Alterations In Cortical Excitability Research Articles

Cerebral-Cerebellar Cortical Activity and Connectivity Underlying Sensory Trick in Cervical Dystonia.

The objective of this study was to investigate the activity and connectivity of cerebral and cerebellar cortices underlying the sensory trick (ST) effects in patients with cervical dystonia (CD), using electroencephalography (EEG). We recruited 15 CD patients who exhibited clinically effective ST and 15 healthy controls (HCs) who mimicked the ST maneuver. EEG signals and multiple-channel electromyography (EMG) were recorded simultaneously during resting and acting stages. EEG source analysis and functional connectivity were performed. To account for the effects of sensory processing, we calculated relative power changes as the difference in power spectral density between resting and the maneuver execution. ST induced a decrease in low gamma (30-50 Hz) spectral power in the primary sensory and cerebellar cortices, which remained lower than in HCs during the maintenance period. Compared with HCs, patients exhibited consistently strengthened connectivity within the sensorimotor network during the maintenance period, particularly in the primary sensory-sensorimotor cerebellum connection. The application of ST resulted in altered cortical excitability and functional connectivity regulated by gamma oscillation in CD patients, suggesting that this effect cannot be solely attributed to motor components. The cerebellum may play important roles in mediating the ST effects.

Does migraine affect central auditory processing abilities?

ObjectiveMigraine is a neurological disease associated with an altered cortical excitability level. Several studies have investigated the relationship between migraine and central auditory processing (CAP), with deficits in CAP being common among migraine patients. However, studies on the factors affecting these CAP changes observed in migraine patients are still few and controversial. This study aims to investigate CAP changes in migraine patients with Duration Pattern Test (DPT) and Frequency Pattern Test (FPT), which have not been used in previous studies. MethodsSixty subjects were divided into two groups and one migraine subgroup: control group, twenty normal healthy subjects, fourty subjects diagnosed with migraine. They were evaluated using the CAP test including DPT and FPT. To identify the variables and possible effects of the variables, a questionnaire describing the characteristics of migraine features was administered to participants with migraine. ResultsNo significant difference was found the between the control and study group in CAP tests scores. No significant correlation was found between migraine characteristics and CAP tests scores. Males had significantly higher FPT scores in both ears than females (p<0.05). Significant statistical negative correlation was found between age and FPT scores for both ears and left DPT scores (p<0.05). ConclusionAlthough migraine patients generally showed lower CAP ability than the control group, no significant difference was observed between them. This was also valid for subgroups of migraine. However, as age increased in the migraine group, a significant decrease in CAP performance was observed. It was observed that male migraine patients had better CAP ability, especially FPT scores. Migraine may affect performance in CAP depending on gender and age factors.

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD)

BackgroundThis study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). MethodsThe study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. ResultsAcute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. ConclusionsThe moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy: A Positron Emission Tomography and Transcranial Magnetic Stimulation Study

Introduction: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABA_A receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls. Methods: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [¹¹C]flumazenil positron emission tomography to assess GABA_A receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABA_A receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABA_A receptor activity, long-interval intracortical inhibition representing GABA_B receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability. Results: No significant differences in baseline GABA_A receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABA_A receptor availability and TMS outcomes. Changes in GABA_A receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT. Conclusion: We found that a change in GABA_A receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.

Females with painful temporomandibular disorders present higher intracortical facilitation relative to pain-free controls.

This study aimed to investigate cortical excitability differences in the primary motor cortex (M1) hand representation between individuals with temporomandibular disorders (TMD) and healthy controls. We assessed resting motor thresholds, motor-evoked potentials (MEPs), intracortical inhibition, and intracortical facilitation and explored potential associations with clinical and psychosocial characteristics in the TMD group. We recruited 36 female participants with TMD and 17 pain-free controls. Transcranial magnetic stimulation (TMS) was used to assess M1 cortical excitability. Correlations between clinical and psychosocial factors and cortical excitability measures were also evaluated. Patients with TMD showed significantly higher intracortical facilitation at 12ms (z = 1.98, p = 0.048) and 15ms (z = 2.65, p = 0.008) when compared to controls. Correlations revealed associations between intracortical facilitation and pain interference, sleep quality, depressive symptoms, and pain catastrophizing in the TMD group. Females with TMD exhibit heightened motor cortex intracortical facilitation in the hand representation, potentially indicating altered cortical excitability beyond the motor face area. This suggests a role for cortical excitability in TMD pathophysiology, influenced by psychosocial factors. Understanding cortical excitability in TMD may inform targeted interventions. Psychosocial variables may play a role in cortical excitability, emphasizing the multidimensional nature of TMD-related pain. Further research is needed to confirm and expand upon these findings, with potential implications for the management of TMD and related pain conditions.

The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

Combined transcranial magnetic stimulation and electroencephalography reveals alterations in cortical excitability during pain.

Transcranial magnetic stimulation (TMS) has been used to examine inhibitory and facilitatory circuits during experimental pain and in chronic pain populations. However, current applications of TMS to pain have been restricted to measurements of motor evoked potentials (MEPs) from peripheral muscles. Here, TMS was combined with electroencephalography (EEG) to determine whether experimental pain could induce alterations in cortical inhibitory/facilitatory activity observed in TMS-evoked potentials (TEPs). In Experiment 1 (n=29), multiple sustained thermal stimuli were administered to the forearm, with the first, second, and third block of thermal stimuli consisting of warm but non-painful (pre-pain block), painful (pain block) and warm but non-painful (post-pain block) temperatures, respectively. During each stimulus, TMS pulses were delivered while EEG (64 channels) was simultaneously recorded. Verbal pain ratings were collected between TMS pulses. Relative to pre-pain warm stimuli, painful stimuli led to an increase in the amplitude of the frontocentral negative peak ~45 ms post-TMS (N45), with a larger increase associated with higher pain ratings. Experiments 2 and 3 (n=10 in each) showed that the increase in the N45 in response to pain was not due to changes in sensory potentials associated with TMS, or a result of stronger reafferent muscle feedback during pain. This is the first study to use combined TMS-EEG to examine alterations in cortical excitability in response to pain. These results suggest that the N45 TEP peak, which indexes GABAergic neurotransmission, is implicated in pain perception and is a potential marker of individual differences in pain sensitivity.

Combined transcranial magnetic stimulation and electroencephalography reveals alterations in cortical excitability during pain

Transcranial magnetic stimulation (TMS) has been used to examine inhibitory and facilitatory circuits during experimental pain and in chronic pain populations. However, current applications of TMS to pain have been restricted to measurements of motor evoked potentials (MEPs) from peripheral muscles. Here, TMS was combined with electroencephalography (EEG) to determine whether experimental pain could induce alterations in cortical inhibitory/facilitatory activity observed in TMS-evoked potentials (TEPs). In Experiment 1 (n=29), multiple sustained thermal stimuli were administered to the forearm, with the first, second, and third block of thermal stimuli consisting of warm but non-painful (pre-pain block), painful (pain block) and warm but non-painful (post-pain block) temperatures, respectively. During each stimulus, TMS pulses were delivered while EEG (64 channels) was simultaneously recorded. Verbal pain ratings were collected between TMS pulses. Relative to pre-pain warm stimuli, painful stimuli led to an increase in the amplitude of the frontocentral negative peak ~45 ms post-TMS (N45), with a larger increase associated with higher pain ratings. Experiments 2 and 3 (n=10 in each) showed that the increase in the N45 in response to pain was not due to changes in sensory potentials associated with TMS, or a result of stronger reafferent muscle feedback during pain. This is the first study to use combined TMS-EEG to examine alterations in cortical excitability in response to pain. These results suggest that the N45 TEP peak, which indexes GABAergic neurotransmission, is implicated in pain perception and is a potential marker of individual differences in pain sensitivity.

Acute Aerobic Exercise at Different Intensities Modulates Motor Learning Performance and Cortical Excitability in Sedentary Individuals.

Converging evidence indicates the beneficial effects of aerobic exercise on motor learning performance. Underlying mechanisms might be an impact of aerobic exercise on neuroplasticity and cortical excitability. Evidence suggests that motor learning and cortical excitability alterations correlate with the intensity of aerobic exercise and the activity level of participants. Thus, this study aims to investigate the effects of different aerobic exercise intensities on motor learning and cortical excitability in sedentary individuals. The study was conducted in a crossover and double-blind design. Twenty-six healthy sedentary individuals (13 women and 13 men) performed a motor learning task and received a cortical excitability assessment before and after a single session of low-, moderate-, and high-intensity aerobic exercise or a control intervention. The study revealed that motor learning performance and cortical excitability were significantly enhanced in the moderate-intensity aerobic exercise, compared with the other conditions. These findings suggest aerobic exercise intensity-dependent effects on motor learning in sedentary adults. The underlying mechanism might be an exercised-induced alteration of cortical excitability, specifically a reduction of GABA activity.

Using TMS to evaluate altered cortical excitability underlying epilepsy syndromes

Using TMS to evaluate altered cortical excitability underlying epilepsy syndromes

Age-dependent increased sag amplitude in human pyramidal neurons dampens baseline cortical activity.

Aging involves various neurobiological changes, although their effect on brain function in humans remains poorly understood. The growing availability of human neuronal and circuit data provides opportunities for uncovering age-dependent changes of brain networks and for constraining models to predict consequences on brain activity. Here we found increased sag voltage amplitude in human middle temporal gyrus layer 5 pyramidal neurons from older subjects and captured this effect in biophysical models of younger and older pyramidal neurons. We used these models to simulate detailed layer 5 microcircuits and found lower baseline firing in older pyramidal neuron microcircuits, with minimal effect on response. We then validated the predicted reduced baseline firing using extracellular multielectrode recordings from human brain slices of different ages. Our results thus report changes in human pyramidal neuron input integration properties and provide fundamental insights into the neuronal mechanisms of altered cortical excitability and resting-state activity in human aging.

A single bout of aerobic exercise modulates motor learning performance and cortical excitability in humans

BackgroundEvidence indicates beneficial effects of aerobic exercise on motor learning performance, which might be caused by the impact of aerobic exercise on cortical excitability. It is thus suggested that physiological effects of aerobic exercise on cortical excitability determine the effects of aerobic exercise on motor learning. Nevertheless, respective results usually come from independent studies, and a prove of the causal relationship between neurophysiological and motor learning effects is still missing. This study aims to explore the impact of a single bout of aerobic exercise on brain physiology and motor learning, and the association between these phenomena in humans MethodThe study was conducted in a cross-over design. In twenty healthy subjects, cortical excitability and motor learning were assessed before and after a single bout of aerobic exercise or a control intervention ResultsThe results show that aerobic exercise improved motor sequence learning and enhanced cortical excitability in humans. Furthermore, a correlation between the exercise-dependent alteration of cortical excitability (short intracortical inhibition, which is determined primarily by the GABAergic system) and improvement of motor learning has been found DiscussionThe study found motor learning performance-improving effects of aerobic exercise, and these results might be explained by an exercised-caused alteration of cortical excitability, especially a reduction of GABA activity.

Modulation of spontaneous motor unit potentials by a new motor cortical magnetic stimulation method in amyotrophic lateral sclerosis

Patients with amyotrophic lateral sclerosis (ALS) show altered cortical excitability. In this study, we measure modulation of spontaneous motor unit potentials (sMUPs) in hand muscles by multifocal cortical stimulation with a newly developed wearable transcranial rotating permanent magnet stimulator (TRPMS). We conducted cross-sectional and longitudinal electromyographic assessments in 40 and 20 ALS patients, respectively, of the stimulation-induced peak increase in the count of sMUPs in two hand muscles modulated by unilateral TRPMS stimulation of the primary motor cortex. We measured peak sMUP counts during several short sessions consisting of 10 stimuli over 60s and 30s post-stimulation periods. The longitudinal component involved an initial assessment at an early stage of the disease and up to five follow-up assessments at least 3months apart. TRPMS stimulation produced no device-related adverse effects. It showed an inverted V-shaped modulation of the peak sMUP counts as a function of ALS functional rating scale revised scores. The ratios of ALS subjects showing peak sMUP count increases between early and intermediate stages (χ2 = 4.086, df = 1, p = 0.043) and intermediate and late stages (χ2 = 4.29, df = 1, p = 0.038) in cross-sectional data were significantly different. Longitudinal assessment also produced a significant (z = 2.31, p = 0.021) result, with all subjects showing a post-initial visit increase in peak sMUP counts. These results are consistent with delayed onset of upper motor neuronal dysfunction with respect to onset of clinical features. However, the above results need to be confirmed in a larger sample of patients and with multiple lines of evidence.

Age-related Changes in Cortical Excitability Linked to Decreased Attentional and Inhibitory Control

Understanding age-related changes in cortical excitability and their relation to cognitive functions will help to improve interventions based on non-invasive brain stimulation that aim to support cognitive function in older adults. Here, we investigate the relationship between cortical excitability, executive function, and underlying neural activity in samples of healthy young and older adults. These participants performed a Simon task during electroencephalogram (EEG) recording. During the task, participants had to respond to the colour of a lateralized stimulus while ignoring its spatial location. We studied event-related brain potential correlates of attentional and inhibitory control [i.e., the posterior contralateral negativity (N2pc) and central contralateral negativity (N2cc), respectively] related to the Simon task performance. We also used transcranial magnetic stimulation (TMS) EEG coregistration. In detail, we applied single-pulse TMS during EEG recording in order to analyse global mean field power (GMFP) and TMS-evoked potentials (TEPs) as correlates of cortical excitability. We found lower GMFP amplitude within 101–200 ms in older compared to young adults. Moreover, older adults showed smaller N45 amplitude and slower P180 latency. These findings suggest cortical excitability alterations related to ageing. Older adults also exhibited longer reaction times and N2pc and N2cc latencies, indicating that it took them longer to allocate attention to the target stimulus and inhibit the tendency to respond to the attended location. Finally, in older adults, cortical excitability alterations correlated with longer reaction times and N2pc latencies. These results suggest that age-related alterations in cortical excitability represent a dysfunctional change associated with physiological ageing.

Abnormalities in resting-state EEG microstates are a vulnerability marker of migraine

BackgroundResting-state EEG microstates are thought to reflect brief activations of several interacting components of resting-state brain networks. Surprisingly, we still know little about the role of these microstates in migraine. In the present study, we attempted to address this issue by examining EEG microstates in patients with migraine without aura (MwoA) during the interictal period and comparing them with those of a group of healthy controls (HC).MethodsResting-state EEG was recorded in 61 MwoA patients (50 females) and 66 HC (50 females). Microstate parameters were compared between the two groups. We computed four widely identified canonical microstate classes A-D.ResultsMicrostate classes B and D displayed higher time coverage and occurrence in the MwoA patient group than in the HC group, while microstate class C exhibited significantly lower time coverage and occurrence in the MwoA patient group. Meanwhile, the mean duration of microstate class C was significantly shorter in the MwoA patient group than in the HC group. Moreover, among the MwoA patient group, the duration of microstate class C correlated negatively with clinical measures of headache-related disability as assessed by the six-item Headache Impact Test (HIT-6). Finally, microstate syntax analysis showed significant differences in transition probabilities between the two groups, primarily involving microstate classes B, C, and D.ConclusionsBy exploring EEG microstate characteristics at baseline we were able to explore the neurobiological mechanisms underlying altered cortical excitability and aberrant sensory, affective, and cognitive processing, thus deepening our understanding of migraine pathophysiology.

Altered Visual Cortical Excitability Is Associated With Psychopathological Symptoms in Major Depressive Disorder.

Previous studies suggest that in people with major depressive disorder (MDD), there exists a perturbation of the normal balance between the excitatory and inhibitory neurotransmitter systems in the visual cortex, indicating the possibility of altered visual cortical excitability. However, investigations into the neural activities of the visual cortex in MDD patients yielded inconsistent findings. The present study aimed to evaluate the visual cortical excitability utilizing a paired-pulse stimulation paradigm in patients with MDD and to access the paired-pulse behavior of recording visual evoked potentials (VEPs) as a marker of MDD. We analyzed the amplitudes of VEPs and paired-pulse suppression (PPS) at four different stimulus onset asynchronies (SOAs) spanning 93 ms to 133 ms. Further, the relationship between PPS and the symptom severity of depression was investigated using Spearman's correlation. We found that, whereas the first VEP amplitude remained unchanged, the second VEP amplitude was significantly higher in the MDD group compared to the healthy controls. As a result, the amplitude ratio (second VEP amplitude/first VEP amplitude) increased, indicating reduced PPS and thus increased excitability in the visual cortex. Moreover, we found the amplitude ratios had a significantly positive correlation with the symptom severity of depression in MDD, indicating a clinically useful biomarker for MDD. Our findings provide new insights into the changes in the excitation-inhibition balance of visual cortex in MDD, which could pave the way for specific clinical interventions.

Transcranial direct current stimulation improve symptoms and modulates cortical inhibition in obsessive-compulsive disorder: A TMS-EEG study

BackgroundObsessive-compulsive disorder (OCD) is a disabling condition for which approximately 40% of patients do not respond to first-line treatment. Transcranial direct current stimulation (tDCS) is a safe and accessible technique that modulates cortical excitability and inhibition, but evidence of its efficacy for OCD is insufficient. ObjectiveTo investigate the efficacy of tDCS for OCD and alterations of cortical excitability and inhibition after treatment measured by concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). MethodsTwenty-four OCD patients underwent 10 20-min sessions of 1.5 mA high-definition tDCS with a cathode placed over the right orbitofrontal cortex (OFC) and anode electrodes set around the cathodal electrode. TMS-EEG was performed before and after tDCS treatment. OCD symptom severitys was assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Beck Depression Inventory-Ⅱ (BDI-Ⅱ), and Beck Anxiety Inventory (BAI) were used to assess the severity of depression and anxiety symptoms. Twenty-seven healthy controls were recruited with TMS-EEG recorded. ResultsFollowing tDCS, the Y-BOCS, BDI-Ⅱ, and BAI scores decreased significantly (all p = 0.000). TMS-evoked N100 amplitude, thought to be related to GABAB receptor function, was significantly reduced after tDCS (Z = -2.143, p = 0.032) which was higher in OCD patients than in healthy controls at baseline (Z = -2.151, p = 0.031). LimitationsPharmacotherapy during tDCS treatment may influence the effect of tDCS and EEG. ConclusionsCathodal high-definition tDCS applied over the OFC could improve OCD, depression, and anxiety symptoms along with alleviation of GABAB receptor function.

Neuromodulation by means of phase-locked auditory stimulation affects key marker of excitability and connectivity during sleep

The propagating pattern of sleep slow waves (high-amplitude oscillations < 4.5 Hz) serves as a blueprint of cortical excitability and brain connectivity. Phase-locked auditory stimulation is a promising tool for the modulation of ongoing brain activity during sleep; however, its underlying mechanisms remain unknown. Here, eighteen healthy young adults were measured with high-density electroencephalography in three experimental conditions; one with no stimulation, one with up- and one with down-phase stimulation; ten participants were included in the analysis. We show that up-phase auditory stimulation on a right prefrontal area locally enhances cortical involvement and promotes traveling by increasing the propagating distance and duration of targeted small-amplitude waves. On the contrary, down-phase stimulation proves more efficient at perturbing large-amplitude waves and interferes with ongoing traveling by disengaging cortical regions and interrupting high synchronicity in the target area as indicated by increased traveling speed. These results point out different underlying mechanisms mediating the effects of up- and down-phase stimulation and highlight the strength of traveling wave analysis as a sensitive and informative method for the study of connectivity and cortical excitability alterations.

Isometric agonist and antagonist muscle activation interacts differently with 140-Hz transcranial alternating current stimulation aftereffects at different intensities.

During transcranial electric stimulation, increasing intracellular Ca2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1 mA does not increase excitability, compatible with too strong intracellular Ca2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of "leaky membranes" under activation, surround inhibition, intracellular Ca2+ increase, and their role in the aftereffects of tACS.NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations.

Dosage-Dependent Impact of Acute Serotonin Enhancement on Transcranial Direct Current Stimulation Effects.

BackgroundThe serotonergic system has an important impact on basic physiological and higher brain functions. Acute and chronic enhancement of serotonin levels via selective serotonin reuptake inhibitor administration impacts neuroplasticity in humans, as shown by its effects on cortical excitability alterations induced by non-invasive brain stimulation, including transcranial direct current stimulation (tDCS). Nevertheless, the interaction between serotonin activation and neuroplasticity is not fully understood, particularly considering dose-dependent effects. Our goal was to explore dosage-dependent effects of acute serotonin enhancement on stimulation-induced plasticity in healthy individuals.MethodsTwelve healthy adults participated in 7 sessions conducted in a crossover, partially double-blinded, randomized, and sham-controlled study design. Anodal and cathodal tDCS was applied to the motor cortex under selective serotonin reuptake inhibitor (20 mg/40 mg citalopram) or placebo medication. Motor cortex excitability was monitored by single-pulse transcranial magnetic stimulation.ResultsUnder placebo medication, anodal tDCS enhanced, and cathodal tDCS reduced, excitability for approximately 60–120 minutes after the intervention. Citalopram enhanced and prolonged the facilitation induced by anodal tDCS regardless of the dosage while turning cathodal tDCS-induced excitability diminution into facilitation. For the latter, prolonged effects were observed when 40 mg was administrated.ConclusionsAcute serotonin enhancement modulates tDCS after-effects and has largely similar modulatory effects on motor cortex neuroplasticity regardless of the specific dosage. A minor dosage-dependent effect was observed only for cathodal tDCS. The present findings support the concept of boosting the neuroplastic effects of anodal tDCS by serotonergic enhancement, a potential clinical approach for the treatment of neurological and psychiatric disorders.