Bun Yamagata

Detection of hypofrontality in drivers with Alzheimer's disease by near-infrared spectroscopy

It is important to appropriately evaluate the driving performance of elderly persons. In the present study, near-infrared spectroscopy (NIRS) was employed to investigate differences of brain function between individuals with Alzheimers disease (n=12) and healthy elderly controls (n=14) while they were being tested using a driving simulator. Changes of the oxyhemoglobin level in the prefrontal areas of each subject were measured by NIRS during a driving task (collision avoidance). Compared with healthy controls, the Alzheimers disease group showed a less prominent increase of oxyhemoglobin in the prefrontal cortex during the collision avoidance task. The correlation between delay in braking and changes of oxyhemoglobin was positive in the healthy controls and negative in the Alzheimers disease group, suggesting that a task-related prefrontal increase of oxyhemoglobin has different implications under normal and pathological conditions. NIRS is a potentially useful tool for real-time monitoring of prefrontal activity during simulated or actual driving.

Transcranial Magnetic Stimulation of the Parietal Cortex Facilitates Spatial Working Memory: Near-Infrared Spectroscopy Study

The present study investigated whether transcranial magnetic stimulation (TMS) to the parietal cortex improves the performance of healthy persons in a spatial working memory (WM) task. The effect of TMS on the frontal cortex was examined by measuring oxygenated hemoglobin (oxy-Hb) with near-infrared spectroscopy. Fifty-two healthy persons received either 100% resting motor threshold TMS at 5 Hz (real TMS) or sham TMS while engaged in a spatial WM task or a control visuospatial attention task. TMS was applied to either the left or the right parietal cortex during the delay period of the task. Reaction times improved in the spatial WM task, but not in the control task, with real TMS, whereas sham TMS had no effect. This improvement was only observed when TMS was applied to the right parietal cortex. Application of real TMS to the right parietal cortex also significantly increased frontal oxy-Hb levels during the WM task, but reduced oxy-Hb during the control task. These results suggest that TMS to the right parietal cortex may selectively facilitate spatial WM. Hemispheric asymmetry and the frontoparietal network theory may explain the observed effect of right parietal TMS on spatial WM.

Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: A multimodal brain imaging study

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.

Differentiating early and late‐onset depression with multichannel near‐infrared spectroscopy

Background:  Individuals with late‐life depression can be divided into two categories, those with early and late‐onset depression (EOD and LOD, respectively). It has been reported that LOD has more accentuated subcortical vascular lesions and frontal lobe dysfunction (hypofrontality). The aim of the present study was to examine whether LOD exhibits more prominent hypofrontality than EOD during performance of the word fluency task (WFT) under multichannel near‐infrared spectroscopy (NIRS), a newly developed non‐invasive functional neuroimaging technique.

Effect of Parietal Transcranial Magnetic Stimulation on Spatial Working Memory in Healthy Elderly Persons - Comparison of Near Infrared Spectroscopy for Young and Elderly

In a previous study, we succeeded in improving the spatial working memory (WM) performance in healthy young persons by applying transcranial magnetic stimulation (TMS) to the parietal cortex and simultaneously measuring the oxygenated hemoglobin (oxy-Hb) level using near-infrared spectroscopy (NIRS). Since an improvement in WM was observed when TMS was applied to the right parietal cortex, the oxy-Hb distribution seemed to support a model of hemispheric asymmetry (HA). In the present study, we used the same study design to evaluate healthy elderly persons and investigated the effect of TMS on WM performance in the elderly, comparing the results with those previously obtained from young persons. The application of TMS did not affect WM performance (both reaction time and accuracy) of 38 elderly participants (mean age  = 72.5 years old). To investigate the reason for this result, we conducted a three-way ANOVA examining oxy-Hb in both young and elderly participants. For the right parietal TMS site in the elderly, TMS significantly decreased the oxy-Hb level during WM performance; this result was the opposite of that observed in young participants. An additional three-way ANOVA was conducted for each of the 52 channels, and a P value distribution map was created. The P value maps for the young participants showed a clearly localized TMS effect for both the WM and control task, whereas the P map for the elderly participants showed less significant channels and localization. Further analysis following the time course revealed that right-side parietal TMS had almost no effect on the frontal cortex in the elderly participants. This result can most likely be explained by age-related differences in HA arising from the over-recruitment of oxy-Hb, differentiation in the parietal cortex, and age-related alterations of the frontal-parietal networks.

The psychological impact of disclosing amyloid status to Japanese elderly: a preliminary study on asymptomatic patients with subjective cognitive decline

ABSTRACTIn Japan, 4.6 million people are living with dementia and the number is expected to rise to 7 million by 2025. Amyloid-β (Aβ) positron emission tomography (PET) is used for cognitively normal Japanese people with or without subjective cognitive decline (SCD) for the purpose of clinical trials or diagnosis. Nevertheless, no empirical studies have been conducted on the safety of disclosing amyloid status to such populations. We conducted amyloid PET imaging on 42 participants (Aβ positive (n = 10) and negative (n = 32)). State anxiety and depression were measured at pre- and post-disclosure, and test-related distress at post-disclosure. Mean state anxiety and depression scores were below the cut-off through pre- and post-disclosure in the Aβ positive and negative groups. State anxiety and depression did not change over time and were not different between groups. Mean test-related distress scores were within normal limits at post-disclosure in both groups. No significant difference was found between groups. Disclosing Aβ positive results did not cause greater mood disturbance than negative results in a short period of time. The short-term psychological safety of disclosing Aβ PET results to asymptomatic Japanese adults with SCD was indicated.

P300 component of event-related potentials in persons with asperger disorder

Summary: In the present study, we investigated auditory event-related potentials in adults with Asperger disorder and normal controls using an auditory oddball task and a novelty oddball task. Task performance and the latencies of P300 evoked by both target and novel stimuli in the two tasks did not differ between the two groups. Analysis of variance revealed that there was a significant interaction effect between group and electrode site on the mean amplitude of the P300 evoked by novel stimuli, which indicated that there was an altered distribution of the P300 in persons with Asperger disorder. In contrast, there was no significant interaction effect on the mean P300 amplitude elicited by target stimuli. Considering that P300 comprises two main subcomponents, frontal-central-dominant P3a and parietal-dominant P3b, our results suggested that persons with Asperger disorder have enhanced amplitude of P3a, which indicated activated prefrontal function in this task.

Sigma-1 receptor concentration in plasma of patients with late-life depression: a preliminary study

Background Recently, the sigma-1 receptor has been shown to play a significant role in the neural transmission of mood by regulating N-methyl-D-aspartate receptors. Additionally, the sigma-1 receptor has been reported to influence cognitive functions including learning and memory. In this study, we measured plasma sigma-1 receptor concentrations before and after antidepressant treatment in patients with late-life major depressive disorder (MDD) and explored whether changes in depressive status are related to sigma-1 receptor concentrations. Methods The study participants were 12 subjects with late-life MDD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. All of the participants were over 60 years old. Immediately prior to and 8 weeks after the start of treatment, sigma-1 receptor concentration and mental status, including depressive symptoms (Hamilton Depression Rating Scale; HAM-D), were measured. Treatment for depression was performed according to a developed algorithm based on the choice of treatments. We examined the association between changes in sigma-1 receptor concentration and HAM-D scores during antidepressant treatment. For the measurement of plasma sigma-1 receptor concentration, blood plasma samples were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Western blots were performed using a specific antibody that acts against the sigma-1 receptor, and the net densities of each band were quantified. Results All participants showed improvement in depressive symptoms, which was indicated by a significant decrease in the HAM-D scores. The mean plasma sigma-1 receptor concentration also increased significantly following antidepressant treatment. However, no significant correlations were found between changes in plasma sigma-1 receptor concentration and changes in HAM-D scores. Conclusion In this preliminary study, we demonstrated that the sigma-1 receptor concentration in plasma increases following antidepressant treatment in patients with late-life MDD. Further studies are warranted to confirm this finding with a larger number of patients.

Preliminary use of insulin-like growth factor-i as a biomarker for sorting high-dose donepezil responders among japanese patients with alzheimer's disease

Treatment with donepezil (maximum dose, 10 mg/day) was recently approved in Japan for severe Alzheimers disease (AD). We examined the usefulness of serum insulin-like growth factor-I (IGF-I) level as a biomarker for predicting responders to 10 mg/day-donepezil treatment among mild-to-moderate AD patients. The study population consisted of 23 mild-to-moderate AD patients, who were non-responders to 5 mg/day-donepezil treatment. AD patients were divided into responders and non-responders based on changes in mini-mental state examination (MMSE) scores before and 12 weeks after increasing donepezil dose from 5 to 10 mg/day. Before increasing donepezil dose, based on serum IGF-I levels and MMSE scores positively correlated with each other, AD patients were classified into three groups. Group A (n=6) had IGF-I<or=99 ng/mL and MMSE<or=18, group B (n=9) had IGF-I<or=99 ng/mL and MMSE>18, and group C (n=8) had IGF-I>99 ng/mL and MMSE>18. Serum IGF-I levels were significantly lower in groups A and B than group C. After 10 mg/day-donepezil treatment, the mean MMSE improved significantly only in group A. The prevalence of responders to the treatment was markedly greater in group A than in groups B and C. These results suggested that decreased serum IGF-I level combined with low MMSE score may be a useful biomarker for predicting responders to 10 mg/day-donepezil treatment in mild-to-moderate AD patients exhibiting a poor response to 5 mg/day-donepezil treatment.

Visual text hallucinations of thoughts in an alexic woman

In this report we describe a patient with a clinical diagnosis of dementia with Lewy bodies, who had hallucinations of reading her thoughts in the air although she was alexic and unable to read. She also had severe visuoperceptual deficits and closing-in phenomenon. SPECT imaging demonstrated hypoperfusion of the left parieto-occipital cortices together with hyperperfusion of the left orbitofronto-temporal areas. Her visual text hallucinations may represent another type of textual hallucinations related to syntacto-semantic network hyperactivation, which is implicated in auditory hallucinations in schizophrenia.