Cortical Inhibitory Mechanisms Research Articles

Amelioration of Focal Hand Dystonia via Low-Frequency Repetitive Somatosensory Stimulation.

Dystonia presents a growing concern based on evolving prevalence insights. Previous research found that, in cervical dystonia, high-frequency repetitive somatosensory stimulation (RSS; HF-RSS) applied on digital nerves paradoxically diminishes sensorimotor inhibitory mechanisms, whereas low-frequency RSS (LF-RSS) increases them. However, direct testing on affected body parts was not conducted. This study aims to investigate whether RSS applied directly to forearm muscles involved in focal hand dystonia can modulate cortical inhibitory mechanisms and clinical symptoms. We applied HF-RSS and LF-RSS, the latter either synchronously or asynchronously, on forearm muscles involved in dystonia. Outcome measures included paired-pulse somatosensory evoked potentials, spatial lateral inhibition measured by double-pulse somatosensory evoked potentials, short intracortical inhibition tested with transcranial magnetic stimulation, electromyographic activity from dystonic muscles, and behavioral measures of hand function. Both synchronous and asynchronous low-frequency somatosensory stimulation improved cortical inhibitory interactions, indicated by increased short intracortical inhibition and lateral spatial inhibition, as well as decreased amplitude of paired-pulse somatosensory evoked potentials. Opposite effects were observed with high-frequency stimulation. Changes in electrophysiological markers were paralleled by behavioral outcomes: although low-frequency stimulations improved hand function tests and reduced activation of dystonic muscles, high-frequency stimulation operated in an opposite direction. Our findings confirm the presence of abnormal homeostatic plasticity in response to RSS in the sensorimotor system of patients with dystonia, specifically in inhibitory circuits. Importantly, this aberrant response can be harnessed for therapeutic purposes through the application of low-frequency electrical stimulation directly over dystonic muscles. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Central sensitization mechanisms in chronic migraine with medication overuse headache: a study of thalamocortical activation and lateral cortical inhibition.

It is unclear whether cortical hyperexcitability in chronic migraine with medication overuse headache (CM-MOH) is due to increased thalamocortical drive or aberrant cortical inhibitory mechanisms. Somatosensory evoked potentials (SSEP) were performed by electrical stimulation of the median nerve (M), ulnar nerve (U) and simultaneous stimulation of both nerves (MU) in 27 patients with CM-MOH and, for comparison, in 23 healthy volunteers (HVs) of a comparable age distribution. We calculated the degree of cortical lateral inhibition using the formula: 100 - [MU/(M + U) × 100] and the level of thalamocortical activation by analyzing the high frequency oscillations (HFOs) embedded in parietal N20 median SSEPs. Compared to HV, CM-MOH patients showed higher lateral inhibition (CM-MOH 52.2% ± 15.4 vs. HV 40.4% ± 13.3; p = 0.005), which positively correlated with monthly headache days, and greater amplitude of pre-synaptic HFOs (p = 0.010) but normal post-synaptic HFOs (p = 0.122). Our findings suggest that central neuronal circuits are highly sensitized in CM-MOH patients, at both thalamocortical and cortical levels. The observed changes could be due to the combination of dysfunctional central pain control mechanisms, hypersensitivity and hyperresponsiveness directly linked to the chronic intake of acute migraine drugs.

Late cortical disinhibition in focal hand dystonia.

In writer's cramp (WC), a form of focal hand dystonia, cortical GABAergic inhibitory mechanisms are altered and may cause involuntary tonic contractions while writing. The objective of this study was to explore the time course of long-interval intracortical inhibition (LICI) that involves gamma-amino butyric acid (GABA)-B transmission and late cortical disinhibition (LCD) (that combines GABA-A and GABA-B mechanisms) in patients with WC and in control subjects. A double pulse transcranial magnetic stimulation protocol was used to evoke LICI and LCD while the subjects either gripped a cylinder between their thumb and index fingers or relaxed all their upper limb muscles. We measured the ratio between primed and unprimed motor evoked potential in the first dorsal interosseous at interstimulus intervals ranging between 60 and 300ms. Though the cortical silent period was not different between the groups, LICI lasted longer in patients with WC, that is, LCD was delayed for more than 30ms and reached a higher level. In addition to the alteration of inhibitory mechanism mediated by GABA-B transmission, LCD which probably involves presynaptic inhibition is also modified in patients with WC with possible consequences on the activity of primary motor cortex inhibitory and excitatory circuits which control the hand muscles.caus.

Increased interhemispheric somatomotor functional connectivity and mirror overflow in ADHD

Mirror overflow is a developmental phenomenon defined as unintentional movements that mimic the execution of intentional movements in homologous muscles on the opposite side of the body. In children with attention-deficit/hyperactivity disorder (ADHD), mirror overflow is commonly excessive, abnormally persistent, and correlated with ADHD symptom severity. As such, it represents a promising clinical biomarker for disinhibited behavior associated with ADHD. Yet, the neural underpinnings of mirror overflow in ADHD remain unclear. Our objective was to test whether intrinsic interhemispheric functional connectivity between homologous regions of the somatomotor network (SMN) is associated with mirror overflow in school age children with and without ADHD using resting state functional magnetic resonance imaging. To this end, we quantified mirror overflow in 119 children (8–12 years old, 62 ADHD) during a finger sequencing task using finger twitch transducers affixed to the index and ring fingers. Group ICA was used to identify right- and left-lateralized SMNs and subject-specific back reconstructed timecourses were correlated to obtain a measure of SMN interhemispheric connectivity. We found that children with ADHD showed increased mirror overflow (p < 0.001; d = 0.671) and interhemispheric SMN functional connectivity (p = 0.023; d = 0.521) as compared to typically developing children. In children with ADHD, but not the typically developing children, there was a significant relationship between interhemispheric SMN functional connectivity and mirror overflow (t = 2.116; p = 0.039). Our findings of stronger interhemispheric functional connectivity between homologous somatomotor regions in children with ADHD is consistent with previous transcranial magnetic stimulation and diffusion-tractography imaging studies suggesting that interhemispheric cortical inhibitory mechanisms may be compromised in children with ADHD. The observed brain-behavior correlation further suggests that abnormally strong interhemispheric SMN connectivity in children with ADHD may diminish their ability to suppress overflow movements.

Transcranial magnetic stimulation in child neurology

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation used for research and diagnostic purposes, as well as for the treatment of a number of diseases as one of the methods of neuromodulation. In pediatrics, TMS is most often used to assess the normal maturation of the corticospinal tract when stimulating the motor areas of the cortex of healthy children with a short single pulse magnetic stimulus, and recording motor evoked potentials from different muscles of the upper and lower extremities, as well as calculating the central motor conduction time. This technique is also used in pediatric neurology to determine conduction disturbances of the pulse along the corticospinal tract and to test neuroplasticity in damage to motor areas of the cerebral cortex and descending motor pathways in such diseases as cerebral palsy, stroke, and multiple sclerosis. Another aspect of TMS application is the evaluation of cortical inhibitory mechanisms with an assessment of the indices of the cortical silent period and the ipsilateral silent period, which often change with central nervous system lesions. With TMS it is also possible to map the cortical representation of a particular muscle, which is used to evaluate functional changes of the cerebral cortex in various neurological diseases. For an accurate implementation of the TMS mapping technique, complex navigation equipment must be currently used with focal TMS. The article describes in detail these and other diagnostic methods of TMS used in child neurology. The possibilities of the therapeutic use of repetitive TMS in childrens neurological diseases are considered in separate sections.

Hyperexcitability and impaired intracortical inhibition in patients with fragile-X syndrome

Fragile-X syndrome (FXS) is characterized by neurological and psychiatric problems symptomatic of cortical hyperexcitability. Recent animal studies identified deficient γ-aminobutyricacid (GABA) inhibition as a key mechanism for hyperexcitability in FXS, but the GABA system remains largely unexplored in humans with the disorder. The primary objective of this study was to assess GABA-mediated inhibition and its relationship with hyperexcitability in patients with FXS. Transcranial magnetic stimulation (TMS) was used to assess cortical and corticospinal inhibitory and excitatory mechanisms in 18 patients with a molecular diagnosis of FXS and 18 healthy controls. GABA-mediated inhibition was measured with short-interval intracortical inhibition (GABAA), long-interval intracortical inhibition (GABAB), and the corticospinal silent period (GABAA+B). Net intracortical facilitation involving glutamate was assessed with intracortical facilitation, and corticospinal excitability was measured with the resting motor threshold. Results showed that FXS patients had significantly reduced short-interval intracortical inhibition, increased long-interval intracortical inhibition, and increased intracortical facilitation compared to healthy controls. In the FXS group, reduced short-interval intracortical inhibition was associated with heightened intracortical facilitation. Taken together, these results suggest that reduced GABAA inhibition is a plausible mechanism underlying cortical hyperexcitability in patients with FXS. These findings closely match those observed in animal models, supporting the translational validity of these markers for clinical research.

Training-, muscle- and task-specific up- and downregulation of cortical inhibitory processes.

Motor cortical contribution was shown to be important for balance control and for ballistic types of movements. However, little is known about the role of cortical inhibitory mechanisms and even less about long(er)-term adaptations of these inhibitory processes. Therefore, the aim of the present study was to investigate the role of intracortical inhibition before and after four weeks of explosive or balance training. Two groups of subjects participated for four weeks either in an explosive training programme of the plantar flexor muscles or in a balance training programme on unstable devices. Adaptations in short-interval intracortical inhibition (SICI) were assessed by applying paired-pulse TMS to the soleus muscle during dynamic plantar flexions, balance perturbations and at rest. Furthermore, SICI was assessed for the untrained tibialis anterior muscle. The results show task-, muscle- and group-specific adaptations in SICI after the training (p=.021) with significantly increased SICI after balance training in the balance task and decreased SICI after explosive training in the ballistic task. The training also caused task- and group-specific behavioural adaptations indicated by improved balance performance after balance training and increased ballistic performance after explosive training. There were no changes in SICI when measured at rest or in the untrained tibialis anterior muscle. This study shows that long(er)-term training improves the ability to modulate cortical inhibitory processes in a task- and muscle-specific manner.

Short-interval intracortical inhibition: Comparison between conventional and threshold-tracking techniques

BackgroundShort-interval intracortical inhibition (SICI) is conventionally measured as the relative amplitude reduction of motor evoked potentials (MEPs) by subthreshold conditioning stimuli. In threshold-tracking SICI (T-SICI), stimulus intensity is instead adjusted repeatedly to maintain a constant MEP and inhibition is measured as the relative threshold increase. T-SICI is emerging as a useful diagnostic test, but its relationship to conventional amplitude SICI (A-SICI) is unclear. ObjectiveTo compare T-SICI and its reliability with conventional A-SICI measurements. MethodsIn twelve healthy volunteers (6 men, median age 30 years), conventional and T-SICI were recorded at conditioning stimuli (CS) of 50–80% resting motor threshold (RMT) and interstimulus interval of 2.5 ms. Measurements were repeated on the same day and at least a week later by a single operator. ResultsAcross the CS range, mean group T-SICI showed a strong linear relationship to the mean group values measured by conventional technique (y = 29.7–0.3x, R2 = 0.99), but there was considerable interindividual variability. At CS 60–80% RMT, T-SICI had excellent intraday (intraclass correlation coefficient, ICC, 0.81–0.92) and adequate-to-excellent interday (ICC 0.61–0.88) reproducibility. Conventional SICI took longer to complete (median of 5.8 vs 3.8 min, p < 0.001) and tended to have poorer reproducibility (ICC 0.17–0.42 intraday, 0.37–0.51 interday). With T-SICI, smaller sample sizes were calculated for equally powered interventional studies. ConclusionThe close relationship between conventional and T-SICI suggests that both techniques reflect similar cortical inhibitory mechanisms. Threshold-tracking measurements of SICI may be able to improve reproducibility, to shorten acquisition time and to reduce sample sizes for interventional studies compared with the conventional technique.

Frequency of gamma oscillations in humans is modulated by velocity of visual motion.

Gamma oscillations are generated in networks of inhibitory fast-spiking (FS) parvalbumin-positive (PV) interneurons and pyramidal cells. In animals, gamma frequency is modulated by the velocity of visual motion; the effect of velocity has not been evaluated in humans. In this work, we have studied velocity-related modulations of gamma frequency in children using MEG/EEG. We also investigated whether such modulations predict the prominence of the "spatial suppression" effect (Tadin D, Lappin JS, Gilroy LA, Blake R. Nature 424: 312-315, 2003) that is thought to depend on cortical center-surround inhibitory mechanisms. MEG/EEG was recorded in 27 normal boys aged 8-15 yr while they watched high-contrast black-and-white annular gratings drifting with velocities of 1.2, 3.6, and 6.0°/s and performed a simple detection task. The spatial suppression effect was assessed in a separate psychophysical experiment. MEG gamma oscillation frequency increased while power decreased with increasing velocity of visual motion. In EEG, the effects were less reliable. The frequencies of the velocity-specific gamma peaks were 64.9, 74.8, and 87.1 Hz for the slow, medium, and fast motions, respectively. The frequency of the gamma response elicited during slow and medium velocity of visual motion decreased with subject age, whereas the range of gamma frequency modulation by velocity increased with age. The frequency modulation range predicted spatial suppression even after controlling for the effect of age. We suggest that the modulation of the MEG gamma frequency by velocity of visual motion reflects excitability of cortical inhibitory circuits and can be used to investigate their normal and pathological development in the human brain.

Pruritus: Do Aδ fibers play a role?

Neuropathological and molecular basis of pruritus has not been clarified and the presence of certain specific neural circuits have been proposed. Our aim in this study was to evaluate the role of Aδ fibers in the neural circuits of pruritus by cutaneous silent period (CSP). Thirty-six patients with chronic idiopathic generalized pruritus and 32 healthy controls were enrolled in the study. CSP and nerve conduction studies of upper and lower extremities were performed in both groups. Latencies of CSP in the upper and lower extremities were observed to be prolonged in the patient group compared with the controls while durations were shortened (all P<0.001). However, these values were not correlated with sex, age, duration or severity of the disease (all P>0.05). Our data suggest that pruritus may be developed by a nerve conduction abnormality in the afferent fibers of Aδ, or cortical hypersensitivity, abnormality of the cortical inhibitory mechanisms or lack of inhibition in the intermediate spinal inhibitory neurons generating CSP. This topic needs to be evaluated thoroughly in larger series with more detailed studies.

Alterations of motor cortical excitability and anatomy in Unverricht‐Lundborg disease

Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms.

EEG alpha and cortical inhibition in affective attention

Recent progress in cognitive neuroscience suggests that alpha activity may reflect selective cortical inhibition involved in signal amplification, rather than neural idling. Unfortunately, these theoretical advances remain largely ignored in affective neuroscience. To address this limitation the present paper proposes a novel research avenue aimed at using alpha to elucidate cortical inhibitory mechanisms involved in affective processes. The proposal is illustrated by developing inhibitory accounts of affective attention and affective tuning phenomena. The emergent predictions were tested using event-related perturbations from 73 students evaluating affective and nonaffective aspects of five types of emotional images. The results revealed that upper alpha power was increased by affective content in general and aversive stimuli in particular from 350ms at posterior and from 575ms at central sites. The evaluation task interacted with affective content only at a liberal statistical significance level in late posterior alpha. These results are generally in line with the proposed inhibitory accounts of affective attention and tuning, although the evidence is preliminary rather than conclusive. As confirmation of functional origins of alpha in affect remains beyond the scope of a single study, this paper aims to inspire further extrapolation of the inhibitory account of alpha within affective neuroscience.

Long-range inhibitory mechanisms in the visual system are impaired in migraine sufferers

After viewing dynamic noise surrounding a homogeneous grey patch (artificial scotoma), observers perceive a prolonged twinkling-noise after-image within the unstimulated area. It has been suggested that noise-stimulated neurons induce a long-range inhibition in neurons within the artificial scotoma, which generates a rebound signal perceived as twinkling noise following noise termination. We used this paradigm to test whether migraineurs have enhanced excitability or weakened inhibition. Twinkling-noise duration was measured in 13 headache-free volunteers, 13 migraineurs with aura and 13 migraineurs without aura. The durations of the after-image were significantly shorter for both migraine groups compared to controls. Enhanced excitation of noise-activated neurons in migraineurs would produce stronger rebound activity and longer after-image durations, while weakened inhibitory mechanisms would diminish the rebound activity and shorten the after-image durations compared to control subjects. The results suggest that cortical inhibitory mechanisms might be impaired in migraineurs with and without aura.

Changes in saccadic eye movement (SEM) and quantitative EEG parameter in bipolar patients

BackgroundThere is increasing evidence that neurocognitive dysfunction is associated with the different states in Bipolar Disorder. Gamma coherence is strongly related to cognitive processes and cortico-cortical communication. This paper aims at shedding light on the relationship between cortical gamma coherence within bipolar patients and a control group during a prosaccadic attention task. We hypothesized that gamma coherence oscillations act as a main neural mechanism underlying information processing which changes in bipolar patients. MethodThirty-two (12 healthy controls and 20 bipolar patients) subjects were enrolled in this study. The subjects performed a prosaccadic attention task while their brain activity pattern was recorded using quantitative electroencephalography (20 channels). ResultsWe observed that the maniac group presented lower saccade latency when compared to depression and control groups. The main finding was a greater gamma coherence for control group in the right hemisphere of both frontal and motor cortices caused by the execution of a prosaccadic attention task. LimitationsThe findings need to be confirmed in larger samples and in bipolar patients before start the pharmacological treatment. ConclusionsOur findings suggest a disrupted connection of the brain's entire functioning of maniac patients and represent a deregulation in cortical inhibitory mechanism. Thus, our results reinforce our hypothesis that greater gamma coherence in the right and left frontal cortices for the maniac group produces a “noise” during information processing and highlights that gamma coherence might be a biomarker for cognitive dysfunction during the manic state.

Cardiac vagal tone predicts inhibited attention to fearful faces.

The neurovisceral integration model (Thayer, J. F., & Lane, R. D., 2000, A model of neurovisceral integration in emotion regulation and dysregulation. Journal of Affective Disorders, 61, 201-216. doi:10.1016/S0165-0327(00)00338-4) proposes that individual differences in heart rate variability (HRV)-an index of cardiac vagal tone-are associated with attentional and emotional self-regulation. In this article, we demonstrate that individual differences in resting HRV predict the functioning of the inhibition of return (IOR), an inhibitory attentional mechanism highly adaptive to novelty search, in response to affectively significant face cues. As predicted, participants with lower HRV exhibited a smaller IOR effect to fearful versus neutral face cues than participants with higher HRV, which shows a failure to inhibit attention from affectively significant cues and instigate novelty search. In contrast, participants with higher HRV exhibited similar IOR effects to fearful and neutral face cues, which shows an ability to inhibit attention from cues and instigate novelty search. Their ability to inhibit attention was most pronounced to high spatial frequency fearful face cues, suggesting that this effect may be mediated by cortical mechanisms. The current research demonstrates that individual differences in HRV predict attentional inhibition and suggests that successful inhibition and novelty search may be mediated by cortical inhibitory mechanisms among people with high cardiac vagal tone.

Drug-induced changes in cortical inhibition in medication overuse headache

We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 ± 14.2 vs. 108.1 ± 30.1 ms), but similar to that reported in migraineurs (59.9 ± 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 ± 46.4 and 103.8 ± 47.2 ms). Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission.

Effect of pramipexole on cutaneous-silent-period parameters in patients with restless legs syndrome

Objective The aim of this study was to investigate cutaneous-silent-period (CSP) parameters in patients with restless legs syndrome (RLS) and examine the effects of treatment on CSP which, to our knowledge, have not been investigated till date. Methods A total of 25 patients with RLS and 25 healthy volunteers were studied. CSP latency and duration in the upper and lower extremities were examined in the two groups. In RLS patients, the variables were examined before and after pramipexole treatment. Results Lower-extremity CSP latency was longer (106.22 ± 11.69 ms vs. 91.67 ± 8.53 ms; p < 0.001) and CSP duration was shorter (35.50 ± 10.91 ms vs. 49.47 ± 6.43 ms; p < 0.001) in patients, compared with controls. In the patient group, CSP durations in the upper (40.88 ± 7.95 ms vs. 46.84 ± 10.22 ms; p = 0.006) and lower extremities (35.50 ± 10.91 ms vs. 44.91 ± 6.43 ms; p = 0.005) were prolonged after treatment, compared with pre-treatment values. Conclusions Small-fibre neuropathy may exist in RLS. In addition, we suggest that pramipexole may regulate cortical and spinal inhibitory mechanisms. Significance The use of CSP may aid in the diagnosis of RLS and may be used as a measure of treatment effectiveness.

Abnormal facilitatory mechanisms in motor cortex of migraine with aura

Experimental evidence suggests impairment of inhibitory intracortical circuits in migraine, while not much is known about activity of facilitatory intracortical circuits. In the present work we evaluated the effects of high frequency-repetitive transcranial magnetic stimulation (hf-rTMS) on the activity of facilitatory circuits of motor cortex in 18 patients affected by migraine with aura and 18 healthy subjects. Trains of 10 stimuli were applied to the motor cortex at 5-Hz frequency with recording of the EMG traces from the contralateral abductor pollicis brevis muscle (APB). Two intensities of stimulation (110% and 130% of resting motor threshold) were used in order to explore whether motor cortex excitability was differently modulated. Twelve patients underwent hf-rTMS both before and during prophylactic treatment with levetiracetam. Results showed that rTMS delivered at 110% intensity of stimulation at rest had a facilitatory effect on MEP size in untreated patients, while left MEP unchanged in controls. Conversely, when rTMS was applied at 130%, we observed MEP potentiation in healthy subjects and paradoxical MEP inhibition in migraineurs. In treated patients, levetiracetam inhibited MEP size at both 110% and 130% intensity of stimulation. Our findings reveal an opposite response of migraine motor cortex to 5-Hz rTMS when it is delivered at different stimulation intensities, providing evidence of both hyper-responsivity and self-limiting hyperexcitability capacity, in line with studies supporting the concept that under conditions of cortical hyperexcitability inhibitory mechanisms of homeostatic plasticity could be activated.

Effect of Electroconvulsive Therapy on Cortical Excitability in a Patient With Long-Term Remission of Schizophrenia

The exact effects of electroconvulsive therapy (ECT) on the brain are still not accurately known. Hypotheses considered include the effect of ECT on cortical excitability of the brain. The aim of this trial was to assess the changes in cortical excitability in the brain of a patient with remitted schizophrenia, undergoing maintenance ECT. Three successive ECT applications resulted in significant prolongation of the cortical silent period, which implies augmentation of inhibitory cortical mechanisms in the brain, most likely mediated by the GABAergic (GABA, γ-aminobutyric acid) system with direct involvement of GABAB receptors. The actual therapeutic effect of ECT is therefore probably due to facilitation of cortical inhibitory mechanisms induced by GABAergic neurotransmission.

Assessment of postexcitatory inhibition in patients with focal dystonia.

The aim of our present study was to detect whether a generalized disturbance of intracortical inhibitory mechanisms as assessed by transcranial magnetic stimulation (TMS) can be observed in a movement disorder with localized clinical expression, that is, in focal cervical dystonia. We measured motor threshold intensity, central motor conduction time and the duration of postexcitatory inhibition evoked by single and paired stimuli TMS from a small hand muscle in 20 patients with idiopathic cervical dystonia, and 21 healthy volunteers. A significant difference could not be found in any of the neurophysiological parameters between patients and controls. These findings are unlike the observations made in Parkinson's disease and Huntington's disease, where significant changes of postexcitatory inhibition after TMS can be observed. This suggests a lack of widespread change in activity of underlying cortical inhibitory mechanisms, as seen in other diseases of the extrapyramidal system with more generalized clinical involvement.