the Barthel index (BI), and the Medical Research Council (MRC) muscle strength scale at baseline, after the sixth tDCS session and then 1, 2, and 3 months later. Motor cortical excitability was measured with transcranial magnetic stimulation (TMS) at baseline and after the sixth session. RESULTS: By the 3-month follow-up, all groups had improved on all scales with P values ranging from .01 to .0001. Improvement was equal in the Anodal and Cathodal groups. When these treated groups were combined and compared with Sham, significant interactions were seen for the OMCASS and BI scales of functional ability (P = .002 for each). There was increased cortical excitability of the affected hemisphere in all groups with the changes being greater in the real versus sham groups. There were borderline significant improvements in muscle strength. CONCLUSION: A brief course of 2 types of tDCS stimulation is superior to sham stimulation in enhancing the effect of rehabilitation training to improve motor recovery after stroke.

The brighter side of music in dystonia.

OBJECTIVE: To report a patient with genetically proven DYT1 dystonia who shows dramatic improvement in symptoms while playing the piano. DESIGN: Case study. SETTING: Sobell Department for Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, England. PATIENT: A 49-year-old right-handed male civil servant. MAIN OUTCOME MEASURES: The patient was videotaped, and electromyographic activity was recorded from the splenius capitis, sternocleidomastoid, and orbicularis oculi muscles, while he was (1) at rest, (2) playing an electric piano with auditory feedback, and (3) playing an electric piano without auditory feedback (ie, when the sound of the piano is turned off). RESULTS: At baseline, the patient had generalized dystonia with prominent upper limb, neck, and facial involvement. While he was playing the piano, there was an instant and almost complete improvement in dystonia symptoms. The improvement was also noticeable when he played the piano without auditory feedback. There was a significant reduction in electromyographic activity for all recorded muscles when he played the piano, compared with his baseline electromyographic activity. CONCLUSION: This is a unique case of "paradoxical" improvement in dystonia symptoms with activity (ie, playing a piano), in contrast to the typical worsening of dystonia symptoms with activity. We discuss the possible mechanisms underlying this phenomenon. One of the most intriguing features of primary dystonia is the variability of abnormal muscle activity relative to the context in which movement is attempted (eg, the exquisite task specificity of focal hand dystonia or the phenomenon of the geste antagoniste). We present a unique case of an amateur pianist with genetically proven DYT1 dystonia who shows dramatic improvement in generalized dystonia symptoms while playing piano.

Targeting unlesioned pharyngeal motor cortex improves swallowing in healthy individuals and after dysphagic stroke.

BACKGROUND & AIMS: Patients with stroke experience swallowing problems (dysphagia); increased risk of aspiration pneumonia, malnutrition, and dehydration; and have increased mortality. We investigated the behavioral and neurophysiological effects of a new neurostimulation technique (paired associative stimulation [PAS]), applied to the pharyngeal motor cortex, on swallowing function in healthy individuals and patients with dysphagia from stroke. METHODS: We examined the optimal parameters of PAS to promote plasticity by combining peripheral pharyngeal (electrical) with cortical stimulation. A virtual lesion was used as an experimental model of stroke, created with 1-Hz repetitive transcranial magnetic stimulation over the pharyngeal cortex in 12 healthy individuals. We tested whether hemispheric targeting of PAS altered swallowing performance before applying the technique to 6 patients with severe, chronic dysphagia from stroke (mean of 38.8 ± 24.4 weeks poststroke). RESULTS: Ten minutes of PAS to the unlesioned pharyngeal cortex reversed (bilaterally) the cortical suppression induced by virtual lesion (lesioned: F(1,9) = 21.347, P = .001; contralesional: F(1,9) = 9.648, P = .013; repeated-measures analysis of variance) compared with sham PAS. It promoted changes in behavior responses measured with a swallowing reaction time task (F(1,7) = 21.02, P = .003; repeated-measures analysis of variance). In patients with chronic dysphagia, real PAS induced short-term bilateral changes in the brain; the unaffected pharyngeal cortex had increased excitability (P = .001; 95% confidence interval, 0.21-0.05; post hoc paired t test) with reduced penetration-aspiration scores and changes in swallowing biomechanics determined by videofluoroscopy. CONCLUSIONS: The beneficial neurophysiological and behavioral properties of PAS, when applied to unlesioned brain, provide the foundation for further investigation into the use of neurostimulation as a rehabilitative approach for patients with dysphagia from stroke.

The effect of long-term TENS on persistent neuroplastic changes in the human cerebral cortex.

The long-term effect of daily somatosensory stimulation with transcutaneous electrical nerve stimulation (TENS) on reorganization of the motor cortex was investigated in a group of neurologically intact humans. The scalp representation of the corticospinal projection to the finger (APB, ADM) and forearm (FCR, ECR) muscles was mapped by means of transcranial magnetic stimulation (TMS) before and after a 3-week intervention period, using map area and volume, and topographical overlaps between the cortical motor representations of these muscles as primary dependent measures. Findings revealed a significant increase in cortical motor representation of all four muscles for the TENS group from pre to posttest (all, P ≤ 0.026). No significant changes in cortical motor representations were observed in the control group. The present observations highlight the potential benefit of sensory training by means of TENS as a useful complementary therapy in neurorehabilitation.

Human θ burst stimulation enhances subsequent motor learning and increases performance variability.

Intermittent theta burst stimulation (iTBS) transiently increases motor cortex excitability in healthy humans by a process thought to involve synaptic long-term potentiation (LTP), and this is enhanced by nicotine. Acquisition of a ballistic motor task is likewise accompanied by increased excitability and presumed intracortical LTP. Here, we test how iTBS and nicotine influences subsequent motor learning. Ten healthy subjects participated in a double-blinded placebo-controlled trial testing the effects of iTBS and nicotine. iTBS alone increased the rate of learning but this increase was blocked by nicotine. We then investigated factors other than synaptic strengthening that may play a role. Behavioral analysis and modeling suggested that iTBS increased performance variability, which correlated with learning outcome. A control experiment confirmed the increase in motor output variability by showing that iTBS increased the dispersion of involuntary transcranial magnetic stimulation-evoked thumb movements. We suggest that in addition to the effect on synaptic plasticity, iTBS may have facilitated performance by increasing motor output variability; nicotine negated this effect on variability perhaps via increasing the signal-to-noise ratio in cerebral cortex.

Reflex responses of masseter muscles to sound.

Acoustic stimuli can evoke reflex EMG responses (acoustic jaw reflex) in the masseter muscle. Although these were previously ascribed to activation of cochlear receptors, high intensity sound can also activate vestibular receptors. Since anatomical and physiological studies, both in animals and humans, have shown that masseter muscles are a target for vestibular inputs we have recently reassessed the vestibular contribution to masseter reflexes. We found that high intensity sound evokes two bilateral and symmetrical short-latency responses in active unrectified masseter EMG of healthy subjects: a high threshold, early p11/n15 wave and a lower threshold, later p16/n21 wave. Both of these reflexes are inhibitory but differ in their threshold, latency and appearance in the rectified EMG average. Experiments in healthy subjects and in patients with selective lesions showed that vestibular receptors were responsible for the p11/n15 wave (vestibulo-masseteric reflex) whereas cochlear receptors were responsible for the p16/n21 wave (acoustic masseteric reflex). The possible functional significance of the double vestibular control over masseter muscles is discussed.

Adjunctive functional pharyngeal electrical stimulation reverses swallowing disability after brain lesions.

BACKGROUND & AIMS: Oropharyngeal dysphagia is an important disability that occurs after stroke; it contributes to aspiration pneumonia and death, and current modalities for rehabilitation of dysphagia have uncertain efficacy. We therefore examined the role of pharyngeal electrical stimulation (PES) in expediting human swallowing recovery after experimental (virtual) and actual (stroke) brain lesions. METHODS: First, healthy subjects (n = 13) were given 1-Hz repetitive transcranial magnetic stimulation to induce a unilateral virtual lesion in pharyngeal motor cortex followed by active or sham (control) PES. Motor-evoked potentials and swallow accuracy were recorded before and after the lesion to assess PES response. Thereafter, 50 acute dysphagic stroke patients underwent either a dose-response study, to determine optimal parameters for PES (n = 22), or were assigned randomly to groups given either active or sham (control) PES (n = 28). The primary end point was the reduction of airway aspiration at 2 weeks postintervention. RESULTS: In contrast to sham PES, active PES reversed the cortical suppression induced by the virtual lesion (F(7,70) = 2.7; P = .015) and was associated with improvement in swallowing behavior (F(3,42) = 5; P = .02). After stroke, 1 PES treatment each day (U = 8.0; P = .043) for 3 days (U = 10.0) produced improved airway protection compared with controls (P = .038). Active PES also reduced aspiration (U = 54.0; P = .049), improved feeding status (U = 58.0; P = .040), and resulted in a shorter time to hospital discharge (Mantel-Cox log-rank test, P = 0.038). CONCLUSIONS: This pilot study of PES confirms that it is a safe neurostimulation intervention that reverses swallowing disability after virtual lesion or stroke.

Repetitive transcranial magnetic stimulation or transcranial direct current stimulation?

In recent years two techniques have become available to stimulate the human brain noninvasively through the scalp: repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Prolonged application of either method (eg, several hundred TMS pulses [rTMS] or several minutes of tDCS) leads to changes in excitability of the cortex that outlast the period of stimulation. Because of this, besides the implications for experimental neuroscientists, there is increasing interest in the potential for applying either method as a therapy in neurology, psychiatry, rehabilitation, and pain. Given that both techniques lead to the same final result, this article discusses in theory several issues that can help an investigator to decide whether rTMS or tDCS would be more suitable for the scope of the planned work.

Changes in cortical potential associated with modulation of peripheral sympathetic activity in patients with epilepsy.

OBJECTIVES: To examine the immediate and sustained effects of volitional sympathetic modulation, using galvanic skin response (GSR) biofeedback training on cortical excitability in patients with drug-resistant epilepsy. METHODS: Ten patients undertook 12 sessions of GSR biofeedback training over 1 month, during which they were trained to increase sympathetic arousal, using GSR biofeedback. Contingent negative variation (CNV) (a slow cortical potential reflecting cortical arousal and excitability) and the related post imperative negative variation (PINV) were quantified before and after biofeedback treatment. RESULTS: A significant reduction in CNV amplitude was observed in both the short-term (within the first session, after 10 minutes of GSR biofeedback) and long-term (sustained after 12 training sessions). Specifically, the change in baseline CNV amplitude after the 12 training sessions correlated with a percentage reduction in seizure frequency. Furthermore, changes in baseline amplitude of the PINV also correlated with seizure reduction. CONCLUSIONS: Our findings demonstrate that behavioral enhancement of peripheral sympathetic tone (GSR) is associated with modulation of indices of cortical excitability. Moreover, GSR biofeedback training over repeated sessions was associated with a chronic baseline reduction in slow cortical potentials and concurrent therapeutic improvement.