Distinct neural mechanisms for action access and execution in the human brain: insights from an fMRI study.

Goal-directed actions are fundamental to human behavior, whereby inner goals are achieved through mapping action representations to motor outputs. The left premotor cortex (BA6) and the posterior portion of Broca's area (BA44) are two modulatory poles of the action system. However, how these regions support the representation-output mapping within the system is not yet understood. To address this, we conducted a finger-tapping functional magnetic resonance imaging experiment using action categories ranging from specific to general. Our study found distinct neural behaviors in BA44 and BA6 during action category processing and motor execution. During access of action categories, activity in a posterior portion of BA44 (pBA44) decreased linearly as action categories became less specific. Conversely, during motor execution, activity in BA6 increased linearly with less specific categories. These findings highlight the differential roles of pBA44 and BA6 in action processing. We suggest that pBA44 facilitates access to action categories by utilizing motor information from the behavioral context while the premotor cortex integrates motor information to execute the selected action. This finding enhances our understanding of the interplay between prefrontal cortical regions and premotor cortex in mapping action representation to motor execution and, more in general, of the cortical mechanisms underlying human behavior.

Functional Integration of the Subregions of the Primary Motor Cortex: The Impact of Handedness and Hemispheric Lateralization.

OBJECTIVE: Cytoarchitectonic mapping has revealed distinct subregions within Broadmann area 4 (BA 4) - BA 4a and BA 4p - with varying functional roles across tasks. We investigate their functional connectivity using resting-state functional magnetic resonance imaging (rsfMRI) to explore bilateral differences and the impact of handedness on connectivity within major brain networks. METHODS: This retrospective study involved 54 left- and right-handed subjects. We employed regions-to-regions-network rsfMRI analysis to examine the Cytoarchitectonic mapping of BA 4a and BA 4p functional connectivity with eight major brain networks. RESULTS: Our findings reveal differential connectivity patterns in both right-handed and left-handed subjects: Both right-handed subjects' BA 4a and BA 4p subregions exhibit connections to sensorimotor, dorsal attention, frontoparietal, and anterior cerebellar networks. Notably, BA 4a shows unique connectivity to the posterior cerebellum, lateral visual networks, and select salience regions. Similar connectivity patterns are observed in left-handed subjects, with BA 4a linked to sensorimotor, dorsal attention, frontoparietal, and anterior cerebellar networks. However, BA 4a in left-handed subjects shows distinct connectivity only to the posterior cerebellum. In both groups, the right portion of BA 4 demonstrates heightened connectivity compared to the left portion within each subregion. CONCLUSION: Our study uncovers complex patterns of functional connectivity within BA 4a and BA 4p, influenced by handedness. These findings emphasize the importance of considering hemisphere-specific and handedness-related factors in functional connectivity analyses, with potential implications for understanding brain organization in health and neurodegenerative diseases.

Abnormal supplementary motor areas are associated with idiopathic and acquired blepharospasm.

Blepharospasm is a common form of focal dystonia characterized by excessive and involuntary spasms of the orbicularis oculi. In addition to idiopathic blepharospasm, lesions in various brain regions can also cause acquired blepharospasm. Whether these two types of blepharospasm share a common brain network remains largely unknown. Herein, we performed lesion coactivation network mapping, based on meta-analytic connectivity modeling, to test whether lesions causing blepharospasm could be mapped to a common coactivation brain network. We then tested the abnormality of the network in patients with idiopathic blepharospasm (n = 42) compared with healthy controls (n = 44). We identified 21 cases of lesion-induced blepharospasms through a systematic literature search. Although these lesions were heterogeneous, they were part of a co-activated brain network that mainly included the bilateral supplementary motor areas. Coactivation of these regions defines a single brain network that encompasses or is adjacent to most heterogeneous lesions causing blepharospasm. Moreover, the bilateral supplementary motor area is primarily associated with action execution, visual motion, and imagination, and participates in finger tapping and saccades. They also reported decreased functional connectivity with the left posterior cingulate cortex in patients with idiopathic blepharospasm. These results demonstrate a common convergent abnormality of the supplementary motor area across idiopathic and acquired blepharospasms, providing additional evidence that the supplementary motor area is an important brain region that is pathologically impaired in patients with blepharospasm.

Beyond boundaries: investigating shared and divergent connectivity in the pre-/postcentral gyri and supplementary motor area.

OBJECTIVE: This study aimed to comprehensively investigate the functional connectivity of key brain regions involved in motor and sensory functions, namely the precentral gyrus, postcentral gyrus and supplementary motor area (SMA). Using advanced MRI, the objective was to understand the neurophysiological integrative characterizations of these regions by examining their connectivity with eight distinct functional brain networks. The goal was to uncover their roles beyond conventional motor and sensory functions, contributing to a more holistic understanding of brain functioning. METHODS: The study involved 198 healthy volunteers, with the primary methodology being functional connectivity analysis using advanced MRI techniques. The bilateral precentral gyrus, postcentral gyrus and SMA served as seed regions, and their connectivity with eight distinct brain regional functional networks was investigated. This approach allowed for the exploration of synchronized activity between these critical brain areas, shedding light on their integrated functioning and relationships with other brain networks. RESULTS: The study revealed a nuanced landscape of functional connectivity for the precentral gyrus, postcentral gyrus and SMA with the main functional brain networks. Despite their high functional connectedness, these regions displayed diverse functional integrations with other networks, particularly in the salience, visual, cerebellar and language networks. Specific data and statistical significance were not provided in the abstract, but the results suggested unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor and sensory functions. CONCLUSION: The study emphasized the multifaceted roles of the precentral gyrus, postcentral gyrus and SMA. Beyond their crucial involvement in motor and sensory functions, these regions exhibited varied functional integrations with different brain networks. The observed disparities, especially in the salience, visual, cerebellar and language networks, indicated a nuanced and specialized involvement of these regions in diverse cognitive functions. The study underscores the importance of considering the broader neurophysiological landscape to comprehend the intricate roles of these brain areas, contributing to ongoing efforts in unraveling the complexities of brain function.

Impact of augmented reality fiber tractography on the extent of resection and functional outcome of primary motor area tumors.

OBJECTIVE: This study aimed to evaluate the impact of augmented reality intraoperative fiber tractography (AR-iFT) on extent of resection (EOR), motor functional outcome, and survival of patients with primary motor area (M1) intra-axial malignant tumors. METHODS: Data obtained from patients who underwent AR-iFT for M1 primary tumors were retrospectively analyzed and compared with those from a control group who underwent unaugmented reality intraoperative fiber tractography (unAR-iFT). A full asleep procedure with electrical stimulation mapping and fluorescein guidance was performed in both groups. The Neurological Assessment in Neuro-Oncology (NANO), Medical Research Council (MRC), and House-Brackmann grading systems were used for neurological, motor, and facial nerve assessment, respectively. Three-month postoperative NANO and MRC scores were used as outcome measures of the safety of the technique, whereas EOR and survival curves were related to its cytoreductive efficacy. In this study, p < 0.05 indicated statistical significance. RESULTS: This study included 34 and 31 patients in the AR-iFT and unAR-iFT groups, respectively. The intraoperative seizure rate, 3-month postoperative NANO score, and 1-week and 1-month MRC scores were significantly (p < 0.05) different and in favor of the AR-iFT group. However, no difference was observed in the rate of complications. Glioma had incidence rates of 58.9% and 51.7% in the study and control groups, respectively, with no statistical difference. Metastasis had a slightly higher incidence rate in the control group, without statistical significance, and the gross-total resection and near-total resection rates and progression-free survival (PFS) rate were higher in the study group. Overall survival was not affected by the technique. CONCLUSIONS: AR-iFT proved to be feasible, effective, and safe during surgery for M1 tumors and positively affected the EOR, intraoperative seizure rate, motor outcome, and PFS. Integration with electrical stimulation mapping is critical to achieve constant anatomo-functional intraoperative feedback. The accuracy of AR-iFT is intrinsically limited by diffusion tensor-based techniques, parallax error, and fiber tract crowding. Further studies are warranted to definitively validate the benefits of augmented reality navigation in this surgical scenario.

Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans.

BACKGROUND: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. OBJECTIVE/HYPOTHESIS: The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. METHODS: We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). RESULTS: Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. CONCLUSIONS: Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. MATERIALS AND METHODS: Eleven patients with CRPS at one limb (six women, five men, aged 52.0 ± 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as ≥30% reduction in VNS pain score one month after treatment compared with baseline. RESULTS: At baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. CONCLUSIONS: This study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT02817880.

A custom MR-compatible dataglove for fMRI of the human motor cortex at 7T.

We present a custom-built MR-compatible data glove to capture hand motion during concurrent fMRI experiments at 7 Tesla. Thermal and phantom tests showed our data glove can be used safely and without degradation of image quality. Subject-specific Blood Oxygen Level Dependent (BOLD) signal models, for use in fMRI analysis, were constructed based on recorded kinematic measurements. Experiments revealed the relative fMRI BOLD signal contribution of flexing, extending, and sustained isotonic extension. The ability to evaluate subject performance in real-time and create subject-specific BOLD signal models enables a wide range of experimental paradigms with improved data quality.Clinical Relevance- Using an MR compatible dataglove, subject specific Blood Oxygen Signal Level Dependent (BOLD) signal models can be constructed to study how the brain implements fine motor control.

Exaggerated High-Beta Oscillations are Associated with Cortical Thinning at the Motor Cortex in Parkinson's Disease.

Elevated ß oscillations (13-35 Hz) are characteristic pathophysiology in Parkinson's Disease (PD). Cortical thinning has also been reported in the disease, however the relationship between these biomarkers of PD has not been established. By comparing electrophysiological measurements with cortical thickness, this study aims to reveal the pathoetiology of disease and symptoms in PD. Preoperative magnetic resonance imaging (MRI) and intraoperative local field potentials (LFPs) were collected from 34 subjects diagnosed with PD. Cortical surfaces were reconstructed from the images, and cortical thickness was extracted from the subregions where the recording electrode was placed in M1. LFPs were preprocessed and cleaned using a semiautomatic artifact detection algorithm, then power spectral densities (PSD) were computed and periodic and aperiodic frequency components were calculated. Nonparametric Spearman rank correlations assessed the relationship between electrophysiological components (i.e. center frequency (CF), power, bandwidth, 1/f exponent, knee), with cortical thickness. According to the CF of each subject's PSD, the cohort was split into two sub-groups: low-ß peak (13-20 Hz) and high-ß peak (20-35 Hz) groups. There was a significant negative correlation between power and cortical thickness only in the high-ß subgroup (r=-0.48, p(corrected)=0.049). This relationship remained significant when correcting for age (r=-0.52,p=0.015), indicating that the effect of age on cortical thinning was not the determining factor. We did not find significant differences between UPDRS-III motor symptom scores for the low-and high-ß subgroups. Of note is the dominance of high-ß oscillatory power and its relationship with cortical thickness. As suggested by the literature, increased high-ß activity during movement may be exaggerated in PD. These findings suggest that the characteristic cortical thinning in PD causes variation in electrical activity, leading to elevated high-ß activity.Clinical relevance- This multimodal study provides additional insights on the pathophysiology and its relevance with morphology of Parkinson's Disease.

Regular cannabis use alters the neural dynamics serving complex motor control.

Cannabis is the most widely used recreational drug in the United States and regular use has been linked to deficits in attention and memory. However, the effects of regular use on motor control are less understood, with some studies showing deficits and others indicating normal performance. Eighteen users and 23 nonusers performed a motor sequencing task during high-density magnetoencephalography (MEG). The MEG data was transformed into the time-frequency domain and beta responses (16-24 Hz) during motor planning and execution phases were imaged separately using a beamformer approach. Whole-brain maps were examined for group (cannabis user/nonuser) and time window (planning/execution) effects. As expected, there were no group differences in task performance (e.g., reaction time, accuracy, etc.). Regular cannabis users exhibited stronger beta oscillations in the contralateral primary motor cortex compared to nonusers during the execution phase of the motor sequences, but not during the motor planning phase. Similar group-by-time window interactions were observed in the left superior parietal, right inferior frontal cortices, right posterior insular cortex, and the bilateral motor cortex. We observed differences in the neural dynamics serving motor control in regular cannabis users compared to nonusers, suggesting regular users may employ compensatory processing in both primary motor and higher-order motor cortices to maintain adequate task performance. Future studies will need to examine more complex motor control tasks to ascertain whether this putative compensatory activity eventually becomes exhausted and behavioral differences emerge.

Degeneracy in the neurological model of auditory speech repetition.

Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage.

Association between activity in the ventral premotor cortex and spinal cord activation during force generation-A combined cortico-spinal fMRI study.

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is associated with the activity in the cerebral primary motor and premotor areas is poorly understood. Here, we conducted combined cortico-spinal functional magnetic resonance imaging during a simple visually guided isometric force generation task in 20 healthy young subjects. Activation was localized in the right cervical spinal cord and left primary motor and premotor areas. The main finding is that spinal activation was negatively correlated with ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation, while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding that extends our understanding of human motor function beyond the animal literature.

Altered effective connectivity from cerebellum to motor cortex in chronic low back pain: A multivariate pattern analysis and spectral dynamic causal modeling study.

To explore the central processing mechanism of pain perception in chronic low back pain (cLBP) using multi-voxel pattern analysis (MVPA) based on the static and dynamic fractional amplitude of low-frequency fluctuations (fALFF) analysis, and spectral dynamic causal modeling (spDCM). Thirty-two patients with cLBP and 29 matched healthy controls (HCs) for the first cohort and 24 patients with cLBP and 22 HCs for the validation cohort underwent resting-state fMRI scan. The alterations in static and dynamic fALFF were as classification features to distinguish patients with cLBP from HCs. The brain regions gotten from the MVPA results were used for further spDCM analysis. We found that the most discriminative brain regions that contributed to the classification were the right supplementary motor area (SMA.R), left paracentral lobule (PCL.L), and bilateral cerebellar Crus II. The spDCM results displayed decreased excitatory influence from the bilateral cerebellar Crus II to PCL.L in patients with cLBP compared with HCs. Moreover, the conversion of effective connectivity from the bilateral cerebellar Crus II to SMA.R from excitatory influence to inhibitive influence, and the effective connectivity strength exhibited partially mediated effects on Chinese Short Form Oswestry Disability Index Questionnaire (C-SFODI) scores. Our findings suggest that the cerebellum and its weakened or inhibited connections to the motor cortex may be one of the underlying feedback pathways for pain perception in cLBP, and partially mediate the degree of dysfunction.

Intraoperative Augmented Reality Fiber Tractography for Primary Motor Area Glioma Resection.

The implementation of intraoperative augmented reality fiber tractography (iAR-FT) into the surgical workflow for high-grade supratentorial gliomas has been shown to be effective and safe in maximizing the extent of resection and progression-free survival through the surgeon's enhanced 3-dimensional awareness of the spatial localization of fiber tracts.1-3 Primary motor area tumors present special challenges due to the high eloquence of the precentral gyrus and risk of postoperative onset or worsening of motor deficits, as well as limited postoperative plasticity.4 Although essential, electrical stimulation mapping (ESM) techniques have a number of limitations with respect to primary motor pathways, including a higher risk of intraoperative stimulation-evoked seizures, a risk of false negatives in the presence of preoperative deficits, a nonnegligible risk of permanent deterioration even in the presence of negative stimulation maps, and, most importantly, limited spatial resolution.4-8 The rationale for integrating ESM and iAR-FT is to compensate for the limitations of the former in terms of morphologic and spatial representation of fiber tracts. The benefits of coupling iAR-FT with ESM techniques allow for continuous integrated anatomical-functional feedback during surgery. In Video 1 we describe the key technical aspects and benefits of iAR-FT-assisted surgery for maximal safe gross total resection of a primary motor area grade IV astrocytoma.

Connecting the dots: harnessing dual-site transcranial magnetic stimulation to quantify the causal influence of medial frontal areas on the motor cortex.

Dual-site transcranial magnetic stimulation has been widely employed to investigate the influence of cortical structures on the primary motor cortex. Here, we leveraged this technique to probe the causal influence of two key areas of the medial frontal cortex, namely the supplementary motor area and the medial orbitofrontal cortex, on primary motor cortex. We show that supplementary motor area stimulation facilitates primary motor cortex activity across short (6 and 8 ms) and long (12 ms) inter-stimulation intervals, putatively recruiting cortico-cortical and cortico-subcortico-cortical circuits, respectively. Crucially, magnetic resonance imaging revealed that this facilitatory effect depended on a key morphometric feature of supplementary motor area: individuals with larger supplementary motor area volumes exhibited more facilitation from supplementary motor area to primary motor cortex for both short and long inter-stimulation intervals. Notably, we also provide evidence that the facilitatory effect of supplementary motor area stimulation at short intervals is unlikely to arise from spinal interactions of volleys descending simultaneously from supplementary motor area and primary motor cortex. On the other hand, medial orbitofrontal cortex stimulation moderately suppressed primary motor cortex activity at both short and long intervals, irrespective of medial orbitofrontal cortex volume. These results suggest that dual-site transcranial magnetic stimulation is a fruitful approach to investigate the differential influence of supplementary motor area and medial orbitofrontal cortex on primary motor cortex activity, paving the way for the multimodal assessment of these fronto-motor circuits in health and disease.

The gray matter atrophy and related network changes occur in the higher cognitive region rather than the primary sensorimotor cortex after spinal cord injury.

Objective: This study used functional magnetic resonance imaging (fMRI) to explore brain structural and related network changes in patients with spinal cord injury (SCI). Methods: Thirty-one right-handed SCI patients and 31 gender- and age-matched healthy controls (HC) were included. The gray matter volume (GMV) changes in SCI patients were observed using voxel-based morphometry (VBM). Then, these altered gray matter clusters were used as the regions of interest (ROIs) for whole-brain functional connectivity (FC) analysis to detect related functional changes. The potential association between GMV and FC values with the visual analog scale (VAS), the American Spinal Injury Association (ASIA) score, and the course of injuries was investigated through partial correlation analysis. Results: GMV of the frontal, temporal, and insular cortices was lower in the SCI group than in the HC group. No GMV changes were found in the primary sensorimotor area in the SCI group. Besides, the altered FC regions were not in the primary sensorimotor area but in the cingulate gyrus, supplementary motor area, precuneus, frontal lobe, and insular. Additionally, some of these altered GMV and FC regions were correlated with ASIA motor scores, indicating that higher cognitive regions can affect motor function in SCI patients. Conclusions: This study demonstrated that gray matter and related network reorganization in patients with SCI occurred in higher cognitive regions. Future rehabilitation strategies should focus more on cognitive functions.

Predicting the hotspot location and motor threshold prior to transcranial magnetic stimulation using electric field modelling.

Objective.To investigate whether the motor threshold (MT) and the location of the motor hotspot in transcranial magnetic stimulation (TMS) can be predicted with computational models of the induced electric field.Approach.Individualized computational models were constructed from structural magnetic resonance images of ten healthy participants, and the induced electric fields were determined with the finite element method. The models were used to optimize the location and direction of the TMS coil on the scalp to produce the largest electric field at a predetermined cortical target location. The models were also used to predict how the MT changes as the magnetic coil is moved to various locations over the scalp. To validate the model predictions, the motor evoked potentials were measured from the first dorsal interosseous (FDI) muscle with TMS in the ten participants. Both computational and experimental methods were preregistered prior to the experiments.Main results.Computationally optimized hotspot locations were nearly as accurate as those obtained using manual hotspot search procedures. The mean Euclidean distance between the predicted and the measured hotspot locations was approximately 1.3 cm with a 0.8 cm bias towards the anterior direction. Exploratory analyses showed that the bias could be removed by changing the cortical target location that was used for the prediction. The results also indicated a statistically significant relationship (p< 0.001) between the calculated electric field and the MT measured at several locations on the scalp.Significance.The results show that the individual TMS hotspot can be located using computational analysis without stimulating the subject or patient even once. Adapting computational modelling would save time and effort in research and clinical use of TMS.

TMS over the pre-SMA enhances semantic cognition via remote network effects on task-based activity and connectivity.

BACKGROUND: The continuous decline of executive abilities with age is mirrored by increased neural activity of domain-general networks during task processing. So far, it remains unclear how much domain-general networks contribute to domain-specific processes such as language when cognitive demands increase. The current neuroimaging study explored the potential of intermittent theta-burst stimulation (iTBS) over a domain-general hub to enhance executive and semantic processing in healthy middle-aged to older adults. METHODS: We implemented a cross-over within-subject study design with three task-based neuroimaging sessions per participant. Using an individualized stimulation approach, each participant received once effective and once sham iTBS over the pre-supplementary motor area (pre-SMA), a region of domain-general control. Subsequently, task-specific stimulation effects were assessed in functional MRI using a semantic and a non-verbal executive task with varying cognitive demand. RESULTS: Effective stimulation increased activity only during semantic processing in visual and dorsal attention networks. Further, iTBS induced increased seed-based connectivity in task-specific networks for semantic and executive conditions with high cognitive load but overall reduced whole-brain coupling between domain-general networks. Notably, stimulation-induced changes in activity and connectivity related differently to behavior: While stronger activity of the parietal dorsal attention network was linked to poorer semantic performance, its enhanced coupling with the pre-SMA was associated with more efficient semantic processing. CONCLUSIONS: iTBS modulates networks in a task-dependent manner and generates effects at regions remote to the stimulation site. These neural changes are linked to more efficient semantic processing, which underlines the general potential of network stimulation approaches in cognitive aging.

Neuromodulation of the Left Inferior Frontal Cortex Affects Social Monitoring during Motor Interactions.

Motor interactions require observing and monitoring a partner's performance as the interaction unfolds. Studies in monkeys suggest that this form of social monitoring might be mediated by the activity of the ventral premotor cortex (vPMc), a critical brain region in action observation and motor planning. Our previous fMRI studies in humans showed that the left vPMc is indeed recruited during social monitoring, but its causal role is unexplored. In three experiments, we applied online anodal or cathodal transcranial direct current stimulation over the left lateral frontal cortex during a music-like interactive task to test the hypothesis that neuromodulation of the left vPMc affects participants' performance when a partner violates the agent's expectations. Participants played short musical sequences together with a virtual partner by playing one note each in turn-taking. In 50% of the trials, the partner violated the participant's expectations by generating the correct note through an unexpected movement. During sham stimulation, the partner's unexpected behavior led to a slowdown in the participant's performance (observation-induced posterror slowing). A significant interaction with the stimulation type showed that cathodal and anodal transcranial direct current stimulation induced modulation of the observation-induced posterror slowing in opposite directions by reducing or enhancing it, respectively. Cathodal stimulation significantly reduced the effect compared to sham stimulation. No effect of neuromodulation was found when the partner behaved as expected or when the observed violation occurred within a context that was perceptually matched but noninteractive in nature. These results provide evidence for the critical causal role that the left vPMc might play in social monitoring during motor interactions, possibly through the interplay with other brain regions in the posterior medial frontal cortex.