Modulation Of Cortical Excitability Research Articles

BDNF genotype influence the efficacy of rTMS in stroke patients

Brain-derived neurotrophic factor (BDNF) genotype can influence neural response to repetitive transcranial magnetic stimulation (rTMS) in normal individuals. In this study we established personalized stimulus intensity of facilitatory rTMS according to BDNF genotype in stroke patients. Twenty-two chronic stroke patients were enrolled. All patients underwent three different sessions of rTMS over the ipsilesional M1 in randomized order with a washout period exceeding 24h: first condition, high-frequency rTMS with sub-threshold intensity; second condition, high-frequency rTMS with supra-threshold intensity; third condition, sham rTMS. Cortical excitability in the affected hemisphere was assessed with motor evoked potentials (MEPs) before and after stimulation. Data were analyzed according to BDNF genotype. Six [27.3%] and 16 [72.7%] participants were classified in the Val/Val group and Met allele group, respectively. In each group, significant increases were observed in the amplitude of MEPs after the stimulation in the first and second conditions (p<0.05), but not in the third condition. However, a significantly higher increase of amplitude of MEPs was observed between the first and second conditions in only the Val/Val group (p<0.05). BDNF genotype and stimulus intensity should be considered when high-frequency rTMS is used for the modulation of cortical excitability in patients with chronic stroke.

Modulation of Cortical Excitability by Transcranial Direct Current Stimulation

Modulation of Cortical Excitability by Transcranial Direct Current Stimulation

A local signature of LTP-like plasticity induced by repetitive paired associative stimulation.

Repetitive paired associative stimulation (rPAS) repeatedly pairs electrical nerve stimulation (ENS) with transcranial magnetic stimulation (TMS) of the contralateral motor hand area (M1) at 5Hz frequency. So far, there are only few studies concerning the effects of PAS on the modulation of EEG power. Hence, aim of the present study was to investigate rPAS long term after-effects on cortical excitability looking at EEG power spectra. In four experimental sessions, separated by 2weeks interval, 12 awake subjects received rPAS of the right median nerve and left M1 at a fixed interval (ISI) of 25ms (real condition), 5Hz-TMS on left M1, 5Hz-ENS, of the right median nerve, and rPAS with changing ISI (sham condition). We measured peak-to-peak MEP amplitude, evoked from the target muscle (right abductor pollicis brevis muscle) at rest and the absolute power (POW) in four frequency bands: α (8-12Hz), β (13-30), θ (4-7) and δ (1-3), under rest conditions. All these parameters were evaluated in three detection blocks: baseline, immediately after and after 30' from the end of the conditioning protocol. Real rPAS induced a long-lasting homotopic cortical excitability modulation, as indexed by MEP amplitude increase, that was paralleled by a long-lasting reduction of α/β-POW and by a widespread θ-δ-POW modulation. rPAS applied over the sensory-motor cortex induced an LTP-like plasticity, as indexed by a robust reduction in the α/β POW positively correlated with the MEP amplitude increase. rPAS25ms may be a useful tool for motor neurorehabilitation promoting a sensory-motor coupling within β oscillations.

Prestimulus Oscillations in the Alpha Band of the EEG Are Modulated by the Difficulty of Feature Discrimination and Predict Activation of a Sensory Discrimination Process

Recent work has demonstrated that the occipital-temporal N1 component of the ERP is sensitive to the difficulty of visual discrimination, in a manner that cannot be explained by simple differences in low-level visual features, arousal, or time on task. These observations provide evidence that the occipital-temporal N1 component is modulated by the application of top-down control. However, the timing of this control process remains unclear. Previous work has demonstrated proactive, top-down modulation of cortical excitability for cued spatial attention or feature selection tasks. Here, the possibility that a similar top-down process facilitates performance of a difficult stimulus discrimination task is explored. Participants performed an oddball task at two levels of discrimination difficulty, with difficulty manipulated by modulating the similarity between target and nontarget stimuli. Discrimination processes and cortical excitability were assessed via the amplitude of the occipital-temporal N1 component and prestimulus alpha oscillation of the EEG, respectively. For correct discriminations, prestimulus alpha power was reduced, and the occipital-temporal N1 was enhanced in the hard relative to the easy condition. Furthermore, within the hard condition, prestimulus alpha power was reduced, and the occipital-temporal N1 was enhanced for correct relative to incorrect discriminations. The generation of ERPs contingent on relative prestimulus alpha power additionally suggests that diminished alpha power preceding stimulus onset is related to enhancement of the occipital-temporal N1. As in spatial attention, proactive control appears to enhance cortical excitability and facilitate discrimination performance in tasks requiring nonspatial, feature-based attention, even in the absence of competing stimulus features.

Posture-related modulation of cortical excitability in the tibialis anterior muscle in humans

Corticospinal excitability in the lower leg muscles is enhanced during standing as compared to other postures. In the present study, we investigated how the excitability of intracortical circuits that control the tibialis anterior muscle (TA) is modulated during standing. Short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were assessed by the paired-pulse transcranial magnetic stimulation technique during standing (STD) and sitting (SIT) with a comparable background activity level in both the soleus and the TA muscle. The results demonstrated that SICI was less effective during STD than during SIT, whereas ICF was more effective during STD than during SIT. These findings suggest that the excitabilities of these cortical neural circuits are modulated depending on posture. A decrease in SICI and an increase in ICF may reflect subliminal enhancement of the cortical excitability in the TA muscle during standing as compared with that during sitting.

Opposing effects of dopamine antagonism in a motor sequence task-tiapride increases cortical excitability and impairs motor learning.

The dopaminergic system is involved in learning and participates in the modulation of cortical excitability (CE). CE has been suggested as a marker of learning and use-dependent plasticity. However, results from separate studies on either motor CE or motor learning challenge this notion, suggesting opposing effects of dopaminergic modulation upon these parameters: while agonists decrease and antagonists increase CE, motor learning is enhanced by agonists and disturbed by antagonists. To examine whether this discrepancy persists when complex motor learning and motor CE are measured in the same experimental setup, we investigated the effects of dopaminergic (DA) antagonism upon both parameters and upon task-associated brain activation. Our results demonstrate that DA-antagonism has opposing effects upon motor CE and motor sequence learning. Tiapride did not alter baseline CE, but increased CE post training of a complex motor sequence while simultaneously impairing motor learning. Moreover, tiapride reduced activation in several brain regions associated with motor sequence performance, i.e., dorsolateral PFC (dlPFC), supplementary motor area (SMA), Broca's area, cingulate and caudate body. Blood-oxygenation-level-dependent (BOLD) intensity in anterior cingulate and caudate body, but not CE, correlated with performance across groups. In summary, our results do not support a concept of CE as a general marker of motor learning, since they demonstrate that a straightforward relation of increased CE and higher learning success does not apply to all instances of motor learning. At least for complex motor tasks that recruit a network of brain regions outside motor cortex, CE in primary motor cortex is probably no central determinant for learning success.

Hyperplasticity in Autism Spectrum Disorder confers protection from Alzheimer’s disease

Autism Spectrum Disorders (ASD) currently affects approximately 1% of the population causing grave disability and necessitating a better understanding of the currently enigmatic etiology of these disorders. Recent data suggest that some patients with ASD may have a dysfunction in brain plasticity (specifically data from animal models and human studies suggest a propensity toward excessive amount of plasticity). Plasticity is essential to the establishment and maintenance of brain circuitry; however, too much plasticity may lead to instability of structural connections and compromise of functional systems necessary for cognition and behavior. Multiple lines of evidence suggest that plasticity declines throughout the age-span and may underlie age-related cognitive decline. We hypothesize that individuals whose cortex begins as relatively “hyperplastic” (such as may be seen in ASD) should then be relatively protected from age-related cognitive decline (which we suggest is related to a reduction in plasticity). In the current study, we conducted a multiple linear regression using age and diagnosis as predictor variables in order to evaluate strength of the relationship between age, diagnosis or an interaction of the two factors and the degree of modulation in cortical excitability by transcranial magnetic stimulation as an index of cortical plasticity. Results indicate that across the age-span individuals with ASD show a consistently increased modulation of cortical excitability as compared to typically developing individuals, such that the general slope of decline across the age span is matched across both groups. We have argued that an individual’s risk of age-related cognitive decline (and risk for manifesting symptoms of dementia) depends on the individual’s starting point and slopes of change in plasticity efficiency over the lifespan. Therefore, our results suggest that individuals with ASD might be relatively protected from age-related cognitive decline and the risk of dementia.

TDCS increases cortical excitability: Direct evidence from TMS–EEG

Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the resting membrane potential in a polarity-dependent fashion: anodal stimulation increases cortical excitability in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS, and to what extent the stimulation of a given cerebral region may affect the activity of anatomically connected regions, remain unclear. In the present study, we used a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) in order to explore local and global cortical excitability modulation during and after active and sham tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 15 min of tDCS over the right PPC, while EEG was recorded from 60 channels.For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for three temporal windows: 0–50, 50–100, and 100–150 msec. The global index was computed on all 60 channels. The local indexes were computed in six clusters of electrodes: left and right in frontal, parietal and temporal regions.GMFP increased, compared to baseline, both during and after active tDCS in the 0–100 msec temporal window. LMFP increased after the end of stimulation in parietal and frontal clusters bilaterally, while no difference was found in the temporal clusters. In sum, a diffuse rise of cortical excitability occurred, both during and after active tDCS. This evidence highlights the spreading of the effects of anodal tDCS over remote cortical regions of stimulated and contralateral hemispheres.

P685: Modulation of cortical excitability after motor learning by action observation

P685: Modulation of cortical excitability after motor learning by action observation

LP16: Modulation of cortical excitability by grouped electrical stimulation protocols

LP16: Modulation of cortical excitability by grouped electrical stimulation protocols

Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model

Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15min on and 15min off) starting 45min after middle cerebral artery occlusion and lasting 4h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048).Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans.

Cognitive related electrophysiological changes induced by non-invasive cortical electrical stimulation in crack-cocaine addiction.

Prefrontal dysfunction is a hallmark in drug addiction, yet interventions exploring modulation of prefrontal cortex function in drug addiction have not been fully investigated with regard to physiological alterations. We tested the hypothesis that non-invasive prefrontal stimulation would change neural activity in crack-cocaine addiction, investigating the effects of transcranial Direct Current Stimulation (tDCS) of Dorsolateral Prefrontal Cortex (DLPFC) induced cortical excitability modulation on the visual P3 Event Related Potentials (ERP) component under neutral and drug cue exposition in crack-cocaine addicts. Thirteen crack-cocaine users were randomly distributed to receive five applications (once a day, every other day) of bilateral (left cathodal/right anodal) tDCS (20 min, 2 mA, 35 cm2) or sham tDCS over the DLPFC. Brain activity was measured under crack-related or neutral visual-cued ERPs. There were significant differences in P3-related parameters when comparing group of stimulation (active vs. sham tDCS) and number of sessions (single vs. repetitive tDCS). After a single session of tDCS, P3 current intensity in the left DLPFC increased during neutral cues and decreased during crack-related cues. This effect was opposite to what was observed in the sham-tDCS group. In contrast, repetitive tDCS increased current density not only in the DLPFC, but also in a wider array of prefrontal areas, including presumably the frontopolar cortex (FPC) orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), when subjects were visualizing crack-related cues. Thus, single and repetitive application of tDCS can impact cognitive processing of neutral and especially crack-related visual cues in prefrontal areas, which may be of importance for treatment of crack-cocaine addiction.

Neuromodulation of parietal and motor activity affects motor planning and execution

Transcranial direct current stimulation (tDCS) is a non-invasive tool, which effectively modulates behavior, and related brain activity. When applied to the primary motor cortex (M1), tDCS affects motor function, enhancing or decreasing performance of both healthy participants and brain-damaged patients. Beyond M1, the posterior parietal cortex (PPC) is also crucially involved in controlling and guiding movement. Therefore, we explored whether the modulation of cortical excitability within PPC can also affect hand motor function in healthy right-handed participants. In Experiment 1, anodal tDCS (2 mA, 10 min) was applied to PPC and to M1 of both hemispheres. Skilled motor function of the non-dominant left hand, measured using the Jebsen–Taylor Hand Function Test (JTT), improved after anodal tDCS of the right, contralateral M1, as well as after the anodal stimulation of the left, ipsilateral PPC. Conversely, in Experiment 2, cathodal tDCS of the left PPC, or of the right M1, reduced motor performance of the left hand. Finally, Experiment 3 shows that the anodal tDCS of the left PPC selectively facilitated action planning, while the anodal tDCS of the right M1 modulated action execution only.This evidence shows that motor improvement induced by left parietal and right motor stimulations relies on substantial different mechanisms, opening up novel perspectives in the neurorehabilitation of stroke patients with motor and apraxic disorders.

Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation

Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS) combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation (TMS) of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface (BMI) environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

Interhemispheric modulation of dual-mode, noninvasive brain stimulation on motor function.

ObjectiveTo investigate the effects of simultaneous, bihemispheric, dual-mode stimulation using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on motor functions and cortical excitability in healthy individuals.MethodsTwenty-five healthy, right-handed volunteers (10 men, 15 women; mean age, 25.5 years) were enrolled. All participants received four randomly arranged, dual-mode, simultaneous stimulations under the following conditions: condition 1, high-frequency rTMS over the right primary motor cortex (M1) and sham tDCS over the left M1; condition 2, high-frequency rTMS over the right M1 and anodal tDCS over the left M1; condition 3, high-frequency rTMS over the right M1 and cathodal tDCS over the left M1; and condition 4, sham rTMS and sham tDCS. The cortical excitability of the right M1 and motor functions of the left hand were assessed before and after each simulation.ResultsMotor evoked potential (MEP) amplitudes after stimulation were significantly higher than before stimulation, under the conditions 1 and 2. The MEP amplitude in condition 2 was higher than both conditions 3 and 4, while the MEP amplitude in condition 1 was higher than condition 4. The results of the Purdue Pegboard test and the box and block test showed significant improvement in conditions 1 and 2 after stimulation.ConclusionSimultaneous stimulation by anodal tDCS over the left M1 with high-frequency rTMS over the right M1 could produce interhemispheric modulation and homeostatic plasticity, which resulted in modulation of cortical excitability and motor functions.

P 147. Impaired modulation of intracortical inhibition during Go–Stop task in schizophrenia

Background Impaired inhibition has been reported in patients with schizophrenia in a variety of cognitive and motor tasks. Recent transcranial magnetic stimulation studies performed during rest show reduced cortical inhibition in primary motor cortex (M1) at rest in schizophrenia patients, supporting the hypothesis of impaired GABA-ergic inhibition as an underlying mechanism. However, cortical excitability and intracortical inhibition in M1 are highly task-dependent, for example, inhibiting a planned motor response leads to reduced excitability and enhanced intracortical inhibition. Studies on task-dependent cortical excitability and inhibition are lacking in schizophrenia. The aim of this study was therefore to investigate cortical excitability and intracortical inhibition during voluntary motor inhibition in patients with schizophrenia. Methods 25 stabilized patients with schizophrenia (DSMIV) and a group of 23 age-comparable healthy volunteers were included. We used a modified version of the Go–Stop task to study voluntary motor inhibition. This task consisted of moving the index finger in response to Go and Stop signals. In 30% of trials the subject received a visual cue to inhibit the prepared finger lift. Paired-pulse transcranial magnetic stimulation (TMS) was used to measure M1 excitability and short-latency intracortical inhibition (SICI%) during three phases of the task: (i) early without movement preparation (Early); (ii) late with preparation of finger lift (Late prep ); and (iii) late with inhibition of finger lift (Late inhib ). Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. Results Patients and control subjects performed equally on the voluntary inhibition task, with similar stop signal reaction times (mean SSRT controls 189 ± 21 ms and patients 186 ± 31 ms, P = 0.6). TMS at rest revealed similar resting and active motor thresholds in patients and controls (P > 0.9). The cortical silent period was shorter in the patients but did not differ significantly (mean controls 162 ± 30 ms and patients 147 ± 61 ms, P = 0.36). During the Go–Stop task, cortical excitability was similar in patients and controls with a task-dependent modulation of MEPs (mean RMS MEPs: Early = 477 μV, Late prep = 854 μV, and Late inhib = 531 μV; effect of Phase, P F = 4.5, P = 0.02) with posthoc comparisons revealing a significant reduction in the Late inhib phase in patients compared to controls ( P = 0.02). In patients the SICI% during Late inhib correlated negatively with SSRT ( R = − 0.72, P inhib had longer SSRT. Conclusions To our knowledge this is the first study on task-dependent modulation of cortical excitability and intracortical inhibition in patients with schizophrenia. We show that patients with schizophrenia have reduced SICI during voluntary inhibition of a prepared finger lift. Surprisingly, there were no differences found in task performance or in MEP amplitudes during the task. These findings show that schizophrenia patients are capable of inhibiting motor tasks despite having reduced intracortical inhibition. This suggests the use of compensatory mechanisms in voluntary motor inhibition in stabilized schizophrenia patients.

Reduced plastic brain responses to repetitive transcranial magnetic stimulation in severe obstructive sleep apnea syndrome

Abnormalities in cortical excitability have been proposed to underlie the pathophysiology of various neurocognitive manifestations of obstructive sleep apnea syndrome (OSAS). Transcranial magnetic stimulation (TMS) provides a noninvasive method for study and modulation of cortical excitability in the human brain, and repetitive TMS (rTMS) has been proven useful for neurophysiologic investigation in various neurologic conditions. We aimed to investigate cortical excitability in patients with OSAS during wakefulness and to determine if rTMS would change the abnormal excitability patterns. Measures of motor cortical and corticospinal excitability (resting motor threshold [RMT], motor-evoked potential [MEP] amplitude, and cortical silent period [CSP]) were taken before and after a session of 10-Hz rTMS applied to the motor cortex in 13 individuals with untreated severe OSAS (apnea-hypopnea index [AHI]>30) and 12 age- and sex-matched healthy controls (HC). OSAS subjects had a significantly higher RMT (P<.003) and a longer CSP duration (P<.002) compared to HC. No difference was observed between MEP values of OSAS subjects and HC (P>.05). In response to rTMS, the HC group had a significant increase in CSP and MEP values from baseline, which were absent in OSAS subjects. Individuals with OSAS demonstrated increased motor cortex inhibition, which did not respond to 10-Hz rTMS. As rTMS-induced changes in MEP and CSP involve a separate neurotransmitter system (N-methyl-d-aspartate [NMDA] and gamma-aminobutyric acid [GABA], respectively), these findings suggest a widespread alteration in cortical neurophysiology in severe OSAS subjects that requires clarification with further exploration.

Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4 × 1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4 × 1 montage (4 × cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4 × 1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4 × 1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4 × 1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4 × 1-Ring montage for cortically targeted neuromodulation.

Interactions between autonomic cardiovascular regulation and cortical activity: A CNV study

The study investigated interactions between autonomic cardiovascular regulation and cortical activity. In 54 healthy subjects, baroreflex sensitivity (BRS) and respiratory sinus arrhythmia (RSA) were assessed at resting conditions. As an EEG indicator of cortical excitability, the contingent negative variation (CNV) was induced using a constant foreperiod reaction time task. At bivariate level, only RSA showed a moderate positive correlation with the CNV recorded at frontal electrodes. However, when common variance of BRS and RSA was controlled for in multiple regression analysis, an inverse association between BRS and the frontal CNV also arose. The inverse association between BRS and the CNV is discussed as reflecting bottom-up modulation of cortical excitability by baroreceptor afferents. The positive correlation between RSA and the CNV may relate to the interplay between prefrontal processing and cardiac vagal tone.

Motor Cortical Plasticity in Parkinson’s Disease

In Parkinson’s disease (PD), there are alterations of the basal ganglia (BG) thalamocortical networks, primarily due to degeneration of nigrostriatal dopaminergic neurons. These changes in subcortical networks lead to plastic changes in primary motor cortex (M1), which mediates cortical motor output and is a potential target for treatment of PD. Studies investigating the motor cortical plasticity using non-invasive transcranial magnetic stimulation (TMS) have found altered plasticity in PD, but there are inconsistencies among these studies. This is likely because plasticity depends on many factors such as the extent of dopaminergic loss and disease severity, response to dopaminergic replacement therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity protocol used, medication, and stimulation status in patients treated with deep brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity have been explored in animal models and in PD patients. In addition, many other factors such age, genetic factors (e.g., brain derived neurotropic factor and other neurotransmitters or receptors polymorphism), emotional state, time of the day, physical fitness have been documented to play role in the extent of plasticity induced by TMS in human studies. In this review, we summarize the studies that investigated M1 plasticity in PD and demonstrate how these afore-mentioned factors affect motor cortical plasticity in PD. We conclude that it is important to consider the clinical, demographic, and technical factors that influence various plasticity protocols while developing these protocols as diagnostic or prognostic tools in PD. We also discuss how the modulation of cortical excitability and the plasticity with these non-invasive brain stimulation techniques facilitate the understanding of the pathophysiology of PD and help design potential therapeutic possibilities in this disorder.