Precise motor rhythmicity relies on motor network responsivity.

Rhythmic movements are the building blocks of human behavior. However, given that rhythmic movements are achieved through complex interactions between neural modules, it remains difficult to clarify how the central nervous system controls motor rhythmicity. Here, using a novel tempo-precision trade-off paradigm, we first modeled interindividual behavioral differences in tempo-dependent rhythmicity for various external tempi. We identified 2 behavioral extremes: conventional and paradoxical tempo-precision trade-off types. We then explored the neural substrates of these behavioral differences using task and resting-state functional magnetic resonance imaging. We found that the responsibility of interhemispheric motor network connectivity to tempi was a key to the behavioral repertoire. In the paradoxical trade-off type, interhemispheric connectivity was low at baseline but increased in response to increasing tempo; in the conventional trade-off type, strong baseline connectivity was coupled with low responsivity. These findings suggest that tunable interhemispheric connectivity underlies tempo-dependent rhythmicity control.

Structural neuroplasticity in computer programming beginners.

We examined the structural neuroplastic changes associated with the learning of computer programming in university students with no previous programming experience. They participated in a 15-week course (26 lessons) on the "Processing" computer programming language. We have conducted a longitudinal analysis of gray matter volume (GMV) in the magnetic resonance images obtained before and after learning computer programming. Significant neuroplastic changes appeared in the following 8 sites: the left frontal pole; the right frontal pole; the right medial frontal gyrus; the left cuneus; the left lateral cerebellum (posterior lobule and tuber); the medial cerebellum (uvula and tonsil); the right pallidum; and the left pallidum. The amount of change in the GMV of the right frontal pole correlated positively with the final product score. Furthermore, the amount of change in the GMV of the right medial frontal gyrus and the bilateral pallidum correlated positively with the test scores. Thus, the right frontal pole was presumably associated with the function of persistent attempts to accomplish tasks (goal achievement-related function). The right medial frontal gyrus and the bilateral pallidum were presumably related to deduction and reward functions, respectively. Therefore, multiple brain regions appear to be involved in programming learning through different functions.

Identifying and reverting the adverse effects of white matter hyperintensities on cortical surface analyses.

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.

Contribution of amyloid and putative Lewy body pathologies in neuropsychiatric symptoms.

OBJECTIVES: Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB. METHODS: One hundred and three participants without dementia aged ≥50 years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT-SPECT): Group 1: amyloid-positive and abnormal DAT-SPECT, Group 2: amyloid-negative and abnormal DAT-SPECT, Group 3: amyloid-positive and normal DAT-SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT-SPECT, and Group 5: cognitively normal with amyloid-negative and normal DAT-SPECT. RESULTS: The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni-corrected p = 0.012). The MBI total score (Bonferroni-corrected p = 0.011) and MBI impulse dyscontrol score (Bonferroni-corrected p = 0.033) in Group 4 were significantly higher than those in Group 5. CONCLUSION: The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms.

Aberrant Cerebello-Cortical Connectivity in Pianists With Focal Task-Specific Dystonia.

Musician's dystonia is a type of focal task-specific dystonia (FTSD) characterized by abnormal muscle hypercontraction and loss of fine motor control specifically during instrument playing. Although the neuropathophysiology of musician's dystonia remains unclear, it has been suggested that maladaptive functional abnormalities in subcortical and cortical regions may be involved. Here, we hypothesized that aberrant effective connectivity between the cerebellum (subcortical) and motor/somatosensory cortex may underlie the neuropathophysiology of musician's dystonia. Using functional magnetic resonance imaging, we measured the brain activity of 30 pianists with or without FTSD as they played a magnetic resonance imaging-compatible piano-like keyboard, which elicited dystonic symptoms in many but not all pianists with FTSD. Pianists with FTSD showed greater activation of the right cerebellum during the task than healthy pianists. Furthermore, patients who reported dystonic symptoms during the task demonstrated greater cerebellar activation than those who did not, establishing a link between cerebellar activity and overt dystonic symptoms. Using multivoxel pattern analysis, moreover, we found that dystonic and healthy pianists differed in the task-related effective connectivity between the right cerebellum and left premotor/somatosensory cortex. The present study indicates that abnormal cerebellar activity and cerebello-cortical connectivity may underlie the pathophysiology of FTSD in musicians.

Thoughts on vigor in the motor and cognitive domains.

We feel exhausted after working mentally hard even while just sitting on a chair, suggesting the concept of cognitive vigor. Do movement vigor and cognitive vigor share control mechanisms? Functions of the basal ganglia-cortical circuits, which are regulated by the midbrain dopaminergic system, appear to underlie both movement vigor and cognitive vigor.

Age of Acquisition of Mandarin Modulates Cortical Thickness in High-Proficient Cantonese-Mandarin Bidialectals.

Previous studies showed that the onset age of second language acquisition (AoA-L2) can modulate brain structure of bilinguals. However, the underlying mechanism of anatomical plasticity induced by AoA-L2 is still a question in debate. In order to explore the issue, we recruited two groups of native Cantonese-Mandarin speakers, the early group began to speak in Mandarin at about 3.5 and the late group at about 6.5 years old. In addition, the early group had earlier experience in reading Chinese characters than the late group did. Through estimating the cortical thickness (CT), we found that (1) compared with the late group, the early group had thicker CT in the lateral occipital region, left middle temporal gyrus, and left parahippocampal region, which are all involved in visuospatial processing, probably reflecting the effect induced by the earlier or later experiences in processing the characters of Chinese for the two groups; and (2) compared with the late group, the early group had thicker CT in left superior parietal region, which is believed to be involved in language switching, maybe for the early group had the earlier experience in switching back and forth between Cantonese and Mandarin and therefore recruited the executive control network earlier. Our findings revealed the effects of the AoA-L2 in oral language acquisition as well as in written language acquisition as the main determinants of bilingual language structural representation in human brain.

Ventral striatum links motivational and motor networks during operant-conditioned movement in rats.

Voluntary actions require motives. It is already known that the medial prefrontal cortex (MPFC) assess the motivational values. However, it remains unclear how the motivational process gains access to the motor execution system in the brain. Here we present evidence that the ventral striatum (VS) plays a hub-like role in mediating motivational and motor processing in operant behavior. We used positron emission tomography (PET) to detect the neural activation areas associated with motivational action. Using obtained regions, partial correlation analysis was performed to examine how the motivational signals propagate to the motor system. The results revealed that VS activity propagated to both MPFC and primary motor cortex through the thalamus. Moreover, muscimol injection into the VS suppressed the motivational behavior, supporting the idea of representations of motivational signals in VS that trigger motivational behavior. These results suggest that the VS-thalamic pathway plays a pivotal role for both motivational processing through interactions with the MPFC and for motor processing through interactions with the motor BG circuits.

Distinct roles of brain activity and somatotopic representation in pathophysiology of focal dystonia.

Two main neural mechanisms including loss of cortical inhibition and maladaptive plasticity have been thought to be involved in the pathophysiology of focal task-specific dystonia. Such loss of inhibition and maladaptive plasticity likely correspond to cortical overactivity and disorganized somatotopy, respectively. However, the most plausible mechanism of focal task-specific dystonia remains unclear. To address this question, we assessed brain activity and somatotopic representations of motor-related brain areas using functional MRI and behavioral measurement in healthy instrumentalists and patients with embouchure dystonia as an example of focal task-specific dystonia. Dystonic symptoms were measured as variability of fundamental frequency during long tone playing. We found no significant differences in brain activity between the embouchure dystonia and healthy wind instrumentalists in the motor-related areas. Assessment of somatotopy, however, revealed significant differences in the somatotopic representations of the mouth area for the right somatosensory cortex between the two groups. Multiple-regression analysis revealed brain activity in the primary motor and somatosensory cortices, cerebellum, and putamen was significantly associated with variability of fundamental frequency signals representing dystonic symptoms. Conversely, somatotopic representations in motor-related brain areas were not associated with variability of fundamental frequency signals in embouchure dystonia. The present findings suggest that abnormal motor-related network activity and aberrant somatotopy correlate with different aspects of mechanisms underlying focal task-specific dystonia.

Phase-Amplitude Coupling of Neural Oscillations Can Be Effectively Probed with Concurrent TMS-EEG.

Despite the widespread use of transcranial magnetic stimulation (TMS), knowledge of its neurophysiological mode of action is still incomplete. Recently, TMS has been proposed to synchronise neural oscillators and to thereby increase the detectability of corresponding oscillations at the population level. As oscillations in the human brain are known to interact within nested hierarchies via phase-amplitude coupling, TMS might also be able to increase the macroscopic detectability of such coupling. In a concurrent TMS-electroencephalography study, we therefore examined the technique's influence on theta-gamma, alpha-gamma, and beta-gamma phase-amplitude coupling by delivering single-pulse TMS (sTMS) and repetitive TMS (rTMS) over the left motor cortex and right visual cortex of healthy participants. The rTMS pulse trains were of 5 Hz, 11 Hz, and 23 Hz for the three coupling variations, respectively. Relative to sham stimulation, all conditions showed transient but significant increases in phase-amplitude coupling at the stimulation site. In addition, we observed enhanced coupling over various other cortical sites, with a more extensive propagation during rTMS than during sTMS. By indicating that scalp-recorded phase-amplitude coupling can be effectively probed with TMS, these findings open the door to the technique's application in manipulative dissections of such coupling during human cognition and behaviour in healthy and pathological conditions.

Neural correlates of temporal updating and reasoning in association with neuropsychiatric disorders.

Here we argue how Hoerl & McCormack's dual system proposal may change the current view about the neural correlates underlying temporal information processing. We also consider that the concept of the dual system may help characterize various timing disabilities in neuropsychiatric disorders from the new perspective.

Aberrant cortical excitability reflects the loss of hand dexterity in musician's dystonia.

KEY POINTS: Dystonia is a movement disorder characterized by abnormalities at multifaceted aspects of motor dexterity and neural functions. Evidence bridging between pathophysiology and movement abnormalities is limited. A novel finding was that in focal task-specific dystonia (FTSD), an aberrantly reduced inhibition at the motor cortex was related to the temporal imprecision of the dexterous finger movements, whereas an elevated facilitation was associated with an abnormally sluggish transition of finger movements from flexion to extension. We newly identified two sets of behavioural-physiological covariations as hallmarks of hand FTSD, which is clinically significant because these findings provide novel evidence connecting distinct types of malfunctions within the motor cortex at rest with distinct aspects of motor dexterity degradation in FTSD patients. ABSTRACT: Focal task-specific dystonia (FTSD) compromises dexterous movements. A proposed pathophysiological mechanism of FTSD involves malfunction of the motor cortex (M1). However, no evidence is yet available regarding whether and how malfunctions of M1 are responsible for the loss of motor dexterity. Here, we addressed this issue by assessing both M1 excitability and detailed movement parameters, as well as their relationships. Transcranial magnetic stimulation was applied over M1 in 20 pianists with FTSD, 20 healthy pianists and 20 non-musicians. The patients demonstrated both reduced short-interval intracortical inhibition (SICI) and elevated intracortical facilitation (ICF) compared with the healthy controls. This indicates that the abnormal cortical excitability reflects pathophysiology but not current skills. Hand motor dexterity was evaluated by position sensors during piano playing at two tempi. The patients showed delayed transition from finger flexion to extension at the fastest tempo and greater timing variability of the finger movements. Furthermore, multivariate analyses identified distinct sets of covariation between cortical excitability and dexterity measures. Namely, the SICI measure and ICF measure were associated with the temporal variability of the movements and the quickness of the transition from flexion to extension, respectively. Specifically, the reduced inhibition and elevated facilitation at M1 in pianists was related to the temporal imprecision and impairment of quick transitions in the sequential finger movements. The present study provides novel evidence associating M1 malfunctions with dexterity loss.

Resting-state basal ganglia network codes a motor musical skill and its disruption From dystonia.

BACKGROUND: Musician's dystonia critically impacts professional musicians' careers as they may lose musical skills, which have been acquired through long and intensive training. Yet the pathophysiology of musician's dystonia and its link to the neural mechanisms supporting musical skills is poorly understood. We tested if resting-state functional connectivity might reflect an aspect of musical skill linked to the pathophysiology of musician's dystonia. We also tested a second hypothesis that the region with altered resting-state functional connectivity might be correlated with a quantitative measure of musical skills. METHODS: We studied 21 patients with musician's dystonia affecting their hands and 34 healthy musicians, using resting-state functional magnetic resonance imaging and behavioral assessment. We tested between-group differences of resting-state functional connectivity throughout the whole brain using independent component analysis. RESULTS: We found abnormal basal ganglia resting-state functional connectivity in the putamina of patients with musician's dystonia compared with those of healthy musicians (P = 0.035 corrected for multiple comparisons). We also found that the temporal precision of keystrokes was correlated with basal ganglia functional connectivity in the putamina of healthy pianists (r = 0.72, P = 0.0005), but not in pianists with musician's dystonia (r = -0.11, P = 0.64). CONCLUSIONS: We show that abnormalities of the putamen exist even at rest in musician's dystonia, whereas putaminal abnormality has previously been reported during a task. Moreover, basal ganglia resting-state functional connectivity in the putamen represented training levels in healthy musicians, and its disruption was associated with musician's dystonia. This novel finding hints at the pathophysiological mechanisms by which musician's dystonia follows extensive musical training. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Validation of brain-derived signals in near-infrared spectroscopy through multivoxel analysis of concurrent functional magnetic resonance imaging.

Near-infrared spectroscopy (NIRS) is a convenient and safe brain-mapping tool. However, its inevitable confounding with hemodynamic responses outside the brain, especially in the frontotemporal head, has questioned its validity. Some researchers attempted to validate NIRS signals through concurrent measurements with functional magnetic resonance imaging (fMRI), but, counterintuitively, NIRS signals rarely correlate with local fMRI signals in NIRS channels, although both mapping techniques should measure the same hemoglobin concentration. Here, we tested a novel hypothesis that different voxels within the scalp and the brain tissues might have substantially different hemoglobin absorption rates of near-infrared light, which might differentially contribute to NIRS signals across channels. Therefore, we newly applied a multivariate approach, a partial least squares regression, to explain NIRS signals with multivoxel information from fMRI within the brain and soft tissues in the head. We concurrently obtained fMRI and NIRS signals in 9 healthy human subjects engaging in an n-back task. The multivariate fMRI model was quite successfully able to predict the NIRS signals by cross-validation (interclass correlation coefficient = ∼0.85). This result confirmed that fMRI and NIRS surely measure the same hemoglobin concentration. Additional application of Monte-Carlo permutation tests confirmed that the model surely reflects temporal and spatial hemodynamic information, not random noise. After this thorough validation, we calculated the ratios of the contributions of the brain and soft-tissue hemodynamics to the NIRS signals, and found that the contribution ratios were quite different across different NIRS channels in reality, presumably because of the structural complexity of the frontotemporal regions. Hum Brain Mapp 38:5274-5291, 2017. © 2017 Wiley Periodicals, Inc.

Synthesis and evaluation of 11C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression.

Upregulated monocarboxylate transporters (MCTs) in tumors are considered diagnostic imaging targets. Herein, we synthesized the positron emission tomography probe candidates coumarin analogs 2 and 3, and showed 55 times higher affinity of 2 for MCTs than a representative MCT inhibitor. Whereas [11C]2 showed low tumor accumulation, probably due to adduct formation with plasma proteins, [11C]2 showed high initial brain uptake, suggesting that the scaffold of 2 has properties that are preferable in imaging probes for the astrocyte-neuron lactate shuttle. Although further optimization of 2 is required, our findings can be used to inform the development of MCT-targeted imaging agents.

Neuroanatomical correlates of brain-computer interface performance.

Brain-computer interfaces (BCIs) offer a potential means to replace or restore lost motor function. However, BCI performance varies considerably between users, the reasons for which are poorly understood. Here we investigated the relationship between sensorimotor rhythm (SMR)-based BCI performance and brain structure. Participants were instructed to control a computer cursor using right- and left-hand motor imagery, which primarily modulated their left- and right-hemispheric SMR powers, respectively. Although most participants were able to control the BCI with success rates significantly above chance level even at the first encounter, they also showed substantial inter-individual variability in BCI success rate. Participants also underwent T1-weighted three-dimensional structural magnetic resonance imaging (MRI). The MRI data were subjected to voxel-based morphometry using BCI success rate as an independent variable. We found that BCI performance correlated with gray matter volume of the supplementary motor area, supplementary somatosensory area, and dorsal premotor cortex. We suggest that SMR-based BCI performance is associated with development of non-primary somatosensory and motor areas. Advancing our understanding of BCI performance in relation to its neuroanatomical correlates may lead to better customization of BCIs based on individual brain structure.

Dynamic neural network reorganization associated with second language vocabulary acquisition: a multimodal imaging study.

It remains unsettled whether human language relies exclusively on innately privileged brain structure in the left hemisphere or is more flexibly shaped through experiences, which induce neuroplastic changes in potentially relevant neural circuits. Here we show that learning of second language (L2) vocabulary and its cessation can induce bidirectional changes in the mirror-reverse of the traditional language areas. A cross-sectional study identified that gray matter volume in the inferior frontal gyrus pars opercularis (IFGop) and connectivity of the IFGop with the caudate nucleus and the superior temporal gyrus/supramarginal (STG/SMG), predominantly in the right hemisphere, were positively correlated with L2 vocabulary competence. We then implemented a cohort study involving 16 weeks of L2 training in university students. Brain structure before training did not predict the later gain in L2 ability. However, training intervention did increase IFGop volume and reorganization of white matter including the IFGop-caudate and IFGop-STG/SMG pathways in the right hemisphere. These "positive" plastic changes were correlated with the gain in L2 ability in the trained group but were not observed in the control group. We propose that the right hemispheric network can be reorganized into language-related areas through use-dependent plasticity in young adults, reflecting a repertoire of flexible reorganization of the neural substrates responding to linguistic experiences.

Topographic representation of an occluded object and the effects of spatiotemporal context in human early visual areas.

Occlusion is a primary challenge facing the visual system in perceiving object shapes in intricate natural scenes. Although behavior, neurophysiological, and modeling studies have shown that occluded portions of objects may be completed at the early stage of visual processing, we have little knowledge on how and where in the human brain the completion is realized. Here, we provide functional magnetic resonance imaging (fMRI) evidence that the occluded portion of an object is indeed represented topographically in human V1 and V2. Specifically, we find the topographic cortical responses corresponding to the invisible object rotation in V1 and V2. Furthermore, by investigating neural responses for the occluded target rotation within precisely defined cortical subregions, we could dissociate the topographic neural representation of the occluded portion from other types of neural processing such as object edge processing. We further demonstrate that the early topographic representation in V1 can be modulated by prior knowledge of a whole appearance of an object obtained before partial occlusion. These findings suggest that primary "visual" area V1 has the ability to process not only visible or virtually (illusorily) perceived objects but also "invisible" portions of objects without concurrent visual sensation such as luminance enhancement to these portions. The results also suggest that low-level image features and higher preceding cognitive context are integrated into a unified topographic representation of occluded portion in early areas.

Dissociable neural representations of wrist motor coordinate frames in human motor cortices.

There is a growing interest in how the brain transforms body part positioning in the extrinsic environment into an intrinsic coordinate frame during motor control. To explore the human brain areas representing intrinsic and extrinsic coordinate frames, this fMRI study examined neural representation of motor cortices while human participants performed isometric wrist flexions and extensions in different forearm postures, thereby applying the same wrist actions (representing the intrinsic coordinate frame) to different movement directions (representing the extrinsic coordinate frame). Using sparse logistic regression, critical voxels involving pattern information that specifically discriminates wrist action (flexion vs. extension) and movement direction (upward vs. downward) were identified within the primary motor and premotor cortices. Analyses of classifier weights further identified contributions of the primary motor cortex to the intrinsic coordinate frame and the ventral and dorsal premotor cortex and supplementary motor area proper to the extrinsic coordinate frame. These results are consistent with existing findings using non-human primates and demonstrate the distributed representations of independent coordinate frames in the human brain.