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Dalam pemmbicaraan tentang metodologi studi Islamisasi yang dapat diterapkan untuk studi Islam sebagaimana telah dikemukakan dalam beberapa karangan untuk makalah maupun untuk buku (Uka Tjandrasasmita, 1961: 92-97; 1976:77-86; 1978: 141-160) Dalam tulisan-tulisan tersebut dibicarakan mengenai beberapa teori kedatangan dan penyebaran Islam berdasarkan beberapa ahli yang pernah mempersoalkannya dalam tulisan-tulisan yang mereka terbitkan.

Mismatch negativity (MMN) has gained attention as a biomarker for psychosis and a translational intermediate phenotype in animal models of psychosis, including rodents and non-human primates. MMN has been linked to global functioning (Global Assessment of Functioning [GAF] score) and prognosis (psychosis onset or remission), suggesting that MMN reflects activities beyond auditory processing alone. This review examines the 45-year history of MMN from the perspective of psychiatric researchers and discusses current advances in computational and translational research on MMN, summarizing the current understanding of the MMN generation mechanism. We then address the essential question, "What do we observe through MMN?" Currently, we regard the relationship between global functioning in the real world and MMN as the key to answering this question. As a preliminary investigation, we analyzed the relationship between GAF as an objective variable and MMN, diagnosis, and basic epidemiological factors (age, sex, premorbid intelligence quotient) as explanatory variables (total n = 201, healthy controls: n = 41, patients with psychiatric disorders: n = 160) without assuming diagnostic categories. The relationship between functional outcomes and MMN was confirmed without a case-control design. Finally, we propose that new neurophysiological studies should acknowledge psychophysiological responses such as emotion, intention, and autonomic responses, as well as behavioral differences among participants beyond the dichotomy between healthy controls and patients. Measurements could be conducted in various settings from the participant's perspective. We discuss the potential for research investigating psychosis based on the interaction between individuals and the environment, using MMN as an illustrative model., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Humans can selectively process information and make decisions by directing their attention to desired locations in their daily lives. Numerous studies have shown that attention increases the rate of correct responses and shortens reaction time, and it has been hypothesized that this phenomenon is caused by an increase in sensitivity of the sensory signals to which attention is directed. The present study employed psychophysical methods and electroencephalography (EEG) to test the hypothesis that attention accelerates the onset of information accumulation. Participants were asked to discriminate the motion direction of one of two random dot kinematograms presented on the left and right sides of the visual field, one of which was cued by an arrow in 80% of the trials. The drift-diffusion model was applied to the percentage of correct responses and reaction times in the attended and unattended fields of view. Attention primarily increased sensory sensitivity and shortened the time unrelated to decision making. Next, we measured centroparietal positivity (CPP), an EEG measure associated with decision making, and found that CPP latency was shorter in attended trials than in unattended trials. These results suggest that attention not only increases sensory sensitivity but also accelerates the initiation of decision making., (© 2024. The Author(s).)

Sound frequency and duration are essential auditory components. The brain perceives deviations from the preceding sound context as prediction errors, allowing efficient reactions to the environment. Additionally, prediction error response to duration change is reduced in the initial stages of psychotic disorders. To compare the spatiotemporal profiles of responses to prediction errors, we conducted a human electrocorticography study with special attention to high gamma power in 13 participants who completed both frequency and duration oddball tasks. Remarkable activation in the bilateral superior temporal gyri in both the frequency and duration oddball tasks were observed, suggesting their association with prediction errors. However, the response to deviant stimuli in duration oddball task exhibited a second peak, which resulted in a bimodal response. Furthermore, deviant stimuli in frequency oddball task elicited a significant response in the inferior frontal gyrus that was not observed in duration oddball task. These spatiotemporal differences within the Parasylvian cortical network could account for our efficient reactions to changes in sound properties. The findings of this study may contribute to unveiling auditory processing and elucidating the pathophysiology of psychiatric disorders., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To make flexible decisions in dynamic environments, the brain must integrate behaviorally relevant information while simultaneously discarding irrelevant information. This study aimed to investigate the mechanisms responsible for discarding irrelevant information during context-dependent decision-making. We trained two macaque monkeys to switch between direction and depth discrimination tasks in successive trials. During decision-making, the strength of the motion or depth signal changes transiently at various times, introducing a brief pulse. We assessed the effects of pulse on behavioral choices. Consistent with previous findings, early relevant pulses, such as motion pulses during direction discrimination, had a significantly larger effect compared to late pulses. Critically, the effects of irrelevant pulses, such as motion pulses during depth discrimination, exhibited an initial minimal effect, followed by an increase and subsequent decrease as a function of pulse timing. Gating mechanisms alone, aimed at discarding irrelevant information, did not account for the observed time course of pulse effects. Instead, the observed increase in the effects of irrelevant pulses with time suggested the involvement of a leaky integration mechanism. The results suggested that the brain controls the amount of disposal in accumulating sensory evidence during flexible decision-making., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Auditory sensory processing is assumed to occur in a hierarchical structure including the primary auditory cortex (A1), superior temporal gyrus, and frontal areas. These areas are postulated to generate predictions for incoming stimuli, creating an internal model of the surrounding environment. Previous studies on mismatch negativity have indicated the involvement of the superior temporal gyrus in this processing, whereas reports have been mixed regarding the contribution of the frontal cortex. We designed a novel auditory paradigm, the "cascade roving" paradigm, which incorporated complex structures (cascade sequences) into a roving paradigm. We analyzed electrocorticography data from six patients with refractory epilepsy who passively listened to this novel auditory paradigm and detected responses to deviants mainly in the superior temporal gyrus and inferior frontal gyrus. Notably, the inferior frontal gyrus exhibited broader distribution and sustained duration of deviant-elicited responses, seemingly differing in spatio-temporal characteristics from the prediction error responses observed in the superior temporal gyrus, compared with conventional oddball paradigms performed on the same participants. Moreover, we observed that the deviant responses were enhanced through stimulus repetition in the high-gamma range mainly in the superior temporal gyrus. These features of the novel paradigm may aid in our understanding of auditory predictive coding., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although cortical feedback signals are essential for modulating feedforward processing, no feedback error signal across hierarchical cortical areas has been reported. Here, we observed such a signal in the auditory cortex of awake common marmoset during an oddball paradigm to induce auditory duration mismatch negativity. Prediction errors to a deviant tone presentation were generated as offset calcium responses of layer 2/3 neurons in the rostral parabelt (RPB) of higher-order auditory cortex, while responses to non-deviant tones were strongly suppressed. Within several hundred milliseconds, the error signals propagated broadly into layer 1 of the primary auditory cortex (A1) and accumulated locally on top of incoming auditory signals. Blockade of RPB activity prevented deviance detection in A1. Optogenetic activation of RPB following tone presentation nonlinearly enhanced A1 tone response. Thus, the feedback error signal is critical for automatic detection of unpredicted stimuli in physiological auditory processing and may serve as backpropagation-like learning., (© 2023. The Author(s).)

The overrepresentation of centrifugal motion in the middle temporal visual area (area MT) has long been thought to provide an efficient coding strategy for optic flow processing. However, this overrepresentation compromises the detection of approaching objects, which is essential for survival. In the present study, we revisited this long-held notion by reanalyzing motion selectivity in area MT of three macaque monkeys (two males, one female) using random-dot stimuli instead of spot stimuli. We found no differences in the number of neurons tuned to centrifugal versus centripetal motion; however, centrifugally tuned neurons showed stronger tuning than centripetally tuned neurons. This was attributed to the heightened suppression of responses in centrifugal neurons to centripetal motion compared with that of centripetal neurons to centrifugal motion. Our modeling implies that this intensified suppression accounts for superior detection performance for weak centripetal motion stimuli. Moreover, through Fisher information analysis, we establish that the population sensitivity to motion direction in peripheral vision corresponds well with retinal motion statistics during forward locomotion. While these results challenge established concepts, considering the interplay of logarithmic Gaussian receptive fields and spot stimuli can shed light on the previously documented overrepresentation of centrifugal motion. Significantly, our findings reconcile a previously found discrepancy between MT activity and human behavior, highlighting the proficiency of peripheral MT neurons in encoding motion direction efficiently. SIGNIFICANCE STATEMENT The efficient coding hypothesis states that sensory neurons are tuned to specific, frequently experienced stimuli. Whereas previous work has found that neurons in the middle temporal (MT) area favor centrifugal motion, which results from forward locomotion, we show here that there is no such bias. Moreover, we found that the response of centrifugal neurons for centripetal motion was more suppressed than that of centripetal neurons for centrifugal motion. Combined with modeling, this provides a solution to a previously known discrepancy between reported centrifugal bias in MT and better detection of centripetal motion by human observers. Additionally, we show that population sensitivity in peripheral MT neurons conforms to an efficient code of retinal motion statistics during forward locomotion., (Copyright © 2023 the authors.)

Much of our flexible behavior is dependent on responding efficiently to relevant information while discarding irrelevant information. Little is known, however, about how neural pathways governing sensory-motor associations can rapidly switch to accomplish such flexibility. Here, we addressed this question by electrically microstimulating middle temporal (MT) neurons selective for both motion direction and binocular disparity in monkeys switching between direction and depth discrimination tasks. Surprisingly, we frequently found that the observed psychophysical bias precipitated by delivering microstimulation to neurons whose preferred direction and depth were related to opposite choices in the two tasks was substantially shifted toward a specific movement. Furthermore, these effects correlated with behavioral switching performance. Our findings suggest that the outputs of sensory signals are task specific and that irrelevant sensory-motor pathways are gated depending on task demand so as to accomplish rapid attentional switching., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Flexible decision making is an indispensable ability for humans. A subanesthetic dose of ketamine, an N-methyl-D-aspartate receptor antagonist, impairs this flexibility in a manner that is similar to patients with schizophrenia; however how it affects neural processes related to decision making remains unclear. Here, we report that ketamine administration impairs neural processing related to context-dependent decision making, and delays the onset of decision making. We recorded single unit activity in the lateral intraparietal area (LIP) while monkeys switched between a direction-discrimination task and a depth-discrimination task. Ketamine impaired choice accuracy for incongruent stimuli that required different decisions depending on the task, for the direction-discrimination task. Neural sensitivity to irrelevant depth information increased with ketamine during direction discrimination in LIP, indicating impaired processing of irrelevant information. Furthermore, the onset of decision-related neural activity was delayed in conjunction with an increased reaction time irrespective of task and stimulus congruency. Neural sensitivity and response onset of the middle temporal area (MT) were not modulated by ketamine, indicating that ketamine worked on neural decision processes downstream of MT. These results suggest that ketamine administration may impair what information to process and when to process it for the purpose of achieving flexible decision making., (© 2022. The Author(s).)

Sensory prediction is considered an important element of mismatch negativity (MMN) whose reduction is well known in patients with schizophrenia. Omission MMN is a variant of the MMN which is elicited by the absence of a tone previously sequentially presented. Omission MMN can eliminate the effects of sound differences in typical oddball paradigms and affords the opportunity to identify prediction-related signals in the brain. Auditory predictions are thought to reflect bottom-up and top-down processing within hierarchically organized auditory areas. However, the communications between the various subregions of the auditory cortex and the prefrontal cortex that generate and communicate sensory prediction-related signals remain poorly understood. To explore how the frontal and temporal cortices communicate for the generation and propagation of such signals, we investigated the response in the omission paradigm using electrocorticogram (ECoG) electrodes implanted in the temporal, lateral prefrontal, and orbitofrontal cortices of macaque monkeys. We recorded ECoG data from three monkeys during the omission paradigm and examined the functional connectivity between the temporal and frontal cortices by calculating phase-locking values (PLVs). This revealed that theta- (4-8 Hz), alpha- (8-12 Hz), and low-beta- (12-25 Hz) band synchronization increased at tone onset between the higher auditory cortex and the frontal pole where an early omission response was observed in the event-related potential (ERP). These synchronizations were absent when the tone was omitted. Conversely, low-beta-band (12-25 Hz) oscillation then became stronger for tone omission than for tone presentation approximately 200 ms after tone onset. The results suggest that auditory input is propagated to the frontal pole via the higher auditory cortex and that a reciprocal network may be involved in the generation of auditory prediction and prediction error. As impairments of prediction may underlie MMN reduction in patients with schizophrenia, an aberrant hierarchical temporal-frontal network might be related to this pathological condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Suda, Tada, Matsuo, Kawasaki, Saigusa, Ishida, Mitsui, Kumano, Kirihara, Suzuki, Matsumoto, Hasegawa, Kasai and Uka.)

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Traditional neuroscience sees sensory perception as a simple feedforward process. This view is challenged by the predictive coding model in recent years due to the robust evidence researchers had found on how our prediction could influence perception. In the first half of this article, we reviewed the concept of predictive brain and some empirical evidence of sensory prediction in visual and auditory processing. The predictive function along the auditory pathway was mainly studied by mismatch negativity (MMN)-a brain response to an unexpected disruption of regularity. We summarized a range of MMN paradigms and discussed how they could contribute to the theoretical development of the predictive coding neural network by the mechanism of adaptation and deviance detection. Such methodological and conceptual evolution sharpen MMN as a tool to better understand the structural and functional brain abnormality for neuropsychiatric disorder such as schizophrenia., (Copyright © 2020 Fong, Law, Uka and Koike.)

Mismatch negativity (MMN) is a negative deflection of the auditory event-related potential (ERP) elicited by an abrupt change in a sound presented repeatedly. In patients with schizophrenia, MMN is consistently reduced, which makes it a promising biomarker. A non-human primate (NHP) model of MMN based on scalp electroencephalogram (EEG) recordings can provide a useful translational tool, given the high structural homology of the prefrontal and auditory cortices between NHPs, such as macaques, and humans. However, in previous MMN studies, the NHP models used did not allow for comparison with humans because of differences in task settings. Moreover, duration-deviant MMN (dMMN), whose reduction is larger than that in the frequency-deviant MMN (fMMN) in patients with schizophrenia, has never been demonstrated in NHP models. In this study, we determined whether dMMN can be observed in macaque scalp EEG recordings. EEGs were recorded from frontal electrodes (Fz) in two Japanese macaques. Consistent with clinical settings, auditory stimuli consisted of two pure tones, a standard and a deviant tone, in an oddball paradigm. The deviant and standard tones differed in duration (50 and 100 ms for the standard and deviant tones, respectively). A robust dMMN with a latency of around 200 ms, comparable to that in humans, was observed in both monkeys. A comparison with fMMN showed that the dMMN latency was the longer of the two. By bridging the gap between basic and clinical research, our results will contribute to the development of innovative therapeutic strategies for schizophrenia., (Copyright © 2020 Tada, Suda, Kirihara, Koshiyama, Fujioka, Usui, Araki, Kasai and Uka.)

Altered gamma oscillations have attracted considerable attention as an index of the excitation/inhibition (E/I) imbalance in schizophrenia and other neuropsychiatric disorders. The auditory steady-state response (ASSR) has been the most robust probe of abnormal gamma oscillatory dynamics in schizophrenia. Here, we review recent ASSR studies in patients with schizophrenia and other neuropsychiatric disorders. Preclinical ASSR research, which has contributed to the elucidation of the underlying pathophysiology of these diseases, is also discussed. The developmental trajectory of the ASSR has been explored and may show signs of the maturation and disruption of E/I balance in adolescence. Animal model studies have shown that synaptic interactions between parvalbumin-positive GABAergic interneurons and pyramidal neurons contribute to the regulation of E/I balance, which is related to the generation of gamma oscillation. Therefore, ASSR alteration may be a significant electrophysiological finding related to the E/I imbalance in neuropsychiatric disorders, which is a cross-disease feature and may reflect clinical staging. Future studies regarding ASSR generation, especially in nonhuman primate models, will advance our understanding of the brain circuit and the molecular mechanisms underlying neuropsychiatric disorders.

Auditory mismatch negativity (MMN) is an electrophysiological response to a deviation from regularity. This response is considered pivotal to understanding auditory processing, particularly in the pre-attentive phase. However, previous findings suggest that MMN is a product of N1 adaptation/enhancement, which reflects lower-order auditory processing. The separability of these two components remains unclear and is considered an important issue in the field of neuroscience. The aim of the present study was to spatiotemporally differentiate MMN from N1 adaptation using human electrocorticography (ECoG). Auditory evoked potentials under the classical oddball (OD) task as well as the many standards (MS) task were recorded in three patients with epilepsy whose lateral cortices were widely covered with high-density electrodes. Close observation identified an electrode at which N1 adaptation was temporally separated from MMN, whereas N1 adaptation was partially incorporated into MMN at other electrodes. Since N1 adaptation occurs in the N1 population, we spatially compared MMN with N1 obtained from the MS task instead of N1 adaptation. As a result, N1 was observed in a limited area around the Sylvian fissure adjacent to A1, whereas MMN was noted in wider areas, including the temporal, frontal, and parietal lobes. MMN was thus considered to be differentiated from N1 adaptation. The results suggest that MMN is not merely a product of the neural adaptation of N1 and instead represents higher-order processes in auditory deviance detection. These results will contribute to strengthening the foundation of future research in this field., (Copyright © 2020 Takasago, Kunii, Komatsu, Tada, Kirihara, Uka, Ishishita, Shimada, Kasai and Saito.)

Mismatch negativity (MMN) reduction is one of the most robust findings among several neurophysiological and neurocognitive measures in patients with schizophrenia. MMN is a promising biomarker for schizophrenia because of the following properties: 1) its relationship with early psychosis, including clinical high-risk (CHR); 2) its relationship with the functional abilities of patients; and 3) its translatability into basic research using animal models. Specifically, the utility of the passive auditory oddball paradigm that does not require subjects to make behavioral responses enables identical physiological activities to be obtained from both experimental animals and patients. This advantage has contributed to clarifying the generating mechanism of MMN in various animal studies. We reviewed clinical reports focused on early psychosis; specifically differential effects of deviance type and relationships to clinical and functional outcome. For the utility of MMN as a tool for translational research, we next reviewed recent MMN studies in rodents and nonhuman primates (NHP) as well as studies using intracranial recordings in humans, a rare opportunity to detect neural signals in vivo in humans. Neural computations of MMN, such as adaptation, deviance detection, and predictive coding, have been recent topics for understanding MMN generating mechanisms. Finally, several significant research questions were provided for future directions. MMN research could contribute to innovative, novel, therapeutic strategies in the future by becoming a bridge between basic and clinical research., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The auditory steady-state response (ASSR) has been used to detect auditory processing deficits in patients with psychiatric disorders. However, the methodology of ASSR recording from the brain surface has not been standardized in preclinical studies, limiting its use as a translational biomarker. The sites of maximal ASSR in humans are the vertex and/or middle frontal area, although it has been suggested that the auditory cortex is the source of the ASSR. We constructed and validated novel methods for ASSR recording using a switchable pedestal which allows ASSR recording alternatively from temporal or parietal cortex with a wide range of frequencies in freely moving rats. We further evaluated ASSR as a translational tool by assessing the effect of ketamine. The ASSR measured at parietal cortex did not show clear event-related spectral perturbation (ERSP) or inter-trial coherence (ITC) in any frequency bands or a change with ketamine. In contrast, the ASSR at temporal cortex showed clear ERSP and ITC where 40 Hz was maximal in both gamma-band frequencies. Ketamine exerted a biphasic effect in ERSP at gamma bands. These findings suggest that temporal cortex recording with a wide frequency range is a robust methodology to detect ASSR, potentially enabling application as a translational biomarker in psychiatric and developmental disorders.

Auditory contextual processing has been assumed to be based on a hierarchical structure consisting of the primary auditory cortex, superior temporal gyrus (STG), and frontal lobe. Recent invasive studies on mismatch negativity (MMN) have revealed functional segregation for auditory contextual processing such as neural adaptation in the primary auditory cortex and prediction in the frontal lobe. However, the role of the STG remains unclear. We obtained induced activity in the high gamma band as mismatch response (MMR), an electrocorticographic (ECoG) counterpart to scalp MMN, and the components of MMR by analyzing ECoG data from patients with refractory epilepsy in an auditory oddball task paradigm. We found that MMR localized mainly in the bilateral posterior STGs, and that deviance detection largely accounted for MMR. Furthermore, adaptation was identified in a limited number of electrodes on the superior temporal plane. Our findings reveal a mixed contribution of deviance detection and adaptation depending on location in the STG. Such spatial considerations could lead to further understanding of the pathophysiology of relevant psychiatric disorders., (© 2018 Wiley Periodicals, Inc.)

In Japan, traditional gender roles of women, especially the role of motherhood, may cause early career resignations in female physicians and a shortage of female researchers. Besides this gender issue, a general physician shortage is affecting basic science fields. Our previous study suggested that female physicians could be good candidates for the basic sciences because such work offers good work-life balance. However, the attractiveness for female physicians of working in the basic sciences, including work-life balance, is not known. In a 2012 nationwide cross-sectional questionnaire survey, female physicians holding tenured positions in the basic sciences at Japan's medical schools were asked an open-ended question about positive aspects of basic sciences that clinical medicine lacks, and we analyzed 58 respondents' comments. Qualitative analysis using the Kawakita Jiro method revealed four positive aspects: research attractiveness, priority on research productivity, a healthy work-life balance, and exemption from clinical duties. The most consistent positive aspect was research attractiveness, which was heightened by medical knowledge and clinical experience. The other aspects were double-edged swords; for example, while the priority on research productivity resulted in less gender segregation, it sometimes created tough competition, and while exemption from clinical duties contributed to a healthy work-life balance, it sometimes lowered motivation as a physician and provided unstable income. Overall, if female physicians lack an intrinsic interest in research and seek good work-life balance, they may drop out of research fields. Respecting and cultivating students' research interest is critical to alleviating the physician shortage in the basic sciences.

Both the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) are major targets for neuromodulation therapy for movement disorders. An example of such a therapy is deep brain stimulation (DBS). The striatum is the primary target for pharmacological treatment of these disorders. To further our understanding of both the functional relationships among motor nuclei and the mechanisms of therapies for movement disorders, it is important to clarify how changing the neuronal activity of one target, either by medication or by artificial electrical stimulation, affects the other connected nuclei. To investigate this point, we recorded single-unit activity from tonically active neurons (TANs), which are putative cholinergic interneurons in the striatum, of healthy monkeys (Macaca fuscata) during electrical stimulation of the STN or GPi. Both STN stimulation and GPi stimulation reduced the TAN spike rate. Local infusion of a D2 receptor antagonist in the striatum blocked the reduction in spike rate induced by STN stimulation but not that induced by GPi stimulation. Further, STN stimulation induced phasic dopamine release in the striatum as revealed by in vivo fast-scan cyclic voltammetry. These results suggest the presence of multiple, strong functional relationships among the STN, GPi, and striatum that have different pathways and imply distinct therapeutic mechanisms for STN- and GPi-DBS., (© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: In Japan, the field of Basic Sciences encompasses clinical, academic, and translational research, as well as the teaching of medical sciences, with both an MD and PhD typically required. In this study, it was hypothesized that the characteristics of a Basic Sciences career path could offer the professional advancement and personal fulfillment that many female medical doctors would find advantageous. Moreover, encouraging interest in Basic Sciences could help stem shortages that Japan is experiencing in medical fields, as noted in the three principal contributing factors: premature resignation of female clinicians, an imbalance of female physicians engaged in research, and a shortage of medical doctors in the Basic Sciences. This study examines the professional and personal fulfillment expressed by Japanese female medical doctors who hold positions in Basic Sciences. Topics include career advancement, interest in medical research, and greater flexibility for parenting., Methods: A cross-sectional questionnaire survey was distributed at all 80 medical schools in Japan, directed to 228 female medical doctors whose academic rank was assistant professor or higher in departments of Basic Sciences in 2012. Chi-square tests and the binary logistic regression model were used to investigate the impact of parenthood on career satisfaction, academic rank, salary, etc., Results: The survey response rate of female physicians in Basic Sciences was 54.0%. Regardless of parental status, one in three respondents cited research interest as their rationale for entering Basic Sciences, well over twice other motivations. A majority had clinical experience, with clinical duties maintained part-time by about half of respondents and particularly parents. Only one third expressed afterthoughts about relinquishing full-time clinical practice, with physicians who were parents expressing stronger regrets. Parental status had little effect on academic rank and income within the Basic Sciences, CONCLUSION: Scientific curiosity and a desire to improve community health are hallmarks of those choosing a challenging career in medicine. Therefore, it is unsurprising that interest in research is the primary motivation for a female medical doctor to choose a career in Basic Sciences. Additionally, as with many young professionals with families, female doctors seek balance in professional and private lives. Although many expressed afterthoughts relinquishing a full-time clinical practice, mothers generally benefited from greater job flexibility, with little significant effect on career development and income as Basic Scientists.

Motion perception plays an important role in everyday life. The investigation of the neural mechanisms underlying the distinguishing of the direction of motion has broadly expanded our understanding of the neural mechanisms of not only visual motion processing but also how integration of visual information is linked with intentional behavior. The lateral intraparietal (LIP) cortex is a crucial area involved in perceptual decision making and oculomotor planning. Here, I have reviewed the neural mechanisms underlying visual motion processing and describe how intentional behavior results from motion information.

Observers have difficulty identifying a target in their peripheral vision in the presence of surrounding stimuli. Although hypotheses addressing this phenomenon have been proposed, such as the integration of stimuli and surround suppression in the higher-order visual cortex, no direct comparisons of the psychophysical and neuronal sensitivities have been performed. Here we measured the performance of monkeys with a variant of the direction discrimination task using a center/surround bipartite random-dot stimulus while simultaneously recording from isolated neurons from the middle temporal visual area (MT). The psychophysical threshold increased with the addition of a task-irrelevant noise annulus that surrounded the task-relevant motion stimuli. The neuronal threshold of MT neurons also increased at a spatial scale similar to the psychophysical threshold. This suggests that the impaired ability in our task resulted from impairment in the MT area. Importantly, reduced neuronal performance was due to both a reduced response to preferred motion and an enhanced response to nonpreferred motion. These observations suggest that impairment caused by surrounding noise results from interactions between stimuli and noise and not from a reduction in the response of visual neurons., (Copyright © 2014 the American Physiological Society.)

Purpose: Hypertension is associated with substantial morbidity in Japan. The aim of this work was to evaluate whether hypertension is associated with white matter microstructural changes by using diffusional kurtosis imaging (DKI)., Methods: We explored the regional patterns of white matter alteration in 15 hypertensive middle-aged male participants and 11 normotensive controls by using DKI-based whole-brain analysis. In addition, we investigated whether the observed white matter microstructural changes were related to systolic or diastolic blood pressure by using Pearson's correlation coefficient analysis., Results: Mean diffusional kurtosis (MDK) values were significantly higher in hypertensive participants than in normotensive participants (P < 0.05; family-wise error correction for multiple comparisons), indicating widespread microstructural changes in white matter. Moreover, we noted a statistically significant positive correlation between systolic and diastolic blood pressure and MDK values of the whole brain., Conclusion: Our study suggests that microstructural white matter changes occur in middle-aged men with hypertension, even before the onset of cerebrovascular disease. Thus, DKI might be used as a screening tool for risk of cerebrovascular disease. This highlights the need to further elucidate the relationship between hypertension and DKI of the brain.

How the visual system reconstructs global patterns of motion from components is an important issue in vision. Conventional studies using plaids have shown that approximately one-third of neurons in cortical area MT respond to one-dimensional (1D) components of a moving pattern (component cells), whereas another third responds to the global two-dimensional (2D) motion of a pattern (pattern cells). Conversely, studies using spots of light or random dots that contain multiple orientations have seldom reported directional tuning that is consistent with 1D motion preference. To bridge the gap between these studies, we recorded from isolated neurons in macaque area MT and measured tuning for velocity (direction and speed) using random dot stimuli. We used the "intersection of constraints" principle to classify our population into pattern-direction-selective (PDS) neurons and component-direction-selective (CDS) neurons. We found a larger proportion of PDS cells (68%) and a smaller proportion of CDS cells (8%) compared with prior studies using plaids. We further compared velocity tuning, measured using random dot stimuli, with direction tuning, measured using plaids. Although there was a correlation between the degree of preference for 2D over 1D motion of the two measurements, tuning seemed to prefer 2D motion using random dot stimuli. Modeling analyses suggest that integration across orientations contributes to the 2D motion preference of both dots and plaids, but opponent inhibition mainly contributes to the 2D motion preference of plaids. We conclude that MT neurons become more capable of identifying a particular 2D velocity when stimuli contain multiple orientations.

Numerous psychophysical studies have described perceptual learning as long-lasting improvements in perceptual discrimination and detection capabilities following practice. Where and how long-term plastic changes occur in the brain is central to understanding the neural basis of perceptual learning. Here, neurophysiological research using non-human primates is reviewed to address the neural mechanisms underlying visual perceptual learning. Previous studies have shown that training either has no effect on or only weakly alters the sensitivity of neurons in early visual areas, but more recent evidence indicates that training can cause long-term changes in how sensory signals are read out in the later stages of decision making. These results are discussed in the context of learning specificity, which has been crucial in interpreting the mechanisms underlying perceptual learning. The possible mechanisms that support learning-related plasticity are also discussed., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI., Research Design and Methods: Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF., Results: In the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = -0.56, P < 0.04)., Conclusions: Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.

The number of physicians engaged in basic sciences and teaching is sharply decreasing in Japan. To alleviate this shortage, central government has increased the quota of medical students entering the field. This study investigated medical students' interest in basic sciences in efforts to recruit talent. A questionnaire distributed to 501 medical students in years 2 to 6 of Juntendo University School of Medicine inquired about sex, grade, interest in basic sciences, interest in research, career path as a basic science physician, faculties' efforts to encourage students to conduct research, increases in the number of lectures, and practical training sessions on research. Associations between interest in basic sciences and other variables were examined using χ(2) tests. From among the 269 medical students (171 female) who returned the questionnaire (response rate 53.7%), 24.5% of respondents were interested in basic sciences and half of them considered basic sciences as their future career. Obstacles to this career were their original aim to become a clinician and concerns about salary. Medical students who were likely to be interested in basic sciences were fifth- and sixth-year students, were interested in research, considered basic sciences as their future career, considered faculties were making efforts to encourage medical students to conduct research, and wanted more research-related lectures. Improving physicians' salaries in basic sciences is important for securing talent. Moreover, offering continuous opportunities for medical students to experience research and encouraging advanced-year students during and after bedside learning to engage in basic sciences are important for recruiting talent.

The ability to switch between tasks is critical for animals to behave according to context. Although the association between the prefrontal cortex and task switching has been well documented, the ultimate modulation of sensory-motor associations has yet to be determined. Here, we modeled the results of a previous study showing that task switching can be accomplished by communication from distinct populations of sensory neurons. We proposed a leaky-integrator model where relevant and irrelevant information were stored separately in two integrators and task switching was achieved by leaking information from the irrelevant integrator. The model successfully explained both the behavioral and neuronal data. Additionally, the leaky-integrator model showed better performance than an alternative model, where irrelevant information was discarded by decreasing the weight on irrelevant information, when animals initially failed to commit to a task. Overall, we propose that flexible switching is, in part, achieved by actively controlling the amount of leak of relevant and irrelevant information.

The number of physicians engaged in basic science and teaching is sharply decreasing in Japan. To alleviate this shortage, central government has increased the quota of medical students entering the field. This study aimed to determine the characteristics of physicians who are engaged in basic science in efforts to recruit talent. A questionnaire was distributed to all 30 physicians in the basic science departments of Juntendo University School of Medicine. Question items inquired about sex, years since graduation, years between graduation and time entering basic science, clinical experience, recommending the career to medical students, expected obstacles to students entering basic science, efforts to inspire students in research, increased number of lectures and practical training sessions on research, and career choice satisfaction. Correlations between the variables were examined using χ(2) tests. Overall, 26 physicians, including 7 female physicians, returned the questionnaire (response rate 86.7%). Most physicians were satisfied with their career choice. Medical students were deemed not to choose basic science as their future career, because they aimed to become clinicians and because they were concerned about salary. Women physicians in basic science departments were younger than men. Women physicians also considered themselves to make more efforts in inspiring medical students to be interested in research. Moreover, physicians who became basic scientists earlier in their career wanted more research-related lectures in medical education. Improving physicians' salaries in basic science is important to securing talent. In addition, basic science may be a good career path for women physicians to follow.

The visual system faces a trade-off between increased spatial integration of disparate local signals and improved spatial resolution to filter out irrelevant noise. Increased spatial integration is beneficial when signals are weak, whereas increased spatial resolution is particularly beneficial when focusing on a small object in a cluttered natural scene. The receptive field (RF) size of visual cortical neurons can be modulated depending on various factors such as sensory context, allowing adaptive integration of sensory signals. In this study, we explored the spatial integration properties of neurons in macaque middle temporal visual area (MT). We hypothesized that spatial resolution would increase when high-contrast noise was presented simultaneously with a visual stimulus, enabling focus on a small object in a cluttered scene. To test this hypothesis, we mapped the RFs of MT neurons of two fixating monkeys in a 5 × 5 grid manner using a small patch of random-dot motion. To examine the effects of noise on RF profile, a dynamic noise (0% coherence dots) of varying diameter was concurrently presented at the RF center. We found that RF size decreased when noise diameter increased. Analyses based on the response normalization model and area summation provided evidence for the potential contribution of spatial summation properties within the RF and surround suppression to the apparent contraction of RF size. Our results suggest that MT neurons integrate smaller regions of motion signals when signals are embedded in noise, an efficient strategy to filter out surrounding noise.

Human judgment is frequently impaired by distracters extending across our field of view. How we extract relevant information from a spatially restricted region in a complex scene in spite of this impairment is an important issue in vision. Recently, it has been shown that this impairment can be reduced by increasing the number of surrounding distracters without changing the density, thus increasing the total area covered by the distracters. Little, however, is known regarding the underlying mechanism(s). Here, we tested the hypothesis that visual impairment by distracters is due to integration of irrelevant information across space, and that further addition of distracters produces contraction of the spatial integration field. Human subjects were instructed to judge the direction of motion within a center disk and to ignore motion noise in the surrounding annulus in a random dot kinematogram. We observed a non-monotonic effect of the size of the annulus, in which the subjects' discrimination thresholds at first increased, and then decreased as the size of the annulus became larger. We further investigated how weak coherent motion in the surrounding annulus interferes with the subjects' performance. Importantly, we found that the amount of interference decreases with the addition of surrounding motion noise, consistent with the hypothesis that the addition of distracters produces contraction of the range of spatial integration. Our results suggest that integration within a visual receptive field causes impairment by distracters across our visual field, and that contraction of the range of integration can counteract this impairment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Neurons in extrastriate visual areas have large receptive fields (RFs) compared with those in primary visual cortex (V1), suggesting extensive spatial integration. To examine the spatial integration of neurons in area MT, we modeled the RFs of MT neurons based on a symmetrical (Gaussian) integration of V1 outputs and tested the model using single-unit recording in two fixating macaque monkeys. Because visual representation in V1 is logarithmically compressed along eccentricity, the resulting RF model is log-Gaussian along the radial axis in polar coordinates. To test the log-Gaussian model, the RF of each neuron was mapped on a 5 x 5 grid using a small patch of random dots drifting at the preferred velocity of the neuron. The majority of MT neurons had RFs with a steeper slope near the fovea and a shallower slope away from the fovea. Among various two-dimensional Gaussian models fitted to the RFs, the log-Gaussian model provided the best description. The fitted parameters revealed that the range of sampling by MT neurons has no systematic relationship with eccentricities, consistent with a recent study for V4 neurons. Our results suggest that MT neurons integrate inputs from constant-sized patches of V1 cortex.

The processes underlying dynamic changes in human behavior during real situations contain much irrelevant information and represent a key issue facing neuroscientists. Although the roles played by the frontal cortex in this switching behavior have been well documented, little is known regarding how neural pathways governing sensorimotor associations accomplish such a switch. We addressed this question by recording activities of middle temporal (MT) neurons in monkeys switching between direction versus depth discrimination tasks. Although the monkeys successfully switched between the tasks, neural sensitivity did not change as a function of task. More importantly, neurons that signaled the same motor output showed trial-to-trial covariation between neuronal responses and perceptual judgments during both tasks, whereas neurons that signaled the opposite motor output showed no covariation in either task. These results suggest that task switching is accomplished via communication from distinct populations of neurons when sensorimotor associations switch within a short time period.

Binocular disparity is an important visual cue that gives rise to the perception of depth. Disparity signals are widely spread across the visual cortex, but their relative role is poorly understood. Here, we addressed the correlation between the responses of disparity-selective neurons in the occipitotemporal (ventral) visual pathway and the behavioral discrimination of stereoscopic depth. We recorded activity of disparity-selective neurons in the inferior temporal cortex (IT) while monkeys were engaged in a fine stereoscopic depth discrimination (stereoacuity) task. We found that trial-to-trial fluctuations in neuronal responses correlated with the monkey's perceptual choice. We suggest that disparity signals in the IT, located in the ventral visual pathway, are functionally linked to the discrimination of fine-grain depth.