Longitudinal reduction in brain volume in patients with schizophrenia and its association with cognitive function.

Establishing a brain biomarker for schizophrenia is strongly desirable not only to support diagnosis by psychiatrists but also to help track the progressive changes in the brain over the course of the illness. A brain morphological signature of schizophrenia was reported in a recent study and is defined by clusters of brain regions with reduced volume in schizophrenia patients compared to healthy individuals. This signature was proven to be effective at differentiating patients with schizophrenia from healthy individuals, suggesting that it is a good candidate brain biomarker of schizophrenia. However, the longitudinal characteristics of this signature have remained unclear. In this study, we examined whether these changes occurred over time and whether they were associated with clinical outcomes. We found a significant change in the brain morphological signature in schizophrenia patients with more brain volume loss than the natural, age-related reduction in healthy individuals, suggesting that this change can capture a progressive morphological change in the brain. We further found a significant association between changes in the brain morphological signature and changes in the full-scale intelligence quotient (IQ). The patients with IQ improvement showed preserved brain morphological signatures, whereas the patients without IQ improvement showed progressive changes in the brain morphological signature, suggesting a link between potential recovery of intellectual abilities and the speed of brain pathology progression. We conclude that the brain morphological signature is a brain biomarker that can be used to evaluate progressive changes in the brain that are associated with cognitive impairment due to schizophrenia.

Feasibility Study for a Microstrip Transmission Line RF Coil Integrated with a PET Detector Module in a 7T Human MR Imaging System.

PURPOSE: The purpose of this study was to do a feasibility study on a microstrip transmission line (MS) RF coil for a positron emission tomography (PET) insert in a 7 Tesla human MRI system. The proposed MS coil integrated the RF shield of the PET detector as the ground conductor of the coil. We called the integrated module "MS PET coil." METHODS: A single-channel MS PET coil was developed with an integrated RF-shielded PET detector module. For comparison, we also studied a conventional MS coil with a single-layer ground conductor. A lutetium fine silicate (LFS) scintillation crystal block (14 × 14 × 4-layer) with a silicon photomultiplier (Hamamatsu Photonics K.K., Shizuoka, Japan) and a front-end readout circuit board were mounted inside the shield cage of the MS PET coil. The MS PET coil was studied with and without PET detectors. All three coil configurations were studied with a homogeneous phantom in a 7T MRI system (Siemens Healthineers, Erlangen, Germany). PET data measurements were conducted using a Cesium-137 radiation point source. RESULTS: The MR images were similar for the MS coil and the empty MS PET coil, as well as for the cases of MS PET coil with and without PET measurements. Compared to the empty MS PET coil (without PET detector and cable RF shield), decreases in SNR, increases in image noise and RF power, and a slight decrease in resonance frequency were seen for the case of the MS PET coil with the detector and cable shield. Differences in the PET energy histograms or in the crystal identification maps with and without MRI measurements were negligible. CONCLUSIONS: Both the MRI and PET performances of the MS PET coil showed responses that matched the MS coil responses. The performance variations of MRI data with and without PET measurement and PET data with and without MR imaging were negligible.

High-resolution EEG source localization in personalized segmentation-free head model with multi-dipole fitting.

Objective. Electroencephalograms (EEGs) are often used to monitor brain activity. Several source localization methods have been proposed to estimate the location of brain activity corresponding to EEG readings. However, only a few studies evaluated source localization accuracy from measured EEG using personalized head models in a millimeter resolution. In this study, based on a volume conductor analysis of a high-resolution personalized human head model constructed from magnetic resonance images, a finite difference method was used to solve the forward problem and to reconstruct the field distribution.Approach. We used a personalized segmentation-free head model developed using machine learning techniques, in which the abrupt change of electrical conductivity occurred at the tissue interface is suppressed. Using this model, a smooth field distribution was obtained to address the forward problem. Next, multi-dipole fitting was conducted using EEG measurements for each subject (N= 10 male subjects, age: 22.5 ± 0.5), and the source location and electric field distribution were estimated.Main results.For measured somatosensory evoked potential for electrostimulation to the wrist, a multi-dipole model with lead field matrix computed with the volume conductor model was found to be superior than a single dipole model when using personalized segmentation-free models (6/10). The correlation coefficient between measured and estimated scalp potentials was 0.89 for segmentation-free head models and 0.71 for conventional segmented models. The proposed method is straightforward model development and comparable localization difference of the maximum electric field from the target wrist reported using fMR (i.e. 16.4 ± 5.2 mm) in previous study. For comparison, DUNEuro based on sLORETA was (EEG: 17.0 ± 4.0 mm). In addition, somatosensory evoked magnetic fields obtained by Magnetoencephalography was 25.3 ± 8.5 mm using three-layer sphere and sLORETA.Significance. For measured EEG signals, our procedures using personalized head models demonstrated that effective localization of the somatosensory cortex, which is located in a non-shallower cortex region. This method may be potentially applied for imaging brain activity located in other non-shallow regions.

"Brain-breath" interactions: respiration-timing-dependent impact on functional brain networks and beyond.

Breathing is a natural daily action that one cannot do without, and it sensitively and intensely changes under various situations. What if this essential act of breathing can impact our overall well-being? Recent studies have demonstrated that breathing oscillations couple with higher brain functions, i.e., perception, motor actions, and cognition. Moreover, the timing of breathing, a phase transition from exhalation to inhalation, modulates specific cortical activity and accuracy in cognitive tasks. To determine possible respiratory roles in attentional and memory processes and functional neural networks, we discussed how breathing interacts with the brain that are measured by electrophysiology and functional neuroimaging: (i) respiration-dependent modulation of mental health and cognition; (ii) respiratory rhythm generation and respiratory pontomedullary networks in the brainstem; (iii) respiration-dependent effects on specific brainstem regions and functional neural networks (e.g., glutamatergic PreBötzinger complex neurons, GABAergic parafacial neurons, adrenergic C1 neurons, parabrachial nucleus, locus coeruleus, temporoparietal junction, default-mode network, ventral attention network, and cingulo-opercular salience network); and (iv) a potential application of breathing manipulation in mental health care. These outlines and considerations of "brain-breath" interactions lead to a better understanding of the interoceptive and cognitive mechanisms that underlie brain-body interactions in health conditions and in stress-related and neuropsychiatric disorders.

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers.

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.

Verifying the Accuracy of Hemodynamic Analysis Using High Spatial Resolution 3D Phase-contrast MR Imaging on a 7T MR System: Comparison with a 3T System.

PURPOSE: Hemodynamics is important in the initiation, growth, and rupture of intracranial aneurysms. Since intracranial aneurysms are small, a high-field MR system with high spatial resolution and high SNR is desirable for this hemodynamic analysis. The purpose of this study was to investigate whether the accuracy of MR fluid dynamic (MRFD) results based on 3D phase-contrast MR (3D PC MR, non-electrocardiogram[ECG]-gated 4D Flow MRI) data from a human cerebrovascular phantom and human healthy subjects obtained by a 7T MR system was superior to those by a 3T MR system. METHODS: 3D PC MR and 3D time of flight MR angiography (3D TOF MRA) imaging were performed on a 3T MR system and a 7T MR system for a human cerebrovascular phantom and 10 healthy human subjects, and MRFD analysis was performed using these data. The MRFD results from each MR system were then compared with the following items based on the computational fluid dynamics (CFD) results: 3D velocity vector field; correlation coefficient (R), angular similarity index (ASI), and magnitude similarity index (MSI) of blood flow velocity vectors. RESULTS: In the MRFD results of 3D velocity vectors of the cerebrovascular phantom, noise-like vectors were observed near the vascular wall on the 3T MR system, but no noise was observed on the 7T MR system, showing results similar to those of CFD. In the MRFD results of the cerebrovascular phantom and healthy subjects, the correlation coefficients R, ASI, and MSI of the 7T MR system were higher than those of the 3T MR system, and ASI and MSI of healthy human subjects were significantly different between the two systems. CONCLUSIONS: The accuracy of high spatial resolution MRFD using the 7T MR system exceeded that of the 3T MR system.

Premovement activity in the mesocortical system links peak force but not initiation of force generation under incentive motivation.

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement "Ready" period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation.

Cortico-striatal activity associated with fidget spinner use: an fMRI study.

Fidget spinners are said to be a very successful toy, and it's said that it has a good impact on attention for children with ADHD and hand motor control. However, there is limited scientific evidence to support these claims, and there is a lack of data on neurobiological responses to rotating fidget spinners. To better understand the mechanism whereby fidget spinners affect motor behavior, we tried to identify the neural correlates of rotating fidget spinners using functional magnetic resonance imaging and non-magnetic fidget spinners with five types of ease of rotation. As a result, we confirmed that the pre/postcentral gyrus, middle temporal gyrus, supplementary motor area (SMA), cerebellum, and striatum are activated when rotating spinners. Furthermore, the SMA was activated more with easier-to-rotate spinners. Additionally, a psychophysiological interaction analysis revealed increased functional connectivity between the SMA and the caudate while rotating fidget spinners compared to just holding them. These results suggest that the fine motor control associate with spinning a fidget spinner is supported by the cortico-striatal circuits involved in planning and reward.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Validity of functional assessment for control of trunk in patients with subacute stroke: a multicenter, cross-sectional study.

[Purpose] The purpose of this study was to clarify the criterion validity, construct validity, and feasibility of the Functional Assessment for Control of Trunk (FACT). [Participants and Methods] This study was a multicenter, cross-sectional study of patients with subacute stroke at three Japanese rehabilitation hospitals. To clarify feasibility, we examined the differences in the measurement time between FACT and the Trunk Impairment Scale (TIS). For the criterion validity of FACT, correlations between FACT, TIS, and the trunk items of the Stroke Impairment Assessment Set (SIAS) were examined using Spearman's rank correlation coefficient. For the construct validity of FACT, we examined the correlations with the other assessments. [Results] Seventy-three patients participated in this study. The measurement time was significantly shorter for FACT (212.6 ± 79.2 s) than TIS (372.4 ± 199.6 s). For criterion validity, FACT correlated significantly with TIS (r=0.896) and two SIAS trunk items (r=0.453, 0.594). For construct validity, significant correlations were found for FACT and other tests (r=0.249-0.797). Areas under the curve for FACT and TIS were 0.809 and 0.812, respectively, and the cutoff values for walking independence were 9 and 13 points, respectively. [Conclusion] For inpatients with stroke, FACT offered feasibility, criterion validity, and construct validity.

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

A Patient with Transverse Colon Cancer Complicated by Cowden Syndrome Administered FOLFOXIRI + Bevacizumab Therapy.

Cowden syndrome is characterized by several clinical features related to tumorous lesions primarily consisting of systemic hamartomas. The mutation of a tumor suppressor gene, the PTEN gene, is etiologically involved. As gastrointestinal lesions, polyps of all digestive tracts involving the esophagus to rectum develop. In patients with Cowden syndrome, the risk of colorectal cancer may increase. However, the characteristics of colorectal cancer in these patients remain to be clarified and sufficient findings regarding chemotherapy have not been obtained. A 39-year-old man was treated with a colonic stent for colitis obstructive due to circumferential transverse colon carcinoma. After decompression, elective extended laparoscopic right hemicolectomy was performed. Preoperative systemic detailed examination revealed characteristic dermal/mucosal findings, polyposis of the upper digestive tract, and a thyroid tumor. On PTEN gene sequencing, a mutation was detected at codon 130 of exon 5, leading to a diagnosis of Cowden syndrome. Postoperative adjuvant chemotherapy was performed for 6 months, but recurrent peritoneal dissemination was observed 1 month after its completion. FOLFOXIRI + bevacizumab therapy was started. Transiently, a partial response was achieved in peritoneally disseminated nodes according to the RECIST. There was no increase in the volume of cancerous ascites. However, an increase in the volume of ascites and local relapse were noted at the completion of the tenth course. The regimen was switched to FOLFIRI + panitumumab, but peritoneal dissemination exacerbated and the patient died 18 months after surgery.

Functional Connectivity Pattern Using Resting-state fMRI as an Assessment Tool for Spatial Neglect during the Recovery Stage of Stroke: A Pilot Study.

PURPOSE: To determine if functional connectivity measured with resting-state functional MRI could be used as a tool to assess unilateral spatial neglect during stroke recovery. METHODS: Resting-state functional MRI was performed on 13 stroke patients with lesions in the right cerebral hemisphere and 31 healthy subjects. The functional connectivity score was defined as a correlation of a target region with the right inferior parietal lobule. Spatial neglect was measured with a behavioral inattention test. RESULTS: First, the functional connectivity scores between the right inferior parietal lobule and right inferior frontal gyrus, including the opercular and triangular parts, were significantly decreased in stroke patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Second, the functional connectivity scores between the bilateral inferior parietal lobules were also significantly decreased in patients with unilateral spatial neglect compared with patients without unilateral spatial neglect and were significantly correlated with the behavioral inattention test score. Third, negative functional connectivity scores between the right inferior parietal lobule and bilateral medial orbitofrontal cortexes, which are related to the default mode network, were detected in patients without unilateral spatial neglect in contrast to a reduction of this negative tendency in patients with unilateral spatial neglect. The functional connectivity scores between these regions were significantly different between patients with and without unilateral spatial neglect and were negatively correlated with the behavioral inattention test score. CONCLUSION: Though still in the pilot research stage and using a small number of cases, our findings are consistent with the hypothesis that functional connectivity maps generated with resting-state functional MRI may be used as a tool to evaluate unilateral spatial neglect during stroke recovery.

Association Study Between White Matter Microstructure and Intelligence Decline in Schizophrenia.

Patients with schizophrenia can exhibit intelligence decline, which is an important element of cognitive impairment. Previous magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have altered gray matter structures and functional connectivity associated with intelligence decline defined by a difference between premorbid and current intelligence quotients (IQs). However, it has remained unclear whether white matter microstructures are related to intelligence decline. In the present study, the indices of diffusion tensor imaging (DTI) obtained from 138 patients with schizophrenia and 554 healthy controls were analyzed. The patients were classified into three subgroups based on intelligence decline: deteriorated (94 patients), preserved (42 patients), and compromised IQ (2 patients) groups. Given that the DTI of each subject was acquired using either one of two different MRI scanners, we analyzed DTI indices separately for each scanner group. In the comparison between the deteriorated IQ group and the healthy controls, differences in some DTI indices were noted in three regions of interest irrespective of the MRI scanners, whereas differences in only one region of interest were noted between the preserved IQ group and the healthy controls. However, the comparisons between the deteriorated and preserved IQ groups did not show any reproducible differences. Together with the previous findings, it is thought that gray matter structures and functional connectivity are more promising as markers of intelligence decline in schizophrenia than white matter microstructures.

Case of laparoscopic parastomal hernia repair using modified Sugarbaker mesh method.

A 75-year-old woman underwent sigmoid colon resection and transverse colostomy for perforation of the diverticulum of the sigmoid colon at 70 years of age at another hospital. She was referred to our hospital with complaints of abdominal discomfort 3 months prior to presentation. Abdominal computed tomography revealed a parastomal hernia (PSH). We performed laparoscopic repair using the Sugarbaker approach with a Symbotex Composite Mesh™ and laparoscopic adhesive intestinal repair. The patient's post-operative course was unremarkable, and she was transferred to the Department of Internal Medicine after 10 days. There was no recurrence 6 months after surgery. Tension-free surgery using a mesh has been reported to be effective in preventing the recurrence of PSH. We performed a laparoscopic modified Sugarbaker mesh method using the Symbotex Composite Mesh™ with collagen film to repair an abdominal hernia.

Respiration-timing-dependent changes in activation of neural substrates during cognitive processes.

We previously showed that cognitive performance declines when the retrieval process spans an expiratory-to-inspiratory (EI) phase transition (an onset of inspiration). To identify the neural underpinning of this phenomenon, we conducted functional magnetic resonance imaging (fMRI) while participants performed a delayed matching-to-sample (DMTS) recognition memory task with a short delay. Respiration during the task was monitored using a nasal cannula. Behavioral data replicated the decline in memory performance specific to the EI transition during the retrieval process, while an extensive array of frontoparietal regions were activated during the encoding, delay, and retrieval processes of the task. Within these regions, when the retrieval process spanned the EI transition, activation was reduced in the anterior cluster of the right temporoparietal junction (TPJa, compared to cases when the retrieval process spanned the inspiratory-to-expiratory phase transition) and the left and right middle frontal gyrus, dorsomedial prefrontal cortex, and somatosensory areas (compared to cases when the retrieval process did not span any phase transition). These results in task-related activity may represent respiratory interference specifically in information manipulation rather than memory storage. Our findings demonstrate a cortical-level effect of respiratory phases on cognitive processes and highlight the importance of the timing of breathing for successful performance.

Cerebro-cerebellar interactions in nonhuman primates examined by optogenetic functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) is a promising approach for the simultaneous and extensive scanning of whole-brain activities. Optogenetics is free from electrical and magnetic artifacts and is an ideal stimulation method for combined use with fMRI. However, the application of optogenetics in nonhuman primates (NHPs) remains limited. Recently, we developed an efficient optogenetic intracortical microstimulation method of the primary motor cortex (M1), which successfully induced forelimb movements in macaque monkeys. Here, we aimed to investigate how optogenetic M1 stimulation causes neural modulation in the local and remote brain regions in anesthetized monkeys using 7-tesla fMRI. We demonstrated that optogenetic stimulation of the M1 forelimb and hindlimb regions successfully evoked robust direct and remote fMRI activities. Prominent remote activities were detected in the anterior and posterior lobes in the contralateral cerebellum, which receive projections polysynaptically from the M1. We further demonstrated that the cerebro-cerebellar projections from these M1 regions were topographically organized, which is concordant with the somatotopic map in the cerebellar cortex previously reported in macaques and humans. The present study significantly enhances optogenetic fMRI in NHPs, resulting in profound understanding of the brain network, thereby accelerating the translation of findings from animal models to humans.

Neural correlates with individual differences in temporal prediction during auditory-motor synchronization.

Temporal prediction ability is vital for movement synchronization with external rhythmic stimuli (sensorimotor synchronization); however, little is known regarding individual variations in temporal prediction ability and its neural correlates. We determined the underlying neural correlates of temporal prediction and individual variations during auditory-motor synchronization. We hypothesized that the non-primary motor cortices, such as the premotor cortex and supplementary motor area, are the key brain regions that correlate individual variations in prediction ability. Functional magnetic resonance imaging (7T) was performed for 18 healthy volunteers who tapped to 3 types of auditory metronome beats: isochronous, tempo change, and random. The prediction ability was evaluated using prediction/tracking ratios that were computed based on cross-correlations between tap timing and pacing events. Participants with a higher prediction/tracking ratio (i.e. stronger predictive tendency) tapped to metronome beats more accurately and precisely. The prediction/tracking ratio was positively correlated with the activity in the bilateral dorsal premotor cortex (PMd), suggesting that the bilateral PMd explains the individual variation in prediction ability. These results indicate that the PMd is involved in generating a model for temporal prediction of auditory rhythm patterns and its activity would reflect model accuracy, which is critical for accurate and precise sensorimotor synchronization.