Hand Area Of Motor Cortex Research Articles

Navigated TMS combined with EEG in mild cognitive impairment and Alzheimer's disease: A pilot study

Our aim was to assess the potential of navigated transcranial magnetic stimulation (TMS)-evoked electroencephalographic (EEG) responses in studying neuronal reactivity and cortical connectivity in Alzheimer's disease (AD) and in mild cognitive impairment (MCI). We studied 14 right-handed subjects: five patients with AD, five patients with MCI and four healthy controls. Fifty TMS-pulses at an intensity of 110% of individually determined motor threshold were delivered to the hand area of primary motor cortex (M1) with navigated brain stimulation (NBS). Spreading of primary NBS-evoked neuronal activity was monitored with a compatible 60-channel EEG, and analyzed in time, frequency and spatial-domains. We found significantly reduced TMS-evoked P30 (time-locked response 30ms after the magnetic stimulation) in the AD subjects. This reduction was seen in the temporo-parietal area ipsilateral to stimulation side as well as in the contralateral fronto-central cortex corresponding to the sensorimotor network, which is anatomically interconnected with the stimulated M1. In addition, there was a significant decrease in the N100 amplitude in the MCI subjects when compared with the control subjects. Thus, the combination of NBS and EEG revealed prominent changes in functional cortical connectivity and reactivity in the AD subjects. This pilot study suggests that the method may provide a novel tool for examining the degree and progression of dementia.

Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation

Paired associative stimulation (PAS) can increase motor cortical excitability, possibly by long-term potentiation (LTP)-like mechanisms. As the capability of the cortex for plasticity decreases with age, we were interested here in testing interindividual variability and age-dependency of the PAS effect. Motor-evoked potentials (MEPs) were recorded from the resting right abductor pollicis brevis muscle before and for 30 min after PAS in 27 healthy subjects (22-71 years of age). PAS consisted of 225 pairs (rate, 0.25 Hz) of right median nerve stimulation followed at an interval equaling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms by transcranial magnetic stimulation of the hand area of left primary motor cortex (PAS(N20+2)). The PAS(N20+2)-induced changes in MEP amplitude (ratio post PAS/pre PAS) were highly variable (1.00 +/- 0.07, range 0.36-1.68). Fourteen subjects showed the expected LTP-like MEP increase (responders) while 13 subjects showed a long-term depression (LTD)-like MEP decrease (non-responders). Responders had a significantly lower resting motor threshold (RMT) and minimum stimulus intensity to elicit MEPs of 1 mV (MEP(1 mV)) than non-responders. RMT and MEP(1 mV) correlated significantly negatively with the PAS(N20+2) effect. The absolute PAS(N20+2) effect size irrespective of its direction decreased with age (r = -0.57, P = 0.002), i.e., LTP-like and LTD-like plasticity were large in young subjects but substantially smaller in elderly subjects. In conclusion, measures of motor cortical excitability (RMT, MEP(1 mV)) and age determine direction and magnitude of PAS effects in individual subjects.

T-DCS-preconditioned low-frequency rTMS of the hand area of M1 to improve bradykinesia in Parkinson's disease

Introduction: State of the art treatment for idiopathic Parkinson-Syndrom (IPS) is dopaminergic medication or deep brain stimulation. Both strategies allow a distinct amelioration of symptoms, but have side effects or are invasive. Transcranial direct current stimulation (tDCS) and repetetive transcranial magnetic stimulation (rTMS) are safe, non-invasive methods to modulate cortical excitability. We investigated the effect of tDCS-preconditioned 1Hz rTMS over the hand area of the primary motor cortex to improve bradykinesia of the upper limb in IPS.

Isolated ring finger palsy due to cortical infarction of the primary motor cortex hand area

Isolated ring finger palsy due to cortical infarction of the primary motor cortex hand area

Contact forces evoked by transcranial magnetic stimulation of the motor cortex in a multi-finger grasp

Transcranial magnetic stimulation (TMS) is a tool of choice to study the functionality of the corticospinal pathway. In this study, we used single-pulse TMS at different intensities and during different levels of grasping force, to stimulate the hand area of the left primary motor cortex (M1). We measured, the TMS-evoked forces, or motor evoked forces (MEFs) in a multi-fingered three-point grasp in addition of the conventional motor evoked potentials (MEPs) from the right forearm and intrinsic hand muscles. This paper aims at presenting the viability of this innovative approach and some preliminary results. The timing (i.e., latencies and peak times), amplitudes and directions of the MEF were analyzed. We found that the TMS evoked synergistic increases of the force magnitudes, akin to those observed when participants voluntarily increased the grip force. The MEF sizes and MEP amplitudes increased with TMS intensity in most cases. The grip force (which measures the overall force involved in the grasp) and the net force (which measures the net effect of all contact forces exerted on the object) seem to be differently affected by single TMS pulses of the motor cortex.

Action verbs and the primary motor cortex: A comparative TMS study of silent reading, frequency judgments, and motor imagery

Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMSM1 vs. TMSvertex) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation within the same experiment: subjects indicated with their left foot when they (i) had finished reading, (ii) had judged whether the corresponding movement involved a hand rotation after simulating the hand movement, and (iii) had judged whether they would frequently encounter the action verb in a newspaper (TASK: silent reading, motor imagery, and frequency judgment). Response times were compared between TMSM1 and TMSvertex, both applied at different time points after stimulus onset (DELAY: 150, 300, 450, 600, and 750ms).TMSM1 differentially modulated task performance: there was a significant facilitatory effect of TMSM1 for the imagery task only (about 88ms), with subjects responding about 10% faster (compared to TMSvertex). In contrast, response times for silent reading and frequency judgments were unaffected by TMSM1. No differential effect of the time point of TMSM1 was observed.The differential effect of TMSM1 when subjects performed a motor imagery task (relative to performing silent reading or frequency judgments with the same set of verbs) suggests that the primary motor cortex is critically involved in processing action verbs only when subjects are simulating the corresponding movement. This task-dependent effect of hand motor cortex TMS on the processing of hand-related action verbs is discussed with respect to the notion of embodied cognition and the associationist theory.

Theta-burst stimulation: Remote physiological and local behavioral after-effects

Theta-burst stimulation (TBS), a novel repetitive transcranial magnetic stimulation (TMS) protocol, is capable of suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after the end of a conditioning train over the motor cortex. It remains unknown whether TBS leads to effects on motor cortical excitability when applied to contralateral brain sites distant but connected to motor cortex and whether TBS triggers measurable changes in force control. Subjects received bursts (50 Hz) of three subthreshold magnetic stimuli repeated at 5 Hz for 20 s (TBS-300) or 40 s (TBS-600) over the hand area of the left motor cortex (M1 LEFT). With TBS-300, conditioning of right motor cortex (M1 RIGHT), right dorsal premotor cortex (PMd RIGHT), and a mid-occipital (MO) region also were tested. Corticospinal excitability was probed by evoking MEPs in abductor pollicis brevis (APB) muscle by single suprathreshold stimuli over M1 LEFT or M1 RIGHT before and after TBS. Force level control was assessed in an isometric right thumb abduction task. With TBS-600, the time course of physiological and behavioral changes was monitored. TBS over either of the motor cortices reduced the amplitude of MEP in the contralateral APB and increased it in the ipsilateral APB. In contrast, conditioning TBS over PMd RIGHT or MO did not modify MEP size. Post-TBS right thumb force level control was impaired, with contralateral M1 LEFT stimulation only, for a duration of at least 5 min. TBS may induce remote physiological effects and reveals local functional properties of the underlying brain region.

Isolated Hand Palsy Due to Cortical Infarction: Localization of the Motor Hand Area

To evaluate the cortical presentation of the hand area according to MRI images of the infarcted area in patients who have predominantly hand weakness. "Pseudoperipheral palsy" is an old term employed to describe a rare clinical picture consisting of predominant weakness of the hand in association with cerebral infarction. Because the organization of the cortical efferent area of the hand has not been fully defined, this phenomenon merits attention. Recent advances in functional imaging have stimulated renewed interest in the cortical mapping of various body parts, particularly that of the hand. The patients who had isolated hand palsy due to cerebral infarction underwent clinical examination and cerebral MRI investigation to locate the exact lesion site. Eight patients (6 men, 2 women) aged 55 to 80 years (mean 69 years) were included in this study. All had at least one risk factor for cerebrovascular disease. All our 8 patients presented with hand palsy and lesions were detected in the contralateral precentral gyrus in all cases. The lesions were located in the middle to lower portion of the anterior wall of the central sulcus just posterior to the intersection of the superior frontal and precentral sulci. Our findings indicate that the hand area in the cerebral motor cortex is located in the middle to lower portion of the anterior wall of the central sulcus, that is, in Brodmann area 4. We present our 8 patients showing isolated hand palsy due to a discrete cortical infarction on MRI to expand the knowledge about cortical localization of the hand area.

Dynamics of cortical neurovascular coupling analyzed by simultaneous DC-magnetoencephalography and time-resolved near-infrared spectroscopy

Functional magnetic resonance imaging (fMRI) visualizes activated brain areas with a high spatial resolution. The activation signal is determined by the local change of cerebral blood oxygenation, blood volume and blood flow which serve as surrogate marker for the neuronal signal itself. Here, the complex coupling between these parameters and the electrophysiologic activity is characterized non-invasively in humans during a simple motor task using simultaneously DC-magnetoencephalography (DC-MEG), for the detection of neuronal signals, and time-resolved near-infrared spectroscopy (trNIRS), for cortical metabolic/vascular responses: over the left primary motor cortex hand area of healthy subjects DC-fields and trNIRS parameters followed closely the 30 s motor task cycles, i.e., finger movements of the right hand alternating with rest. In subjects showing a sufficient signal-to-noise ratio the analysis of variance of photon time of flight proved that the task-related trNIRS changes originated from the cortex. While onset and relaxation started simultaneously, trNIRS signals reached 50% of the maximum level 1–4 s later than the DC-MEG-signals. The non-invasive ‘dual’ setup helps to characterize simultaneously the two complementary aspects of the ‘hemodynamic inverse problem’, i.e., the coupling of neuronal and vascular/metabolic signals, in healthy subjects and provides a new analysis perspective for pathophysiological coupling concepts in diverse diseases, e.g., in stroke, hypertension and Alzheimer’s disease.

Corticospinal control of the thumb–index grip depends on precision of force control: a transcranial magnetic stimulation and functional magnetic resonance imagery study in humans

The corticospinal system (CS) is well known to be of major importance for controlling the thumb-index grip, in particular for force grading. However, for a given force level, the way in which the involvement of this system could vary with increasing demands on precise force control is not well-known. Using transcranial magnetic stimulation and functional magnetic resonance imagery, the present experiments investigated whether increasing the precision demands while keeping the averaged force level similar during an isometric dynamic low-force control task, involving the thumb-index grip, does affect the corticospinal excitability to the thumb-index muscles and the activation of the motor cortices, primary and non-primary (supplementary motor area, dorsal and ventral premotor and in the contralateral area), at the origin of the CS. With transcranial magnetic stimulation, we showed that, when precision demands increased, the CS excitability increased to either the first dorsal interosseus or the opponens pollicis, and never to both, for similar ongoing electromyographic activation patterns of these muscles. With functional magnetic resonance imagery, we demonstrated that, for the same averaged force level, the amplitude of blood oxygen level-dependent signal increased in relation to the precision demands in the hand area of the contralateral primary motor cortex in the contralateral supplementary motor area, ventral and dorsal premotor area. Together these results show that, during the course of force generation, the CS integrates online top-down information to precisely fit the motor output to the task's constraints and that its multiple cortical origins are involved in this process, with the ventral premotor area appearing to have a special role.

Structural Plasticity: Rewiring the Brain

Experience may shape brain structure. Recent studies in which brain connections were traced in monkeys who had learnt a new skill or recovered from an injury suggest that extensive rewiring is possible, even in the adult brain.

Excitation threshold of the motor cortex estimated with transcranial magnetic stimulation electroencephalography

The excitation threshold of the human motor cortex was estimated on the basis of electroencephalographic responses evoked by transcranial magnetic stimulation. The hand area of the primary motor cortex was stimulated at 10 intensities, for seven healthy individuals. The four dominant peaks of the overall brain response could be reliably determined when stimulation was intense enough to induce a cortical electric field of approximately 33-44 mV/mm. This may be estimated as the threshold for evoking measurable brain activity by motor-cortex transcranial magnetic stimulation. The remarkably low threshold reflects the excellent sensitivity of the combination of transcranial magnetic stimulation and electroencephalography for the study of neuronal function of the cortex.

Sensorimotor memory for fingertip forces during object lifting: The role of the primary motor cortex

When an object is repetitively lifted, the scaling of grip force is influenced by the mechanical properties of the preceding lift, suggesting the formation of a sensorimotor memory. Similar effects on force scaling are observed when the subsequent lift is performed with the hand opposite to the preceding lift. We used neuronavigated rTMS over the hand area of the dominant primary motor cortex to investigate its role in setting up sensorimotor memory. After ten lifts of a novel object with the dominant hand either rTMS or a period of motor rest commenced, until another set of lifts was performed with either the same or opposite hand. Compared to motor rest, rTMS caused underestimation of the object's weight when given 10 or 30s after the previous set of lifts, but overestimation of the object's weight when applied 60 or 120s after the previous set of lifts, regardless of the hand performing the lift. Our interpretation of the data is that (a) the primary motor cortex is essential for setting up sensorimotor memory related to the mechanical object properties during manipulation and (b) rTMS can induce bidirectional changes of grip efficiency within the dynamics of sensorimotor integration.

Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's cramp

Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients.

Modular Organization of Finger Movements by the Human Central Nervous System

The motor system may generate automated movements, such as walking, by combining modular spinal motor synergies. However, it remains unknown whether a modular neuronal architecture is sufficient to generate the unique flexibility of human finger movements, which rely on cortical structures. Here we show that finger movements evoked by transcranial magnetic stimulation (TMS) of the primary motor cortex reproduced distinctive features of the spatial representation of voluntary movements as identified in previous neuroimaging studies, consistent with naturalistic activation of neuronal elements. Principal component analysis revealed that the dimensionality of TMS-evoked movements was low. Principal components extracted from TMS-induced finger movements resembled those derived from end-postures of voluntary movements performed to grasp imagined objects, and a small subset of them was sufficient to reconstruct these movements with remarkable fidelity. The motor system may coordinate even the most dexterous movements by using a modular architecture involving cortical components.

Associative Plasticity in Human Motor Cortex During Voluntary Muscle Contraction

TMS pulses over the hand area of motor cortex activate different subpopulations of synaptic connections if the direction of the induced current in the brain is reversed from posterior-anterior (PA) direction to anterior-posterior (AP). We tested whether this also made a difference to the after-effects of paired associative stimulation (PAS: ulnar nerve stimulation followed 25 ms later by a transcranial magnetic stimulation pulse). If 50 pairs of stimuli (0.1 Hz) were applied using conventional suprathreshold PA-PAS in resting subjects, there was no effect on motor-evoked potentials (MEPs) in the first dorsal interosseous muscle. In contrast if the same number of pulses were given while subjects made a small tonic (5% maximum) contraction, MEPs were facilitated and resting motor threshold reduced when AP but not PA pulses were used. Subsequent experiments employed subthreshold TMS (95% of the active motor threshold) during voluntary muscle contraction. MEP facilitation accompanied by reduced AP threshold occurred when PAS was given using AP pulses (AP-Sub-PAS), whereas PAS using PA pulses (PA-Sub-PAS) had no excitatory effect. There was no facilitation if the ulnar nerve stimulus was replaced by digital nerve stimulation. There was a tendency for short interval intracortical inhibition (SICI) to decrease and intracortical facilitation (ICF) to increase after AP-Sub-PAS. We propose that the increased effectiveness of AP-Sub-PAS over PA-Sub-PAS is due to the fact that AP TMS more readily activates I3 inputs to corticospinal neurons and hence that these are an important component of associative plasticity in the human motor cortex.

Intracortical inhibition and facilitation in adolescents with idiopathic scoliosis

Objective: The etiology of adolescent idiopathic scoliosis (AIS) is still unknown. As this spine deformity parallels spine deformities in patients with Parkinson's disease or dystonia, it is discussed that AIS might be caused by a movement disorder, e.g. a form of dystonia. In dystonia short-interval intracortical inhibition (SICI) of motor cortex is significantly reduced compared to healthy subjects. This study assessed SICI and intracortical facilitation (ICF) by transcranial magnetic stimulation (TMS) in patients with AIS and age-matched healthy subjects. Methods: In 11 patients with AIS (15.3±1.7; 7f, 3m; right convex thoracic scoliosis) and 9 healthy subjects (15.6±2.3 years; 8f, 1m) SICI and ICF were evaluated with a paired pulse paradigm (interstimulus intervals (ISI) of 1, 2, 3, 10 and 15 ms). For each ISI, 8 stimuli were randomly applied with a figure-of-8-coil (MagStim Co, Uk) over the left and right hemispheric hot spots of the motor cortex hand area. According to the Kujirai protocol (J Physiol 1993, 471: 501), the intensity of the conditioning stimulus was set at 80% of the resting motor threshold and the test stimulus was set to evoke an MEP of 1.5 mV amplitude. Motor evoked potentials (MEPs) were recorded from the right and left Abd. pollicis brevis muscles (APB). SICI and ICF were quantified as percentage of conditioned over unconditioned MEP amplitudes. Results: Patients with AIS and healthy adolescents showed a similarly marked SICI at ISIs of 1, 2 and 3 ms in the right APB (26±18% / 28±26%; 50±41% / 49±34%; 35±18% / 30±16%; n.s.) and left APB (35±22% / 27±18%; 48±39% / 51±27%; 41±22% / 30±16%; n.s.). Patients with AIS and healthy adolescents also demonstrated a similar ICF at the ISIs of 10 and 15 ms in the right APB (121±64% / 152±61%; 139±52% / 145±65%, n.s) and left APB (146±46% / 130±45%; 188±113% / 123±46%, n.s.). Conclusion The normal SICI and ICF in patients with AIS is in contrast to one previous report (Domenech; Neurology 1997, 48: A344) and findings of reduced SICI in focal dystonia. Therefore, our findings do not support the view that AIS is a form of focal dystonia.

Cortical hemoglobin-concentration changes under the coil induced by single-pulse TMS in humans: a simultaneous recording with near-infrared spectroscopy

We measured cortical hemoglobin-concentration changes under the coil induced by single-pulse transcranial magnetic stimulation (TMS) using a technique of simultaneous recording with near-infrared spectroscopy (NIRS). Single-pulse TMS was delivered over the hand area of the left primary motor cortex at an intensity of 100, 120, or 140% of the active motor threshold (AMT). NIRS recordings were also made during sham stimulation. These four different stimulation sessions (TMS at three intensities and sham stimulation) were performed both when the subject slightly contracted the right first dorsal interosseous muscle and when relaxed it (active and resting conditions). Under the active condition with TMS at 100% AMT, we observed a transient increase in oxy-hemoglobin (oxy-Hb), which was significantly larger than sham stimulation. Under the resting conditions with TMS at 120 and 140% AMT, we observed significant decreases in both deoxy-hemoglobin (deoxyHb) and total-hemoglobin (total-Hb) as compared to sham stimulation. We suggest that the increase of oxy-Hb concentration at 100% AMT under the active condition reflects an add-on effect by TMS to the active baseline and that decrease of deoxy-Hb and total-Hb concentrations at 120 and 140% AMT under the resting condition are due to reduced baseline firings of the corticospinal tract neurons induced by a lasting inhibition provoked by a higher intensity TMS.

High‐frequency repetitive transcranial magnetic stimulation over the hand area of the primary motor cortex disturbs predictive grip force scaling

When we repetitively lift an object, our grip force is influenced by the mechanical object properties of the preceding lift, irrespective of whether the subsequent lift is performed with the same hand or the hand opposite to the preceding lift. This study investigates if repetitive high-frequency transcranial magnetic stimulation (rTMS) over the dominant primary motor cortex affects this relationship. After completion of 10 lifts of an object using the dominant hand, rTMS was applied over the dominant primary motor cortex for 20 s. On the first lift following rTMS, the peak grip force was significantly higher than on the lift preceding rTMS. Moreover, this measure remained elevated throughout the following set of lifts after rTMS. rTMS did not change the peak lift force generated by more proximal arm muscles. The same effect was observed when the lifts following rTMS over the dominant motor cortex were performed with the ipsilateral hand. These effects were not observed when subjects rested both hands on their lap or when a sham stimulation was applied for the same period of time. These preliminary data suggest that rTMS over the sensorimotor cortex disturbs predictive grip force planning.

Slow rTMS to the somatosensory cortex attenuates afferent inhibition in patients with writer's cramp

Previous studies have shown a number of functional abnormalities in the somatosensory system including a distorted functional organisation of the somatosensory cortex (S1) in patients with writer's cramp. Here we tested the hypothesis that these functional alterations render S1 more susceptible to the „inhibitory“ effects of low-frequency repetitive transcranial magnetic stimulation (rTMS). To this end, we explored the effects of subthreshold 1Hz rTMS (1200 stimuli) given to S1 on clinical symptoms (writing speed) and short latency afferent inhibition (SAI), a measure of sensorimotor integration, in seven writer's cramp patients and eight healthy subjects. In a control experiment, patients also received rTMS to the motor cortex hand area (M1). SAI was tested in the relaxed first dorsal interosseous muscle (FDI) of the dominant hand using conditioning electrical stimulation of the index finger and TMS pulses given over the contralateral M1 at interstimulus intervals (ISI) of 25, 30 and 40 ms. Baseline SAI did not differ between patients and healthy subjects. S1 but not M1 rTMS reduced SAI in patients with significant changes occurring at an ISI of 25 ms. There were no clinical changes. rTMS had no effects on SAI in healthy subjects.