Modulation Of Cortical Excitability Research Articles

Anodal transcranial direct current stimulation could modulate cortical excitability reflecting central cholinergic dysfunction

Background: Anodal transcranial direct current stimulation (tDCS) is known for accentuate excitability in simulating area. We aim to investigate modulation of cortical excitability after anodal tDCS stimulation using various transcranial magnetic stimulation parameters.

A History of Concussion Affects Relevancy-Based Modulation of Cortical Responses to Tactile Stimuli.

Modulating cortical excitability based on a stimulus’ relevance to the task at hand is a component of sensory gating, and serves to protect higher cortical centers from being overwhelmed with irrelevant information (McIlroy et al., 2003; Kumar et al., 2005; Wasaka et al., 2005). This study examined relevancy-based modulation of cortical excitability, and corresponding behavioral responses, in the face of distracting stimuli in participants with and without a history of concussion (mean age 22 ± 3 SD years; most recent concussion 39.1 ± 30 SD months). Participants were required to make a scaled motor response to the amplitudes of visual and tactile stimuli presented individually or concurrently. Task relevance was manipulated, and stimuli were occasionally presented with irrelevant distractors. Electroencephalography (EEG) and task accuracy data were collected from participants with and without a history of concussion. The somatosensory-evoked N70 event-related potential (ERP) was significantly modulated by task relevance in the control group but not in those with a history of concussion, and there was a significantly greater cost to task accuracy in the concussion history group when relevant stimuli were presented with an irrelevant distractor. This study demonstrated that relevancy-based modulation of electrophysiological responses and behavioral correlates of sensory gating differ in people with and without a history of concussion, even after patients were symptom-free and considered recovered from their injuries.

P69 Searching for the sweet spot: Balancing tDCS intensity for cortical excitability modulation with double blinding integrity

P69 Searching for the sweet spot: Balancing tDCS intensity for cortical excitability modulation with double blinding integrity

Does alpha phase modulate visual target detection? Three experiments with tACS-phase-based stimulus presentation.

In recent years, the influence of alpha (7–13 Hz) phase on visual processing has received a lot of attention. Magneto‐/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. Studies with transcranial alternating current stimulation (tACS) aim to modulate oscillations and causally impact task performance. Here, we applied right occipital tACS (O2 location) to assess the functional role of alpha phase in a series of experiments. We presented visual stimuli at different pre‐determined, experimentally controlled, phases of the entraining tACS signal, hypothesizing that this should result in an oscillatory pattern of visual performance in specifically left hemifield detection tasks. In experiment 1, we applied 10 Hz tACS and used separate psychophysical staircases for six equidistant tACS‐phase conditions, obtaining contrast thresholds for detection of visual gratings in left or right hemifield. In experiments 2 and 3, tACS was at EEG‐based individual peak alpha frequency. In experiment 2, we measured detection rates for gratings with (pseudo‐)fixed contrast. In experiment 3, participants detected brief luminance changes in a custom‐built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one‐cycle sinusoid. However, post hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT for specifically left hemifield targets in both experiments 1 and 2 (not measured in experiment 3). This observation requires future confirmation, but is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.

A North American History of Cannabis Use in the Treatment of Epilepsy.

Cannabis has been used for millennia in religious ceremonies, for recreation and for its medicinal qualities. There are multiple accounts detailing the specific ailments cannabis has been used to treat, many of which have included epilepsy. Racial discrimination and political stigmatization led to prohibition, which limited both patients' and researchers' access to the drug through the 20th century. Recently, academic interest has been renewed in cannabis, especially regarding the modulation of cortical excitability via the human endocannabinoid system. Modern research has produced several promising studies regarding the treatment of epileptic encephalopathies. Legalization of marijuana in Canada has potentially allowed for further trials, but it is by no means an end to the controversy surrounding the treatment of epilepsy with cannabinoids.

TRANSCRANIAL DIRECT-CURRENT STIMULATION IN COMBINATION WITH EXERCISE: A SYSTEMATIC REVIEW

ABSTRACT Introduction Transcranial direct-current stimulation (tDCS) is a noninvasive technique that allows the modulation of cortical excitability and can produce changes in neuronal plasticity. The application of tDCS has recently been associated with physical activity. Objectives To verify the effect of Transcranial Direct-Current Stimulation (tDCS) in combination with physical exercise, characterizing methodological aspects of the technique. Methods In the database search, studies with animals, other neuromodulation techniques and opinion and review articles were excluded. Publications up to 2016 were selected and the methodological quality of the articles was verified through the PEDro scale. Results The majority of studies (86%) used tDCS on the motor cortex area, with anodal current and the allocation of monocephalic electrodes (46.5%). The prevalent current intensity was 2mA (72%), with duration of 20min (55.8%). The profile of the research participants was predominantly of subjects aged up to 60 years (72.1%). The outcomes were favorable for the use of anodal tDCS in combination with physical exercise. Conclusion Transcranial Direct-Current Stimulation is a promising technique when used in combination with aerobic and anaerobic exercises; however, it is necessary to investigate concurrent exercise. Level of Evidence II; Therapeutic Studies Investigating the Results of Treatment (systematic review of Level II studies or Level I studies with inconsistent results).

Cortical Excitability Dynamics During Fear Processing.

Background:Little is known about the modulation of cortical excitability in the prefrontal cortex during fear processing in humans. Here, we aimed to transiently modulate and test the cortical excitability during fear processing using transcranial magnetic stimulation (TMS) and brain oscillations in theta and alpha frequency bands with electroencephalography (EEG).Methods:We conducted two separate experiments (no-TMS and TMS). In the no-TMS experiment, EEG recordings were performed during the instructed fear paradigm in which a visual cue (CS+) was paired with an aversive unconditioned stimulus (electric shock), while the other visual cue was unpaired (CS-). In the TMS experiment, in addition the TMS was applied on the right dorsomedial prefrontal cortex (dmPFC). The participants also underwent structural MRI (magnetic resonance imaging) scanning and were assigned pseudo-randomly to both experiments, such that age and gender were matched. The cortical excitability was evaluated by time-frequency analysis and functional connectivity with weighted phase lag index (WPLI). We further linked the excitability patterns with markers of stress coping capability.Results:After visual cue onset, we found increased theta power in the frontal lobe and decreased alpha power in the occipital lobe during CS+ relative to CS- trials. TMS of dmPFC increased theta power in the frontal lobe and reduced alpha power in the occipital lobe during CS+. The TMS pulse increased the information flow from the sensorimotor region to the prefrontal and occipital regions in the theta and alpha bands, respectively during CS+ compared to CS-. Pre-stimulation frontal theta power (0.75–1 s) predicted the magnitude of frontal theta power changes after stimulation (1–1.25 s). Finally, the increased frontal theta power during CS+ compared to CS- was positively correlated with stress coping behavior.Conclusion:Our results show that TMS over dmPFC transiently modulated the regional cortical excitability and the fronto-occipital information flows during fear processing, while the pre-stimulation frontal theta power determined the strength of achieved effects. The frontal theta power may serve as a biomarker for fear processing and stress-coping responses in individuals and could be clinically tested in mental disorders.

Dynamic Modulation of Cortical Excitability during Visual Active Sensing

SUMMARYVisual physiology is traditionally investigated by presenting stimuli with gaze held constant. However, during active viewing of a scene, information is actively acquired using systematic patterns of fixations and saccades. Prior studies suggest that during such active viewing, both nonretinal, saccade-related signals and “extra-classical” receptive field inputs modulate visual processing. This study used a set of active viewing tasks that allowed us to compare visual responses with and without direct foveal input, thus isolating the contextual eye movement-related influences. Studying nonhuman primates, we find strong contextual modulation in primary visual cortex (V1): excitability and response amplification immediately after fixation onset, transiting to suppression leading up to the next saccade. Time-frequency decomposition suggests that this amplification and suppression cycle stems from a phase reset of ongoing neuronal oscillatory activity. The impact of saccade-related contextual modulation on stimulus processing makes active visual sensing fundamentally different from the more passive processes investigated in traditional paradigms.

Impaired attentional modulation of sensorimotor control and cortical excitability in schizophrenia.

Impairments in attentional, working memory and sensorimotor processing have been consistently reported in schizophrenia. However, the interaction between cognitive and sensorimotor impairments and the underlying neural mechanisms remains largely uncharted. We hypothesized that altered attentional processing in patients with schizophrenia, probed through saccadic inhibition, would partly explain impaired sensorimotor control and would be reflected as altered task-dependent modulation of cortical excitability and inhibition. Twenty-five stabilized patients with schizophrenia, 17 unaffected siblings and 25 healthy control subjects were recruited. Subjects performed visuomotor grip force-tracking alone (single-task condition) and with increased cognitive load (dual-task condition). In the dual-task condition, two types of trials were randomly presented: trials with visual distractors (requiring inhibition of saccades) or trials with addition of numbers (requiring saccades and addition). Both dual-task trial types required divided visual attention to the force-tracking target and to the distractor or number. Gaze was measured during force-tracking tasks, and task-dependent modulation of cortical excitability and inhibition were assessed using transcranial magnetic stimulation. In the single-task, patients with schizophrenia showed increased force-tracking error. In dual-task distraction trials, force-tracking error increased further in patients, but not in the other two groups. Patients inhibited fewer saccades to distractors, and the capacity to inhibit saccades explained group differences in force-tracking performance. Cortical excitability at rest was not different between groups and increased for all groups during single-task force-tracking, although, to a greater extent in patients (80%) compared to controls (40%). Compared to single-task force-tracking, the dual-task increased cortical excitability in control subjects, whereas patients showed decreased excitability. Again, the group differences in cortical excitability were no longer significant when failure to inhibit saccades was included as a covariate. Cortical inhibition was reduced in patients in all conditions, and only healthy controls increased inhibition in the dual-task. Siblings had similar force-tracking and gaze performance as controls but showed altered task-related modulation of cortical excitability and inhibition in dual-task conditions. In patients, neuropsychological scores of attention correlated with visuomotor performance and with task-dependant modulation of cortical excitability. Disorganization symptoms were greatest in patients with weakest task-dependent modulation of cortical excitability. This study provides insights into neurobiological mechanisms of impaired sensorimotor control in schizophrenia showing that deficient divided visual attention contributes to impaired visuomotor performance and is reflected in impaired modulation of cortical excitability and inhibition. In siblings, altered modulation of cortical excitability and inhibition is consistent with a genetic risk for cortical abnormality.

Differential role of prefrontal, temporal and parietal cortices in verbal and figural fluency: Implications for the supramodal contribution of executive functions

Verbal and figural fluency are related to executive functions (EFs), but the extent to which they benefit from executive resources and their respective cortical representations is not clear. Moreover, different brain areas and cognitive functions are involved in fluency processing. This study investigated effects of modulation of cortical excitability in the left dorsolateral prefrontal cortex (l-DLPFC), left temporal area and right posterior parietal cortex (r-PPC) with transcranial direct current stimulation (tDCS), on verbal and figural fluency. Fifteen healthy adult participants received anodal l-DLPFC (F3), anodal left temporal (T3), anodal r-PPC (P4) and sham tDCS (15 min, 1.5 mA). After five minutes of stimulation, participants underwent the verbal fluency (i.e., semantic and phonemic fluency tasks) and figural fluency tasks. Participants significantly generated more words with phonemic cues during anodal l-DLPFC tDCS and more words with semantic cues during both anodal left temporal and anodal l-DLPFC tDCS. In contrast, they generated more unique figures under anodal r-PPC and anodal l-DLPFC tDCS. Our results implicate that prefrontal regions and EFs are shared anatomical correlates and cognitive processes relevant for both, verbal and figural fluency (supramodal contribution of DLPFC activation), whereas r-PPC and left temporal cortex are more specifically involved in figural and semantic fluency (modality-specific contribution).

Analysis of the Factors Related to the Effectiveness of Transcranial Current Stimulation in Upper Limb Motor Function Recovery after Stroke: a Systematic Review.

Transcranial direct current stimulation is one of the non-invasive techniques whose main mechanism of action is based on its modulation of cortical excitability. The objective of this study is to analyze the variables (i.e, demographics, clinicals, stimulation parameters) that could influence into the responses during rehabilitation of the upper extremity in patients with stroke. Our systematic review has been performed by searching full-text articles published from January 2008 to December 2018 in Embase, Medline, PubMed and Cochrane Library databases. Studies with adult patients with ischemic or hemorrhagic stroke at any stage of evolution were included. We compared interventions with any type of transcranial direct current stimulation (anodal, cathodal or bihemispheric, also known as dual) regarding improvement of upper extremity motor function. We included 14 studies with 368 patients, of whom almost 89% have ischemic etiology and more than half are males. Most patients were considered subacute or chronic, while only two studies were selected with patients in the acute phase. Different methods of using transcranial direct current stimulation with several complementary therapies were identified, such as virtual reality, robot therapy, Occupational Therapy, Physiotherapy, Constraint Induced Movement Therapy or Peripheral Nerve Stimulation. In conclusion, there is not significant evidence due to heterogeneity of clinical data and therapies. Clinical studies with greater number of participants and protocols standardized could outline this assessment in future studies.

Modulation of cortical excitability during symptom provocation after single session repetitive transcranial magnetic stimulation in patients with obsessive compulsive disorder

Modulation of cortical excitability during symptom provocation after single session repetitive transcranial magnetic stimulation in patients with obsessive compulsive disorder

Effects of electrode angle-orientation on the impact of transcranial direct current stimulation on motor cortex excitability

Background: For the effects of transcranial direct current stimulation (tDCS), electrical field distribution and coverage of the target areas play a decisive role. In this study, we explored the effect of different angle-orientations of tDCS electrodes applied over the upper limb motor cortex (M1) on motor cortex excitability in healthy volunteers. Methods: Twelve individuals received 1 mA anodal or cathodal tDCS through 35cm2 electrodes over M1 for 15 minutes. The M1 electrode-orientation was following the right-left longitudinal plane or positioned with 45° deviation from the midsagittal plane. Transcranial magnetic stimulation was used to examine tDCS-generated cortical excitability effects. Coverage of underlying brain and electrical field orientation was also investigated with computational modeling. Results: Cortical excitability modulation was observed only when the electrode was aligned with 45° angle, which covered a larger area of the motor cortex. Conclusion: an electrode angle-orientation of 45° induces superior neuroplastic effects of M1 due to a better alignment with the motor cortex.

μ-Rhythm Extracted With Personalized EEG Filters Correlates With Corticospinal Excitability in Real-Time Phase-Triggered EEG-TMS

Ongoing brain activity has been implicated in the modulation of cortical excitability. The combination of electroencephalography (EEG) and transcranial magnetic stimulation (TMS) in a real-time triggered setup is a novel method for testing hypotheses about the relationship between spontaneous neuronal oscillations, cortical excitability, and synaptic plasticity. For this method, a reliable real-time extraction of the neuronal signal of interest from scalp EEG with high signal-to-noise ratio (SNR) is of crucial importance. Here we compare individually tailored spatial filters as computed by spatial-spectral decomposition (SSD), which maximizes SNR in a frequency band of interest, against established local C3-centered Laplacian filters for the extraction of the sensorimotor μ-rhythm. Single-pulse TMS over the left primary motor cortex was synchronized with the surface positive or negative peak of the respective extracted signal, and motor evoked potentials (MEP) were recorded with electromyography (EMG) of a contralateral hand muscle. Both extraction methods led to a comparable degree of MEP amplitude modulation by phase of the sensorimotor μ-rhythm at the time of stimulation. This could be relevant for targeting other brain regions with no working benchmark such as the local C3-centered Laplacian filter, as sufficient SNR is an important prerequisite for reliable real-time single-trial detection of EEG features.

Transcranial Direct Current Stimulation in Neurodegenerative Disorders.

Cortical excitability modulation and neuroplasticity are considered essential mechanisms for improving clinical and cognitive abilities in neurodegenerative disorders (NDDs). In such context, transcranial direct current stimulation (tDCS) shows great promise for facilitating remodeling of neurosynaptic organization. The aim of this review was to provide an overview of how tDCS is currently used as a neurorehabilitation strategy in some NDDs. We describe results from studies in which tDCS was applied in mild cognitive impairment, Alzheimer's disease, and primary progressive aphasia. Currently, findings related to the ability of tDCS to restore cognitive dysfunctions and behavioral impairments in these NDDs do not seem to support the notion that tDCS shows clear therapeutic efficacy in patients with mild cognitive impairment, Alzheimer disease, and primary progressive aphasia. This is probably because tDCS research in this area is still in its early stages. Methodological concerns, such as differences in tDCS parameters (eg, intensity or duration), target sites, and study design (eg, the relationship between tDCS and the rehabilitation strategy), or the use of underpowered sample sizes may also contribute to these outcomes. Nevertheless, it is important to note that almost no studies have evaluated how the underlying neurophysiological state of patients should guide the application of tDCS. These results should not prevent the use of tDCS in these NDDs, but they should trigger a deeper evaluation of how tDCS should be used. Transcranial direct current stimulation cannot be considered a neurorehabilitation apparatus by itself but should be instead viewed as a method for weakly modulating existing brain excitability. Future studies should aim to improve our understanding of the neurophysiological mechanisms that underlie the clinical effects of tDCS with the final goal of designing and performing individualized stimulation protocols that can be tailored for each NDD patient and combined with other appropriate neurorehabilitation strategies.

Modulation of Cerebellar Cortical Plasticity Using Low-Intensity Focused Ultrasound for Poststroke Sensorimotor Function Recovery

Background. Stroke affects widespread brain regions through interhemispheric connections by influencing bilateral motor activity. Several noninvasive brain stimulation techniques have proved their capacity to compensate the functional loss by manipulating the neural activity of alternative pathways. Over the past few decades, brain stimulation therapies have been tailored within the theoretical framework of modulation of cortical excitability to enhance adaptive plasticity after stroke. Objective. However, considering the vast difference between animal and human cerebral cortical structures, it is important to approach specific neuronal target starting from the higher order brain structure for human translation. The present study focuses on stimulating the lateral cerebellar nucleus (LCN), which sends major cerebellar output to extensive cortical regions. Methods. In this study, in vivo stroke mouse LCN was exposed to low-intensity focused ultrasound (LIFU). After the LIFU exposure, animals underwent 4 weeks of rehabilitative training. Results. During the cerebellar LIFU session, motor-evoked potentials (MEPs) were generated in both forelimbs accompanying excitatory sonication parameter. LCN stimulation group on day 1 after stroke significantly enhanced sensorimotor recovery compared with the group without stimulation. The recovery has maintained for a 4-week period in 2 behavior tests. Furthermore, we observed a significantly decreased level of brain edema and tissue swelling in the affected hemisphere 3 days after the stroke. Conclusions. This study provides the first evidence showing that LIFU-induced cerebellar modulation could be an important strategy for poststroke recovery. A longer follow-up study is, however, necessary in order to fully confirm the effects of LIFU on poststroke recovery.

Anodal Transcranial Direct Current Stimulation (tDCS) Over the Right Primary Motor Cortex (M1) Impairs Implicit Motor Sequence Learning of the Ipsilateral Hand.

Motor sequence learning is associated with the activation of bilateral primary motor cortices (M1). While previous data support the hypothesis that the contralateral M1 is causally involved in the acquisition as well as early consolidation of a motor sequence, the functional significance of the ipsilateral M1 has yet to be solved. Transcranial direct current stimulation (tDCS) allows the non-invasive modulation of cortical excitability. Anodal tDCS applied to the left M1 has been shown to facilitate implicit motor sequence learning of the right hand most likely due to increased excitability. The present study aims at characterizing the functional contribution of the ipsilateral (right) M1 on implicit motor sequence learning of the right hand. To this end, 24 healthy, right-handed subjects received anodal and sham tDCS to the right M1 in a counterbalanced order. Stimulation started 8 min prior to training on a variant of the serial reaction time task (SRTT) with the right hand and persists over the entire training period. The SRTT comprised a fixed eight-digit sequence. A random pattern served as control condition. Reaction times were assessed before and at the end of the acquisition (EoA) immediately after training on the SRTT. The analysis revealed significantly faster reaction times of both hands independent of tDCS condition in sequential trials. However, the gain of reaction times was significantly smaller following anodal as compared to sham tDCS. The data suggest that anodal tDCS applied to the right M1 impairs implicit motor sequence learning of both hands. The underlying mechanism likely involves alterations of the interaction between bilateral M1.

Effects of Cathode Location and the Size of Anode on Anodal Transcranial Direct Current Stimulation Over the Leg Motor Area in Healthy Humans.

Objective: Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) involves passing low currents through the brain and is a promising tool for the modulation of cortical excitability. In this study, we investigated the effects of cathode location and the size of anode for anodal tDCS of the right-leg area of the motor cortex, which is challenging due to its depth and orientation in the inter-hemispheric fissure.Methods: We first computationally investigated the effects of cathode location and the size of the anode to find the best montage for specificity of stimulation effects for the targeted leg motor area using finite element analysis (FEA). We then compared the best electrode montage found from FEA with the conventional montage (contralateral supraorbital cathode) via neurophysiological testing of both, the targeted as well as the contralateral leg motor area.Results: The conventional anodal tDCS electrode montage for leg motor cortex stimulation using a large-anode (5 cm × 7 cm, current strength 2 mA) affected the contralateral side more strongly in both the FEA and the neurophysiological testing when compared to other electrode montages. A small-anode (3.5 cm × 1 cm at 0.2 mA) with the same current density at the electrode surface and identical contralateral supraorbital cathode placement improved specificity. The best cathode location for the small-anode in terms of specificity for anodal tDCS of the right-leg motor area was T7 (10–10 EEG system).Conclusion: A small-anode (3.5 cm × 1 cm) with the same current density at the electrode surface as a large-anode (5 cm × 7 cm) resulted in similar cortical excitability alterations of the targeted leg motor cortex respresentation. In relation to the other stimulation conditions, the small-anode montage with the cathode positioned at T7 resulted in the best specificity.

The effect of intensive physical therapy with repetitive transcranial magnetic stimulation in patients with degenerative cerebellar disease

The studies of repetitive transcranial magnetic stimulation (rTMS) of the brain have demonstrated the modulation of cortical excitability. Combination of rTMS with physical therapy (PT) might affect the therapeutic effects for movement disorders. The aim of this study was to investigate the effect of combination of intensive PT with rTMS in patients with degenerative cerebellar disease. Twelve patients with degenerative cerebellar disease participated in the study. The rTMS and PT were carried out five days a week for three weeks. The gait parameters were determined using a three-dimensional motion analysis system, and the total length and the velocity of the center of pressure (COP) in standing position using a stabilometer and the International Cooperative Ataxia Rating Scale (ICARS) were assessed in all patients before and after the intervention. The changes in the walking speed, step width, the total length of the COP and the velocity of the COP in standing position were not significant. The amplitude of the lateral head and body sway when walking were reduced after intervention ( P < 0.01) and the ICARS was improved after the intervention ( P < 0.01). The correlations between the duration of disease and the improvement of walking speed and step width were not significant. The correlations between the disease severity and the improvement of walking speed and step width were significant. In our study, combination of intensive PT and rTMS conferred positive effects on the dynamic balance in patients with degenerative cerebellar disease in earlier stages of the disease.

BDNF Val66Met polymorphism is associated with altered activity-dependent modulation of short-interval intracortical inhibition in bilateral M1.

The BDNF Val66Met polymorphism is associated with impaired short-term plasticity in the motor cortex, short-term motor learning, and intermanual transfer of a procedural motor skill. Here, we investigated the impact of the Val66Met polymorphism on the modulation of cortical excitability and interhemispheric inhibition through sensorimotor practice of simple dynamic skills with the right and left first dorsal interosseous (FDI) muscles. To that end, we compared motor evoked potentials (MEP) amplitudes and short-interval intracortical inhibition (SICI) in the bilateral representations of the FDI muscle in the primary motor cortex (M1), and interhemispheric inhibition (IHI) from the left to right M1, before and after right and left FDI muscle training in an alternated sequence. Val66Met participants did not differ from their Val66Val counterparts on motor performance at baseline and following motor training, or on measures of MEP amplitude and IHI. However, while the Val66Val group displayed significant SICI reduction in the bilateral M1 in response to motor training, SICI remained unchanged in the Val66Met group. Further, Val66Val group’s SICI decrease in the left M1, which was also observed following unimanual training with the right hand in the Control Right group, was correlated with motor improvement with the left hand. The potential interaction between left and right M1 activity during bimanual training and the implications of altered activity-dependent cortical excitability on short-term motor learning in Val66Met carriers are discussed.