Neural representations of beat and rhythm in motor and association regions.

Humans perceive a pulse, or beat, underlying musical rhythm. Beat strength correlates with activity in the basal ganglia and supplementary motor area, suggesting these regions support beat perception. However, the basal ganglia and supplementary motor area are part of a general rhythm and timing network (regardless of the beat) and may also represent basic rhythmic features (e.g. tempo, number of onsets). To characterize the encoding of beat-related and other basic rhythmic features, we used representational similarity analysis. During functional magnetic resonance imaging, participants heard 12 rhythms-4 strong-beat, 4 weak-beat, and 4 nonbeat. Multi-voxel activity patterns for each rhythm were tested to determine which brain areas were beat-sensitive: those in which activity patterns showed greater dissimilarities between rhythms of different beat strength than between rhythms of similar beat strength. Indeed, putamen and supplementary motor area activity patterns were significantly dissimilar for strong-beat and nonbeat conditions. Next, we tested whether basic rhythmic features or models of beat strength (counterevidence scores) predicted activity patterns. We found again that activity pattern dissimilarity in supplementary motor area and putamen correlated with beat strength models, not basic features. Beat strength models also correlated with activity pattern dissimilarities in the inferior frontal gyrus and inferior parietal lobe, though these regions encoded beat and rhythm simultaneously and were not driven by beat alone.

Differential Hemodynamic Responses to Motor and Tactile Imagery: Insights from Multichannel fNIRS Mapping.

Tactile and motor imagery are crucial components of sensorimotor functioning and cognitive neuroscience research, yet the neural mechanisms of tactile imagery remain underexplored compared to motor imagery. This study employs multichannel functional near-infrared spectroscopy (fNIRS) combined with image reconstruction techniques to investigate the neural hemodynamics associated with tactile (TI) and motor imagery (MI). In a study of 15 healthy participants, we found that MI elicited significantly greater hemodynamic responses (HRs) in the precentral area compared to TI, suggesting the involvement of different cortical areas involved in two different types of sensorimotor mental imagery. Concurrently, the HRs in S1 and parietal areas exhibited comparable patterns in both TI and MI. During MI, both motor and somatosensory areas demonstrated comparable HRs. However, in TI, somatosensory activation was observed to be more pronounced. Our results highlight the distinctive neural profiles of motor versus tactile imagery and indicate fNIRS technique to be sensitive for this. This distinction is significant for fundamental understanding of sensorimotor integration and for developing advanced neurotechnologies, including imagery-based brain-computer interfaces (BCIs) that can differentiate between different types of mental imagery.

Characteristic Changes of Prefrontal and Motor Areas in Patients with Type 2 Diabetes and Major Depressive Disorder During a Motor Task of Tai Chi Chuan: A Functional Near-Infrared Spectroscopy Study.

AIM: This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. RESULTS: Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

Wide-field calcium imaging of cortical activation and functional connectivity in externally- and internally-driven locomotion.

The role of the cerebral cortex in self-initiated versus sensory-driven movements is central to understanding volitional action. Whether the differences in these two movement classes are due to specific cortical areas versus more cortex-wide engagement is debated. Using wide-field Ca2+ imaging, we compared neural dynamics during spontaneous and motorized treadmill locomotion, determining the similarities and differences in cortex-wide activation and functional connectivity (FC). During motorized locomotion, the cortex exhibits greater activation globally prior to and during locomotion starting compared to spontaneous and less during steady-state walking, during stopping, and after termination. Both conditions are characterized by FC increases in anterior secondary motor cortex (M2) nodes and decreases in all other regions. There are also cortex-wide differences; most notably, M2 decreases in FC with all other nodes during motorized stopping and after termination. Therefore, both internally- and externally-generated movements widely engage the cortex, with differences represented in cortex-wide activation and FC patterns.

Effects of high-definition tDCS targeting individual motor hotspot with EMG-driven robotic hand training on upper extremity motor function: a pilot randomized controlled trial.

BACKGROUND: Delivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors. METHODS: In this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group. RESULTS: HDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation. CONCLUSIONS: Stimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

Embodiment in episodic memory through premotor-hippocampal coupling.

Episodic memory (EM) allows us to remember and relive past events and experiences and has been linked to cortical-hippocampal reinstatement of encoding activity. While EM is fundamental to establish a sense of self across time, this claim and its link to the sense of agency (SoA), based on bodily signals, has not been tested experimentally. Using real-time sensorimotor stimulation, immersive virtual reality, and fMRI we manipulated the SoA and report stronger hippocampal reinstatement for scenes encoded under preserved SoA, reflecting recall performance in a recognition task. We link SoA to EM showing that hippocampal reinstatement is coupled with reinstatement in premotor cortex, a key SoA region. We extend these findings in a severe amnesic patient whose memory lacked the normal dependency on the SoA. Premotor-hippocampal coupling in EM describes how a key aspect of the bodily self at encoding is neurally reinstated during the retrieval of past episodes, enabling a sense of self across time.

Individual contralesional recruitment in the context of structural reserve in early motor reorganization after stroke.

The concept of structural reserve in stroke reorganization assumes that the relevance of the contralesional hemisphere strongly depends on the brain tissue spared by the lesion in the affected hemisphere. Recent studies, however, have indicated that the contralesional hemisphere's impact exhibits region-specific variability with concurrently existing maladaptive and supportive influences. This challenges traditional views, necessitating a nuanced investigation of contralesional motor areas and their interaction with ipsilesional networks. Our study focused on the functional role of contralesional key motor areas and lesion-induced connectome disruption early after stroke. Online TMS data of twenty-five stroke patients was analyzed to disentangle interindividual differences in the functional roles of contralesional primary motor cortex (M1), dorsal premotor cortex (dPMC), and anterior interparietal sulcus (aIPS) for motor function. Connectome-based lesion symptom mapping and corticospinal tract lesion quantification were used to investigate how TMS effects depend on ipsilesional structural network properties. At group and individual levels, TMS interference with contralesional M1 and aIPS but not dPMC led to improved performance early after stroke. At the connectome level, a more disturbing role of contralesional M1 was related to a more severe disruption of the structural integrity of ipsilesional M1 in the affected motor network. In contrast, a detrimental influence of contralesional aIPS was linked to less disruption of the ipsilesional M1 connectivity. Our findings indicate that contralesional areas distinctively interfere with motor performance early after stroke depending on ipsilesional structural integrity, extending the concept of structural reserve to regional specificity in recovery of function.

Evaluation of Driver's Brain Activity Associated with Advanced Driving Skills Such as Cornering.

Evaluating the driving ability of a vehicle is important in the development of in-vehicle systems and the training of driving skills. Driving ability has been investigated extensively in terms of recognition, judgment, and operation. However, the role of the brain in advanced driving operations within the limits of vehicle performance has not been thoroughly investigated. In this study, we perform functional magnetic resonance imaging to evaluate brain functions associated with advanced driving skills when drivers are shown a video of cornering involving a vehicle slipping sideways. Based on the results, the skilled driver group indicates broad activity in both the right and left parietal associations, right-side primary somatosensory, left-side premotor, and supplementary motor areas. Because the premotor cortex is a region involved in the execution of movement, whereas the supplementary motor cortex is a region involved in spontaneous movement, it is assumed that the skilled drivers visualized the driving operation, and that the brain functions necessary for the operation are activated. These findings indicate that drivers with high skill levels exhibit distinctive brain activities. We believe that a further understanding regarding the brains of skilled drivers will facilitate the development of in-vehicle control that incorporates high driving skills and training.

Cerebellar Metabolic Connectivity during Treadmill Walking before and after Unilateral Dopamine Depletion in Rats.

Compensatory changes in brain connectivity keep motor symptoms mild in prodromal Parkinson's disease. Studying compensation in patients is hampered by the steady progression of the disease and a lack of individual baseline controls. Furthermore, combining fMRI with walking is intricate. We therefore used a seed-based metabolic connectivity analysis based on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake in a unilateral 6-OHDA rat model. At baseline and in the chronic phase 6-7 months after lesion, rats received an intraperitoneal injection of [18F]FDG and spent 50 min walking on a horizontal treadmill, followed by a brain PET-scan under anesthesia. High activity was found in the cerebellar anterior vermis in both conditions. At baseline, the anterior vermis showed hardly any stable connections to the rest of the brain. The (future) ipsilesional cerebellar hemisphere was not particularly active during walking but was extensively connected to many brain areas. After unilateral dopamine depletion, rats still walked normally without obvious impairments. The ipsilesional cerebellar hemisphere increased its activity, but narrowed its connections down to the vestibulocerebellum, probably aiding lateral stability. The anterior vermis established a network involving the motor cortex, hippocampus and thalamus. Adding those regions to the vermis network of (previously) automatic control of locomotion suggests that after unilateral dopamine depletion considerable conscious and cognitive effort has to be provided to achieve stable walking.

Sensory and motor cortices parcellations estimated via distance-weighted sparse representation with application to autism spectrum disorder.

BACKGROUND: Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. METHODS: Resting-state functional magnetic resonance imaging data (NTD = 266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. RESULTS: We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (p < 0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (p < 0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (p < 0.05/80). LIMITATIONS: The generalizability of the segmentation model requires further evaluation. CONCLUSIONS: This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD.

A visual representation of the hand in the resting somatomotor regions of the human brain.

Hand visibility affects motor control, perception, and attention, as visual information is integrated into an internal model of somatomotor control. Spontaneous brain activity, i.e., at rest, in the absence of an active task, is correlated among somatomotor regions that are jointly activated during motor tasks. Recent studies suggest that spontaneous activity patterns not only replay task activation patterns but also maintain a model of the body's and environment's statistical regularities (priors), which may be used to predict upcoming behavior. Here, we test whether spontaneous activity in the human somatomotor cortex as measured using fMRI is modulated by visual stimuli that display hands vs. non-hand stimuli and by the use/action they represent. A multivariate pattern analysis was performed to examine the similarity between spontaneous activity patterns and task-evoked patterns to the presentation of natural hands, robot hands, gloves, or control stimuli (food). In the left somatomotor cortex, we observed a stronger (multivoxel) spatial correlation between resting state activity and natural hand picture patterns compared to other stimuli. No task-rest similarity was found in the visual cortex. Spontaneous activity patterns in somatomotor brain regions code for the visual representation of human hands and their use.

Concurrent tDCS-fMRI after stroke reveals link between attention network organization and motor improvement.

Restoring motor function after stroke necessitates involvement of numerous cognitive systems. However, the impact of damage to motor and cognitive network organization on recovery is not well understood. To discover correlates of successful recovery, we explored imaging characteristics in chronic stroke subjects by combining noninvasive brain stimulation and fMRI. Twenty stroke survivors (6 months or more after stroke) were randomly assigned to a single session of transcranial direct current stimulation (tDCS) or sham during image acquisition. Twenty healthy subjects were included as controls. tDCS was limited to 10 min at 2 mA to serve as a mode of network modulation rather than therapeutic delivery. Fugl-Meyer Assessments (FMA) revealed significant motor improvement in the chronic stroke group receiving active stimulation (p = 0.0005). Motor changes in this group were correlated in a data-driven fashion with imaging features, including functional connectivity (FC), surface-based morphometry, electric field modeling and network topology, focusing on relevant regions of interest. We observed stimulation-related changes in FC in supplementary motor (p = 0.0029), inferior frontal gyrus (p = 0.0058), and temporo-occipital (p = 0.0095) areas, though these were not directly related to motor improvement. The feature most strongly associated with FMA improvement in the chronic stroke cohort was graph topology of the dorsal attention network (DAN), one of the regions surveyed and one with direct connections to each of the areas with FC changes. Chronic stroke subjects with a greater degree of motor improvement had lower signal transmission cost through the DAN (p = 0.029). While the study was limited by a small stroke cohort with moderate severity and variable lesion location, these results nevertheless suggest a top-down role for higher order areas such as attention in helping to orchestrate the stroke recovery process.

Neuroimaging of motor recovery after ischemic stroke - functional reorganization of motor network.

The long-term motor outcome of acute stroke patients may be correlated to the reorganization of brain motor network. Abundant neuroimaging studies contribute to understand the pathological changes and recovery of motor networks after stroke. In this review, we summarized how current neuroimaging studies have increased understanding of reorganization and plasticity in post stroke motor recovery. Firstly, we discussed the changes in the motor network over time during the motor-activation and resting states, as well as the overall functional integration trend of the motor network. These studies indicate that the motor network undergoes dynamic bilateral hemispheric functional reorganization, as well as a trend towards network randomization. In the second part, we summarized the current study progress in the application of neuroimaging technology to early predict the post-stroke motor outcome. In the third part, we discuss the neuroimaging techniques commonly used in the post-stroke recovery. These methods provide direct or indirect visualization patterns to understand the neural mechanisms of post-stroke motor recovery, opening up new avenues for studying spontaneous and treatment-induced recovery and plasticity after stroke.

Neural networks associated with eye movements in congenital blindness.

Recent studies have shown that during the typical resting-state, echo planar imaging (EPI) time series obtained from the eye orbit area correlate with brain regions associated with oculomotor control and lower-level visual cortex. Here, we asked whether congenitally blind (CB) shows similar patterns, suggesting a hard-wired constraint on connectivity. We find that orbital EPI signals in CB do correlate with activity in the motor cortex, but less so with activity in the visual cortex. However, the temporal patterns of this eye movement-related signal differed strongly between CB and sighted controls. Furthermore, in CB, a few participants showed uncoordinated orbital EPI signals between the two eyes, each correlated with activity in different brain networks. Our findings suggest a retained circuitry between motor cortex and eye movements in blind, but also a moderate reorganization due to the absence of visual input, and the inability of CB to control their eye movements or sense their positions.

Identifying biomarkers related to motor function in chronic stroke: A fNIRS and TMS study.

BACKGROUND: Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits. METHOD: Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl-Meyer scores. Resting-state FC was assessed using functional near-infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation. RESULTS: Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex-primary motor cortex (PMC-M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ2 = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC-M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86). CONCLUSION: Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network-based therapies targeting predictive biomarkers to improve rehabilitation outcomes.

Tumor-Specific Alterations in Motor Cortex Excitability and Tractography of the Corticospinal Tract-A Navigated Transcranial Magnetic Stimulation Study.

BACKGROUND: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. METHODS: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance - LTD) were measured. RESULTS: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p < 0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). CONCLUSIONS: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas.

Structural and functional features characterizing the brains of individuals with higher controllability of motor imagery.

Motor imagery is a higher-order cognitive brain function that mentally simulates movements without performing the actual physical one. Although motor imagery has attracted the interest of many researchers, and mental practice utilizing motor imagery has been widely used in sports training and post-stroke rehabilitation, neural bases that determine individual differences in motor imagery ability are not well understood. In this study, using controllability of motor imagery (CMI) test that can objectively evaluate individual ability to manipulate one's imaginary postures, we examined structural and functional features characterizing the brains of individuals with higher controllability of motor imagery, by analyzing T1-weighted structural MRI data obtained from 89 participants and functional MRI data obtained from 28 of 89 participants. The higher CMI test scorers had larger volume in the bilateral superior frontoparietal white matter regions. The CMI test activated the bilateral dorsal premotor cortex (PMD) and superior parietal lobule (SPL); specifically, the left PMD and/or the right SPL enhanced functional coupling with the visual body, somatosensory, and motor/kinesthetic areas in the higher scorers. Hence, controllability of motor imagery is higher for those who well-develop superior frontoparietal network, and for those whose this network accesses these sensory areas to predict the expected multisensory experiences during motor imagery. This study elucidated for the first time the structural and functional features characterizing the brains of individuals with higher controllability of motor imagery, and advanced understanding of individual differences in motor imagery ability.

Motor cortex activation mediates associations between striatal dopamine depletion and manual dexterity in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) presents with a progressive decline in manual dexterity, attributed to dysfunction in the basal ganglia-thalamus-cortex loop, influenced by dopaminergic deficits in the striatum. Recent research suggests that the motor cortex may play a pivotal role in mediating the relationship between striatal dopamine depletion and motor function in PD. Understanding this connection is crucial for comprehending the origins of manual dexterity impairments in PD. Therefore, our study aimed to explore how motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD. MATERIALS AND METHODS: We enrolled 26 mildly affected PD patients in their off-medication phase to undergo [18F]FDOPA PET/CT scans for evaluating striatal dopaminergic function. EEG recordings were conducted during bimanual anti-phase finger tapping tasks to evaluate motor cortex activity, specifically focusing on Event-Related Desynchronization in the beta band. Manual dexterity was assessed using the Purdue Pegboard Test. Regression-based mediation analysis was conducted to examine whether motor cortex activation mediates the association between striatal dopamine depletion and manual dexterity in PD. RESULTS: Mediation analysis revealed a significant direct effect of putamen dopamine depletion on manual dexterity for the affected hand and assembly tasks (performed with two hands), with motor cortex activity mediating this association. In contrast, while caudate nucleus dopamine depletion showed a significant direct effect on manual dexterity, motor cortex mediation on this association was not observed. CONCLUSION: Our study confirms the association between striatum dopamine depletion and impaired manual dexterity in PD, with motor cortex activity mediating this relationship.

Brain activity changes after high/low frequency stimulation in a nonhuman primate model of central post-stroke pain.

Central post-stroke pain (CPSP) is a chronic pain resulting from a lesion in somatosensory pathways. Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) that target the primary motor cortex (M1), have shown promise for the treatment of CPSP. High-frequency (Hf) rTMS exhibits analgesic effects compared to low-frequency (Lf) rTMS; however, its analgesic mechanism is unknown. We aimed to elucidate the mechanism of rTMS-induced analgesia by evaluating alterations of tactile functional magnetic resonance imaging (fMRI) due to Hf- and Lf-rTMS in a CPSP monkey model. Consistent with the patient findings, the monkeys showed an increase in pain threshold after Hf-rTMS, which indicated an analgesic effect. However, no change after Lf-rTMS was observed. Compared to Lf-rTMS, Hf-rTMS produced enhanced tactile-evoked fMRI signals not only in M1 but also in somatosensory processing regions, such as the primary somatosensory and midcingulate cortices. However, the secondary somatosensory cortex (S2) was less active after Hf-rTMS than after Lf-rTMS, suggesting that activation of this region was involved in CPSP. Previous studies showed pharmacological inhibition of S2 reduces CPSP-related behaviors, and the present results emphasize the involvement of an S2 inhibitory system in rTMS-induced analgesia. Verification using the monkey model is important to elucidate the inhibition system.

Gradient of microstructural damage along the dentato-thalamo-cortical tract in Friedreich ataxia.

OBJECTIVE: The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. METHODS: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross-sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. RESULTS: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. INTERPRETATION: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex.