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Unilateral spatial neglect (USN) was originally regarded as a parietal syndrome, but it has become evident that USN is a disturbance in the widespread attention network. Here, we focused on an interaction between spatial neglect and non-spatial aspect of attention deficit, and aimed to establish a novel evaluation approach based on the characteristics of the spatial distribution of reaction times. We tested 174 patients with right hemisphere damage and divided them based on their prescreening scores on the Behavioral Inattention Test (BIT): (1) USN++ (n = 79: BIT131), (2) USN+ (n = 47: BIT≥131 with history of USN), and (3) RHD (n = 48: without neglect symptom). The patients were asked to conduct a touch panel-based pointing task toward 2D-arranged (seven columns × five rows) circular targets on a PC monitor, and the reaction time to each object was recorded. To evaluate aspects of attention deficit and neglect symptoms, we calculated the total average of the reaction time for all objects (RT

Highlights • Patients with chronic pain due to postherpetic neuralgia (PHN) were used. • Hemodynamic activity in the dorsolateral prefrontal cortex (dlPFC) was analyzed. • PHN showed less placebo effects and smaller hemodynamic responses in the right dlPFC. • PHN symptoms were associated with smaller placebo effects and right dlPFC responses. • Deficits in placebo effects due to dlPFC disturbance are involved in chronic pain., The dorsolateral prefrontal cortex (dlPFC) is functionally linked to the descending pain modulation system and has been implicated in top down pain inhibition, including placebo analgesia. Therefore, functions of the dlPFC may be impaired in patients with chronic pain. Postherpetic neuralgia (PHN) is one of several syndromes with chronic neuropathic pain. In the present study, we investigated possible dysfunction of the dlPFC in chronic pain using patients with PHN. In a conditioning phase, heathy controls (n = 15) and patients with PHN (n = 7) were exposed to low (LF) and high (HF) frequency tones associated with noxious stimuli: weak (WS) and strong (SS) electrical stimulation, respectively. After the conditioning, cerebral hemodynamic activity was recorded from the bilateral dlPFC while the subjects were subjected to the cue tone-noxious electrical stimulation paradigm, in which incorrectly cued noxious stimuli were sometimes delivered to induce placebo and nocebo effects. The results indicated that hemodynamic responses to the LF tone in the right dlPFC was significantly lower in patients with PHN compared to the healthy controls. Furthermore, the same hemodynamic responses in the right dlPFC were correlated with placebo effects. In addition, clinical symptoms of PHN were negatively correlated to cerebral hemodynamic responses in the right dlPFC and magnitudes of the placebo effects. The results suggest that the right dlPFC, which is closely associated with the descending pain modulation system, is disturbed in PHN.

Amyloid β-protein (Aβ) molecules tend to aggregate and subsequently form low MW (LMW) oligomers, high MW (HMW) aggregates such as protofibrils, and ultimately fibrils. These Aβ species can generally form amyloid plaques implicated in the neurodegeneration of Alzheimer disease (AD), but therapies designed to reduce plaque load have not demonstrated clinical efficacy. Recent evidence implicates amyloid oligomers in AD neuropathology, but the precise mechanisms are uncertain. We examined the mechanisms of neuronal dysfunction from HMW-Aβ1-42 exposure by measuring membrane integrity, reactive oxygen species (ROS) generation, membrane lipid peroxidation, membrane fluidity, intracellular calcium regulation, passive membrane electrophysiological properties, and long-term potentiation (LTP). HMW-Aβ1-42 disturbed membrane integrity by inducing ROS generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and impaired LTP. The damaging effects of HMW-Aβ1-42 were significantly greater than those of LMW-Aβ1-42. Therapeutic reduction of HMW-Aβ1-42 may prevent AD progression by ameliorating direct neuronal membrane damage.-Yasumoto, T., Takamura, Y., Tsuji, M., Watanabe-Nakayama, T., Imamura, K., Inoue, H., Nakamura, S., Inoue, T., Kimura, A., Yano, S., Nishijo, H., Kiuchi, Y., Teplow, D. B., Ono, K. High molecular weight amyloid β1-42 oligomers induce neurotoxicity via plasma membrane damage.

The subcortical visual pathway including the superior colliculus (SC), pulvinar, and amygdala has been implicated in unconscious visual processing of faces, eyes, and gaze direction in blindsight. Our previous studies reported that monkey SC and pulvinar neurons responded preferentially to images of faces while performing a delayed non-matching to sample (DNMS) task to discriminate different visual stimuli (Nguyen et al., 2013, 2014). However, the contribution of SC and pulvinar neurons to the discrimination of the facial images and subsequent behavioral performance remains unknown. Since gamma oscillations have been implicated in sensory and cognitive processes as well as behavioral execution, we hypothesized that gamma oscillations during neuronal responses might contribute to achieving the appropriate behavioral performance (i.e., a correct response). In the present study, we re-analyzed those neuronal responses in the monkey SC and pulvinar to investigate possible relationships between gamma oscillations in these neurons and behavioral performance (correct response ratios) during the DNMS task. Gamma oscillations of SC and pulvinar neuronal activity were analyzed in three phases around the stimulus onset [inter-trial interval (ITI): 1000ms before trial onset; Early: 0-200ms after stimulus onset; and Late: 300-500ms after stimulus onset]. We found that human facial images elicited stronger gamma oscillations in the early phase than the ITI and late phase in both the SC and pulvinar neurons. Furthermore, there was a significant correlation between strengths of gamma oscillations in the early phase and behavioral performance in both the SC and pulvinar. The results suggest that gamma oscillatory activity in the SC and pulvinar contributes to successful behavioral performance during unconscious perceptual and behavioral processes.

Sensorimotor incongruence (SMI) is associated with pathological pain, such as phantom limb pain. Additionally, patients with pathological pain and brain dysfunction typically present with movement disorders, including diminished voluntary control and increased variability in bimanual movement performance. In healthy subjects, SMI leads to dysesthesia and bimanual movement motor dysfunction. However, the brain localization of this activity remains unclear, particularly in SMI-induced dysesthesia and decrease in movement accuracy. In this study, 17 healthy participants were asked to perform repetitive flexion/extension exercises with their wrists in a congruent/incongruent position while viewing the activity in a mirror. Indeed, SMI induced dysesthesia and decreased bimanual movement accuracy. Moreover, beta band activities of the bilateral presupplementary (P 0.01) and bilateral cingulate (P 0.05) motor areas were decreased. Collectively, our findings indicate that SMI induces dysesthesia and movement disorders and reduces beta band activities in motor-related areas.

Eye tracking is an effective tool for identifying behavioural aspects of unilateral spatial neglect (USN), which is a common neurological syndrome that develops after a right hemisphere lesion. Here, we attempted to elucidate how the neglect symptom affects the symmetry of the gaze pattern, by performing an analysis of gaze distribution during the free viewing of a pair of horizontally flipped images. Based on their Behavioural Inattention Test (BIT) scores, 41 patients with right-hemisphere damage were classified into those with USN (n = 27) and those without USN (right hemisphere damaged - RHD; n = 14). Eye movement was recorded while the patients viewed six pairs of horizontally flipped images on a computer display. A pair of flipped images has both similar and consistent elements, as well as a reversed spatial location of objects (right-left). We calculated the gaze distribution, extent of gaze shift, total gaze distance, and gaze velocity in each direction. Our results demonstrated a significantly larger rightward gaze shift in the USN group, which showed a significant correlation with the BIT score. More importantly, the extent of gaze shift and total gaze distance were similarly modulated by the contents of the displayed images in both the USN and RHD groups. Our findings suggest that analyses of gaze distribution during the free viewing of a pair of horizontally flipped images have the potential to precisely reveal neglect behaviour, and our results provide important implications for rehabilitation.

Technical reasoning refers to making inferences about how to use tools. The degree of technical reasoning is indicated by the bias of the gaze (fixation) on the functional part of the tool when in use. Few studies have examined whether technical reasoning differs between familiar and unfamiliar novel tools. In addition, what effect the intention to use the tool has on technical reasoning has not been determined. This study examined gaze shifts in relation to familiar or unfamiliar tools, under three conditions (free viewing, lift, and use), among 14 healthy adults (mean age ± standard deviation, 29.4 ± 3.9 years). The cumulative fixation time on the functional part of the tool served as a quantitative indicator of the degree of technical reasoning. The two-way analysis of variance for tools (familiar and unfamiliar) and conditions (free viewing, lift, and use) revealed that the cumulative fixation time significantly increased under free viewing and use conditions, compared to lift conditions. Relative to the free viewing condition, cumulative fixation time for unfamiliar tools significantly decreased in the lift condition and significantly increased in the use condition. Importantly, the results showed that technical reasoning was performed in both the use and the free viewing conditions. However, technical reasoning in the free viewing condition was not as strong as in the use condition. The difference between technical reasoning in free viewing and use conditions may indicate the difference between automatic and intentional technical reasoning.

Walking speed is strongly influenced by the severity of motor paralysis in post-stroke patients. Nevertheless, some patients with mild motor paralysis still walk slowly. Factors associated with this difference in walking speed have not been elucidated. To confirm walking characteristics of patients with mild motor paralysis and slow walking speed, this study identified patient subgroups based on the association between the severity of motor paralysis and walking speed. Fugl-Meyer assessment synergy score (FMS) and the walking speed were measured (n = 42), and cluster analysis was performed based on the association between FMS and walking speed to identify the subgroups. FMS and walking speed were associated (ρ = 0.50); however, some patients walked slowly despite only mild motor paralysis. Cluster analysis using FMS and walking speed as the main variables classified patients into subgroups. Patients with mild motor paralysis (FMS: 18.4 ± 2.09 points) and slow walking speed (0.28 ± 0.14 m/s) exhibited poorer trunk stability, increased co-contraction of the shank muscle, and increased intramuscular coherence in walking compared to other clusters. This group was identified by their inability to fully utilize the residual potential of motor function. In walking training, intervention in instability and excessive cortical control may be effective.

Background Human clinical studies reported that several electroencephalographical (EEG) parameters can be used as biomarkers of psychiatric disorders. EEGs recorded from non-human primates (monkeys) is useful for understanding of human pathologies of psychiatric disorders and development of new therapeutic agents. New methods In this study, we expand a previous non-invasive head holding system with face masks for awake monkeys to be applied to scalp EEG recording. The new design of a head holding system allows to attach scalp EEG electrodes on the positions comparable to human electrode placement and to present auditory stimuli. Results With this system, we could record auditory evoked potentials (AEPs) in auditory sensory gating and oddball paradigms, which are often used as biomarkers of psychiatric disorders in animal models and human patients. The recorded AEPs were comparable to previous human clinical data. Comparison with existing methods Compared with previous non-invasive head holding systems, top, side (cheek and ears), and rear of the head can be open for attachment of EEG electrodes and auditory stimulation in the present system. Conclusions The results suggest that the present system is useful in EEG recording from awake monkeys. Furthermore, this system can be applied to eye-tracking and chronic intra-cerebral recording experiments., Neuroscience; Neurology; Physiology; Behavioral test; Cognition; Consciousness; Mental disorder; Veterinary medicine; Biological psychiatry; Non-invasive head holding; Pre-clinical translational research; EEG; Non-human primates

Growing evidence suggests that oxidative stress due to amyloid β (Aβ) accumulation is involved in Alzheimer’s disease (AD) through the formation of amyloid plaque, which leads to hyperphosphorylation of tau, microglial activation, and cognitive deficits. The dysfunction or phenotypic loss of parvalbumin (PV)-positive neurons has been implicated in cognitive deficits. Astaxanthin is one of carotenoids and known as a highly potent antioxidant. We hypothesized that astaxanthin’s antioxidant effects may prevent the onset of cognitive deficits in AD by preventing AD pathological processes associated with oxidative stress. In the present study, we investigated the effects of astaxanthin intake on the cognitive and pathological progression of AD in a mouse model of AD. The AppNL-G-F/NL-G-F mice were fed with or without astaxanthin from 5-to-6 weeks old, and cognitive functions were evaluand using a Barnes maze test at 6 months old. PV-positive neurons were investigated in the hippocampus. Aβ42 deposits, accumulation of microglia, and phosphorylated tau (pTau) were immunohistochemically analyzed in the hippocampus. The hippocampal anti-oxidative status was also investigated. The Barnes maze test indicated that astaxanthin significantly ameliorated memory deficits. Astaxanthin reduced Aβ42 deposition and pTau-positive areal fraction, while it increased PV-positive neuron density and microglial accumulation per unit fraction of Aβ42 deposition in the hippocampus. Furthermore, astaxanthin increased total glutathione (GSH) levels, although 4-hydroxy-2,3-trans-nonenal (4-HNE) protein adduct levels (oxidative stress marker) remained high in the astaxanthin supplemented mice. The results indicated that astaxanthin ameliorated memory deficits and significantly reversed AD pathological processes (Aβ42 deposition, pTau formation, GSH decrease, and PV-positive neuronal deficits). The elevated GSH levels and resultant recovery of PV-positive neuron density, as well as microglial activation, may prevent these pathological processes.

To develop a real-time neurofeedback system from the anterior prefrontal cortex (aPFC) using functional near-infrared spectroscopy (fNIRS) for motor rehabilitation, we investigated the effects of motor imagery training with neurofeedback from the aPFC on hand dexterity and cerebral hemodynamic activity during a motor rehabilitation task. Thirty-one right-handed healthy subjects participated in this study. They received motor imagery training six times for 2 weeks under fNIRS neurofeedback from the aPFC, in which they were instructed to increase aPFC activity. The real group subjects (n = 16) were shown real fNIRS neurofeedback signals from the aPFC, whereas the sham group subjects (n = 15) were shown irrelevant randomized signals during neurofeedback training. Before and after the training, hand dexterity was assessed by a motor rehabilitation task, during which cerebral hemodynamic activity was also measured. The results indicated that aPFC activity was increased during the training, and performance improvement rates in the rehabilitation task after the training was increased in the real group when compared with the sham group. Improvement rates of mean aPFC activity across the training were positively correlated with performance improvement rates in the motor rehabilitation task. During the motor rehabilitation task after the training, the hemodynamic activity in the left somatosensory motor-related areas [premotor area (PM), primary motor area (M1), and primary somatosensory area (S1)] was increased in the real group, whereas the hemodynamic activity was increased in the supplementary motor area in the sham group. This hemodynamic activity increases in the somatosensory motor-related areas after the training correlated with aPFC activity during the last 2 days of motor imagery training. Furthermore, improvement rates of M1 hemodynamic activity after the training was positively correlated with performance improvement rates in the motor rehabilitation task. The results suggest that the aPFC might shape activity in the somatosensory motor-related areas to improve hand dexterity. These findings further suggest that the motor imagery training using neurofeedback signals from the aPFC might be useful to patients with motor disability.

BackgroundCompression of myofascial trigger points (MTrPs) in muscles is reported to reduce chronic musculoskeletal pain. Although the prefrontal cortex (PFC) is implicated in development of chronic pain, the mechanisms of how MTrP compression at low back regions affects PFC activity remain under debate. In this study, we investigated effects of MTrP compression on brain hemodynamics and EEG oscillation in subjects with chronic low back pain.MethodsThe study was a prospective, randomized, parallel-group trial and an observer and subject-blinded clinical trial. Thirty-two subjects with chronic low back pain were divided into two groups: subjects with compression at MTrPs (n = 16) or those with non-MTrPs (n = 16). Compression at MTrP or non-MTrP for 30 s was applied five times, and hemodynamic activity (near-infrared spectroscopy; NIRS) and EEGs were simultaneously recorded during the experiment.ResultsThe results indicated that compression at MTrPs significantly (1) reduced subjective pain (P < 0.05) and increased the pressure pain threshold (P < 0.05), (2) decreased the NIRS hemodynamic activity in the frontal polar area (pPFC) (P < 0.05), and (3) increased the current source density (CSD) of EEG theta oscillation in the anterior part of the PFC (P < 0.05). CSD of EEG theta oscillation was negatively correlated with NIRS hemodynamic activity in the pPFC (P < 0.05). Furthermore, functional connectivity in theta bands between the medial pPFC and insula cortex was significantly decreased in the MTrP group (P < 0.05). The functional connectivity between those regions was positively correlated with subjective low back pain (P < 0.05).DiscussionThe results suggest that MTrP compression at the lumbar muscle modulates pPFC activity and functional connectivity between the pPFC and insula, which may relieve chronic musculoskeletal pain.Trial registrationThis trial was registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000033913) on 27 August 2018, at https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000038660.

Human babies respond preferentially to faces or face-like images. It has been proposed that an innate and rapid face detection system is present at birth before the cortical visual pathway is developed in many species, including primates. However, in primates, the visual area responsible for this process is yet to be unraveled. We hypothesized that the superior colliculus (SC) that receives direct and indirect retinal visual inputs may serve as an innate rapid face-detection system in primates. To test this hypothesis, we examined the responsiveness of monkey SC neurons to first-order information of faces required for face detection (basic spatial layout of facial features including eyes, nose, and mouth), by analyzing neuronal responses to line drawing images of: (1) face-like patterns with contours and properly placed facial features; (2) non-face patterns including face contours only; and (3) nonface random patterns with contours and randomly placed face features. Here, we show that SC neurons respond stronger and faster to upright and inverted face-like patterns compared to the responses to nonface patterns, regardless of contrast polarity and contour shapes. Furthermore, SC neurons with central receptive fields (RFs) were more selective to face-like patterns. In addition, the population activity of SC neurons with central RFs can discriminate face-like patterns from nonface patterns as early as 50 ms after the stimulus onset. Our results provide strong neurophysiological evidence for the involvement of the primate SC in face detection and suggest the existence of a broadly tuned template for face detection in the subcortical visual pathway.

Environmental exposure to dioxins, consumption of a high fat diet, and platelet-derived growth factor receptor β signaling in the brain affect feeding behavior, which is an important determinant of body growth. In the present study, we investigated the effects of prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fact diet after weaning on body growth and expression of platelet-derived growth factor receptor β in the brain in rat pups. Subjects from the control and dioxin exposure groups were assigned to 1 of 3 different diet groups: standard diet, high fat diet in the juvenile period, or high fat diet in adulthood. Body weight gain rate in the juvenile high fat diet group and the length gain rate in the adult high fat diet group were greater than the corresponding values in the standard diet group only in male offspring, although the effects of dioxin exposure on growth were not significant. Consumption of a high fat diet decreased platelet-derived growth factor receptor β levels in the amygdala and hippocampus in both sexes compared to control groups, while 2,3,7,8-tetrachlorodibenzo-p-dioxin decreased platelet-derived growth factor receptor platelet-derived growth factor receptor β levels in the amygdala and striatum only in females receiving an high fat diet. Furthermore, platelet-derived growth factor receptor β levels in the hippocampus and platelet-derived growth factor receptor β striatum were inversely correlated with increases in body length, while changes in platelet-derived growth factor receptor β in the amygdala and nucleus accumbens were significantly correlated to body weight gain or body mass index. In conclusion, these findings suggest that these 2,3,7,8-tetrachlorodibenzo-p-dioxin and high fat diet-induced changes in body growth and feeding behaviors might be partially mediated by changes in brain platelet-derived growth factor receptor β levels.

Summary Visuospatial neglect (VSN) is a neurological syndrome of higher brain functions in which an individual fails to detect stimuli on a space that is contralateral to a hemispheric lesion. We performed a comprehensive multivariate analysis based on the principal component analysis (PCA) and cluster analysis in patients with right hemisphere stroke and then performed a determination of different elements of VSN. PCA-based cluster analysis detected distinct aspects of VSN as follows: cluster 1: low arousal and attention state, cluster 2: exogenous neglect, cluster 3: spatial working memory (SWM) deficit. Lesion analysis revealed neural correlates for each cluster and highlighted “disturbance of the ventral attention network” for the stagnation of exogenous attention and “parietal damage” for SWM deficit. Our results reveal a pathological structure of VSN as multiple components of an attention network deficit, and they contribute to the understanding of the mechanisms underlying VSN., Graphical abstract, Highlights • This study attempted to establish the pathological structure of visuospatial neglect • PCA revealed four distinct fundamental components underlying visuospatial neglect • GMM-based clustering detected six subtypes of visuospatial attention network deficit, Medical Imaging; Behavioral Neuroscience; Systems Neuroscience; Computer Modeling

Snakes and conspecific faces are quickly and efficiently detected in primates. Because the medial prefrontal cortex (mPFC) has been implicated in attentional allocation to biologically relevant stimuli, we hypothesized that it might also be highly responsive to snakes and conspecific faces. In this study, neuronal responses in the monkey mPFC were recorded, while monkeys discriminated 8 categories of visual stimuli. Here, we show that the monkey mPFC neuronal responses to snakes and conspecific faces were unique. First, the ratios of the neurons that responded strongly to snakes and monkey faces were greater than those of the neurons that responded strongly to the other stimuli. Second, mPFC neurons responded stronger and faster to snakes and monkey faces than the other categories of stimuli. Third, neuronal responses to snakes were unaffected by low-pass filtering of the images. Finally, activity patterns of responsive mPFC neurons discriminated snakes from the other stimuli in the second 50 ms period and monkey faces in the third period after stimulus onset. These response features indicate that the mPFC processes fast and coarse visual information of snakes and monkey faces, and support the hypothesis that snakes and social environments have shaped the primate visual system over evolutionary time.

Disambiguation of overlapping events is thought to be the hallmark of episodic memory. Recent rodent studies have reported that when navigating overlapping path segments in the different routes place cell activity in the same overlapping path segments were remapped according to different goal locations in different routes. However, it is unknown how hippocampal neurons disambiguate reward delivery in overlapping path segments in different routes. In the present study, we recorded monkey hippocampal neurons during performance of three virtual navigation (VN) tasks in which a monkey alternately navigated two different routes that included overlapping path segments (common central hallway) and acquired rewards in the same locations in overlapping path segments by manipulating a joystick. The results indicated that out of 106 hippocampal neurons, 57 displayed place-related activity (place-related neurons), and 18 neurons showed route-dependent activity in the overlapping path segments, consistent with a hippocampal role in the disambiguation of overlapping path segments. Moreover, 75 neurons showed neural correlates to reward delivery (reward-related neurons), whereas 56 of these 75 reward-related neurons showed route-dependent reward-related activity in the overlapping path segments. The ensemble activity of reward-related neurons represented reward delivery, locations, and routes in the overlapping path segments. In addition, ensemble activity patterns of hippocampal neurons more distinctly represented overlapping path segments than non-overlapping path segments. The present results provide neurophysiological evidence of disambiguation in the monkey hippocampus, consistent with a hippocampal role in episodic memory, and support a recent computational model of “neural differentiation,” in which overlapping items are better represented by repeated retrieval with competitive learning.

Sleep is a physiological state that plays important role in the recovery of fatigue. However, the relationship between the physiological status of sleep and subjective fatigue remains unknown. In the present study, we hypothesized that the non-recovery of fatigue at wake time due to non-restorative sleep might be ascribed to changes in specific parameters of electroencephalography (EEG) and heart rate variability (HRV) in poor sleepers. Twenty healthy female shift-working nurses participated in the study. Subjective fatigue was assessed using the visual analog scale (VAS) at bedtime and wake time. During sleep on the night between 2 consecutive day shifts, the EEG powers at the frontal pole, HRV based on electrocardiograms, and distal-proximal gradient of skin temperature were recorded and analyzed. The results indicated that the subjects with high fatigue on the VAS at wake time exhibited (1) a decrease in deep non-rapid eye movement (NREM) (stageN3) sleep duration in the first sleep cycle; (2) a decrease in REM latency; (3) a decrease in ultra-slow and delta EEG powers, particularly from 30 to 65 min after sleep onset; (4) a decrease in the total power of HRV, particularly from 0 to 30 min after sleep onset; (5) an increase in the very low frequency component of HRV; and (6) a smaller increase in the distal-proximal gradient of skin temperature, than those of the subjects with low fatigue levels. The correlational and structural equation modeling analyses of these parameters suggested that an initial decrease in the total power of HRV from 0 to 30 min after sleep onset might inhibit the recovery from fatigue during sleep (i.e., increase the VAS score at wake time) via its effects on the ultra-slow and delta powers from 30 to 65 min after sleep onset, stageN3 duration in the first sleep cycle, REM latency, and distal-proximal gradient of skin temperature. These findings suggest an important role of these physiological factors in recovery from fatigue during sleep, and that interventions to modify these physiological factors might ameliorate fatigue at wake time.

Although motor training programs have been applied to childhood apraxia of speech (AOS), the neural mechanisms of articulation learning are not well understood. To this aim, we recorded cerebral hemodynamic activity in the left hemisphere of healthy subjects (n = 15) during articulation learning. We used near-infrared spectroscopy (NIRS) while articulated voices were recorded and analyzed using spectrograms. The study consisted of two experimental sessions (modified and control sessions) in which participants were asked to repeat the articulation of the syllables "i-chi-ni" with and without an occlusal splint. This splint was used to increase the vertical dimension of occlusion to mimic conditions of articulation disorder. There were more articulation errors in the modified session, but number of errors were decreased in the final half of the modified session; this suggests that articulation learning took place. The hemodynamic NIRS data revealed significant activation during articulation in the frontal, parietal, and temporal cortices. These areas are involved in phonological processing and articulation planning and execution, and included the following areas: (i) the ventral sensory-motor cortex (vSMC), including the Rolandic operculum, precentral gyrus, and postcentral gyrus, (ii) the dorsal sensory-motor cortex, including the precentral and postcentral gyri, (iii) the opercular part of the inferior frontal gyrus (IFGoperc), (iv) the temporal cortex, including the superior temporal gyrus, and (v) the inferior parietal lobe (IPL), including the supramarginal and angular gyri. The posterior Sylvian fissure at the parietal-temporal boundary (area Spt) was selectively activated in the modified session. Furthermore, hemodynamic activity in the IFGoperc and vSMC was increased in the final half of the modified session compared with its initial half, and negatively correlated with articulation errors during articulation learning in the modified session. The present results suggest an essential role of the frontal regions, including the IFGoperc and vSMC, in articulation learning, with sensory feedback through area Spt and the IPL. The present study provides clues to the underlying pathology and treatment of childhood apraxia of speech.

Objectives We quantitatively examined the motor‐imagery ability in stroke patients using a bimanual circle‐line coordination task (BCT) and clarified the relationship between motor‐imagery ability and motor function of hemiplegic upper limbs and the level of use of paralyzed limbs. Methods We enrolled 31 stroke patients. Tasks included unimanual‐line (U‐L)—drawing straight lines on the nonparalyzed side; bimanual circle‐line (B‐CL)—drawing straight lines with the nonparalyzed limb while drawing circles with the paralyzed limb; and imagery circle‐line (I‐CL)—drawing straight lines on the nonparalyzed side during imagery drawing on the paralyzed side, using a tablet personal computer. We calculated the ovalization index (OI) and motor‐imagery ability (image OI). We used the Fugl–Meyer motor assessment (FMA), amount of use (AOU), and quality of motion (QOM) of the motor activity log (MAL) as the three variables for cluster analysis and performed mediation analysis. Results Clusters 1 (FMA

Unilateral spatial neglect is a common neurological syndrome following predominantly right hemispheric stroke. While most patients lack insight into their neglect behaviour and do not initiate compensatory behaviours in the early recovery phase, some patients recognize it and start to pay attention towards the neglected space. We aimed to characterize visual attention capacity in patients with unilateral spatial neglect with specific focus on cortical processes underlying compensatory gaze shift towards the neglected space during the recovery process. Based on the Behavioural Inattention Test score and presence or absence of experience of neglect in their daily life from stroke onset to the enrolment date, participants were divided into USN+‰‰+ (do not compensate, n = 15), USN+ (compensate, n = 10), and right hemisphere damage groups (no neglect, n = 24). The patients participated in eye pursuit-based choice reaction tasks and were asked to pursue one of five horizontally located circular objects flashed on a computer display. The task consisted of 25 trials with 4-s intervals, and the order of highlighted objects was randomly determined. From the recorded eye tracking data, eye movement onset and gaze shift were calculated. To elucidate the cortical mechanism underlying behavioural results, electroencephalagram activities were recorded in three USN+‰‰+, 13 USN+ and eight patients with right hemisphere damage. We found that while lower Behavioural Inattention Test scoring patients (USN+‰‰+) showed gaze shift to non-neglected space, some higher scoring patients (USN+) showed clear leftward gaze shift at visual stimuli onset. Moreover, we found a significant correlation between Behavioural Inattention Test score and gaze shift extent in the unilateral spatial neglect group (r = -0.62, P < 0.01). Electroencephalography data clearly demonstrated that the extent of increase in theta power in the frontal cortex strongly correlated with the leftward gaze shift extent in the USN+‰‰+ and USN+ groups. Our results revealed a compensatory strategy (continuous attention to the neglected space) and its neural correlates in patients with unilateral spatial neglect. In conclusion, patients with unilateral spatial neglect who recognized their own neglect behaviour intentionally focused on the neglected space as a compensatory strategy to avoid careless oversight.

Emerging evidence suggests that traditional diets and nutrition have a significant impact on brain development, and could contribute to the promotion of mental health and prevention of psychiatric disorders in children and adolescents. Moreover, deficits in parvalbumin (PV)-immunoreactive and/or GABAergic neurons are closely associated with various psychiatric disorders in children and adolescents. To investigate the possible neural mechanisms of diet involvement in mental health, we analyzed the effects of dried-bonito dashi (Japanese fish broth) (DBD) on PV-immunoreactive neurons and emotional behaviors in young mice.Male mice after weaning were fed DBD for 60 days, and tested with a resident-intruder test for aggressiveness and a forced swimming test for depression-like symptoms. After the behavioral testing, PV-immunoreactive neurons in the brain were immunohistochemically analyzed.The results indicated that DBD intake decreased aggressiveness and depression-like symptoms, and increased the densities of PV-immunoreactive neurons in the medial prefrontal cortex (mPFC), amygdala, hippocampus, and superior colliculus. These behavioral changes were correlated with the densities of PV-immunoreactive neurons in the mPFC, amygdala, and hippocampus. However, subdiaphragmatic vagotomy did not affect the effects of DBD on emotional behaviors, although it nonspecifically decreased the densities of PV-immunoreactive neurons.The results suggest that DBD might modulate emotional behaviors by promoting PV-immunoreactive and/or GABAergic neuronal activity through parallel routes. The present results highlight a new mechanism for diet involvement in brain functions, and suggest that DBD might have therapeutic potential for the promotion of mental health.

Limb apraxia is a higher brain dysfunction that typically occurs after left hemispheric stroke and its cause cannot be explained by sensory disturbance or motor paralysis. The comparison of motor signals and visual feedback to generate errors, i.e., visuo-motor integration, is important in motor control and motor learning, which may be impaired in apraxia. However, in apraxia after stroke, it is unknown whether there is a specific deficit in visuo-motor temporal integration compared to visuo-tactile and visuo-proprioceptive temporal integration. We examined the precision of visuo-motor temporal integration and sensory-sensory (visuo-tactile and visuo-proprioception) temporal integration in apraxia after stroke by using a delayed visual feedback detection task with three different conditions (tactile, passive movement, and active movement). The delay detection threshold and the probability curve for delay detection obtained in this task were quantitative indicators of the respective temporal integration functions. In addition, we performed subtraction and voxel-based lesion-symptom mapping to identify the brain lesions responsible for apraxia and deficits in visuo-motor temporal integration. The behavioral experiments showed that the delay detection threshold was extended and that the probability curve for delay detection was less steep in apraxic patients compared to controls (pseudo-apraxic patients and unaffected patients), only for the active movement condition, and not for the tactile and passive movement conditions. Furthermore, the severity of apraxia was significantly correlated with the delay detection threshold and the steepness of the probability curve in the active movement condition. These results indicated that multisensory (i.e., visual, tactile, and proprioception) feedback was normally temporally integrated, but motor prediction and visual feedback were not correctly temporally integrated in apraxic patients. That is, apraxic patients had difficulties with visuo-motor temporal integration. Lesion analyses revealed that both apraxia and the distortion of visuo-motor temporal integration were associated with lesions in the fronto-parietal motor network, including the left inferior parietal lobule and left inferior frontal gyrus. We suppose that damage to the left inferior fronto-parietal network could cause deficits in motor prediction for visuo-motor temporal integration, but not for sensory-sensory (visuo-tactile and visuo-proprioception) temporal integration, leading to the distortion of visuo-motor temporal integration in patients with apraxia.

Certain eating behaviors are characterized by a trend of elevated food consumption. However, neural mechanisms mediating the motivation for food consumption are not fully understood. Food impacts the brain-rewarding-system via both oral-sensory and post-ingestive information. Recent studies have reported an important role of visceral gut information in mediating dopamine (DA) release in the brain rewarding system. This is independent of oral sensation, suggesting a role of the gut-brain-DA-axis in feeding behavior. In this study, we investigated the effects of intra-gastric (IG) self-administration of glucose on neuronal firings in the nucleus accumbens (NA) of water-deprived rats. Rats were trained in an operant-licking paradigm. During training, when the light was on for 2 min (light-period), rats were required to lick a spout to acquire the water oral-intake learning, and either an IG self-infusion of 0.4 M glucose (GLU group) or water (H2O group). Rats rested in the dark-period (3 min) following the light-period. Four cycles of the operant-licking paradigm consisting of the light–dark periods were performed per day, for 4 consecutive days. In the test session, the same rats licked the same spout to acquire the IG self-administration of the corresponding solutions, without oral water ingestion (dry licking). Behavioral results indicated IG self-administration of glucose elicits more dry-licking behavior than that of water. Neurophysiological results indicated in the dark period, coefficient of variance (CV) measuring the inter-spike interval variability of putative medial spiny neurons (pMSNs) in the NA was reduced in the H2O group compared to the GLU group, while there was no significant difference in physical behaviors in the dark period between the two groups. Since previous studies reported that DA release increases CV of MSNs, the present results suggest that greater CV of pMSNs in the GLU group reflects greater DA release in the NA and elevated motivation in the GLU group, which might increase lickings in the test session in the GLU group compared to the H2O group.

The hippocampal formation (HF) is implicated in a comparator that detects sensory conflict (mismatch) among convergent inputs. This suggests that new place cells encoding the new configuration with sensory mismatch develop after the HF learns to accept the new configuration as a match. To investigate this issue, HF CA1 place cell activity in rats was analyzed after the adaptation of the rats to the same sensory mismatch condition. The rats were placed on a treadmill on a stage that was translocated in a figure 8-shaped pathway. We recorded HF neuronal activities under three conditions; (1) an initial control session, in which both the stage and the treadmill moved forward, (2) a backward (mismatch) session, in which the stage was translocated backward while the rats locomoted forward on the treadmill, and (3) the second control session. Of the 161 HF neurons, 56 place-differential activities were recorded from the HF CA1 subfield. These place-differential activities were categorized into four types; forward-related, backward-related, both-translocation-related, and session-dependent. Forward-related activities showed predominant spatial firings in the forward sessions, while backward-related activities showed predominant spatial firings in the backward sessions. Both-translocation-related activities showed consistent spatial firings in both the forward and backward conditions. On the other hand, session-dependent activities showed different spatial firings across the sessions. Detailed analyses of the place fields indicated that mean place field sizes were larger in the forward-related, backward-related, and both-translocation-related activities than in the session-dependent activities. Furthermore, firing rate distributions in the place fields were negatively skewed and asymmetric, which is similar to place field changes that occur after repeated experience. These results demonstrate that the HF encodes a naturally impossible new configuration of sensory inputs after adaptation, suggesting that the HF is capable of updating its stored memory to accept a new configuration as a match by repeated experience.

Although, clinical studies reported hyperactivation of the auditory system and amygdala in patients with auditory hallucinations (hearing others' but not one's own voice, independent of any external stimulus), neural mechanisms of self/other attribution is not well understood. We recorded neuronal responses in the dorsal amygdala including the lateral amygdaloid nucleus to ultrasonic vocalization (USVs) emitted by subjects and conspecifics during free social interaction in 16 adult male rats. The animals emitting the USVs were identified by EMG recordings. One-quarter of the amygdalar neurons (15/60) responded to 50 kHz calls by the subject and/or conspecifics. Among the responsive neurons, most neurons (Type-Other neurons; 73%, 11/15) responded only to calls by conspecifics but not subjects. Two Type-Self neurons (13%, 2/15) responded to calls by the subject but not those by conspecifics, although their response selectivity to subjects vs. conspecifics was lower than that of Type-Other neurons. The remaining two neurons (13%) responded to calls by both the subject and conspecifics. Furthermore, population coding of the amygdalar neurons represented distinction of subject vs. conspecific calls. The present results provide the first neurophysiological evidence that the amygdala discriminately represents affective social calls by subject and conspecifics. These findings suggest that the amygdala is an important brain region for self/other attribution. Furthermore, pathological activation of the amygdala, where Type-Other neurons predominate, could induce external misattribution of percepts of vocalization.

In this study, we propose a novel markerless motion capture system (MCS) for monkeys, in which 3D surface images of monkeys were reconstructed by integrating data from four depth cameras, and a skeleton model of the monkey was fitted onto 3D images of monkeys in each frame of the video. To validate the MCS, first, estimated 3D positions of body parts were compared between the 3D MCS-assisted estimation and manual estimation based on visual inspection when a monkey performed a shuttling behavior in which it had to avoid obstacles in various positions. The mean estimation error of the positions of body parts (3-14 cm) and of head rotation (35-43°) between the 3D MCS-assisted and manual estimation were comparable to the errors between two different experimenters performing manual estimation. Furthermore, the MCS could identify specific monkey actions, and there was no false positive nor false negative detection of actions compared with those in manual estimation. Second, to check the reproducibility of MCS-assisted estimation, the same analyses of the above experiments were repeated by a different user. The estimation errors of positions of most body parts between the two experimenters were significantly smaller in the MCS-assisted estimation than in the manual estimation. Third, effects of methamphetamine (MAP) administration on the spontaneous behaviors of four monkeys were analyzed using the MCS. MAP significantly increased head movements, tended to decrease locomotion speed, and had no significant effect on total path length. The results were comparable to previous human clinical data. Furthermore, estimated data following MAP injection (total path length, walking speed, and speed of head rotation) correlated significantly between the two experimenters in the MCS-assisted estimation (r = 0.863 to 0.999). The results suggest that the presented MCS in monkeys is useful in investigating neural mechanisms underlying various psychiatric disorders and developing pharmacological interventions.