Age-related alterations in default mode network: impact on working memory performance

The default mode network (DMN) is a set of functionally connected brain regions which shows deactivation (task-induced deactivation, TID) during a cognitive task. Evidence shows an age-related decline in task-load-related modulation of the activity within the DMN during cognitive tasks. However, the effect of age on the functional coupling within the DMN and their relation to cognitive performance has hitherto been unexplored. Using functional magnetic resonance imaging, we investigated functional connectivity within the DMN in older and younger subjects during a working memory task with increasing task load. Older adults showed decreased connectivity and ability to suppress low frequency oscillations of the DMN. Additionally, the strength of the functional coupling of posterior cingulate (pCC) with medial prefrontal cortex (PFC) correlated positively with performance and was lower in older adults. pCC was also negatively coupled with task-related regions, namely the dorsolateral PFC and cingulate regions. Our results show that in addition to changes in canonical task-related brain regions, normal aging is also associated with alterations in the activity and connectivity of brain regions within the DMN. These changes may be a reflection of a deficit in cognitive control associated with advancing age that results in deficient resource allocation to the task at hand.     

Motor demand-dependent improvement in accuracy following low-frequency transcranial magnetic stimulation of left motor cortex

The role of primary motor cortex (M1) in the control of voluntary movements is still unclear. In brain functional imaging studies of unilateral hand performance, bilateral M1 activation is inconsistently observed, and disruptions of M1 using repetitive transcranial magnetic stimulation (rTMS) lead to variable results in the hand motor performance. As the motor tasks differed qualitatively in these studies, it is conceivable that M1 contribution differs depending on the level of skillfulness. The objective of the present study was to determine whether M1 contribution to hand motor performance differed depending on the level of precision of the motor task. Here, we used low-frequency rTMS of left M1 to determine its effect on the performance of a pointing task that allows the parametric increase of the level of precision and thereby increase the level of required precision quantitatively. We found that low-frequency rTMS improved performance in both hands for the task with the highest demand on precision, whereas performance remained unchanged for the tasks with lower demands. These results suggest that the functional relevance of M1 activity for motor performance changes as a function of motor demand. The bilateral effect of rTMS to left M1 would also support the notion of M1 functions at a higher level in motor control by integrating afferent input from nonprimary motor areas.     

Cortical activity in precision- versus power-grip tasks: an fMRI study

Most manual grips can be divided in precision and power grips on the basis of phylogenetic and functional considerations. We used functional magnetic resonance imaging to compare human brain activity during force production by the right hand when subjects used a precision grip and a power grip. During the precision-grip task, subjects applied fine grip forces between the tips of the index finger and the thumb. During the power-grip task, subjects squeezed a cylindrical object using all digits in a palmar opposition grasp. The activity recorded in the primary sensory and motor cortex contralateral to the operating hand was higher when the power grip was applied than when subjects applied force with a precision grip. In contrast, the activity in the ipsilateral ventral premotor area, the rostral cingulate motor area, and at several locations in the posterior parietal and prefrontal cortices was stronger while making the precision grip than during the power grip. The power grip was associated predominately with contralateral left-sided activity, whereas the precision-grip task involved extensive activations in both hemispheres. Thus our findings indicate that in addition to the primary motor cortex, premotor and parietal areas are important for control of fingertip forces during precision grip. Moreover, the ipsilateral hemisphere appears to be strongly engaged in the control of precision-grip tasks performed with the right hand.     

Motor sequence learning with the nondominant left hand

Whereas the human right hemisphere is active during execution of contralateral hand movements, the left hemisphere is engaged for both contra- and ipsilateral movements, at least for right-handed subjects. Whether this asymmetry is also found during motor learning remains unknown. Implicit sequence learning by the nondominant left hand was examined with the serial reaction time (SRT) task during functional brain imaging. As learning progressed, increases in brain activity were observed in left lateral premotor cortex (PMC) and bilaterally in supplementary motor areas (SMA), with the increase significantly greater in the left hemisphere. The left SMA site was similar to one previously identified with right-hand learning, suggesting that this region is critical for representing a sequence independent of effector. Learning with the left hand also recruited a widespread set of temporal and frontal regions, suggesting that motor skill learning with the nondominant hand develops within both cognitive and motor-related functional networks. After skill acquisition, subjects performed the SRT task with their right hands, and sequence transfer was tested with the original and a mirror-ordered sequence. With the original sequence, the stimulus sequence and series of response locations remained unchanged, but the finger movements were different. With the mirror-ordered sequence, the response sequence involved finger movements homologous to those used during training. Performance of the original and mirror sequence by the right hand was significantly better than with random stimuli. Mirror transformation of the sequence by the right hand was associated with a marked increase in regional activity in the left motor cortex, consistent with a role for sequential transformation at this level of the motor output pathway.     

Hemispheric differences in the relationship between corticomotor excitability changes following a fine-motor task and motor learning

Motor performance induces a postexercise increase in corticomotor excitability that may be associated with motor learning. We investigated whether there are hemispheric differences in the extent and/or time course of changes in corticomotor excitability following a manipulation task (Purdue pegboard) and their relationship with motor performance. Single- and paired-pulse (3 ms) transcranial magnetic stimulation (TMS) was used to assess task-induced facilitation of the muscle evoked potential (MEP) and intracortical inhibition (ICI) for three intrinsic hand muscles acting on digits 1, 2, and 5. Fifteen right-handed subjects performed three 30-s pegboard trials with left or right hand in separate sessions. TMS was applied to contralateral motor cortex before and after performance. Number of pegs placed was higher with the right hand, and performance improved (motor learning) with both hands over the three trials. MEP facilitation following performance was short-lasting (<15 min), selective for muscles engaged in gripping the pegs, and of similar magnitude in left and right hands. ICI was reduced immediately following performance with the right hand, but not the left. The extent of MEP facilitation was positively correlated with motor learning for the right hand only. We conclude that the pegboard task induces a selective, short-lasting change in excitability of corticospinal neurons controlling intrinsic hand muscles engaged in the task. Only left hemisphere changes were related to motor learning. This asymmetry may reflect different behavioral strategies for performance improvement with left and right upper limb in this task or hemispheric differences in the control of skilled hand movements.     

Motor cortex activation induced by a mirror: evidence from lateralized readiness potentials

Similar motor regions are activated during voluntarily executed or observed movements. We investigated whether observing movements of one's own hand through a mirror will generate activations in the cortical motor regions of both the moving and nonmoving hands. Using the lateralized readiness potential (LRP), an electrophysiological correlate of premotor activation in the primary motor cortex, we recorded evoked responses to movements while subjects were viewing the performing (right) hand through a mirror placed sagittally, giving the impression that the left hand was performing the task. Reliable LRPs were recorded in relation to the seen hand, indicating motor cortex activity in the contralateral hemisphere of the inactive hand while the opposite hand was performing the movement.     

Impact of changed positive and negative task-related brain activity on word-retrieval in aging

Previous functional imaging studies that compared activity patterns in older and younger adults during nonlinguistic tasks found evidence for 2 phenomena: older participants usually show more pronounced task-related positive activity in the brain hemisphere that is not dominant for the task and less pronounced negative task-related activity in temporo-parietal and midline brain regions. The combined effects of these phenomena and the impact on word retrieval, however, have not yet been assessed. We used functional magnetic resonance imaging to explore task-related positive (active task > baseline) and negative activity (baseline > active task) during semantic and phonemic verbal fluency tasks. Increased right frontal positive activity during the semantic task and reduced negative activity in the right hemisphere during both tasks was associated with reduced performance in older subjects. No substantial relationship between changes in positive and negative activity was observed in the older participants, pointing toward 2 partially independent but potentially co-occurring processes. Underlying causes of the observed functional network inefficiency during word retrieval in older adults need to be determined in the future.     

Age-related changes in the topological architecture of the brain during hand grip

Neuroanatomical changes in the aging brain are widely distributed rather than focal. We investigated age-related changes in large-scale functional brain networks by applying graph theory to functional magnetic resonance imaging data acquired during a simple grip task with either dominant or nondominant hand. We measured the effect of age on efficiency of information transfer within a series of hierarchical functional networks composed of the whole brain or component parts of the whole brain. Global efficiency was maintained with aging during dominant hand use, primarily due to increased efficiency in parietal-occipital-cerebellar-related networks. During nondominant hand use, global efficiency, as well as efficiency within ipsilateral hemisphere and between hemispheres declined with age. This was attributable largely to frontal-temporal-limbic-cerebellar-related networks. Increased efficiency with age was seen in networks involving parietal-occipital regions, but unlike for dominant hand use, this topological reconfiguration could not maintain the level of global efficiency. Here, graph theoretical approaches have demonstrated both compensatory and noncompensatory changes in topological configuration of large-scale networks during aging depending on the task.     

Figural memory performance and functional magnetic resonance imaging activity across the adult lifespan

We examined performance and functional magnetic resonance imaging activity in participants (n = 235) aged 17–81 years on a nonverbal recognition memory task, figural memory. Reaction time, error rate, and response bias measures indicated that the youngest and oldest participants were faster, made fewer errors, and showed a more conservative response bias than participants in the median age ranges. Encoding and Recognition phases activated a distributed bilateral network encompassing prefrontal, subcortical, lateral, and medial temporal and occipital regions. Activation during Encoding phase did not correlate with age. During Recognition, task-related activation for correctly identified targets (Hit-Targets) correlated linearly positively with age; nontask related activity correlated negative quadratically with age. During correctly identified distractors (Hit-Distractors) activity in task-related regions correlated positive linearly with age, nontask activity showed positive and negative quadratic relationships with age. Missed-Targets activity did not correlate with age. We concluded that figural memory performance and functional magnetic resonance imaging activity during Recognition but not Encoding was affected both by continued maturation of the brain in the early 20s and compensatory recruitment of additional brain regions during recognition memory in old age.     

The ipsilateral motor cortex contributes to cross-limb transfer of performance gains after ballistic motor practice

Although it has long been known that practicing a motor task with one limb can improve performance with the limb opposite, the mechanisms remain poorly understood. Here we tested the hypothesis that improved performance with the untrained limb on a fastest possible (i.e. ballistic) movement task depends partly on cortical circuits located ipsilateral to the trained limb. The idea that crossed effects, which are important for the learning process, might occur in the 'untrained' hemisphere following ballistic training is based on the observation that tasks requiring strong descending drive generate extensive bilateral cortical activity. Twenty-one volunteers practiced a ballistic index finger abduction task with their right hand, and corticospinal excitability was assessed in two hand muscles (first dorsal interosseus, FDI; adductor digiti minimi, ADM). Eight control subjects did not train. After training, repetitive transcranial magnetic stimulation (rTMS; 15 min at 1 Hz) was applied to the left (trained) or right (untrained) motor cortex to induce a 'virtual lesion'. A third training group received sham rTMS, and control subjects received rTMS to the right motor cortex. Performance and corticospinal excitability (for FDI) increased in both hands for training but not control subjects. rTMS of the left, trained motor cortex specifically reduced training-induced gains in motor performance for the right, trained hand, and rTMS of the right, untrained motor cortex specifically reduced performance gains for the left, untrained hand. Thus, cortical processes within the untrained hemisphere, ipsilateral to the trained hand, contribute to early retention of ballistic performance gains for the untrained limb.     

Effective Connectivity of Cortical Sensorimotor Networks During Finger Movement Tasks: A Simultaneous fNIRS,fMRI, EEG Study

Recently, interest has been growing to understand the underlying dynamic directional relationship between simultaneously activated regions of the brain during motor task performance. Such directionality analysis (or effective connectivity analysis), based on non-invasive electrophysiological (electroencephalography—EEG) and hemodynamic (functional near infrared spectroscopy—fNIRS; and functional magnetic resonance imaging—fMRI) neuroimaging modalities can provide an estimate of the motor task-related information flow from one brain region to another. Since EEG, fNIRS and fMRI modalities achieve different spatial and temporal resolutions of motor-task related activation in the brain, the aim of this study was to determine the effective connectivity of cortico-cortical sensorimotor networks during finger movement tasks measured by each neuroimaging modality. Nine healthy subjects performed right hand finger movement tasks of different complexity (simple finger tapping-FT, simple finger sequence-SFS, and complex finger sequence-CFS). We focused our observations on three cortical regions of interest (ROIs), namely the contralateral sensorimotor cortex (SMC), the contralateral premotor cortex (PMC) and the contralateral dorsolateral prefrontal cortex (DLPFC). We estimated the effective connectivity between these ROIs using conditional Granger causality (GC) analysis determined from the time series signals measured by fMRI (blood oxygenation level-dependent-BOLD), fNIRS (oxygenated-O₂Hb and deoxygenated-HHb hemoglobin), and EEG (scalp and source level analysis) neuroimaging modalities. The effective connectivity analysis showed significant bi-directional information flow between the SMC, PMC, and DLPFC as determined by the EEG (scalp and source), fMRI (BOLD) and fNIRS (O₂Hb and HHb) modalities for all three motor tasks. However the source level EEG GC values were significantly greater than the other modalities. In addition, only the source level EEG showed a significantly greater forward than backward information flow between the ROIs. This simultaneous fMRI, fNIRS and EEG study has shown through independent GC analysis of the respective time series that a bi-directional effective connectivity occurs within a cortico-cortical sensorimotor network (SMC, PMC and DLPFC) during finger movement tasks.     

Adult age differences in the functional neuroanatomy of visual attention: a combined fMRI and DTI study

We combined measures from event-related functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and cognitive performance (visual search response time) to test the hypotheses that differences between younger and older adults in top-down (goal-directed) attention would be related to cortical activation, and that white matter integrity as measured by DTI (fractional anisotropy, FA) would be a mediator of this age-related effect. Activation in frontal and parietal cortical regions was overall greater for older adults than for younger adults. The relation between activation and search performance supported the hypothesis of age differences in top-down attention. When the task involved top-down control (increased target predictability), performance was associated with frontoparietal activation for older adults, but with occipital (fusiform) activation for younger adults. White matter integrity (FA) exhibited an age-related decline that was more pronounced for anterior brain regions than for posterior regions, but white matter integrity did not specifically mediate the age-related increase in activation of the frontoparietal attentional network.     

Neural activity of supplementary and primary motor areas in monkeys and its relation to bimanual and unimanual movement sequences

A chronic single-unit study of motor cortical activity was undertaken in two monkeys trained to perform a bimanually coordinated task. The hypothesis was tested that the supplementary motor area plays a specific role in coordinating the two hands for common goal-oriented actions. With this objective, a special search was made for neurons that might exhibit properties exclusively related to bimanual task performance. Monkeys learned to reach for and to pull open a spring-loaded drawer with one hand, while the other hand reached out to grasp food from the drawer recess. The two hands were precisely coordinated for achievement of this goal. Monkeys also performed, in separate blocks of trials, only the pulling or grasping movements, using the same hands as in the bimanual task. Task-related activity of 348 neurons from the supplementary motor area and 341 neurons from the primary motor area, each examined in the bimanual and in both unimanual tasks, was recorded in the two hemispheres. Most neurons from the supplementary motor area were recorded within its caudal microexcitable portion. Contrary to expectation, the proportion of neurons with activity patterns related exclusively to the bimanual task was small, but somewhat higher in the supplementary motor area (5%) than in the primary motor cortex (2%). Another group of neurons that were equally modulated during the bimanual as well as to both unimanual task components might also contribute in controlling bimanual actions. Such "task-dependent" rather than "effector-dependent" activity patterns were more common in neurons of the supplementary motor area (19%) than of the primary motor cortex (5%). Bilateral receptive fields were also more numerous among the supplementary motor area neurons. However, a large majority of neurons from primary and supplementary motor areas had activity profiles clearly related only to contralateral hand movements (65% in the primary motor and 51% in the supplementary motor area). A similar group of neurons showed an additional slight modulation with ipsilateral movements; they were equally common in the two areas (14% and 16%, respectively) and their significance for bimanual coordination is questionable. Summed activity profiles of all neurons recorded in the primary and supplementary motor areas of the same hemisphere were compared. The modulations of the three histograms, corresponding to the two unimanual and the bimanual tasks, were similar for the two motor areas, i.e. prominent with bimanual and contralateral movements and weak with ipsilateral movements. It is concluded that the supplementary motor area is likely to contribute to bimanual coordination, perhaps more than the primary motor cortex, but that it is not a defining function for the former cortical area. Instead, it is suggested that the supplementary motor area is part of a callosally interconnected and distributed network of frontal and parietal cortical areas that together orchestrate bimanual coordination.     

Paired-pulse transcranial magnetic stimulation of primary somatosensory cortex differentially modulates perception and sensorimotor transformations

Intermodal selective attention is generally associated with facilitation of relevant information. However, recent studies demonstrate reduced activation of primary somatosensory cortex (S1) with continuous vibrotactile tracking during bimodal stimulation. Reduced activation has been hypothesized to reflect an interaction between the sensorimotor and intermodal requirements of the tracking task. Recently, it has been shown that transcranial magnetic stimulation (TMS) involving a supra-threshold test stimulus (TS) preceded by a sub-threshold conditioning stimulus (CS) adversely affects tactile perception by altering excitability of local intracortical circuits. The purpose of the current paper was to use TMS to assess the effects of differential sensorimotor requirements in the right sensorimotor cortex upon local intracortical networks and sensory processing in the left primary somatosensory cortex during constant multimodal stimulation. Single and paired-pulse TMS was used to probe intracortical networks in S1 and sensory processing during a sensorimotor task where a vibrotactile stimulus to the right index finder guided either continuous or discrete sensorimotor responses of the left hand. It was hypothesized that paired-pulse TMS would alter local intracortical networks and reduce performance during the discrete sensorimotor task, but that these effects would be mitigated during the continuous sensorimotor task, possibly a reflection of reduced S1 activation observed previously during a similar continuous sensorimotor task. Regardless of sensorimotor requirements, single-pulse TMS delivered over S1 decreased sensorimotor performance. Paired-pulse TMS further decreased sensorimotor performance only when the vibrotactile stimulus guided a discrete motor response but not when it was required to continuously guide the motor response. This effect disappeared when the TS was replaced by a sub-threshold stimulus. These results suggest that the CS facilitates sensory output neurons during perceptual detection but that differential responsiveness of local cortical networks in S1 suppresses the CS effects during continuous sensory-guided movement. This study highlights the importance of sensorimotor requirements in determining the net result of task-related sensory processing in S1.     

Neural networks involved in mathematical thinking: evidence from linear and non-linear analysis of electroencephalographic activity

Using linear and non-linear methods, electroencephalographic (EEG) signals were measured at various brain regions to provide information regarding patterns of local and coordinated activity during performance of three arithmetic tasks (number comparison, single-digit multiplication, and two-digit multiplication) and two control tasks that did not require arithmetic operations. It was hypothesized that these measures would reveal the engagement of local and increasingly complex cortical networks as a function of task specificity and complexity. Results indicated regionally increased neuronal signalling as a function of task complexity at frontal, temporal and parietal brain regions, although more robust task-related changes in EEG-indices of activation were derived over the left hemisphere. Both linear and non-linear indices of synchronization among EEG signals recorded from over different brain regions were consistent with the notion of more "local" processing for the number comparison task. Conversely, multiplication tasks were associated with a widespread pattern of distant signal synchronizations, which could potentially indicate increased demands for neural networks cooperation during performance of tasks that involve a greater number of cognitive operations.     

White matter integrity of motor connections related to training gains in healthy aging

Impaired motor skill acquisition is a feature of older age. Acquisition of new motor skills requires the interplay between different cortical motor areas. Using diffusion tensor imaging we reconstructed cortico-cortical connections between the primary motor cortex (M1) and secondary motor areas in 11 older and 11 young participants who took part in a motor skill acquisition paradigm with the nondominant left hand. Examining the extent to which tract-related integrity correlated with training gains we found that white matter integrity of fibers connecting contralateral M1 with both contralateral (r = 0.85) and ipsilateral supplementary motor areas (r = 0.92) were positively associated in old participants. Also, fibers connecting contralateral M1 with ipsilateral dorsal premotor (r = 0.82) and fibers connecting ipsilateral dorsal premotor and supplementary motor area (r = 0.88) were positively related to skill acquisition (all p < 0.05). A similar structure-behavior relationship was not present in the young control subjects suggesting a critical role of brain structural integrity for motor learning in healthy aging.     

Distributed cortical networks for focused auditory attention and distraction

We used behavioral measures and functional magnetic resonance imaging (fMRI) to study the effects of parametrically varied task-irrelevant pitch changes in attended sounds on loudness-discrimination performance and brain activity in cortical surface maps. Ten subjects discriminated tone loudness in sequences that also included infrequent task-irrelevant pitch changes. Consistent with results of previous studies, the task-irrelevant pitch changes impaired performance in the loudness discrimination task. Auditory stimulation, attention-enhanced processing of sounds and motor responding during the loudness discrimination task activated supratemporal (auditory cortex) and inferior parietal areas bilaterally and left-hemisphere (contralateral to the hand used for responding) motor areas. Large pitch changes were associated with right hemisphere supratemporal activations as well as widespread bilateral activations in the frontal lobe and along the intraparietal sulcus. Loudness discrimination and distracting pitch changes activated common areas in the right supratemporal gyrus, left medial frontal cortex, left precentral gyrus, and left inferior parietal cortex.     

Primary sensorimotor cortex activation with task-performance after fatiguing hand exercise

We have compared functional MRI signals in primary sensorimotor cortex (SM1) during a paced motor task of each hand before and after unimanual (right hand) fatiguing exercise. Our aims were to determine whether the degree of activation is different when a motor task is performed after a fatiguing exercise, and whether there are any differences in activation between movement of the fatigued and non-fatigued hands. There was a significant reduction in the number of voxels activated in SM1 in the hemisphere contralateral to movement of both the fatigued hand (38±5 pre-exercise versus 21±3 post-exercise; P<0.05) and the non-fatigued hand (32±4 pre-exercise vs 18±4 post-exercise; P<0.05). There was no significant difference in the magnitude of the functional magnetic resonance imaging signal before or after exercise, however, the variance increased significantly after exercise (6.0±0.5 pre-exercise vs 7.3±0.6 post-exercise; P<0.01). Reduced functional activation in SM1 may reflect increased variability in the activation rather than a reduction in activation of cortical motor networks after fatigue.     

Distinguishable brain activation networks for short- and long-term motor skill learning

The acquisition of a new motor skill is characterized first by a short-term, fast learning stage in which performance improves rapidly, and subsequently by a long-term, slower learning stage in which additional performance gains are incremental. Previous functional imaging studies have suggested that distinct brain networks mediate these two stages of learning, but direct comparisons using the same task have not been performed. Here we used a task in which subjects learn to track a continuous 8-s sequence demanding variable isometric force development between the fingers and thumb of the dominant, right hand. Learning-associated changes in brain activation were characterized using functional MRI (fMRI) during short-term learning of a novel sequence, during short-term learning after prior, brief exposure to the sequence, and over long-term (3 wk) training in the task. Short-term learning was associated with decreases in activity in the dorsolateral prefrontal, anterior cingulate, posterior parietal, primary motor, and cerebellar cortex, and with increased activation in the right cerebellar dentate nucleus, the left putamen, and left thalamus. Prefrontal, parietal, and cerebellar cortical changes were not apparent with short-term learning after prior exposure to the sequence. With long-term learning, increases in activity were found in the left primary somatosensory and motor cortex and in the right putamen. Our observations extend previous work suggesting that distinguishable networks are recruited during the different phases of motor learning. While short-term motor skill learning seems associated primarily with activation in a cortical network specific for the learned movements, long-term learning involves increased activation of a bihemispheric cortical-subcortical network in a pattern suggesting "plastic" development of new representations for both motor output and somatosensory afferent information.     

Fatigue suppresses ipsilateral intracortical facilitation

Experimental data in animals and humans have demonstrated connections between right and left motor cortices. Interactions between these cortical areas can be explored with electrical or magnetic stimulation. In the present study we examined the interhemispheric effect of fatigue on intracortical facilitation (ICF) and inhibition (ICI) using a paired-pulse transcranial magnetic stimulation (TMS) paradigm. Ten healthy subjects performed pinch grips with their left hand with 50% maximum voluntary contraction (MVC) until fatigue occurred. In the control experiment, the same number of pinch grips was performed with 5% MVC without inducing fatigue. Motor evoked potentials (MEP) produced by single and paired pulse TMS over the left motor cortex were recorded from right first dorsal interosseous muscle (FDI) and right abductor digiti minimi muscle (ADM) before and after the tasks. ICF of the right FDI was significantly reduced after fatigue ( P=0.0008). Fifteen minutes after finishing the task ICF had returned to baseline values. There was no change of ICF of right FDI in the control experiment without inducing fatigue. In both experiments the right ADM did not show significant MEP changes. Additional control experiments showed that M-responses and F-waves were unchanged in right FDI after performing the fatigue task with left FDI, and TMS test pulse amplitudes were significantly reduced in left FDI after fatigue. Fatigue caused by pinch grips induces a short-lasting and task-specific suppression of intracortical facilitation in the motor cortex of an homologous contralateral hand muscle. These results indicate interhemispheric interactions between the two motor cortices that are still effective after cessation of movements.