Tetsu Hirosawa

Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naïve patients with schizophrenia

Schizophrenia has been postulated to involve impaired neuronal cooperation in large-scale neural networks, including cortico-cortical circuitry. Alterations in gamma band oscillations have attracted a great deal of interest as they appear to represent a pathophysiological process of cortical dysfunction in schizophrenia. Gamma band oscillations reflect local cortical activities, and the synchronization of these activities among spatially distributed cortical areas has been suggested to play a central role in the formation of networks. To assess global coordination across spatially distributed brain regions, Omega complexity (OC) in multichannel EEG was proposed. Using OC, we investigated global coordination of resting-state EEG activities in both gamma (30-50 Hz) and below-gamma (1.5-30 Hz) bands in drug-naïve patients with schizophrenia and investigated the effects of neuroleptic treatment. We found that gamma band OC was significantly higher in drug-naïve patients with schizophrenia compared to control subjects and that a right frontal electrode (F3) contributed significantly to the higher OC. After neuroleptic treatment, reductions in the contribution of frontal electrodes to global OC in both bands correlated with the improvement of schizophrenia symptomatology. The present study suggests that frontal brain processes in schizophrenia were less coordinated with activity in the remaining brain. In addition, beneficial effects of neuroleptic treatment were accompanied by improvement of brain coordination predominantly due to changes in frontal regions. Our study provides new evidence of improper intrinsic brain integration in schizophrenia by investigating the resting-state gamma band activity.

Lateralized Theta Wave Connectivity and Language Performance in 2- to 5-Year-Old Children

Recent neuroimaging studies support the view that a left-lateralized brain network is crucial for language development in children. However, no previous studies have demonstrated a clear link between lateralized brain functional network and language performance in preschool children. Magnetoencephalography (MEG) is a noninvasive brain imaging technique and is a practical neuroimaging method for use in young children. MEG produces a reference-free signal, and is therefore an ideal tool to compute coherence between two distant cortical rhythms. In the present study, using a custom child-sized MEG system, we investigated brain networks while 78 right-handed preschool human children (32–64 months; 96% were 3-4 years old) listened to stories with moving images. The results indicated that left dominance of parietotemporal coherence in theta band activity (6-8 Hz) was specifically correlated with higher performance of language-related tasks, whereas this laterality was not correlated with nonverbal cognitive performance, chronological age, or head circumference. Power analyses did not reveal any specific frequencies that contributed to higher language performance. Our results suggest that it is not the left dominance in theta oscillation per se, but the left-dominant phase-locked connectivity via theta oscillation that contributes to the development of language ability in young children.

A custom magnetoencephalography device reveals brain connectivity and high reading/decoding ability in children with autism

A subset of individuals with autism spectrum disorder (ASD) performs more proficiently on certain visual tasks than may be predicted by their general cognitive performances. However, in younger children with ASD (aged 5 to 7), preserved ability in these tasks and the neurophysiological correlates of their ability are not well documented. In the present study, we used a custom child-sized magnetoencephalography system and demonstrated that preserved ability in the visual reasoning task was associated with rightward lateralisation of the neurophysiological connectivity between the parietal and temporal regions in children with ASD. In addition, we demonstrated that higher reading/decoding ability was also associated with the same lateralisation in children with ASD. These neurophysiological correlates of visual tasks are considerably different from those that are observed in typically developing children. These findings indicate that children with ASD have inherently different neural pathways that contribute to their relatively preserved ability in visual tasks.

Altered brain connectivity in 3-to 7-year-old children with autism spectrum disorder.

Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity and/or aberrant hemispheric lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, the physiological connectivity of the brain in young children with ASD under conscious conditions has not yet been described. Magnetoencephalography (MEG) is a noninvasive brain imaging technique that is practical for use in young children. MEG produces a reference-free signal and is, therefore, an ideal tool for computing the coherence between two distant cortical rhythms. Using a custom child-sized MEG, we recently reported that 5- to 7-year-old children with ASD (n = 26) have inherently different neural pathways than typically developing (TD) children that contribute to their relatively preserved performance of visual tasks. In this study, we performed non-invasive measurements of the brain activity of 70 young children (3–7 years old, of which 18 were aged 3-4 years), a sample consisting of 35 ASD children and 35 TD children. Physiological connectivity and the laterality of physiological connectivity were assessed using intrahemispheric coherence for 9 frequency bands. As a result, significant rightward connectivity between the parietotemporal areas, via gamma band oscillations, was found in the ASD group. As we obtained the non-invasive measurements using a custom child-sized MEG, this is the first study to demonstrate a rightward-lateralized neurophysiological network in conscious young children (including children aged 3–4 years) with ASD.

Effects of Brain Amyloid Deposition and Reduced Glucose Metabolism on the Default Mode of Brain Function in Normal Aging

Brain β-amyloid (Aβ) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimers disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral Aβ deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and Aβ deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [18F]FDG, Aβ deposits with [11C]PIB, and regional cerebral blood flow during control and working memory tasks by H215O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of Aβ deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable Aβ deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people.

Anterior Prefrontal Hemodynamic Connectivity in Conscious 3- to 7-Year-Old Children with Typical Development and Autism Spectrum Disorder

Socio-communicative impairments are salient features of autism spectrum disorder (ASD) from a young age. The anterior prefrontal cortex (aPFC), or Brodmann area 10, is a key processing area for social function, and atypical development of this area is thought to play a role in the social deficits in ASD. It is important to understand these brain functions in developing children with ASD. However, these brain functions have not yet been well described under conscious conditions in young children with ASD. In the present study, we focused on the brain hemodynamic functional connectivity between the right and the left aPFC in children with ASD and typically developing (TD) children and investigated whether there was a correlation between this connectivity and social ability. Brain hemodynamic fluctuations were measured non-invasively by near-infrared spectroscopy (NIRS) in 3- to 7-year-old children with ASD (n = 15) and gender- and age-matched TD children (n = 15). The functional connectivity between the right and the left aPFC was assessed by measuring the coherence for low-frequency spontaneous fluctuations (0.01 – 0.10 Hz) during a narrated picture-card show. Coherence analysis demonstrated that children with ASD had a significantly higher inter-hemispheric connectivity with 0.02-Hz fluctuations, whereas a power analysis did not demonstrate significant differences between the two groups in terms of low frequency fluctuations (0.01 – 0.10 Hz). This aberrant higher connectivity in children with ASD was positively correlated with the severity of social deficit, as scored with the Autism Diagnostic Observation Schedule. This is the first study to demonstrate aberrant brain functional connectivity between the right and the left aPFC under conscious conditions in young children with ASD.

Reduced prefrontal activation during performance of the Iowa Gambling Task in patients with bipolar disorder

The Iowa Gambling Task (IGT) is a complex decision-making task in which monetary wins and losses guide the development of strategies. The objective of this study was to evaluate hemodynamic responses of patients with bipolar disorder (BD) during performance of the IGT using near-infrared spectroscopy (NIRS). Participants comprised 13 patients and 15 healthy control subjects who were matched for age, sex, handedness, and intelligence quotient. Relative changes in oxygenated and deoxygenated hemoglobin (oxy-Hb and deoxy-Hb) levels in the frontal region were measured using a 46-channel NIRS system. All subjects were evaluated using NIRS during a verbal fluency task (VFT) and the IGT. During performance of the IGT, BD patients showed significantly decreased oxy-Hb levels in the bilateral orbitofrontal cortex (OFC) and left prefrontal cortex (PFC) compared with normal control subjects. However, during the VFT, patients with BD showed no significant changes in oxy-Hb levels compared with control subjects. Changes in oxy-Hb levels in the bilateral OFC and the PFC during the IGT were negatively correlated with total scores on the Hamilton Rating Scale for Depression (HAM-D). Although the IGT was useful for differentiating patients with BP from control subjects, no significant differences in autonomic activity were observed.

Attentional Control and Interpretation of Facial Expression after Oxytocin Administration to Typically Developed Male Adults

Deficits in attentional-inhibitory control have been reported to correlate to anger, hostility, and aggressive behavior; therefore, inhibitory control appears to play an important role in prosocial behavior. Moreover, recent studies have demonstrated that oxytocin (OT) exerts a prosocial effect (e.g., decreasing negative behaviors, such as aggression) on humans. However, it is unknown whether the positively valenced effect of OT on sociality is associated with enhanced attentional-inhibitory control. In the present study, we hypothesized that OT enhances attentional-inhibitory control and that the positively valenced effect of OT on social cognition is associated with enhanced attentional-inhibitory control. In a single-blind, placebo-controlled crossover trial, we tested this hypothesis using 20 healthy male volunteers. We considered a decrease in the hostility detection ratio, which reflects the positively valenced interpretation of other individuals’ facial expressions, to be an index of the positively valenced effects of OT (we reused the results of our previously published study). As a measure of attentional-inhibitory control, we employed a modified version of the flanker task (i.e., a shorter conflict duration indicated higher inhibitory control). These results failed to demonstrate any significant behavioral effects of OT (i.e., neither a positively valenced effect on facial cognition nor an effect on attentional-inhibitory control). However, the enhancement of attentional-inhibitory control after OT administration significantly correlated to the positively valenced effects on the interpretation of uncertain facial cognition (i.e., neutral and ambiguous facial expressions).

Band-specific atypical functional connectivity pattern in childhood autism spectrum disorder

OBJECTIVE Altered brain connectivity has been theorized as a key neural underpinning of autism spectrum disorder (ASD), but recent investigations have revealed conflicting patterns of connectivity, particularly hyper-connectivity and hypo-connectivity across age groups. The application of graph theory to neuroimaging data has become an effective approach for characterizing topographical patterns of large-scale functional networks. We used a graph approach to investigate alteration of functional networks in childhood ASD. METHOD Magnetoencephalographic signals were quantified using graph-theoretic metrics with a phase lag index (PLI) for specific bands in 24 children with autism spectrum disorder and 24 typically developing controls. RESULTS No significant group difference of PLI was found. Regarding topological organization, enhanced and reduced small-worldness, representing the efficiency of information processing, were observed respectively in ASD children, particularly in the gamma band and delta band. CONCLUSIONS Analyses revealed frequency-dependent atypical neural network topologies in ASD children. SIGNIFICANCE Our findings underscore the recently proposed atypical neural network theory of ASD during childhood. Graph theory with PLI applied to magnetoencephalographic signals might be a useful approach for characterizing the frequency-specific neurophysiological bases of ASD.

A pilot study of serotonergic modulation after long‐term administration of oxytocin in autism spectrum disorder

Oxytocin (OT) and the serotonergic system putatively play important roles in autism spectrum disorder (ASD) etiology and symptoms, but no direct neurobiological evidence exists for long‐term OT administration effects on the brains serotonergic system. This pilot study examined 10 male participants with ASD who were administered OT intranasally for 8–10 weeks in an open‐label, single‐arm, nonrandomized, and uncontrolled manner. Positron emission tomography (PET) with a radiotracer (11C)−3‐amino‐4‐(2‐[(dimethylamino)methyl]phenylthio)benzonitrile (11C‐DASB) was used before and after OT treatment. The binding potential of serotonin transporter (11C‐DASB BPND) was then estimated. The main outcome measures were changes in 11C‐DASB BPND and their correlation with changes in symptoms. ASD participants showed significantly elevated 11C‐DASB BPND in the left inferior frontal gyrus extending to the left middle frontal gyrus. No significant correlation was found between the change in any clinical symptom and the change in 11C‐DASB BPND. This report of a pilot study is the first describing long‐term effects of OT on the brains serotonin system in ASD. Additional randomized controlled studies must be conducted to confirm whether activation of the serotonergic system contributes to the prosocial effect of OT in people with ASD. Autism Res 2017, 10: 821–828.