Modulation Of Motor Cortical Excitability Research Articles

Transcranial burst electrical stimulation contributes to neuromodulatory effects in the rat motor cortex.

Transcranial Burst Electrical Stimulation (tBES) is an innovative non-invasive brain stimulation technique that combines direct current (DC) and theta burst stimulation (TBS) for brain neuromodulation. It has been suggested that the tBES protocol may efficiently induce neuroplasticity. However, few studies have systematically tested neuromodulatory effects and underlying neurophysiological mechanisms by manipulating the polarity of DC and TBS patterns. This study aimed to develop the platform and assess neuromodulatory effects and neuronal activity changes following tBES. Five groups of rats were exposed to anodal DC combined with intermittent TBS (tBES+), cathodal DC combined with continuous TBS (tBES-), anodal and cathodal transcranial direct current stimulation (tDCS+ and tDCS-), and sham groups. The neuromodulatory effects of each stimulation on motor cortical excitability were analyzed by motor-evoked potentials (MEPs) changes. We also investigated the effects of tBES on both excitatory and inhibitory neural biomarkers. We specifically examined c-Fos and glutamic acid decarboxylase (GAD-65) using immunohistochemistry staining techniques. Additionally, we evaluated the safety of tBES by analyzing glial fibrillary acidic protein (GFAP) expression. Our findings demonstrated significant impacts of tBES on motor cortical excitability up to 30 min post-stimulation. Specifically, MEPs significantly increased after tBES (+) compared to pre-stimulation (p = 0.026) and sham condition (p = 0.025). Conversely, tBES (-) led to a notable decrease in MEPs relative to baseline (p = 0.04) and sham condition (p = 0.048). Although tBES showed a more favorable neuromodulatory effect than tDCS, statistical analysis revealed no significant differences between these two groups (p > 0.05). Additionally, tBES (+) exhibited a significant activation of excitatory neurons, indicated by increased c-Fos expression (p < 0.05), and a reduction in GAD-65 density (p < 0.05). tBES (-) promoted GAD-65 expression (p < 0.05) while inhibiting c-Fos activation (p < 0.05), suggesting the involvement of cortical inhibition with tBES (-). The expression of GFAP showed no significant difference between tBES and sham conditions (p > 0.05), indicating that tBES did not induce neural injury in the stimulated regions. Our study indicates that tBES effectively modulates motor cortical excitability. This research significantly contributes to a better understanding of the neuromodulatory effects of tBES, and could provide valuable evidence for its potential clinical applications in treating neurological disorders.

Imagined paralysis reduces motor cortex excitability.

Mental imagery is a powerful capability that engages similar neurophysiological processes that underlie real sensory and motor experiences. Previous studies show that motor cortical excitability can increase during mental imagery of actions. In this study, we focused on possible inhibitory effects of mental imagery on motor functions. We assessed whether imagined arm paralysis modulates motor cortical excitability in healthy participants, as measured by motor evoked potentials (MEPs) of the hand induced by near‐threshold transcranial magnetic stimulation (TMS) over the primary motor cortex hand area. We found lower MEP amplitudes during imagined arm paralysis when compared to imagined leg paralysis or baseline stimulation without paralysis imagery. These results show that purely imagined bodily constraints can selectively inhibit basic motor corticospinal functions. The results are discussed in the context of motoric embodiment/disembodiment.

Effects of corticospinal tract integrity on upper limb motor function recovery in stroke patients treated with repetitive transcranial magnetic stimulation.

The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.

Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder

ObjectiveTo test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. Methods44 adult neurotypical (NT) participants (age 21–65, 34 males) and 19 adults with ASD (age 21–58, 17 males) prospectively underwent M1 cTBS. Their data were combined with previously obtained results from 35 NT and 35 ASD adults. ResultsΔMEP at 15 minutes post-cTBS (T15) was a significant predictor of diagnosis (p = 0.04) in the present sample (n=63). T15 remained a significant predictor in a larger sample (n=91) and when partially imputed based on T10–T20 from a yet-greater sample (N=133). T15 also remained a significant predictor of diagnosis among brain-derived neurotrophic factor (BDNF) Met+ and apolipoprotein E (APOE) ε4− subjects (p’s < 0.05), but not among Met− or ε4+ subjects (p’s > 0.19). ConclusionsΔMEP at T15 post-cTBS is a significant biomarker for adults with ASD, and its utility is modulated by BDNF and APOE polymorphisms. SignificanceM1 cTBS response is a physiologic biomarker for adults with ASD in large samples, and controlling for BDNF and APOE polymorphisms can improve its diagnostic utility.

TMS over the posterior cerebellum modulates motor cortical excitability in response to facial emotional expressions.

Evidence suggests that the posterior cerebellum is involved in emotional processing. Specific mechanisms by which the cerebellum contributes to the perception of and reaction to the emotional state of others are not well-known. It is likely that perceived emotions trigger anticipatory/preparatory motor changes. However, the extent to which the cerebellum modulates the activity of the motor cortex to contribute to emotional processing has not been directly investigated. In this study, we assessed whether the activity of the posterior cerebellum influences the modulation of motor cortical excitability in response to emotional stimuli. To this end, we transiently disrupted the neural activity of the left posterior cerebellum using 1Hz repetitive transcranial magnetic stimulation (rTMS) and examined its effect on motor cortical excitability witnessed during emotional face processing (in comparison to the effects of sham rTMS). Motor excitability was measured as TMS-based motor evoked potentials (MEPs) recorded from bilateral first dorsal interosseous (FDI) muscles during the viewing of negative emotional (i.e. fearful) and neutral facial expressions. In line with previous evidence, we found that MEP amplitude was increased during the viewing of fearful compared to neutral faces. Critically, when left posterior cerebellar activity was transiently inhibited with 1Hz rTMS, we observed a reduction in amplitude of MEPs recorded from the contralateral (right) motor cortex during the viewing of emotional (but not neutral) faces. In turn, inhibition of the left posterior cerebellum did not affect the amplitude of MEPs recorded from the ipsilateral motor cortex. Our findings suggest that the posterolateral (left) cerebellum modulates motor cortical response to negative emotional stimuli and may serve as an interface between limbic, cognitive, and motor systems.

Music Form but Not Music Experience Modulates Motor Cortical Activity in Response to Novel Music.

External cues, such as music, improve movement performance in persons with Parkinson’s disease. However, research examining the motor cortical mechanisms by which this occurs is lacking. Research using electroencephalography in healthy young adults has revealed that moving to music can modulate motor cortical activity. Moreover, motor cortical activity is further influenced by music experience. It remains unknown whether these effects extend to corticomotor excitability. Therefore, the primary aim of this study was to determine the effects of novel music on corticomotor excitability using transcranial magnetic stimulation (TMS) in a pilot study of healthy young adults. A secondary aim of this study was to determine the influence of music experience on corticomotor excitability. We hypothesized that corticomotor excitability will change during music conditions, and that it will differ in those with formal music training. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous using single-pulse TMS in three conditions: (1) No Music, (2) Music Condition I, and (3) Music Condition II. Both pieces were set to novel MIDI piano instrumentation and part-writing conventions typical of early nineteenth-century Western classical practices. Results revealed Music Condition II (i.e., more relaxing music) compared to rest increased MEP amplitude (i.e., corticomotor excitability). Music Condition II as compared to Music Condition I (i.e., more activating music) reduced MEP variability (i.e., corticomotor variability). Finally, years of formal music training did not significantly influence corticomotor excitability while listening to music. Overall, results revealed that unfamiliar music modulates motor cortical excitability but is dependent upon the form of music and possibly music preference. These results will be used to inform planned studies in healthy older adults and people with Parkinson’s disease.

Modulation of I-wave generating pathways by theta-burst stimulation: a model of plasticity induction.

Mechanisms underlying plasticity induction by repetitive transcranial magnetic stimulation protocols such as intermittent theta-burst stimulation (iTBS) remain poorly understood. Individual response to iTBS is associated with recruitment of late indirect wave (I-wave) generating pathways that can be probed by the onset latency of transcranial magnetic stimulation applied to primary motor cortex (M1) at different coil orientations. We found an association between late I-wave recruitment [reflected by anterior-posterior (AP)-lateromedial (LM) latency; i.e. the excess latency of motor-evoked potentials generated by transcranial magnetic stimulation with an AP orientation over the latency of motor-evoked potentials evoked by direct activation of corticospinal axons using LM stimulation] and changes in cortical excitability following iTBS, confirming previous studies. AP-LM latency significantly decreased following iTBS, and this decrease correlated with the iTBS-induced increase in cortical excitability across subjects. Plasticity in the motor network may in part derive from a modulation of excitability and the recruitment of late I-wave generating cortical pathways. Plasticity-induction following theta burst transcranial stimulation (TBS) varies considerably across subjects, and the underlying neurophysiological mechanisms remain poorly understood, representing a challenge for scientific and clinical applications. In human motor cortex (M1), recruitment of indirect waves (I-waves) can be probed by the excess latency of motor-evoked potentials elicited by transcranial magnetic stimulation with an anterior-posterior (AP) orientation over the latency of motor-evoked potentials evoked by direct activation of corticospinal axons using lateromedial (LM) stimulation, referred to as the 'AP-LM latency' difference. Importantly, AP-LM latency has been shown to predict individual responses to TBS across subjects. We, therefore, hypothesized that the plastic changes in corticospinal excitability induced by TBS are the result, at least in part, of changes in excitability of these same I-wave generating pathways. In 20 healthy subjects, we investigated whether intermittent TBS (iTBS) modulates I-wave recruitment as reflected by changes in the AP-LM latency. As expected, we found that AP-LM latencies before iTBS were associated with iTBS-induced excitability changes. A novel finding was that iTBS reduced AP-LM latency, and that this reduction significantly correlated with changes in cortical excitability observed following iTBS: subjects with larger reductions in AP-LM latencies featured larger increases in cortical excitability following iTBS. Our findings suggest that plasticity-induction by iTBS may derive from the modulation of I-wave generating pathways projecting onto M1, accounting for the predictive potential of I-wave recruitment. The excitability of I-wave generating pathways may serve a critical role in modulating motor cortical excitability and hence represent a promising target for novel repetitive transcranial magnetic stimulation protocols.

Abstract #161: When stimulating the unaffected (healthy) hemisphere in stroke patients makes sense

Research investigating the use of noninvasive electrical stimulation (e.g., transcranial direct current stimulation (tDCS)) has provided compelling evidence that such stimulation can modulate sensorimotor function, behavior and cognition, and even facilitate recovery of function after a focal brain injury. Our understanding of the mechanisms that lead to such changes is limited, and the influence of variables such as current strength, electrode montage and which regions of the brain to target is the focus of ongoing investigations. The degree of structural and/or functional injury to relevant systems (e.g., hand-motor system, speech-motor system, and swallowing system) and their pathways has been shown to determine natural outcome after a stroke and the response to an experimental intervention. However, the degree of bihemispheric organization of these systems and how redundant a system is organized in the brain seems to contribute to how well a particular system recovers. The premorbid organizational structure might also affect neuroplasticity, since plastic changes such as changes in synapses, axonal sprouting, changes in myelination, could affect the lesional and peri-lesional region as well as homotop regions of the contralesional hemisphere. Plasticity-enhancing tools might have an additive effect, although there are potentially multiple targets depending on the systems organizational structure. tDCS has been shown to modulate motor cortical excitability, modify a stroke-induced abnormal imbalance in inter-hemispheric inhibition, and increase synaptic plasticity if combined with a peripheral rehabilitation therapy. In this talk I will present the responses of different systems in the brain, contrasting a system that is more unihemispherically organized and has less redundancy and with a system that is more bihemispherically organized and has more redundancy. A redundant system has more options for targeted stimulation and electrode montages than a non-redundant system.

Altered modulation of motor cortical excitability by electrical stimulation over the cerebellum in chronic migraine

Previous structural neuroimaging studies suggest that patients with chronic migraine (CM) with and without medication overuse have abnormal structural changes within the cerebellum. In humans, cerebellum exerts a suppressive effect on the contralateral motor cortical response through a cerebello-thalamo-cortical pathway. We recruited 10 patients affected from CM without medication overuse and 10 heathy volunteers (HVs). After a conditioning single pulse high-voltage electrical stimulation delivered over the posterior surface of the mastoid processes, a TMS pulse was delivered over the contralateral motor cortex with 5, 7, 10, and 15 ms interstimulus interval (ISI) in random order. Motor cortical excitability changes were evaluated by amplitude changes of EMG responses from the FDI muscle to motor cortical stimulation. In HVs, suppression occurred at ISI of 5 ms and lasted few milliseconds. In CM patients, conditioning electric stimulation over the cerebellum did not reduce the size of MEPs to test TMS of the motor cortex at conditioning-test intervals of 5 ms. Here, we found neurophysiological evidence for dysfunctional cerebello-thalamo-cortical inhibitory pathway in CM. Whether these functional abnormalities are due to primary abnormal cerebellar inhibitory dysfunction or are secondary to a disrupted cerebellar-thalamic-cortical connectivity, remains to be determined.

Simultaneous stimulation using rTMS and tDCS produces the most effective modulation of motor cortical excitability in healthy subjects: A pilot study

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) can be used to modulate the excitability of the cortex, but instances of the two technologies being used to stimulate two positions of the human brain simultaneously are rare. As an initial investigation into the efficacy, feasibility and safety of such an approach, we compared the effects of simultaneously applying rTMS and cathodal tDCS with that of four other stimulation regimens (cathodal tDCS alone, rTMS alone, rTMS after cathodal tDCS, and sham stimulation) on a single population of subjects consisting of five healthy volunteers. Additionally, we also conducted SimNibs simulations of the electric field patterns that combined rTMS and cathodal tDCS would produce in cerebral cortices of the subjects.Compared with baseline levels, motor evoked potentials (MEPs; used here as a surrogate measure of cortical excitability) were significantly increased with all four ‘real’ stimulation methods (p < 0.05). Compared with sham measurements, significant increases in MEPs were also observed with rTMS alone (p = 0.0021), rTMS after tDCS (p = 0.0004), simultaneous rTMS and tDCS (p < 0.0001), but not with tDCS alone (p = 0.4182). We also determined that simultaneous rTMS and cathodal tDCS induced a significant increase in MEPs compared with the baseline or sham at all-time points, and resulted in the largest significant increase in MEPs. Our simulations show that applying cathodal tDCS at the standard stimulation position would cause only a 5.8% increase in the strength of the electric field produced by rTMS when the two techniques are used in conjunction. Our findings in this study indicate that combining rTMS with cathodal tDCS is not only safe, but highly-effective as well.

Multisensory stimulation to promote upper extremity motor recovery in stroke: A pilot study

Introduction Occupational therapists have been using various preparatory methods as part of the treatment sessions to prepare clients for occupational performance and participation in occupation. Studies have shown sensory stimulation both activates brain areas inducing cortical reorganization and modulates motor cortical excitability for the stimulated afferents, hence re-establishing the disrupted sensorimotor loop due to stroke. This pilot investigates the potential effects of using multisensory stimulation as a preparatory method prior to conventional training (CT) on upper-extremity motor recovery and self-care function in stroke patients. Method This was a quasi-randomized controlled pilot. Twelve participants (age in years = 67.17 + /−11.29) with upper extremity motor deficits were randomly allocated to multisensory therapy (n = 6) or conventional (n = 6) groups for 12-week training. Assessments were conducted at baseline and post-intervention using Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA), Manual Muscle Testing (MMT), Functional Test for the Hemiplegic Upper Extremity (Hong Kong version FTHUE-HK) and Modified Barthel Index (MBI). Results Significant between-group differences were shown in FMA ( p = 0.003), FTHUE-HK ( p = 0.028) and MMT ( p = 0.034). Conclusion Multisensory stimulation could be used as a preparatory method prior to CT in improving upper extremity motor recovery in stroke rehabilitation. Further well-designed larger scale studies are needed to validate the potential benefits of this application.

Modulation of motor cortical excitability with auditory stimulation.

Loud sounds have been demonstrated to increase motor cortex excitability when transcranial magnetic stimulation (TMS) is synchronized with auditory evoked N100 potential measured from electroencephalography (EEG). The N100 potential is generated by an afferent response to sound onset and feature analysis, and upon novel sound it is also related to the arousal reaction. The arousal reaction is known to originate from the ascending reticular activating system of the brain stem and to modulate neuronal activity throughout the central nervous system. In this study we investigated the difference in motor evoked potentials (MEPs) when deviant and novelty stimuli were randomly interspersed in a train of standard tones. Twelve healthy subjects participated in this study. Three types of sound stimuli were used: 1) standard stimuli (800 Hz), 2) deviant stimuli (560 Hz), and 3) novelty stimuli (12 different sounds). In each stimulus sequence 600 stimuli were given. Of these, 90 were deviant stimuli randomly placed between the standard stimuli. Each of 12 novel sounds was presented once in pseudorandomized order. TMS was randomly mixed with the sound stimuli so that it was either synchronized with the individual N100 or trailed the sound onset by 200 ms. All sounds elicited an increase in motor cortex excitability. The type of sound had no significant effect. We also demonstrated that TMS timed at 200-ms intervals caused a significant increment of MEPs. This contradicted our hypothesis that MEP amplitudes to TMS synchronized with N100 would be greater than those to TMS at 200 ms after a sound and remains unexplained. NEW & NOTEWORTHY We demonstrated modulation of motor cortical excitability with parallel auditory stimulus by combining navigated transcranial magnetic stimulation (TMS) with auditory stimuli. TMS was synchronized with auditory evoked potentials considered to be generated by the unconscious attention call process in the auditory system.

Four-pulse transcranial magnetic stimulation using multiple conditioning inputs. Normative MEP responses.

A four-pulse pattern of transcranial magnetic stimulation (TMS) was compared to traditional dual-pulse TMS for its ability to modulate motor cortical excitability. This novel pattern consisted of a three-pulse train of subthreshold conditioning pulses followed by a suprathreshold test pulse (i.e., SC-T). The intervals between these superconditioning (SC) pulses (1, 3, or 6ms) and the follow-on test pulse (1, 3, 10, or 25ms) were varied, and the resultant MEPs were compared to those elicited by: (1) single-pulse TMS; and (2) dual-pulse conditioning-test (C-T) TMS with either short (3ms) or long (10ms) intervals to elicit short-interval intracortical inhibition (SICI) or intracortical facilitation (ICF), respectively. Testing included abductor pollicis brevis (APB) and tibialis anterior (TA) in 15 neurologically normal adults. For superconditioning inputs, 10ms test intervals caused especially strong facilitation of the test MEP, while 1ms test intervals were particularly effective at causing inhibition of the test response. For both muscles and across all subjects, the most effective of the 12 SC-T inputs tested for causing either facilitation or inhibition was-with rare exception-superior to the dual-pulse TMS input for causing facilitation (i.e., ICF) or inhibition (i.e., SICI), while the overall magnitude of effect was more pronounced in APB compared to TA. Nevertheless, after normalization, the impact of a superconditioning input train on the test MEP was similar in APB and TA muscles, suggesting similar mechanisms of action. Limited findings from a single subject with amyotrophic lateral sclerosis (ALS) are included to further illustrate the potential advantages of using a train of conditioning pulses preceding a TMS test pulse to selectively investigate abnormal motor cortical excitatory and inhibitory circuitry.

Pallidal deep brain stimulation modulates cortical excitability and plasticity.

Internal globus pallidus (GPi) deep brain stimulation (DBS) relieves symptoms in dystonia patients. However, the physiological effects produced by GPi DBS are not fully understood. In particular, how a single-pulse GPi DBS changes cortical circuits has never been investigated. We studied the modulation of motor cortical excitability and plasticity with single-pulse GPi DBS in dystonia patients with bilateral implantation of GPi DBS. The cortical evoked potentials from DBS were recorded with electroencephalography. Transcranial magnetic stimulation with a conditioning test paired-pulse paradigm was used to investigate the effect of GPi DBS on the primary motor cortex. How GPi DBS might modulate the motor cortical plasticity was tested using a paired associative stimulation paradigm with repetitive pairs of GPi DBS and motor cortical stimulation at specific time intervals. GPi stimulation produced 2 peaks of cortical evoked potentials with latencies of ∼10 and ∼25 milliseconds in the motor cortical area. Cortical facilitation was observed at ∼10 milliseconds after single-pulse GPi DBS, and cortical inhibition was observed after a ∼25-millisecond interval. Repetitive pairs of GPi stimulation with cortical stimulation at these 2 time intervals produced long-term potentiation-like effects in the motor cortex. Single-pulse DBS modulates cortical excitability and plasticity at specific time intervals. These effects may be related to the mechanism of action of DBS. Combination of DBS with cortical stimulation with appropriate timing has therapeutic potential and could be explored in the future as a method to enhance the effects of neuromodulation for neurological and psychiatric diseases. Ann Neurol 2018;83:352-362.

Temporal alignment of anticipatory motor cortical beta lateralisation in hidden visual-motor sequences.

Performance improves when participants respond to events that are structured in repeating sequences, suggesting that learning can lead to proactive anticipatory preparation. Whereas most sequence‐learning studies have emphasised spatial structure, most sequences also contain a prominent temporal structure. We used MEG to investigate spatial and temporal anticipatory neural dynamics in a modified serial reaction time (SRT) task. Performance and brain activity were compared between blocks with learned spatial‐temporal sequences and blocks with new sequences. After confirming a strong behavioural benefit of spatial‐temporal predictability, we show lateralisation of beta oscillations in anticipation of the response associated with the upcoming target location and show that this also aligns to the expected timing of these forthcoming events. This effect was found both when comparing between repeated (learned) and new (unlearned) sequences, as well as when comparing targets that were expected after short vs. long intervals within the repeated (learned) sequence. Our findings suggest that learning of spatial‐temporal structure leads to proactive and dynamic modulation of motor cortical excitability in anticipation of both the location and timing of events that are relevant to guide action.

Modulation of cognitive cerebello-cerebral functional connectivity by lateral cerebellar continuous theta burst stimulation

Network connectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has revealed the contribution of distinct cerebellar lobules to an array of brain wide networks sub-serving motor and cognitive processes. As distinct cerebellar lobules form relatively accessible nodes of different brain networks, this raises the possibility for site-specific modulation of network connectivity using non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). Continuous theta burst transcranial magnetic stimulation (cTBS) induces long-lasting inhibition of cortical areas. Although previous studies have shown that cTBS of the lateral cerebellum modulates motor cortical excitability and improves symptoms in several movement disorders, the effect on cognitive domains has not been examined. We explored the immediate effects of cTBS in a sham-controlled study on the strength of intrinsic functional connectivity between cerebellar and cortical motor and cognitive regions in 12 participants. Lateral cerebellar cTBS significantly decreased functional connectivity with frontal and parietal cognitive regions, while connectivity with motor regions remained unaltered. Sham stimulation had no effect on either motor or cognitive connectivity. These results show that inhibitory cerebellar stimulation reduces intrinsic functional connectivity between different cortical areas, in keeping with the known connectivity pattern of the cerebellum. The results highlight the plasticity of cerebello-cerebral networks and indicate for the first time that this functional connectivity can be downregulated using an inhibitory neurostimulation paradigm. This may shed light on the pathophysiology of network dysfunction and is a potential treatment for cognitive and movement disorders.

Effects of visual deprivation on primary motor cortex excitability: a study on healthy subjects based on repetitive transcranial magnetic stimulation.

We investigated whether rapid changes in visual input or dark adaptation modify primary motor cortex (M1) excitability in healthy subjects. Repetitive transcranial magnetic stimulation (rTMS), consisting of 10 stimuli delivered at 5Hz at 120% of the resting motor threshold, was delivered over the M1 in 14 healthy volunteers. They were instructed to relax under eyes-open (EO) and eyes-closed (EC) resting conditions. Two experimental sessions were performed. In the first session, subjects were tested under both EO and EC conditions in order to determine whether short visual deprivation affected M1 excitability as tested through changes in the motor-evoked potential (MEP) amplitude during rTMS. In the second session, rTMS was delivered both under EO conditions with room lights on and after 30min of blindfolding to evaluate the effects of prolonged visual deprivation on M1 excitability. Short-term visual deprivation lasting 2.5s left the MEP facilitation unchanged during the 5-Hz rTMS trains, while 30min of blindfolding significantly reduced MEP facilitation. Short-term visual deprivation did not significantly affect M1 excitability, whereas dark adaptation reduced rTMS-induced MEP facilitation, modulating motor cortical excitability.

P258 Combining tDCS with prismatic adaptation for non invasive neuromodulation of the motor cortex

Introduction Prismatic adaptation (PA) shifts visual field laterally and induces lateralized deviations of spatial attention. Recently, it has been suggested that prismatic goggles are also able to modulate brain excitability ( Magnani, 2014 ), with cognitive after-effects documented even in tasks not necessarily spatial in nature ( Oliveri, 2013 ). Objectives The aim of the present study was to test whether prisms can modulate motor cortical excitability similarly as anodal transcranial direct current stimulation (tDCS) does; to test whether neuromodulatory effects obtained from tDCS and prismatic goggles could interact and induce homeostatic changes in brain excitability. Materials and methods Twenty-four subjects were submitted to single-pulse transcranial magnetic stimulation (TMS) over the right M1 to measure their Input–Output (IO) curve as a measure of cortical excitability ( Carroll, 2011 ). Assessment was made in three experimental groups: before and after rightward PA; before and after atDCS of the right M1; before and after rightward PA and atDCS of the right M1. Results A significant increase of the steepness of the IO curve slope on the right motor cortex was found following either rightward PA or atDCS; on the other hand, a decrease of the steepness of the IO curve slope was found after the combination of rightward PA and atDCS. Conclusion These findings suggest that PA could be an additional tool to modulate cortical plasticity in motor cortices and that an increase or a decrease in corticospinal excitability depends on the functional state of the M1 before or at the time of conditioning ( Lang, 2004 ).

EP 129. The effect of tDCS over M1 prior to and during implicit motor sequence learning

Motor learning is an essential skill allowing the acquisition of new movement patterns. Transcranial direct current stimulation (tDCS) has been shown to modulate neuronal excitability along with behavioural performance in a polarity-dependent manner. Besides polarity, the effects of tDCS on motor learning also vary with the timing of stimulation. In order to gain a better understanding regarding the optimal timing of tDCS application to modulate implicit motor sequence learning, motor-cortical tDCS was applied prior to and during training on a serial reaction time task (SRTT). The SRTT employs a fixed sequential pattern of button presses allowing the assessment of implicit motor sequence learning. A random pattern served as control condition. 36 healthy subjects were assigned to one of two experiments: tDCS was applied prior to (experiment 1) or during (experiment 2) SRTT training. Anodal vs. cathodal vs. sham tDCS was applied to the left primary motor cortex (M1) for ten minutes in a counterbalanced order. Reaction times of the right hand were measured at Baseline and after SRTT training (End of Acquisition (EoA)). Anodal tDCS prior to SRTT training yielded a beneficial effect on the acquisition of the motor sequence, i.e. reaction times decreased significantly from Baseline to EoA in the sequential pattern. Moreover, at EoA, reaction times were significantly faster following anodal as compared to cathodal tDCS. Reaction times of the random pattern were not differentially modulated by stimulation polarity indicating a sequence-specific effect. In contrast, tDCS applied during SRTT training did not differentially modulate the acquisition of the motor sequence. These results indicate that the timing of tDCS is a crucial parameter yielding distinct effects on implicit motor sequence learning. Anodal tDCS prior to SRTT training resulted in a facilitation emphasising a beneficial effect of increased left M1 excitability for the subsequent acquisition of a new motor sequence. In contrast, modulation of motor-cortical excitability by tDCS during SRTT training yielded no differential effects. This finding implies that tDCS effects may vary with the activation level during stimulation (rest vs. movement).

The Use and Abuse of Transcranial Magnetic Stimulation to Modulate Corticospinal Excitability in Humans.

The magnitude and direction of reported physiological effects induced using transcranial magnetic stimulation (TMS) to modulate human motor cortical excitability have proven difficult to replicate routinely. We conducted an online survey on the prevalence and possible causes of these reproducibility issues. A total of 153 researchers were identified via their publications and invited to complete an anonymous internet-based survey that asked about their experience trying to reproduce published findings for various TMS protocols. The prevalence of questionable research practices known to contribute to low reproducibility was also determined. We received 47 completed surveys from researchers with an average of 16.4 published papers (95% CI 10.8–22.0) that used TMS to modulate motor cortical excitability. Respondents also had a mean of 4.0 (2.5–5.7) relevant completed studies that would never be published. Across a range of TMS protocols, 45–60% of respondents found similar results to those in the original publications; the other respondents were able to reproduce the original effects only sometimes or not at all. Only 20% of respondents used formal power calculations to determine study sample sizes. Others relied on previously published studies (25%), personal experience (24%) or flexible post-hoc criteria (41%). Approximately 44% of respondents knew researchers who engaged in questionable research practices (range 32–70%), yet only 18% admitted to engaging in them (range 6–38%). These practices included screening subjects to find those that respond in a desired way to a TMS protocol, selectively reporting results and rejecting data based on a gut feeling. In a sample of 56 published papers that were inspected, not a single questionable research practice was reported. Our survey revealed that approximately 50% of researchers are unable to reproduce published TMS effects. Researchers need to start increasing study sample size and eliminating—or at least reporting—questionable research practices in order to make the outcomes of TMS research reproducible.