Previous research has demonstrated that regular exercise modulates motor cortical plasticity and cognitive function, but the influence of short-term high-intensity interval training remains unclear. In the present study, the effect of short-term HIIT on neuroplasticity and executive function was assessed in 32 sedentary females. Half of the participants undertook 2 weeks of HIIT. Paired-pulse transcranial magnetic stimulation was used to measure motor cortical plasticity via short intracortical inhibition and intracortical facilitation. We further adapted the Stroop task (...) using functional near-infrared spectroscopy to evaluate executive function in the participants. The results indicated that, compared with the control group, the HIIT group exhibited decreased ICF. In the Stroop task, the HIIT group displayed greater activation in the left dorsolateral prefrontal cortex and left orbitofrontal cortex even though no significant difference in task performance was observed. These findings indicate that short-term HIIT may modulate motor cortical plasticity and executive function at the neural level. (shrink)

Fourteen healthy children (13.8±2.2 years, range 10 to 16; M:F=5:9) received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300 (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to Transcranial Magnetic Stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were expressed as (...) a ratio and assessed from 1 to 10 minutes (BLOCK1) and 1 to 30 minutes (BLOCK2) using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1) without any clinically reported adverse events. ITBS300 produced significant M1 facilitation (F5,65=3.165, p=0.01) at BLOCK1 and trend level M1 facilitation at BLOCK2 (F10,129=1.69, p=0.089). Although iTBS300 (stimulation duration of 92 seconds at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability. (shrink)

Short-term motor practice leads to plasticity in the primary motor cortex. The purpose of this study is to investigate the factors that determine the increase in corticospinal tract excitability after motor practice, with special focus on two factors; “the level of muscle activity” and “the presence/absence of a goal of keeping the activity level constant.” Fifteen healthy subjects performed four types of rapid thumb adduction in separate sessions. In the “comfortable task” and “forceful task”, the (...) subjects adducted their thumb using comfortable and strong forces. In the “comfortable with a goal task” and “forceful with a goal task”, subjects controlled the muscle activity at the same level as in the C and F, respectively, by adjusting the peak electromyographic amplitude within the target ranges. Paired associative stimulation, which combines peripheral nerve stimulation and transcranial magnetic stimulation, with an inter-stimulus interval of 25 ms was also done. Before and after the motor tasks and PAS25, TMS was applied to the M1. None of the four tasks showed any temporary changes in behavior, meaning no learning occurred. Motor-evoked potential amplitude increased only after the FG and it exhibited a positive correlation with the MEP increase after PAS25, suggesting that FG and PAS25 share at least similar plasticity mechanisms in the M1. Resting motor threshold decreased only after FG, suggesting that FG would also be associated with the membrane depolarization of M1 neurons. These results suggest task-dependent plasticity from the synergistic effect of forceful muscle activity and of setting a goal of keeping the activity level constant. (shrink)

Most discussions of neural plasticity in the context of the Molyneux question focus on changes in the visual cortex, early on during critical periods, or post-surgery after patients are given sight. There are good reasons, based on enactive approaches to perception to ask about plastic changes in the dorsal visual pathway and motor control areas. This essay explores the implications of such changes for the Molyneux question.

Sustained peripheral somatosensory stimulations, such as high-frequency repetitive somatosensory stimulation (HF-RSS) and vibrated stimulation, are effective in altering the balance between excitation and inhibition in the somatosensory cortex (S1) and motor cortex (M1). A recent study reported that whole-hand water flow (WF) stimulation induced neural disinhibition in the M1. Based on previous results, we hypothesized that whole-hand WF stimulation would lead to neural disinhibition in the S1 because there is a strong neural connection between M1 and S1 (...) and aimed to examine whether whole-hand WF stimulation would change the neural balance between excitation and inhibition in the S1. Nineteen healthy volunteers were studied by measuring excitation and inhibition in the S1 before and after each of the four 15-min interventions. The excitation and inhibition in the S1 were assessed using somatosensory evoked potentials (SEPs) and paired-pulse inhibition (PPI) induced by single- and paired-pulse stimulations, respectively. The four interventions were as follows: control, whole-hand water immersion, whole-hand WF, and HF-RSS. The results showed no significant changes in SEPs and PPI following any intervention. However, changes in PPI with an interstimulus interval (ISI) of 30 ms were significantly correlated with the baseline value before whole-hand WF. Thus, the present findings indicated that the whole-hand WF stimulation had a greater decreased neural inhibition in participants with higher neural inhibition in the S1 at baseline. Considering previous results on M1, the present results possibly show that S1 has lower plasticity than M1 and that the duration (15 min) of each intervention may not have been enough to alter the balance of excitation and inhibition in the S1. (shrink)

A decrease in cortical excitability tends to be easily followed by an increase induced by external stimuli via a mechanism aimed at restoring it; this phenomenon is called “homeostatic plasticity.” In recent years, although intervention methods aimed at promoting motor learning using this phenomenon have been studied, an optimal intervention method has not been established. In the present study, we examined whether subsequent motor learning can be promoted further by a repetitive passive movement, which reduces the excitability (...) of the primary motor cortex before motor learning tasks. We also examined the relationship between motor learning and the brain-derived neurotrophic factor. Forty healthy subjects participated. Subjects were divided into two groups of 20 individuals each. The first group was assigned to perform the motor learning task after an intervention consisting in the passive adduction–abduction movement of the right index finger at 5 Hz for 10 min, while the second group was assigned to perform the task without the passive movement. The motor learning task consisted in the visual tracking of the right index finger. The results showed that the corticospinal excitability was transiently reduced after the passive movement in the RPM condition, whereas it was increased to the level detected in the control condition after the motor learning task. Furthermore, the motor learning ability was decreased immediately after the passive movement; however, the motor performance finally improved to the level observed in the control condition. In individuals carrying the Val/Val genotype, higher motor learning was also found to be related to the more remarkable changes in corticospinal excitability caused by the RPM condition. This study revealed that the implementation of a passive movement before a motor learning tasks did not affect M1 excitatory changes and motor learning efficiency; in contrast, in subjects carrying the Val/Val polymorphism, the more significant excitatory changes in the M1 induced by the passive movement and motor learning task led to the improvement of motor learning efficiency. Our results also suggest that homeostatic plasticity occurring in the M1 is involved in this improvement. (shrink)

Transcranial magnetic stimulation studies have demonstrated increased cortical facilitation and reduced inhibition following aerobic exercise, even when examining motor regions separate to the exercised muscle group. These changes in brain physiology following exercise may create favorable conditions for adaptive plasticity and motor learning. One candidate mechanism behind these benefits is the increase in brain-derived neurotropic factor observed following exercise, which can be quantified from a venous blood draw. The aim of this study was to investigate changes in (...) motor cortex excitability and inhibition of the upper limb, and circulating BDNF, following high-intensity interval training on a stationary bicycle. Nineteen sedentary adults participated in a randomized crossover design study involving a single bout of high-intensity interval cycling for 20 min or seated rest. Venous blood samples were collected, and transcranial magnetic stimulation was used to stimulate the extensor carpi radialis, where motor evoked potentials were recorded pre- and post-condition. Following exercise, there was a significant increase in corticospinal excitability measured at 120% of resting motor threshold and a reduction in short-interval cortical inhibition. There was a non-significant 23.6% increase in BDNF levels. Collectively, these results reflect a net reduction in gamma aminobutyric acid ergic synaptic transmission and increased glutamatergic facilitation, resulting in increased corticospinal excitability. This study supports the notion that acute high-intensity exercise provides a potent stimulus for inducing cortical neuroplasticity, which may support enhanced motor learning. (shrink)

Most neuroimaging research in stroke rehabilitation mainly focuses on the neural mechanisms underlying the natural history of post-stroke recovery. However, connectivity mapping from resting-state fMRI is well suited for different neurological conditions and provides a promising method to explore plastic changes for treatment-induced recovery from stroke. We examined the changes in resting-state functional connectivity (RS-FC) of the ipsilesional primary motor cortex (M1) in 10 post-acute stroke patients before and immediately after 4 weeks of robot-assisted bilateral arm therapy (RBAT). (...) Motor performance, functional use of the affected arm, and daily function improved in all participants. Reduced interhemispheric RS-FC between the ipsilesional and contralesional M1 (M1-M1) and the contralesional-lateralized connections were noted before treatment. In contrast, greater M1-M1 functional connectivity and disturbed resting-state networks were observed after RBAT relative to pre-treatment. Increased changes in M1-M1 RS-FC after RBAT were coupled with better motor and functional improvements. Mediation analysis showed the pre-to-post difference in M1-M1 RS-FC was a significant mediator for the relationship between motor and functional recovery. These results show neuroplastic changes and functional recoveries induced by RBAT in post-acute stroke survivors and suggest that interhemispheric functional connectivity in the motor cortex may be a neurobiological marker for recovery after stroke rehabilitation. (shrink)

The acquisition and evolution of speech production, discourse and communication can be negatively impacted by brain malformations. We describe, for the first time, a case of developmental dynamic dysphasia (DDD) in a right-handed adolescent boy (subject D) with cortical malformations involving language-eloquent regions (inferior frontal gyrus) in both the left and the right hemispheres. Language evaluation revealed a markedly reduced verbal output affecting phonemic and semantic fluency, phrase and sentence generation and verbal communication in everyday life. Auditory comprehension, repetition, naming, (...) reading and spelling were relatively preserved, but executive function was impaired. Multimodal neuroimaging showed a malformed cerebral cortex with atypical configuration and placement of white matter tracts bilaterally and abnormal callosal fibers. Dichotic listening showed right hemisphere dominance for language and functional magnetic resonance imaging (fMRI) additionally revealed dissociated hemispheric language representation with right frontal activation for phonology and bilateral dominance for semantic processing. Moreover, subject D also had congenital mirror movements (CMM), defined as involuntary movements of one side of the body that mirror intentional movements of the other side. Transcranial magnetic stimulation and fMRI during voluntary unimanual (left and right) hand movements showed bilateral motor cortex recruitment and tractography revealed a lack of decussation of bilateral corticospinal tracts. Genetic testing aimed to detect mutations that disrupt the development of commissural tracts correlating with CMM (e.g., Germline DCC mutations) was negative. Overall, our findings suggest that DDD in subject D resulted from the underdevelopment of the left inferior frontal gyrus with limited capacity for plastic reorganization by its homologous counterpart in the right hemisphere. Corpus callosum anomalies probably contributed to hinder interhemispheric connectivity necessary to compensate language and communication deficits after left frontal involvement. (shrink)

This article reviews models of the cerebellum and motor learning, from the landmark papers by Marr and Albus through those of the present time. The unique architecture of the cerebellar cortex is ideally suited for pattern recognition, but how is pattern recognition incorporated into motor control and learning systems? The present analysis begins with a discussion of exactly what the cerebellar cortex needs to regulate through its anatomically defined projections to premotor networks. Next, we examine various (...) models showing how the microcircuitry in the cerebellar cortex could be used to achieve its regulatory functions. Having thus defined what it is that Purkinje cells in the cerebellar cortex must learn, we then evaluate theories of motor learning. We examine current models of synaptic plasticity, credit assignment, and the generation of training information, indicating how they could function cooperatively to guide the processes of motor learning. (shrink)

Prefrontal cerebral areas project to Purkinje cells, located in the most lateral part of the cerebellum, via mossy and climbing fibers. The latter olivary error signals reflect the attentional load of the prefrontal cortex. At the cerebral level, LTP-LTD plasticity allows these Purkinje cells to adaptively reinforce the active pyramidal cells involved in the motor sequence.

A core feature of drug-resistant epilepsy is hyperexcitability in the motor cortex, and low-frequency repetitive transcranial magnetic stimulation is a suitable treatment for seizures. However, the antiepileptic effect causing network reorganization has rarely been studied. Here, we assessed the impact of rTMS on functional network connectivity in resting functional networks and their relation to treatment response. Fourteen patients with medically intractable epilepsy received inhibitive rTMS with a figure-of-eight coil over the vertex for 10 days spread across two weeks. (...) We designed a 6-week follow-up phase divided into four time points to investigate FNC and rTMS-induced timing-dependent plasticity, such as seizure frequency and abnormal interictal discharges on electroencephalography. For psychiatric comorbidities, the Hamilton Depression Scale and the Hamilton Anxiety Scale were applied to measure depression and anxiety before and after rTMS. FNC was also compared to that of a cohort of 17 healthy control subjects. The after-effects of rTMS included all subjects that achieved the significant decrease rate of more than 50% in interictal epileptiform discharges and seizure frequency, 12 patients with the reduction rate above 50% compared to the baseline, as well as emotional improvements in depression and anxiety. In the analysis of RSNs, we found a higher synchronization between the sensorimotor network and posterior default-mode network in epileptic patients than in healthy controls. In contrast to pre-rTMS, the results demonstrated a weaker FNC between the anterior DMN and SMN after rTMS, while the FNC between the aDMN and dorsal attention network was greater. Importantly, the depressive score was anticorrelated with the FNC of the aDMN-SMN, which was markedly different in the good and bad response groups treated with rTMS. Based on the vertex suppression by rTMS, it is possible to achieve temporary clinical efficacy by modulating network reorganization in the DMN and SMN for patients with refractory epilepsy. (shrink)

This paper samples the large body of neuroscientific evidence suggesting that each mental function takes place within specific neural structures. For instance, vision appears to occur in the visual cortex, motor control in the motor cortex, spatial memory in the hippocampus, and cognitive control in the prefrontal cortex. Evidence comes from neuroanatomy, neurophysiology, neurochemistry, brain stimulation, neuroimaging, lesion studies, and behavioral genetics. If mental functions take place within neural structures, mental functions cannot survive brain death. (...) Therefore, there is no mental life after brain death. -/- 1. The Neural Localization of Mental Functions - 1.1 Perception and Motor Control - 1.2 Memory - 1.3 Emotion - 1.4 Language - 1.5 Thinking - 1.6 Attention and Consciousness - 1.7 Spirituality -- 2. Objections - 2.1 Linguistic Dualism - 2.2 Mere Correlation - 2.3 Neural Plasticity - 2.4 Intentionality - 2.5 Phenomenal Consciousness - 2.6 Subjectivity - 2.7 Self-Knowledge - 2.8 Free Will - 2.9 Are We Just Indulging in Physicalistic Wishful Thinking? -- 3. Conclusion -- Appendix: Physicalism and the Afterlife. (shrink)

We applaud the spirit of MacNeilage's attempts to better explain the evolution and cortical control of speech by drawing on the vast literature in nonhuman primate neurobiology. However, he oversimplifies motor cortical fields and their known individual functions to such an extent that he undermines the value of his effort. In particular, MacNeilage has lumped together the functional characteristics across multiple mesial and lateral motor cortex fields, inadvertantly creating two hypothetical centers that simply may not exist.

BackgroundNeuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor on motor cortex (...) using Transcranial magnetic stimulation.Materials and MethodsWe examined the primary motor cortex excitability during perception of a pleasant odor or perception of odorless saline. Furthermore, we tested the effect of olfactory imagery of BEO on corticospinal excitability. The increase in motor evoked potential amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability.ResultsThe results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor. The correlation analysis shows an association with neuroticism personality trait and with general olfactory imagery ability.ConclusionBoth perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems. (shrink)

IntroductionPrevious transcranial magnetic stimulation studies have revealed that the activity of the primary motor cortex ipsilateral to an active hand plays an important role in motor control. The aim of this study was to investigate whether the ipsi-M1 excitability would be influenced by goal-directed movement and laterality during unilateral finger movements.MethodTen healthy right-handed subjects performed four finger tapping tasks with the index finger: simple tapping task, Real-word task, Pseudoword task, and Visually guided tapping task. In the Tap (...) task, the subject performed self-paced simple tapping on a touch screen. In the real-word task, the subject tapped letters displayed on the screen one by one to create a Real-word. Because the action had a specific purpose, this task was considered to be goal-directed as compared to the Tap task. In the Pseudoword task, the subject tapped the letters to create a pseudoword in the same manner as in the Real-word task; however, the word was less meaningful. In the VT task, the subject was required to touch a series of illuminated buttons. This task was considered to be less goal-directed than the Pseudoword task. The tasks were performed with the right and left hand, and a rest condition was added as control. Single- and paired-pulse TMS were applied to the ipsi-M1 to measure corticospinal excitability and short- and long-interval intracortical inhibition in the resting first dorsal interosseous muscle.ResultsWe found the smaller SICI in the ipsi-M1 during the VT task compared with the resting condition. Further, both SICI and LICI were smaller in the right than in the left M1, regardless of the task conditions.DiscussionWe found that SICI in the ipsi-M1 is smaller during visual illumination-guided finger movement than during the resting condition. Our finding provides basic data for designing a rehabilitation program that modulates the M1 ipsilateral to the moving limb, for example, for post-stroke patients with severe hemiparesis. (shrink)

IntroductionExcitability of the primary motor cortex measured with TMS has been associated with cognitive dysfunctions in patient populations. However, only a few studies have explored this relationship in healthy adults, and even fewer have considered the role of biological sex.MethodsNinety-seven healthy middle-aged adults completed a TMS protocol and a neuropsychological assessment. Resting Motor Threshold and Long-Interval Intracortical Inhibition were assessed in the left motor cortex and related to attention, episodic memory, working memory, reasoning, and global (...) cognition composite scores to evaluate the relationship between cortical excitability and cognitive functioning.ResultsIn the whole sample, there was a significant association between LICI and cognition; specifically, higher motor inhibition was related to better working memory performance. When the sample was broken down by biological sex, LICI was only associated with working memory, reasoning, and global cognition in men. No associations were found between RMT and cognitive functions.ConclusionGreater intracortical inhibition, measured by LICI, could be a possible marker of working memory in healthy middle-aged adults, and biological sex plays a critical role in this association. (shrink)

Deciding between different voluntary movements implies a continuous control of the competition between potential actions. Many theories postulate a leading role of prefrontal cortices in this executive function, but strong evidence exists that a motor region like the primary motor cortex is also involved, possibly via inhibitory mechanisms. This was already shown during the pre-movement decision period, but not after movement onset. For this pilot experiment we designed a new task compatible with the dynamics of post-onset control (...) to study the silent period duration, a pause in electromyographic activity after single-pulse transcranial magnetic stimulation that reflects inhibitory mechanisms. A careful analysis of the SP during the ongoing movement indicates a gradual increase in inhibitory mechanisms with the level of competition, consistent with an increase in mutual inhibition between alternative movement options. However, we also observed a decreased SP duration for high-competition trials associated with change-of-mind inflections in their trajectories. Our results suggest a new post-onset adaptive process that consists in a transient reduction of GABAergic inhibition within M1 for highly conflicting situations. We propose that this reduced inhibition softens the competition between concurrent motor options, thereby favoring response vacillation, an adaptive strategy that proved successful at improving behavioral performance. (shrink)

Background and ObjectiveThere is vast published literature proposing repetitive transcranial magnetic stimulation technology on the motor cortex for the treatment of neuropathic pain. Systematic reviews focus on a specific problem and do not provide a comprehensive overview of a research area. This study aimed to summarize and analyze the evidence of rTMS on the M1 for NP treatment through a new synthesis method called evidence mapping.MethodsSearches were conducted in PubMed, EMBASE, Epistemonikos, and The Cochrane Library to identify the (...) studies that summarized the effectiveness of rTMS for NP. The study type was restricted to SRs with or without meta-analysis. All literature published before January 23, 2021, was included. Two reviewers independently screened the literature, assessed the methodological quality, and extracted the data. The methodological quality of the included SRs was assessed by using the A Measurement Tool to Assess Systematic Reviews. Data were extracted following a defined population, intervention, comparison, and outcome framework from primary studies that included SRs. The same PICO was categorized into PICOs according to interventions [frequency, number of sessions ] and compared. The evidence map was presented in tables and a bubble plot.ResultsA total of 38 SRs met the eligibility criteria. After duplicate primary studies were removed, these reviews included 70 primary studies that met the scope of evidence mapping. According to the AMSTAR-2 assessment, the quality of the included SRs was critically low. Of these studies, 34 SRs scored “critically low” in terms of methodological quality, 2 SR scored “low,” 1 SR scored “moderate,” and 1 SR scored “high.”ConclusionEvidence mapping is a useful methodology to provide a comprehensive and reliable overview of studies on rTMS for NP. Evidence mapping also shows that further investigations are necessary to highlight the optimal stimulation protocols and standardize all parameters to fill the evidence gaps of rTMS. Given that the methodological quality of most included SRs was “critically low,” further investigations are advised to improve the methodological quality and the reporting process of SRs. (shrink)

Previous studies have shown that changes in gray matter density and volume in the left primary motor cortex are significantly associated with changes in individuals’ verbal intelligence quotient, but not with their performance intelligence quotient. In the present study, we examined the effects of transcranial direct current stimulation over the left primary motor cortex on performance in intelligence tests. We chose four subtests of the Wechsler Adult Intelligence Scale-Chinese Revised version and randomized participants into anodal, cathodal, (...) and sham groups. We found that anodal stimulation significantly improved performance in verbal intelligence subtests compared to cathodal and sham stimulation, while performance intelligence subtest scores did not change in any stimulation condition. These findings suggest that the excitation level of the left primary motor cortex has a unique effect on verbal intelligence. (shrink)

Acute aerobic exercise has been shown to improve fine motor skills and alter activation of the motor cortex. The intensity of exercise may influence M1 activation, and further impact whole-body motor skill performance. The aims of the current study were to compare a whole-body motor skill via a piano task following moderate-intensity training and high-intensity interval training, and to determine if M1 activation is linked to any such changes in performance. Nine subjects, aged 18 ± (...) 1 years completed a control, MIT, and HIIT trial followed by administration of a piano performance task. M1 activation was evaluated by measuring oxyhemoglobin and hemoglobin difference changes during post-exercise piano performance using functional near-infrared spectroscopy. The results indicate that piano performance scores were higher after the MIT trial, but not HIIT trial, compared to the control trial. A negative relationship was detected between heart rate during HIIT and post-HIIT piano scores. M1 activation was significantly increased after the HIIT trial. M1 activation was also positively associated with piano performance when exercise trials and all trials were combined. We found that acute moderate-intensity exercise led to an improvement in complex motor skill performance while higher-intensity exercise increased M1 activation. These results demonstrate that moderate-intensity exercise can prime the nervous system for the acquisition of whole-body motor skills, suggesting that similar exercise protocols may be effective in improving the outcomes of other motor tasks performed during regular routines of daily life. In addition, it appears that improvements in motor task performance may be driven by M1 activation. Our findings provide new mechanistic insight into the complex relationship between exercise intensity, M1 activation, and whole-body motor skill performance. (shrink)

The contribution of action-perception systems of the brain to lexical semantics remains controversial. Here, we used high-definition transcranial direct current stimulation (HD-tDCS) in healthy adults to examine the role of primary (left hand motor area; HMA) and higher-order (left anterior inferior parietal lobe; aIPL) action areas in action-related word processing (action verbs and manipulable nouns) compared to non-action-related control words (non-action verbs and non-manipulable nouns). We investigated stimulation-related effects at three levels of semantic processing: subliminal, implicit, and explicit. Broadly, (...) we found that stimulation of HMA and aIPL resulted in relative facilitation of action-related language processing compared to non-action. HMA stimulation facilitated action verb processing in subliminal and implicit task contexts, suggesting that HMA helps represent action verbs even in semantically shallow tasks. HMA stimulation also facilitated manipulable noun comprehension in an explicit semantic task, suggesting that HMA contributes to manipulable noun comprehension when semantic demands are high. aIPL stimulation facilitated both manipulable noun and action verb processing during an implicit task. We suggest that both HMA and aIPL play a functional role in action semantics. HMA plays a general role in the semantics of actions and manipulable objects, while aIPL is important only when visuo-motor coordination is required for the action. (shrink)