People with high empathy show increased cortical activity around the left medial parieto-occipital sulcus after watching social interaction of on-screen characters.

People with high empathy interpret others' mental states in daily social interactions. To investigate their characteristics of social cognitive processing, we compared neuromagnetic activities between 20 males with high empathy and 23 males with low empathy while watching social interactions between two characters. Twenty stories of four-panel comic strips were presented; the first three panels described social interactions, and the last panel described empathic/nonempathic behaviors. People with high empathy exhibited increased cortical activity in the right occipital region, medial part of the bilateral superior frontal gyri, and right posterior insula while watching social interaction scenes, which suggests that they paid attention to others' faces and bodies, and inferred others' mental states. They also exhibited increased cortical activity in the left superior frontal gyrus while watching empathic behaviors. Moreover, they exhibited increased cortical activity in the region around the left medial parieto-occipital sulcus, which is related to self-projection, while passively watching both empathic and nonempathic endings. Taken together, these results suggest that people with high empathy pay attention to others and actively infer others' mental states while watching social interactions and that they reconstruct others' mental states and intentions through self-projection after watching a sequence of others' behaviors.

A venous mechanism of ventriculomegaly shared between traumatic brain injury and normal ageing.

Recently, age-related timing dissociation between the superficial and deep venous systems has been observed; this was particularly pronounced in patients with normal pressure hydrocephalus, suggesting a common mechanism of ventriculomegaly. Establishing the relationship between venous drainage and ventricular enlargement would be clinically relevant and could provide insight into the mechanisms underlying brain ageing. To investigate a possible link between venous drainage and ventriculomegaly in both normal ageing and pathological conditions, we compared 225 healthy subjects (137 males and 88 females) and 71 traumatic brain injury patients of varying ages (53 males and 18 females) using MRI-based volumetry and a novel perfusion-timing analysis. Volumetry, focusing on the CSF space, revealed that the sulcal space and ventricular size presented different lifespan profiles with age; the latter presented a quadratic, rather than linear, pattern of increase. The venous timing shift slightly preceded this change, supporting a role for venous drainage in ventriculomegaly. In traumatic brain injury, a small but significant disease effect, similar to idiopathic normal pressure hydrocephalus, was found in venous timing, but it tended to decrease with age at injury, suggesting an overlapping mechanism with normal ageing. Structural bias due to, or a direct causative role of ventriculomegaly was unlikely to play a dominant role, because of the low correlation between venous timing and ventricular size after adjustment for age in both patients and controls. Since post-traumatic hydrocephalus can be asymptomatic and occasionally overlooked, the observation suggested a link between venous drainage and CSF accumulation. Thus, hydrocephalus, involving venous insufficiency, may be a part of normal ageing, can be detected non-invasively, and is potentially treatable. Further investigation into the clinical application of this new marker of venous function is therefore warranted.

[Overcoming Fear of Death in Home Caregiving].

This study aimed to clarify the factors for reducing the burden of caregivers caring for terminal patients. We conducted semi-structured interviews with bereaved caregivers, seeking those who had felt neither fear nor anxiety during caregiving; their responses were analyzed using the Steps for Coding and Theorization. The one caregiver who showed neither fear nor anxiety(1)believed in an afterlife,(2)sought a physician who would respect her belief,(3)sought respect for her medical decisions, and(4)found distance to the clinic to be a critical factor. Our findings suggest that doctors' respect for caregivers' beliefs may be an important factor in reducing caregiver burden at the end of life.

Trading of dynamic interaural time and level difference cues and its effect on the auditory motion-onset response measured with electroencephalography.

Interaural time (ITD) and level differences (ILD) constitute the two main cues for sound localization in the horizontal plane. Despite extensive research in animal models and humans, the mechanism of how these two cues are integrated into a unified percept is still far from clear. In this study, our aim was to test with human electroencephalography (EEG) whether integration of dynamic ITD and ILD cues is reflected in the so-called motion-onset response (MOR), an evoked potential elicited by moving sound sources. To this end, ITD and ILD trajectories were determined individually by cue trading psychophysics. We then measured EEG while subjects were presented with either static click-trains or click-trains that contained a dynamic portion at the end. The dynamic part was created by combining ITD with ILD either congruently to elicit the percept of a right/leftward moving sound, or incongruently to elicit the percept of a static sound. In two experiments that differed in the method to derive individual dynamic cue trading stimuli, we observed an MOR with at least a change-N1 (cN1) component for both the congruent and incongruent conditions at about 160-190 ms after motion-onset. A significant change-P2 (cP2) component for both the congruent and incongruent ITD/ILD combination was found only in the second experiment peaking at about 250 ms after motion onset. In sum, this study shows that a sound which - by a combination of counter-balanced ITD and ILD cues - induces a static percept can still elicit a motion-onset response, indicative of independent ITD and ILD processing at the level of the MOR - a component that has been proposed to be, at least partly, generated in non-primary auditory cortex.

Remembering my friends: Medial prefrontal and hippocampal contributions to the self-reference effect on face memories in a social context.

Memories associated with the self are remembered more accurately than those associated with others. The memory enhancement related to the self is known as the self-reference effect (SRE). However, little is known regarding the neural mechanisms underlying the SRE in a social context modulated by social relationships. In the present fMRI study, we investigated encoding-related activation of face memories encoded with the self-referential process in a social context that was manipulated by imagining a person-to-person relationship. Healthy young adults participated in the present study. During encoding, participants encoded unfamiliar target faces by imagining a future friendship with themselves (Self), their friends (Friend), or strangers (Other). During retrieval, participants were presented with target and distracter faces one by one, and they judged whether each face had been previously learned. In the behavioral results, target faces encoded in the Self condition were remembered more accurately than those encoded in the Other condition. fMRI results demonstrated that encoding-related activation in the medial prefrontal cortex (mPFC) was significantly greater in the Self condition than in the Friend or Other conditions. In addition, the generalized psycho-physiological interaction (gPPI) analysis showed that functional connectivity between activation in the hippocampus and the cortical midline structures (CMSs), including the mPFC and precuneus, was significant in the Self but not in the Other condition. These findings suggest that the SRE in a social context could be involved in the interaction between the CMS regions, which are related to the self-referential process, and the hippocampus related to the memory process. Hum Brain Mapp 38:4256-4269, 2017. © 2017 Wiley Periodicals, Inc.

Clinical impact of intraoperative CCEP monitoring in evaluating the dorsal language white matter pathway.

In order to preserve postoperative language function, we recently proposed a new intraoperative method to monitor the integrity of the dorsal language pathway (arcuate fasciculus; AF) using cortico-cortical evoked potentials (CCEPs). Based on further investigations (20 patients, 21 CCEP investigations), including patients who were not suitable for awake surgery (five CCEP investigations) or those without preoperative neuroimaging data (eight CCEP investigations including four with untraceable tractography due to brain edema), we attempted to clarify the clinical impact of this new intraoperative method. We monitored the integrity of AF by stimulating the anterior perisylvian language area (AL) by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. After tumor resection, single-pulse electrical stimuli were also applied to the floor of the removal cavity to record subcortico-cortical evoked potentials (SCEPs) at AL and PL in 12 patients (12 SCEP investigations). We demonstrated that (1) intraoperative dorsal language network monitoring was feasible even when patients were not suitable for awake surgery or without preoperative neuroimaging studies, (2) CCEP is a dynamic marker of functional connectivity or integrity of AF, and CCEP N1 amplitude could even become larger after reduction of brain edema, (3) a 50% CCEP N1 amplitude decline might be a cut-off value to prevent permanent language dysfunction due to impairment of AF, (4) a correspondence (<2.0 ms difference) of N1 onset latencies between CCEP and the sum of SCEPs indicates close proximity of the subcortical stimulus site to AF (<3.0 mm). Hum Brain Mapp 38:1977-1991, 2017. © 2017 Wiley Periodicals, Inc.

Water diffusion reveals networks that modulate multiregional morphological plasticity after repetitive brain stimulation.

Repetitive brain stimulation protocols induce plasticity in the stimulated site in brain slice models. Recent evidence from network models has indicated that additional plasticity-related changes occur in nonstimulated remote regions. Despite increasing use of brain stimulation protocols in experimental and clinical settings, the neural substrates underlying the additional effects in remote regions are unknown. Diffusion-weighted MRI (DWI) probes water diffusion and can be used to estimate morphological changes in cortical tissue that occur with the induction of plasticity. Using DWI techniques, we estimated morphological changes induced by application of repetitive transcranial magnetic stimulation (rTMS) over the left primary motor cortex (M1). We found that rTMS altered water diffusion in multiple regions including the left M1. Notably, the change in water diffusion was retained longest in the left M1 and remote regions that had a correlation of baseline fluctuations in water diffusion before rTMS. We conclude that synchronization of water diffusion at rest between stimulated and remote regions ensures retention of rTMS-induced changes in water diffusion in remote regions. Synchronized fluctuations in the morphology of cortical microstructures between stimulated and remote regions might identify networks that allow retention of plasticity-related morphological changes in multiple regions after brain stimulation protocols. These results increase our understanding of the effects of brain stimulation-induced plasticity on multiregional brain networks. DWI techniques could provide a tool to evaluate treatment effects of brain stimulation protocols in patients with brain disorders.

Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia.

The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease.

Stimulus-driven changes in the direction of neural priming during visual word recognition.

Visual object recognition is generally known to be facilitated when targets are preceded by the same or relevant stimuli. For written words, however, the beneficial effect of priming can be reversed when primes and targets share initial syllables (e.g., "boca" and "bono"). Using fMRI, the present study explored neuroanatomical correlates of this negative syllabic priming. In each trial, participants made semantic judgment about a centrally presented target, which was preceded by a masked prime flashed either to the left or right visual field. We observed that the inhibitory priming during reading was associated with a left-lateralized effect of repetition enhancement in the inferior frontal gyrus (IFG), rather than repetition suppression in the ventral visual region previously associated with facilitatory behavioral priming. We further performed a second fMRI experiment using a classical whole-word repetition priming paradigm with the same hemifield procedure and task instruction, and obtained well-known effects of repetition suppression in the left occipito-temporal cortex. These results therefore suggest that the left IFG constitutes a fast word processing system distinct from the posterior visual word-form system and that the directions of repetition effects can change with intrinsic properties of stimuli even when participants' cognitive and attentional states are kept constant.

Motion-induced disturbance of auditory-motor synchronization and its modulation by transcranial direct current stimulation.

The timing of personal movement with respect to external events has previously been investigated using a synchronized finger-tapping task with a sequence of auditory or visual stimuli. While visuomotor synchronization is more accurate with moving stimuli than with stationary stimuli, it remains unclear whether the same principle holds true in the auditory domain. Although the right inferior-superior parietal lobe (IPL/SPL), a center of auditory motion processing, is expected to be involved in auditory-motor synchronization with moving sounds, its functional relevance has not yet been investigated. The aim of the present study was thus to clarify whether horizontal auditory motion affects the accuracy of finger-tapping synchronized with sounds, as well as whether the application of transcranial direct current stimulation (tDCS) to the right IPL/SPL affects this. Nineteen healthy right-handed participants performed a task in which tapping was synchronized with both stationary sounds and sounds that created apparent horizontal motion. This task was performed before and during anodal, cathodal and sham tDCS application to the right IPL/SPL in separate sessions. The time difference between the onset of the sounds and tapping was larger with apparently moving sounds than with stationary sounds. Cathodal tDCS decreased this difference, anodal tDCS increased the variance of the difference and sham stimulation had no effect. These results supported the hypothesis that auditory motion disturbs efficient auditory-motor synchronization and that the right IPL/SPL plays an important role in tapping in synchrony with moving sounds via auditory motion processing.

Corpus Callosum Pathology as a Potential Surrogate Marker of Cognitive Impairment in Diffuse Axonal Injury.

Diffuse axonal injury is a major form of traumatic brain injury. Neuropsychological assessments and high-resolution structural MRI were conducted using T1-weighted and diffusion tensor imaging. This study included 10 patients with diffuse axonal injury (all men, mean age 30.8±10.5 years) and 12 age- and sex-matched normal control participants. Patients with diffuse axonal injury had widespread volume reductions and lower fractional anisotropy in the corpus callosum (CC) compared with controls. Furthermore, cognitive processing speed was associated with reductions in white matter volume and fractional anisotropy in the CC. These findings suggest that CC pathology may be a potential surrogate marker of the cognitive deficits in these patients.

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes.

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing.

Action observation with kinesthetic illusion can produce human motor plasticity.

After watching sports, people often feel as if their sports skills might have been improved, even without any actual training. On some occasions, this motor skill learning through observation actually occurs. This phenomenon may be due to the fact that both action and action observation (AO) can activate shared cortical areas. However, the neural basis of performance gain through AO has not yet been fully clarified. In the present study, we used transcranial magnetic stimulation to investigate whether primary motor cortex (M1) plasticity is a physiological substrate of AO-induced performance gain and whether AO itself is sufficient to change motor performance. The excitability of M1, especially that of its intracortical excitatory circuit, was enhanced after and during AO with kinesthetic illusion but not in interventions without this illusion. Moreover, behavioral improvement occurred only after AO with kinesthetic illusion, and a significant correlation existed between the performance gain and the degree of illusion. Our findings indicated that kinesthetic illusion is an essential component of the motor learning and M1 plasticity induced by AO, and this insight may be useful for the strategic rehabilitation of stroke patients.

Sleep modulates cortical connectivity and excitability in humans: Direct evidence from neural activity induced by single-pulse electrical stimulation.

Sleep-induced changes in human brain connectivity/excitability and their physiologic basis remain unclear, especially in the frontal lobe. We investigated sleep-induced connectivity and excitability changes in 11 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Single-pulse electrical stimuli were directly injected to a part of the cortices, and cortico-cortical evoked potentials (CCEPs) and CCEP-related high-gamma activities (HGA: 100-200 Hz) were recorded from adjacent and remote cortices as proxies of effective connectivity and induced neuronal activity, respectively. HGA power during the initial CCEP component (N1) correlated with the N1 size itself across all states investigated. The degree of cortical connectivity and excitability changed during sleep depending on sleep stage, approximately showing dichotomy of awake vs. non-rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep partly had properties of both awake and NREM sleep, placing itself in the intermediate state between them. Compared with the awake state, single-pulse stimulation especially during NREM sleep induced increased connectivity (N1 size) and neuronal excitability (HGA increase at N1), which was immediately followed by intense inhibition (HGA decrease). The HGA decrease was temporally followed by the N2 peak (the second CCEP component), and then by HGA re-increase during sleep across all lobes. This HGA rebound or re-increase of neuronal synchrony was largest in the frontal lobe compared with the other lobes. These properties of sleep-induced changes of the cortex may be related to unconsciousness during sleep and frequent nocturnal seizures in frontal lobe epilepsy.

Possible induction of multiple seizure foci due to parietal tumour and anti-NMDAR antibody.

"Formes frustes" of encephalopathy associated with anti-NMDAR antibody have been recently described in cases of chronic epilepsy. We report a young woman with a parietal lesion and anti-NMDAR antibody who acquired bilateral, secondary epileptogenesis in the temporal lobes within a period as short as six years. Removal of the primary epileptogenic lesion of oligoastrocytoma in the right parietal lobe resulted in seizure freedom, disappearance of secondary foci, and substantial decrease of the antibody titre. Chronic exposure to anti-NMDAR antibody, albeit at a low titre, may have resulted in a smoldering chronic course and relatively early acquisition of "reversible" secondary foci without development of a high degree of epileptogenicity and structural changes.

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

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

Silent information regulator 2 homolog 1 counters cerebral hypoperfusion injury by deacetylating endothelial nitric oxide synthase.

BACKGROUND AND PURPOSE: Silent information regulator 2 homolog 1 (SIRT1) is a protein deacetylase that has been reported to suppress neurodegenerative and cardiovascular diseases in model organisms. We hypothesized that neurovascular protection is one of the diverse actions of SIRT1. This study was designed to determine whether SIRT1 protects against the consequences of cerebral hypoperfusion in vivo. METHODS: Sirt1-overexpressing (Sirt1-Tg) mice driven by a prion promoter and their wild-type littermates were subjected to bilateral common carotid artery stenosis using external microcoils. Using Sirt1-Tg mice, we assessed the effect of SIRT1 on cerebral blood flow, cerebral angioarchitecture, histological and ultrastructural changes, and spatial working memory at several time points. We also evaluated the effects of preadministration of SIRT1 inhibitors or endothelial nitric oxide synthase inhibitors on cerebral blood flow after bilateral common carotid artery stenosis in Sirt1-Tg mice. Levels of acetylated and nonacetylated endothelial nitric oxide synthase were measured semiquantitatively with immunoblotting. RESULTS: Cerebral hypoperfusion induced by bilateral common carotid artery stenosis caused memory impairment and histological changes in wild-type littermates. However, these phenotypes were rescued in Sirt1-Tg mice, where cerebral blood flow was maintained even poststenosis. Electron microscopic analyses showed irregularities in the vascular endothelia, such as tight junction openings in wild-type mice, which were absent in Sirt1-Tg littermates. Brain endothelial nitric oxide synthase was acetylated after cerebral hypoperfusion in wild-type littermates but remained unacetylated in Sirt1-Tg mice. Moreover, treatment with SIRT1 inhibitors and endothelial nitric oxide synthase inhibitors abolished the vasculoprotective effects of SIRT1. CONCLUSIONS: Our results indicate that neurovascular endothelial SIRT1 potentiation upregulates the nitric oxide system and counters cerebral hypoperfusion injury. This novel cerebral blood flow-preserving mechanism offers potential molecular targets for future therapeutic intervention.

The contribution of cortical thickness and surface area to gray matter asymmetries in the healthy human brain.

Human cortical gray matter (GM) is structurally asymmetrical and this asymmetry has been discussed to be partly responsible for functional lateralization of human cognition and behavior. Past studies on brain asymmetry have shown mixed results so far, with some studies focusing on the global shapes of the brain's surface, such as gyrification patterns, while others focused on regional brain volumes. In this study, we investigated cortical GM asymmetries in a large sample of right-handed healthy volunteers (n = 101), using a surface-based method which allows to analyze brain cortical thickness and surface area separately. As a result, substantially different patterns of symmetry emerged between cortical thickness and surface area measures. In general, asymmetry is more prominent in the measure of surface compared to that of thickness. Such a detailed investigation of structural asymmetries in the normal brain contributes largely to our knowledge of normal brain development and also offers insights into the neurodevelopmental basis of psychiatric disorders, such as schizophrenia.

Intraoperative dorsal language network mapping by using single-pulse electrical stimulation.

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico-cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language-dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High-frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single-pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high-frequency ES of the white matter produced naming impairment, this "eloquent" subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico- and subcortico-cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network.