Transcranial Magnetic Stimulation Investigation Research Articles

The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.

Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.

An fMRI-Neuronavigated Chronometric TMS Investigation of V5 and Intraparietal Cortex in Motion Driven Attention.

The timing of networked brain activity subserving motion driven attention in humans is currently unclear. Functional MRI (fMRI)-neuronavigated chronometric transcranial magnetic stimulation (TMS) was used to investigate critical times of parietal cortex involvement in motion driven attention. In particular, we were interested in the relative critical times for two intraparietal sulcus (IPS) sites in comparison to that previously identified for motion processing in area V5, and to explore potential earlier times of involvement. fMRI was used to individually localize V5 and middle and posterior intraparietal sulcus (mIPS; pIPS) areas active for a motion driven attention task, prior to TMS neuronavigation. Paired-pulse TMS was applied during performance of the same task at stimulus onset asynchronies (SOAs) ranging from 0 to 180 ms. There were no statistically significant decreases in performance accuracy for trials where TMS was applied to V5 at any SOA, though stimulation intensity was lower for this site than for the parietal sites. For TMS applied to mIPS, there was a trend toward a relative decrease in performance accuracy at the 150 ms SOA, as well as a relative increase at 180 ms. There was no statistically significant effect overall of TMS applied to pIPS, however, there appeared a potential trend toward a decrease in performance at the 0 ms SOA. Overall, these results provide some patterns of potential theoretical interest to follow up in future studies.

The number of stimuli required to reliably assess corticomotor excitability and primary motor cortical representations using transcranial magnetic stimulation (TMS): a systematic review and meta-analysis

BackgroundTranscranial magnetic stimulation (TMS) is a non-invasive means by which to assess the structure and function of the central nervous system. Current practices involve the administration of multiple stimuli over target areas of a participant’s scalp. Decreasing the number of stimuli delivered during TMS assessments would improve time efficiency and decrease participant demand. However, doing so may also compromise the within- or between-session reliability of the technique. The aim of this review was therefore to determine the minimum number of TMS stimuli required to reliably measure (i) corticomotor excitability of a target muscle at a single cranial site and (ii) topography of the primary motor cortical representation of a target muscle across multiple cranial sites.MethodsDatabase searches were performed to identify diagnostic reliability studies published before May 2015. Two independent reviewers extracted data from studies employing single-pulse TMS to measure (i) the corticomotor excitability at a single cranial site or (ii) the topographic cortical organisation of a target muscle across a number of cranial sites. Outcome measures included motor evoked potential amplitude, map volume, number of active map sites and location of the map centre of gravity.ResultsOnly studies comparing the reliability of varying numbers of stimuli delivered to a single cranial site were identified. Five was the lowest number of stimuli that could be delivered to produce excellent within-session motor evoked potential (MEP) amplitude reliability (intraclass correlation coefficient (ICC) = 0.92, 95% CI 0.87 to 0.95). Ten stimuli were required to achieve consistent between-session MEP amplitudes among healthy participants (ICC = 0.89, 95% CI 0.76 to 0.95). However, between-session reliability was influenced by participant characteristics, intersession intervals and target musculature.ConclusionsFurther exploration of the reliability of multi-site TMS mapping is required. Five stimuli produce reliable MEP recordings during single-site TMS investigations involving one session. For single-site analyses involving multiple sessions, ten stimuli are recommended when investigating corticomotor excitability in healthy participants or the upper limb musculature. However, greater numbers of stimuli may be required for clinical populations or assessments involving the lower limb.Systematic review registrationPROSPERO CRD42015024579

Dissociation of the rostral and dorsolateral prefrontal cortex during sequence learning in saccades: a TMS investigation.

This experiment sought to find whether differences exist between the dorsolateral prefrontal cortex (DLPFC) and the medial rostral prefrontal cortex (MRPFC) for performing stimulus-independent and stimulus-oriented tasks, respectively. To find a causal relationship in these areas, we employed the use of trans-cranial magnetic stimulation (TMS). Prefrontal areas were stimulated whilst participants performed random or predictable sequence learning tasks at stimulus onset (1st presentation of the sequence only for both Random and Predictable), or during the inter-sequence interval. Overall, we found that during the predictable task a significant decrease in saccade latency, gain and duration was found when compared to the randomised conditions, as expected and observed previously. However, TMS stimulation in DLPFC during the delay in the predictive sequence learning task reduced this predictive ability by delaying the saccadic onset and generating abnormal reductions in saccadic gains during prediction. In contrast, we found that stimulation during a delay in MRPFC reversed the normal effects on peak velocity of the task with the predictive task revealing higher peak velocity than the randomised task. These findings provide causal evidence for independent functions of DLPFC and MRPFC in performing stimulus-independent processing during sequence learning in saccades.

Different cerebral plasticity of intrinsic and extrinsic hand muscles after peripheral neurotization in a patient with brachial plexus injury: A TMS and fMRI study

Contralateral C7 (CC7) neurotization has been an important approach for brachial plexus injury (BPI). Patients can achieve relatively good grasping function driven by the proximal extrinsic hand muscle (flexor digitorum, FD) after CC7 neurotization, whereas the thumb opposition function driven by the distal intrinsic muscle (abductor pollicis brevis, APB) is poor. The present study aimed to investigate the brain reorganization patterns of the recovery processes of intrinsic and extrinsic hand functions after repairing the median nerve by CC7 neurotization. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to evaluate the cerebral plasticity in one BPI patient after CC7 neurotization. After the CC7 neurotization, the patient showed improvements in the paralyzed hand. Combination of TMS and fMRI investigations demonstrated different cortical reshaping patterns of APB and FD. It was also found that the activated cortical areas of FD were located in bilateral motor cortices, but the area of APB was only located in ipsilateral motor cortex. The cerebral plasticity procedure appeared to be different in the gross and fine motor function recovery processes. It provided a new perspective into the cerebral plasticity induced by CC7 neurotization.

Transcranial Magnetic Stimulation to Investigate Motor Cortical Circuitry and Plasticity in Spinal Cord Injury

Spinal cord injury may lead to complete or incomplete damage to ascending sensory and/or descending motor pathways and therefore alter neural circuits of the primary motor cortex. Transcranial magnetic stimulation (TMS) is a valuable tool for investigating the function of neural circuitry within primary motor cortex and also for promoting plasticity in these circuits for the ultimate purpose of improving the control of movement. For spinal cord injury, information about motor cortical circuits and TMS approaches to induce plasticity in these circuits is steadily emerging. In this review, we discuss TMS investigations of motor cortical circuitry and review TMS approaches to promote plasticity in motor cortical circuitry in spinal cord injury.

Musical groove modulates motor cortex excitability: A TMS investigation

Groove is often described as a musical quality that can induce movement in a listener. This study examines the effects of listening to groove music on corticospinal excitability. Musicians and non-musicians listened to high-groove music, low-groove music, and spectrally matched noise, while receiving single-pulse transcranial magnetic stimulation (TMS) over the primary motor cortex either on-beat or off-beat. We examined changes in the amplitude of the motor-evoked potentials (MEPs), recorded from hand and arm muscles, as an index of activity within the motor system. Musicians and non-musicians rated groove similarly. MEP results showed that high-groove music modulated corticospinal excitability, whereas no difference occurred between low-groove music and noise. More specifically, musicians’ MEPs were larger with high-groove than low-groove music, and this effect was especially pronounced for on-beat compared to off-beat pulses. These results indicate that high-groove music increasingly engages the motor system, and the temporal modulation of corticospinal excitability with the beat could stem from tight auditory–motor links in musicians. Conversely, non-musicians’ MEPs were smaller for high-groove than low-groove music, and there was no effect of on- versus off-beat pulses, potentially stemming from suppression of overt movement. In sum, high-groove music engages the motor system, and previous training modulates how listening to music with a strong groove activates the motor system.

Increased cortical excitability after selective REM sleep deprivation in healthy humans: A transcranial magnetic stimulation study

REM sleep has antiepileptogenic properties whereas, its loss is known to have a proconvulsive role. However, the mechanisms underlying the proepileptogenic effects of REM sleep deprivation are yet not fully understood. The aim of our study was to evaluate the effects of selective REM sleep deprivation (SRD) on cortical excitability in healthy subjects by means of transcranial magnetic stimulation (TMS). Ten normal subjects underwent three TMS sessions: (1) in baseline condition (BL), (2) after SRD by awakening them at each REM sleep onset and (3) after non-rapid eye movement sleep awakenings (NREM-A) as control for potential non-specific effects of interruptions. The TMS investigation included two protocols: (a) the evaluation of motor evoked potentials (MEPs) and silent period (SP) parameters, recorded in response to single pulse magnetic stimulation; (b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-10 ms. After SRD the principal finding observed using single pulse TMS was a significant reduction in the duration of SP whereas, a reduction of intracortical inhibition was found, using the paired-pulse TMS. TMS parameters did not show significant changes after NREM-A with respect to BL. SRD may influence cortical excitability with a reduction of inhibitory intracortical mechanisms, thus supporting the proconvulsant role of REM loss.

Programs for action in superior parietal cortex: A triple-pulse TMS investigation

Converging evidence from neurological patients and functional brain imaging studies strongly supports the notion that the posterior parietal cortex (PPC), especially in the left hemisphere, plays a critical role in both the programming (i.e., setting the initial movement parameters of the reach) and the online control of goal-directed reaching movements. Importantly, however, there is no clear consensus on how different subregions within the PPC contribute to the programming and online control of reaching. In the current study, we investigated the role of the inferior (IPL) and superior (SPL) parietal lobules in reach programming using MRI-guided event-related transcranial magnetic stimulation (TMS). Specifically, we applied triple-pulse (tp) TMS to either the left IPL or the left SPL at different time points during reaching movements either at target onset (programming) or at movement onset (online control) while participants (n=16) made pointing movements to targets in the periphery without visual feedback of the moving hand. Stimulating the SPL but not the IPL resulted in a significant increase in endpoint errors when tp-TMS was applied during the programming phase compared to the online control phase. In short, these data demonstrate that the SPL plays a critical role in real-time movement programming.

The role of the prefrontal cortex in controlling gender-stereotypical associations: A TMS investigation

Stereotypes associated with gender, race, ethnicity and religion are powerful forces in human social interactions. Previous neuroimaging and neuropsychological studies point to a role of the prefrontal cortex in controlling stereotypical responses. Here we used transcranial magnetic stimulation (TMS) in combination with an Implicit Association Test (IAT) to highlight the possible causal role of the left dorsolateral prefrontal cortex (DLPFC) and the right anterior dorsomedial prefrontal cortex (aDMPFC) in controlling gender-stereotypical responses. Young male and female participants were tested. Our results showed that applying TMS over the left DLPFC and the right aDMPFC increased the gender-stereotypical bias in male participants compared to when TMS was applied to a control site (vertex). This suggests that both the left DLPFC and the right aDMPFC play a direct role in stereotyping. Females did not show a significant gender bias on the IAT; correspondingly their responses were unaffected by TMS.

Neurophysiologische Diagnostik interhemisphärischer motorischer Bahnen bei neurodegenerativen Erkrankungen

The corpus callosum (CC) is the morphological correlate of inter-hemispheric connectivity. Its integrity is of great importance for motor function and inter-hemispheric coordination of bimanual movements. Callosal fibre tracts show a high vulnerability as they are involved in number of neurodegenerative disease like parkinsonian syndromes and amyotrophic lateral sclerosis, even at early stages of the diseases. The integrity of callosal fibre bundles may be investigated by magnetic resonance imaging techniques and electrophysiologically by transcranial magnetic stimulation (TMS) investigating the transcallosal inhibition (TI). TMS investigation of the TI may be performed by measurement of the ipsilateral silent period (iSP). Most common findings are a loss or a prolongation of the iSP latency. Alternatively, a double pulse paradigm may be used to demonstrate altered TI. Furthermore, the transcallosal conduction time may be lengthened. TMS investigation of TI may a helpful diagnostic tool and may give new insights into the pathophysiology.

Combining TMS and fMRI: From ‘virtual lesions’ to functional-network accounts of cognition

Transcranial magnetic stimulation (TMS) is increasingly used in Cognitive Neuroscience to study functional contributions of a stimulated brain region to cognitive and perceptual processing. TMS-related behavioural effects are often interpreted as reflecting selective disruption of processing primarily within the stimulated region itself. This approach is now being extended by studies that combine TMS with concurrent neuroimaging measures, such as functional magnetic resonance imaging (fMRI). We discuss some recent combined TMS–fMRI studies and their implications for TMS investigations of cognition and perception. An emerging theme is that TMS does not affect only the stimulated region, but can also influence remote brain areas interconnected with the stimulation site. Such ‘network’ effects of TMS can be anatomically specific, but also context-dependent, changing with the current functional state of the targeted network rather than simply reflecting just fixed, context-invariant anatomical connectivity. Perceptual and behavioural effects of TMS may correspondingly involve TMS influences on remote interconnected brain regions, not solely on the stimulated region itself. Thus, TMS can now be used to study the consequences of functional interactions between the stimulated region and other parts of the network. This may lead beyond strictly modular views of brain function, that emphasize functional properties of single brain areas, towards new perspectives on how functional interactions between remote but interconnected brain regions may support perception and cognition.

Increasing Cortical Excitability: A Possible Explanation For The Proconvulsant Role Of Sleep Deprivation

Sleep deprivation (SD) is known to facilitate both seizures and interictal epileptiform abnormalities. For this reason, it is often used in the routine diagnostic workup of epileptic patients as an activating procedure for eliciting epileptiform and/or seizure patterns in their EEGs. In order to evaluate the effects of SD on cortical excitability, we studied the effects of sleep loss on healthy subjects by transcranial magnetic stimulation (TMS). Seven normal subjects underwent TMS examination in baseline condition and after total sleep deprivation. The TMS investigation included two protocols: a) the evaluation of motor evoked potential and silent period parameters recorded in response to single-pulse magnetic stimulation; and b) the evaluation of the time course of intracortical motor activity tested with paired-pulse TMS applied at inter-stimulus intervals of 1-6 ms. Clinical neurophysiology laboratory in a general hospital. None. After SD, the principal finding observed using single-pulse TMS was a decrease of the silent period duration, whereas a reduction of the intracortical inhibition, in particular at inter-stimulus intervals 1 and 2 ms, was found, using the paired-pulse TMS. Our findings suggest that SD may modify cortical excitability, seen as the balance between inhibitory and excitatory cortical phenomena, which could reduce the epileptic threshold.

Motor control in simple bimanual movements: a transcranial magnetic stimulation and reaction time study

Objective: Simple reaction time (RT) can be influenced by transcranial magnetic stimulation (TMS) to the motor cortex. Since TMS differentially affects RT of ipsilateral and contralateral muscles a combined RT and TMS investigation sheds light on cortical motor control of bimanual movements. Methods: Ten normal subjects and one subject with congenital mirror movements (MM) were investigated with a RT paradigm in which they had to move one or both hands in response to a visual go-signal. Suprathreshold TMS was applied to the motor cortex ipsilateral or contralateral to the moving hand at various interstimulus intervals (ISIs) after presentation of the go-signal. EMG recordings from the thenar muscles of both hands were used to determine the RT. Results: TMS applied to the ipsilateral motor cortex shortened RT when TMS was delivered simultaneously with the go-signal. With increasing ISI between TMS and go-signal the RT was progressively delayed. This delay was more pronounced if TMS was applied contralateral to the moving hand. When normal subjects performed bimanual movements the TMS-induced changes in RT were essentially the same as if they had used the hand in an unimanual task. In the subject with MM, TMS given at the time of the go-signal facilitated both the voluntary and the MM. With increasing ISI, however, RT for voluntary movements and MM increased in parallel. Conclusions: Ipsilateral TMS affects the timing of hand movements to the same extent regardless of whether the hand is engaged in an unimanual or a bimanual movement. It can be concluded, therefore, that in normal subjects simple bimanual movements are controlled by each motor cortex independently. The results obtained in the subject with MM are consistent with the hypothesis that mirror movements originate from uncrossed corticospinal fibres. The alternative hypothesis that a deficit in transcallosal inhibition leads to MM in the contralateral motor cortex is not compatible with the presented data, because TMS applied to the motor cortex ipsilateral to a voluntary moved hand affected voluntary movements and MM to the same extent.

The motor syndrome associated with exaggerated inhibition within the primary motor cortex of patients with hemiparetic.

Following transcranial magnetic stimulation (TMS) at stimulation strength of 1.5 times the resting motor threshold, a silent period (SP) of approximately 180 ms duration can be observed in surface EMG-registrations of tonically activated small hand muscles. This SP is believed to be generated cortically and can be prolonged in stroke patients, but it is not known whether a prolongation of the SP has any functional significance. In order to answer the question of whether enhanced cortical inhibition can contribute to pathophysiology of motor dysfunction we studied stroke patients with clearly prolonged SP durations in the first dorsal interosseus muscle (> 2 times that of the intact side), but with normal magnetically evoked motor potentials. Sixteen patients out of a cohort of 174 consecutive patients presenting with acute hemiparetic stroke fulfilled the inclusion criteria. Serial TMS investigations were performed for up to 2 years post-stroke. In all patients, the SP duration decreased in parallel with clinical improvement. In two patients, intermittent clinical deterioration was accompanied by an increase in the SP duration. In four patients, in addition to a markedly prolonged SP duration, the phenomenon of a complete inability to initiate voluntary muscle activity for several seconds, following TMS, could be observed in a number of trials ('motor arrest'). Detailed clinical analysis revealed that, in addition to hemiparesis, distinct motor disturbances in patients with SP prolongation could be observed. These motor disturbances resembled those of motor neglect and were characterized by motivationally dependent under-utilization of the affected arm, impairment of movement initiation, inability to maintain a constant force level and to scale forces, and impairment of individual finger movements. In 12 of the 16 patients at least one additional behavioural manifestation of neglect was present. We suggest that in stroke patients severe motor dysfunction may be caused by hyperactivity of cortical inhibitory interneurons rather than by direct lesions of descending motor tracts. Cortical hyperinhibition may, in turn, result from damage to any of a number of afferent pathways to the motor cortex which modulate local interneuronal activity.