Increase In Cortical Excitability Research Articles

Influence of sports on cortical excitability in patients with spinal cord injury: a TMS study.

Patients with spinal cord injury (SCI) show abnormal cortical excitability that might be caused by deafferentation. We hypothesize a reduced short-interval intracortical inhibition preceding movement in patients with SCI compared with healthy participants. In addition, we expect that neuroplasticity induced by different types of sports can modulate intracortical inhibition during movement preparation in patients with SCI. We used a reaction test and paired-pulse transcranial magnetic stimulation to record cortical excitability, assessed by measuring amplitudes of motor-evoked potentials in preparation of movement. The participants were grouped as patients with SCI practicing wheelchair dancing (n = 7), other sports (n = 6), no sports (n = 9), and healthy controls (n = 24). There were neither significant differences between healthy participants and the patients nor between the different patient groups. A non-significant trend (p = .238), showed that patients engaged in sports have a stronger increase in cortical excitability compared with patients of the non-sportive group, while the patients in the other sports group expressed the highest increase in cortical excitability. The small sample sizes limit the statistical power of the study, but the trending effect warrants further investigation of different sports on the neuroplasticity in patients with SCI. It is not clear how neuroplastic changes impact the sensorimotor output of the affected extremities in a patient. This needs to be followed up in further studies with a greater sample size.

Contrasting MEG effects of anodal and cathodal high-definition TDCS on sensorimotor activity during voluntary finger movements.

Protocols for noninvasive brain stimulation (NIBS) are generally categorized as "excitatory" or "inhibitory" based on their ability to produce short-term modulation of motor-evoked potentials (MEPs) in peripheral muscles, when applied to motor cortex. Anodal and cathodal stimulation are widely considered excitatory and inhibitory, respectively, on this basis. However, it is poorly understood whether such polarity-dependent changes apply for neural signals generated during task performance, at rest, or in response to sensory stimulation. To characterize such changes, we measured spontaneous and movement-related neural activity with magnetoencephalography (MEG) before and after high-definition transcranial direct-current stimulation (HD-TDCS) of the left motor cortex (M1), while participants performed simple finger movements with the left and right hands. Anodal HD-TDCS (excitatory) decreased the movement-related cortical fields (MRCF) localized to left M1 during contralateral right finger movements while cathodal HD-TDCS (inhibitory), increased them. In contrast, oscillatory signatures of voluntary motor output were not differentially affected by the two stimulation protocols, and tended to decrease in magnitude over the course of the experiment regardless. Spontaneous resting state oscillations were not affected either. MRCFs are thought to reflect reafferent proprioceptive input to motor cortex following movements. Thus, these results suggest that processing of incoming sensory information may be affected by TDCS in a polarity-dependent manner that is opposite that seen for MEPs-increases in cortical excitability as defined by MEPs may correspond to reduced responses to afferent input, and vice-versa.

Acute Effects of Strength and Skill Training on the Cortical and Spinal Circuits of Contralateral Limb

Unilateral strength and skill training increase strength and performance in the contralateral untrained limb, a phenomenon known as cross-education. Recent evidence suggests that similar neural mechanisms might be responsible for the increase in strength and skill observed in the untrained hand after unimanual training. The aims of this study were to: investigate whether a single session of unimanual strength and skill (force-tracking) training increased strength and skill in the opposite hand; measure ipsilateral (untrained) brain (via transcranial magnetic stimulation, TMS) and spinal (via the monosynaptic reflex) changes in excitability occurring after training; measure ipsilateral (untrained) pathway-specific changes in neural excitability (via TMS-conditioning of the monosynaptic reflex) occurring after training. Participants (N = 13) completed a session of unimanual strength (ballistic isometric wrist flexions) and skill (force-tracking wrist flexions) training on two separate days. Strength increased after training in the untrained hand (p = 0.025) but not in the trained hand (p = 0.611). Force-tracking performance increased in both the trained (p = 0.007) and untrained (p = 0.010) hand. Corticospinal excitability increased after force-tracking and strength training (p = 0.027), while spinal excitability was not affected (p = 0.214). TMS-conditioned monosynaptic reflex increased after force-tracking (p = 0.001) but not strength training (p = 0.689), suggesting a possible role of polysynaptic pathways in the increase of cortical excitability observed after training. The results suggest that cross-education of strength and skill at the acute stage is supported by increased excitability of the untrained motor cortex. New & Noteworthy: A single session of isometric wrist flexion strength and skill straining increased strength and skill in the untrained limb. The excitability of the untrained motor cortex increased after strength and skill training. TMS-conditioned H-reflexes increased after skill but not strength training in the untrained hand, indicating that polysynaptic pathways in the increase of cortical excitability observed after skill training.

State-dependent effectiveness of cathodal transcranial direct current stimulation on cortical excitability

The extensive use of transcranial direct current stimulation (tDCS) in experimental and clinical settings does not correspond to an in-depth understanding of its underlying neurophysiological mechanisms. In previous studies, we employed an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG) to track the effect of tDCS on cortical excitability. At rest, anodal tDCS (a-tDCS) over the right Posterior Parietal Cortex (rPPC) elicits a widespread increase in cortical excitability. In contrast, cathodal tDCS (c-tDCS) fails to modulate cortical excitability, being indistinguishable from sham stimulation.Here we investigated whether an endogenous task-induced activation during stimulation might change this pattern, improving c-tDCS effectiveness in modulating cortical excitability.In Experiment 1, we tested whether performance in a Visuospatial Working Memory Task (VWMT) and a modified Posner Cueing Task (mPCT), involving rPPC, could be modulated by c-tDCS. Thirty-eight participants were involved in a two-session experiment receiving either c-tDCS or sham during tasks execution. In Experiment 2, we recruited sixteen novel participants who performed the same paradigm but underwent TMS-EEG recordings pre- and 10 min post- sham stimulation and c-tDCS.Behavioral results showed that c-tDCS significantly modulated mPCT performance compared to sham. At a neurophysiological level, c-tDCS significantly reduced cortical excitability in a frontoparietal network likely involved in task execution. Taken together, our results provide evidence of the state dependence of c-tDCS in modulating cortical excitability effectively. The conceptual and applicative implications are discussed.

Random Tactile Noise Stimulation Reveals Beta-Rhythmic Impulse Response Function of the Somatosensory System.

Both passive tactile stimulation and motor actions result in dynamic changes in beta band (15-30 Hz Hz) oscillations over somatosensory cortex. Similar to alpha band (8-12 Hz) power decrease in the visual system, beta band power also decreases following stimulation of the somatosensory system. This relative suppression of α and β oscillations is generally interpreted as an increase in cortical excitability. Here, next to traditional single-pulse stimuli, we employed a random intensity continuous right index finger tactile stimulation (white noise), which enabled us to uncover an impulse response function (IRF) of the somatosensory system. Contrary to previous findings, we demonstrate a burst-like initial increase rather than decrease of beta activity following white noise stimulation (human participants, N = 18, 8 female). These β bursts, on average, lasted for three cycles and their frequency was correlated with resonant frequency of somatosensory cortex, as measured by a multi-frequency steady-state somatosensory evoked potential (SSSEP) paradigm. Furthermore, beta band bursts shared spectro-temporal characteristics with evoked and resting-state β oscillations. Taken together, our findings not only reveal a novel oscillatory signature of somatosensory processing that mimics the previously reported visual IRFs, but also point to a common oscillatory generator underlying spontaneous β bursts in the absence of tactile stimulation and phase-locked β bursts following stimulation, the frequency of which is determined by the resonance properties of the somatosensory system.SIGNIFICANCE STATEMENTThe investigation of the transient nature of oscillations has gained great popularity in recent years. The findings of bursting activity rather than sustained oscillations in the beta band has provided important insights into its role in movement planning, working memory, inhibition and reactivation of neural ensembles. In this study, we show that also in response to tactile stimulation the somatosensory system responds with ∼3 cycle oscillatory beta band bursts, whose spectro-temporal characteristics are shared with evoked and resting-state beta band oscillatory signatures of the somatosensory system. As similar bursts have been observed in the visual domain, these oscillatory signatures might reflect an important supramodal mechanism in sensory processing.

Effects of prolonged local vibration superimposed to muscle contraction on motoneuronal and cortical excitability.

Introduction: Acute effects of prolonged local vibration (LV) at the central nervous system level have been well investigated demonstrating an altered motoneuronal excitability with a concomitant increase in cortical excitability. While applying LV during isometric voluntary contraction is thought to optimize the effects of LV, this has never been addressed considering the acute changes in central nervous system excitability. Materials and Methods: In the present study, nineteen healthy participants were engaged in four randomized sessions. LV was applied for 30min to the relaxed flexor carpi radialis muscle (VIBRELAXED) or during wrist flexions (i.e. intermittent contractions at 10% of the maximal voluntary contraction: 15s ON and 15s OFF; VIBCONTRACT). A control condition and a condition where participants only performed repeated low-contractions at 10% maximal force (CONTRACT) were also performed. For each condition, motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation and cervicomedullary evoked potentials (CMEPs) elicited by corticospinal tract electrical stimulation were measured before (PRE) and immediately after prolonged LV (POST) to investigate motoneuronal and corticospinal excitability, respectively. We further calculated the MEP/CMEP ratio as a proxy of cortical excitability. Results: No changes were observed in the control nor CONTRACT condition. At POST, CMEP decreased similarly in VIBRELAXED (-32% ± 42%, p < .001) and VIBCONTRACT (-41% ± 32%, p < .001). MEP/CMEP increased by 110% ± 140% (p = .01) for VIBRELAXED and by 120% ± 208% (p = .02) for VIBCONTRACT without differences between those conditions. Discussion: Our results suggest that LV to the flexor carpi radialis muscle, either relaxed or contracted, acutely decreases motoneuronal excitability and induces some priming of cortical excitability.

Hierarchical Bayesian modeling of the relationship between task-related hemodynamic responses and cortical excitability.

Investigating the relationship between task-related hemodynamic responses and cortical excitability is challenging because it requires simultaneous measurement of hemodynamic responses while applying noninvasive brain stimulation. Moreover, cortical excitability and task-related hemodynamic responses are both associated with inter-/intra-subject variability. To reliably assess such a relationship, we applied hierarchical Bayesian modeling. This study involved 16 healthy subjects who underwent simultaneous Paired Associative Stimulation (PAS10, PAS25, Sham) while monitoring brain activity using functional Near-Infrared Spectroscopy (fNIRS), targeting the primary motor cortex (M1). Cortical excitability was measured by Motor Evoked Potentials (MEPs), and the motor task-related hemodynamic responses were measured using fNIRS 3D reconstructions. We constructed three models to investigate: (1) PAS effects on the M1 excitability, (2) PAS effects on fNIRS hemodynamic responses to a finger tapping task, and (3) the correlation between PAS effects on M1 excitability and PAS effects on task-related hemodynamic responses. Significant increase in cortical excitability was found following PAS25, whereas a small reduction of the cortical excitability was shown after PAS10 and a subtle increase occurred after sham. Both HbO and HbR absolute amplitudes increased after PAS25 and decreased after PAS10. The probability of the positive correlation between modulation of cortical excitability and hemodynamic activity was 0.77 for HbO and 0.79 for HbR. We demonstrated that PAS stimulation modulates task-related cortical hemodynamic responses in addition to M1 excitability. Moreover, the positive correlation between PAS modulations of excitability and hemodynamics brought insight into understanding the fundamental properties of cortical function and cortical excitability.

Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers

TAK-653 is a novel AMPA receptor positive allosteric modulator in clinical development for the treatment of major depressive disorder (MDD). This study aimed to measure the functional pharmacodynamic central nervous system (CNS) effects of TAK-653. A randomised, double-blind, placebo-controlled, three-way crossover (placebo, TAK-653 0.5 mg and 6 mg) study with 24 healthy volunteers was performed. NeuroCart tests consisting of body sway (BS), saccadic peak velocity (SPV), smooth pursuit eye movements (SP), adaptive tracking (AT), Bowdle and Bond and Lader Visual Analogue Scales (B-VAS and BL-VAS) and Stroop test were performed pre-dose and 3.5 and 4 h post-dose. Data were analysed using a mixed model analysis of covariance with baseline as covariate. It was found that TAK-653 did not affect BS and subjective drug effects as measured by B-VAS and BL-VAS at either dose level. TAK-653 0.5 mg increased SPV (degrees/second) (19.49 [5.98, 32.99], P = 0.02) and affected Stroop difference in reaction time between correct congruent and correct incongruent answers and number of correct responses in incongruent trials (22.0 [4.0, 40.0], P = 0.05 and −0.3 [−0.5, −0.1], P = 0.02, respectively). TAK-653 6 mg improved AT (%) (1.68 [0.51, 2.84], P = 0.02) and increased SPV (degrees/s) (15.40 [1.91, 28.90], P = 0.06) and SP (%) (2.32 [0.37, 4.27], P = 0.05). Based on these findings it can be concluded that TAK-653 demonstrated a psychostimulant-like pharmacodynamic profile on the NeuroCart consistent with previously reported increase of cortical excitability following Transcranial Magnetic Stimulation (TMS) of the human motor cortex.

Physiological and Neural Changes with Rehabilitation Training in a 53-Year Amputee: A Case Study

Many people who received amputation wear sEMG prostheses to assist in their daily lives. How these prostheses promote muscle growth and change neural activity remains elusive. We recruited a subject who had his left hand amputated for over 53 years to participate in a six-week rehabilitation training using an sEMG prosthesis. We tracked the muscle growth of his left forearm and changes in neural activity over six weeks. The subject showed an increase in fast muscle fiber in his left forearm during the training period. In an analysis of complex networks of neural activity, we observed that the -band network decreased in efficiency but increased in its capability to integrate information. This could be due to an expansion of the network to accommodate new movements enabled by rehabilitation training. Differently, we found that in the -band network, a band frequency related to motor functions, the efficiency of the network initially decreased but started to increase after approximately three weeks. The ability to integrate network information showed an opposite trend compared with its efficiency. rMT values, a measure that negatively correlates with cortical excitability, showed a sharp decrease in the first three weeks, suggesting an increase in cortical excitability. In the last three weeks, there was little to no change. These data indicate that rehabilitation training promoted fast muscle fiber growth and introduced neural activity changes in the subject during the first three weeks of training. Our study gave insights into how rehabilitation training with an sEMG prosthesis could lead to physiological and neural changes in amputees.

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Brain-Derived Neurotrophic Factor Gene Polymorphism Predicts Response to Continuous Theta Burst Stimulation in Chronic Stroke Patients

ObjectivesThe efficacy of repetitive transcranial magnetic stimulation (rTMS) in clinically relevant neuroplasticity research depends on the degree to which stimulation induces robust, reliable effects. The high degree of interindividual and intraindividual variability observed in response to rTMS protocols, such as continuous theta burst stimulation (cTBS), therefore represents an obstacle to its utilization as treatment for neurological disorders. Brain-derived neurotrophic factor (BDNF) is a protein involved in human synaptic and neural plasticity, and a common polymorphism in the BDNF gene (Val66Met) may influence the capacity for neuroplastic changes that underlie the effects of cTBS and other rTMS protocols. While evidence from healthy individuals suggests that Val66Met polymorphism carriers may show diminished or facilitative effects of rTMS compared to their homozygous Val66Val counterparts, this has yet to be demonstrated in the patient populations where neuromodulatory therapies are most relevant. Materials and MethodsWe examined the effects of BDNF Val66Met polymorphism on cTBS aftereffects in stroke patients. We compared approximately 30 log-transformed motor-evoked potentials (LnMEPs) obtained per time point: at baseline and at 0, 10, 20, and 30 min after cTBS-600, from 18 patients with chronic stroke using single TMS pulses. We used linear mixed-effects regression with trial-level data nested by subject for higher statistical power. ResultsWe found a significant interaction between BDNF genotype and pre-/post-cTBS LnMEPs. Val66Val carriers showed decrease in cortical excitability, whereas Val66Met carriers exhibited a modest increase in cortical excitability for 20 min poststimulation, followed by inhibition 30 min after cTBS-600. ConclusionsOur findings strongly suggest that BDNF genotype differentially affects neuroplastic responses to TMS in individuals with chronic stroke. This provides novel insight into potential sources of variability in cTBS response in patients, which has important implications for optimizing the utility of this neuromodulation approach. Incorporating BDNF polymorphism genetic screening to stratify patients prior to use of cTBS as a neuromodulatory technique in therapy or research may optimize response rates.

Hebbian activity-dependent plasticity in white matter.

SummarySynaptic plasticity is required for learning and follows Hebb’s rule, the computational principle underpinning associative learning. In recent years, a complementary type of brain plasticity has been identified in myelinated axons, which make up the majority of brain’s white matter. Like synaptic plasticity, myelin plasticity is required for learning, but it is unclear whether it is Hebbian or whether it follows different rules. Here, we provide evidence that white matter plasticity operates following Hebb’s rule in humans. Across two experiments, we find that co-stimulating cortical areas to induce Hebbian plasticity leads to relative increases in cortical excitability and associated increases in a myelin marker within the stimulated fiber bundle. We conclude that Hebbian plasticity extends beyond synaptic changes and can be observed in human white matter fibers.

Benefits from Repetitive Transcranial Magnetic Stimulation in Post-Stroke Rehabilitation.

Stroke is an acute neurovascular central nervous system (CNS) injury and one of the main causes of long-term disability and mortality. Post-stroke rehabilitation as part of recovery is focused on relearning lost skills and regaining independence as much as possible. Many novel strategies in neurorehabilitation have been introduced. This review focuses on current evidence of the effectiveness of repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation (NIBS), in post-stroke rehabilitation. Moreover, we present the effects of specific interventions, such as low-frequency or high-frequency rTMS therapy, on motor function, cognitive function, depression, and aphasia in post-stroke patients. Collected data suggest that high-frequency stimulation (5 Hz and beyond) produces an increase in cortical excitability, whereas low-frequency stimulation (≤1 Hz) decreases cortical excitability. Accumulated data suggest that rTMS is safe and can be used to modulate cortical excitability, which may improve overall performance. Side effects such as tingling sensation on the skin of the skull or headache are possible. Serious side effects such as epileptic seizures can be avoided by adhering to international safety guidelines. We reviewed clinical studies that present promising results in general recovery and stimulating neuroplasticity. This article is an overview of the current rTMS state of knowledge related to benefits in stroke, as well as its cellular and molecular mechanisms. In the stroke rehabilitation literature, there is a key methodological problem of creating double-blinding studies, which are very often impossible to conduct.

Transcranial Random Noise Stimulation Modulates Neural Processing of Sensory and Motor Circuits, from Potential Cellular Mechanisms to Behavior: A Scoping Review.

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurologic patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioral levels, and discuss how this emerging method might be harnessed to augment perceptual and motor functioning of the human nervous system. Online databases were used to identify papers published in 2008–2021 using tRNS in humans, from which we identified 70 publications focusing on sensory and motor function. Additionally, we interpret the existing evidence by referring to articles investigating the effects of noise stimulation in animal and subcellular models. We review physiological and behavioral findings of tRNS-induced offline after-effects and acute online benefits which manifest immediately when tRNS is applied to sensory or motor cortices. We link these results to evidence showing that activity of voltage-gated sodium ion channels might be an important cellular substrate for mediating these tRNS effects. We argue that tRNS might make neural signal transmission and processing within neuronal populations more efficient, which could contribute to both (1) offline after-effects in the form of a prolonged increase in cortical excitability and (2) acute online noise benefits when computations rely on weak inputs.

Effects of a single session of cathodal transcranial direct current stimulation primed intermittent theta-burst stimulation on heart rate variability and cortical excitability measures

Objectives: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been used as neuromodulators in neuropsychiatric conditions. This study is aimed to find the effects of a single session of priming cathodal tDCS with intermittent theta-burst stimulation (iTBS) over left dorsolateral prefrontal cortex on heart rate variability (HRV) and cortical excitability parameters before and after perturbation. Materials and Methods: The neuromodulatory techniques used in the study were Cathodal tDCS for 20 min followed by iTBS for 3 min on the left dorsolateral prefrontal cortex (DLPFC). HRV variables and TMS parameters were recorded before and after this intervention of combined neuromodulation in 31 healthy volunteers (20 males and 11 females; age range of 19–35 years with Mean ± SD = 24.2 ± 4.7 years). Results: The results showed an overall increase in cortical excitability and parasympathetic dominance in healthy volunteers. Other measures of cortical excitability and HRV did not change significantly following single session of combined neuromodulation. Conclusion: This study showed that there is an overall increase in cortical excitability and parasympathetic dominance in the cohort of healthy volunteers following a combination of neuromodulation involving cathodal tDCS followed by iTBS over left DLPFC. Future studies exploring the effects of other possible combinations with sham stimulation could be carried out to explore the utility of dual stimulation as add-on therapy in disorders.

Repetitive transcranial magnetic stimulation on the modulation of cortical and spinal cord excitability in individuals with spinal cord injury.

Repetitive transcranial magnetic stimulation (rTMS) has been applied for modulating cortical excitability and treating spasticity in neurological lesions. However, it is unclear which rTMS frequency is most effective in modulating cortical and spinal excitability in incomplete spinal cord injury (SCI). To evaluate electrophysiological and clinical repercussions of rTMS compared to sham stimulation when applied to the primary motor cortex (M1) in individuals with incomplete SCI. A total of 11 subjects (35±12 years) underwent three experimental sessions of rTMS (10 Hz, 1 Hz and sham stimulation) in a randomized order at 90%intensity of the resting motor threshold and interspersed by a seven-day interval between sessions. The following outcome measures were evaluated: M1 and spinal cord excitability and spasticity in the moments before (baseline), immediately after (T0), 30 (T30) and 60 (T60) minutes after rTMS. M1 excitability was obtained through the motor evoked potential (MEP); spinal cord excitability by the Hoffman reflex (H-reflex) and homosynaptic depression (HD); and spasticity by the modified Ashworth scale (MAS). A significant increase in cortical excitability was observed in subjects submitted to 10 Hz rTMS at the T0 moment when compared to sham stimulation (p = 0.008); this increase was also significant at T0 (p = 0.009), T30 (p = 0.005) and T60 (p = 0.005) moments when compared to the baseline condition. No significant differences were observed after the 10 Hz rTMS on spinal excitability or on spasticity. No inter-group differences were detected, or in the time after application of 1 Hz rTMS, or after sham stimulation for any of the assessed outcomes. High-frequency rTMS applied to M1 was able to promote increased cortical excitability in individuals with incomplete SCI for at least 60 minutes; however, it did not modify spinal excitability or spasticity.

Analgesia induced by anodal tDCS and high-frequency tRNS over the motor cortex: Immediate and sustained effects on pain perception

BackgroundMany studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. ObjectiveThis study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. MethodsUsing a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. ResultsCompared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. ConclusionsThe analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.

Ketamine and Attentional Bias Toward Emotional Faces: Dynamic Causal Modeling of Magnetoencephalographic Connectivity in Treatment-Resistant Depression.

The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (TRD) and bipolar disorder. While its underlying mechanism of antidepressant action is not fully understood, modulating glutamatergically-mediated connectivity appears to be a critical component moderating antidepressant response. This double-blind, crossover, placebo-controlled study analyzed data from 19 drug-free individuals with TRD and 15 healthy volunteers who received a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) as well as an intravenous infusion of saline placebo. Magnetoencephalographic recordings were collected prior to the first infusion and 6–9 h after both drug and placebo infusions. During scanning, participants completed an attentional dot probe task that included emotional faces. Antidepressant response was measured across time points using the Montgomery-Asberg Depression Rating Scale (MADRS). Dynamic causal modeling (DCM) was used to measure changes in parameter estimates of connectivity via a biophysical model that included realistic local neuronal architecture and receptor channel signaling, modeling connectivity between the early visual cortex, fusiform cortex, amygdala, and inferior frontal gyrus. Clinically, ketamine administration significantly reduced depressive symptoms in TRD participants. Within the model, ketamine administration led to faster gamma aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) transmission in the early visual cortex, faster NMDA transmission in the fusiform cortex, and slower NMDA transmission in the amygdala. Ketamine administration also led to direct and indirect changes in local inhibition in the early visual cortex and inferior frontal gyrus and to indirect increases in cortical excitability within the amygdala. Finally, reductions in depressive symptoms in TRD participants post-ketamine were associated with faster α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) transmission and increases in gain control of spiny stellate cells in the early visual cortex. These findings provide additional support for the GABA and NMDA inhibition and disinhibition hypotheses of depression and support the role of AMPA throughput in ketamine's antidepressant effects.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00088699?term=NCT00088699&draw=2&rank=1, identifier NCT00088699.

Motor adaptation and internal model formation in a robot-mediated forcefield.

Motor adaptation relies on error-based learning for accurate movements in changing environments. However, the neurophysiological mechanisms driving individual differences in performance are unclear. Transcranial magnetic stimulation (TMS)-evoked potential can provide a direct measure of cortical excitability. To investigate cortical excitability as a predictor of motor learning and motor adaptation in a robot-mediated forcefield. A group of 15 right-handed healthy participants (mean age 23 years) performed a robot-mediated forcefield perturbation task. There were two conditions: unperturbed non-adaptation and perturbed adaptation. TMS was applied in the resting state at baseline and following motor adaptation over the contralateral primary motor cortex (left M1). Electroencephalographic (EEG) activity was continuously recorded, and cortical excitability was measured by TMS-evoked potential (TEP). Motor learning was quantified by the motor learning index. Larger error-related negativity (ERN) in fronto-central regions was associated with improved motor performance as measured by a reduction in trajectory errors. Baseline TEP N100 peak amplitude predicted motor learning (P=0.005), which was significantly attenuated relative to baseline (P=0.0018) following motor adaptation. ERN reflected the formation of a predictive internal model adapted to the forcefield perturbation. Attenuation in TEP N100 amplitude reflected an increase in cortical excitability with motor adaptation reflecting neuroplastic changes in the sensorimotor cortex. TEP N100 is a potential biomarker for predicting the outcome in robot-mediated therapy and a mechanism to investigate psychomotor abnormalities in depression.

Evidence of neuroplasticity with robotic hand exoskeleton for post-stroke rehabilitation: a randomized controlled trial

BackgroundA novel electromechanical robotic-exoskeleton was designed in-house for the rehabilitation of wrist joint and Metacarpophalangeal (MCP) joint.ObjectiveThe objective was to compare the rehabilitation effectiveness (clinical-scales and neurophysiological-measures) of robotic-therapy training sessions with dose-matched conventional therapy in patients with stroke.MethodsA pilot prospective parallel randomized controlled study at clinical settings was designed for patients with stroke within 2 years of chronicity. Patients were randomly assigned to receive an intervention of 20 sessions of 45 min each, five days a week for four weeks, in Robotic-therapy Group (RG) (n = 12) and conventional upper-limb rehabilitation in Control-Group (CG) (n = 11). We intended to evaluate the effects of a novel exoskeleton based therapy on the functional rehabilitation outcomes of upper-limb and cortical-excitability in patients with stroke as compared to the conventional-rehabilitation. Clinical-scales– Modified Ashworth Scale, Active Range of Motion, Barthel-Index, Brunnstrom-stage and Fugl-Meyer (FM) scale and neurophysiological measures of cortical-excitability (using Transcranial Magnetic Stimulation) –Motor Evoked Potential and Resting Motor threshold, were acquired pre- and post-therapy.ResultsNo side effects were noticed in any of the patients. Both RG and CG showed significant (p < 0.05) improvement in all clinical motor-outcomes except Modified Ashworth Scale in CG. RG showed significantly (p < 0.05) higher improvement over CG in Modified Ashworth Scale, Active Range of Motion and Fugl-Meyer scale and FM Wrist-/Hand component. An increase in cortical-excitability in ipsilesional-hemisphere was found to be statistically significant (p < 0.05) in RG over CG, as indexed by a decrease in Resting Motor Threshold and increase in the amplitude of Motor Evoked Potential. No significant changes were shown by the contralesional-hemisphere. Interhemispheric RMT-asymmetry evidenced significant (p < 0.05) changes in RG over CG indicating increased cortical-excitability in ipsilesional-hemisphere along with interhemispheric changes.ConclusionRobotic-exoskeleton training showed improvement in motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes in RG could most likely be a consequence of plastic reorganization and use-dependent plasticity.Trial registry number: ISRCTN95291802