Kazuhiro Shinosaki

Medial prefrontal cortex generates frontal midline theta rhythm

Frontal midline theta rhythm (Fm theta) is a distinct theta activity of EEG in the frontal midline area that appears during concentrated performance of mental tasks in normal subjects and reflects focused attentional processing. To tomographically visualize the source current density distributions of Fm theta, we recorded Fm theta by using a 64-channel whole-head MEG system from four healthy subjects, and applied a new analysis method, synthetic aperture magnetometry (SAM), an adaptive beam forming method. Fm theta was observed in the MEG signals over the bilateral frontal regions. SAM analysis showed bilateral medial prefrontal cortices, including anterior cingulate cortex, as the source of Fm theta. This result suggests that focused attention is mainly related to medial prefrontal cortex.

Quantification of EEG irregularity by use of the entropy of the power spectrum

A new method for quantifying irregularity of EEGs is proposed in this study. The entropy, an information measure, determines the uniformity of proportion distribution. The peakedness or flatness of the distribution of the EEG power spectrum, representing EEG rhythmicity, can be measured by the entropy, because the power spectrum consists of proportions of power at each frequency. The irregularity of the EEG was measured by the entropy of the power spectrum, called an irregularity index (II). The II was obtained from the power spectrum at F3, F4, C3, C4, P3, P4, O1 and O2 during rest and mental arithmetic in 10 normal subjects. Relative band powers of delta, theta, alpha and beta bands and alpha peak frequency were also obtained. EEGs during rest were significantly more irregular anteriorly than in the occipital areas. Alpha activity was also more irregular in the anterior region. A greater degree of EEG desynchronization during mental arithmetic was found over the left hemisphere and the right occipital area. The II was more sensitive to such desynchronization than alpha band power and alpha peak frequency. The differences in spectral structures between rest and mental arithmetic conditions, mainly over the left hemisphere, were also confirmed by the Kullback-Leibler information.

Localization of activated areas and directional EEG patterns during mental arithmetic

In a search for the physiological correlates of mental activity, localized EEG desynchronization induced by mental arithmetic was assessed by the entropy of the EEG power spectrum (irregularity index II). The topographic mapping of II can show a localized cortical activation. Directional EEG patterns during mental arithmetic were further examined with a directed mutual information measure (information flow). These two information measures were compared between resting and mental arithmetic conditions in 10 right-handed subjects as well as one left-handed subject. II significantly increased during mental arithmetic in the left temporo-centro-parietal region in right-handed subjects, thus exhibiting its activation. Significant changes in information flow during mental arithmetic were found in the directions mostly from the temporo-centro-parietal region to other areas and within the frontal region in right-handed subjects: information flow from the left temporal and the mid-frontal areas increased and information flow mostly from the left hemisphere decreased. One left-handed subject showed greater II in right post-temporal area. These findings suggest that the left temporo-centro-parietal activation is specific to calculation processing, and the frontal information flow is related to the active performance of mental arithmetic.

Theta rhythm increases in left superior temporal cortex during auditory hallucinations in schizophrenia : a case report

Auditory hallucinations (AH), the perception of sounds and voices in the absence of external stimuli, remain a serious problem for a large subgroup of patients with schizophrenia. Functional imaging of brain activity associated with AH is difficult, since the target event is involuntary and its timing cannot be predicted. Prior efforts to image the patterns of cortical activity during AH have yielded conflicting results. In this study, MEG was used to directly image the brain electrophysiological events associated with AH in schizophrenia. We observed an increase in theta rhythm, as sporadic bursts, in the left superior temporal area during the AH states, whereas there was steady theta band activity in the resting state. The present finding suggests strong association of the left superior temporal cortex with the experience of AH in this patient. This is consistent with the hypothesis that AH arises from areas of auditory cortex subserving receptive language processing.

Spatial distribution of generators of alpha activity

Source determination of alpha activity was studied using the relative power contribution analysis (RPCA) method which allows determination of the relative contributions of different areas to the power of a certain area at different frequencies. In 20 normal subjects, EEGs were recorded from F3, F4, C3, C4, P3, P4, O1 and O2, each referenced to a linked ear. An 8-dimensional autoregressive model was fitted to the EEGs of 10.24 sec. Based on the model, RPCA was performed. For each area, alpha activity was divided into two parts: one originating in its own area (endogenous) and another in the other areas (exogenous). Endogenous alpha activity increased as the area was more posterior. In the anterior regions (frontal and central), endogenous alpha power (power of endogenous alpha activity) was small, while exogenous alpha power was large. In the posterior regions (parietal and occipital), the amount of endogenous alpha power did not differ markedly from that of exogenous alpha power. The posterior regions, which generate more endogenous alpha activity, can be considered to play a dominant role in alpha generating mechanisms. In some subjects, alpha generators with a different frequency from that of the occipital areas were observed.

Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats.

Aim:  While the underlying therapeutic mechanisms of repetitive transcranial magnetic stimulation (rTMS) treatment for depression remain unclear, recent animal studies have suggested that hippocampal neurogenesis might be required for the effects of antidepressant treatments including antidepressant drugs and electroconvulsive therapy. The aim of this study was to examine chronic rTMS effects on hippocampal neurogenesis in rats.

Analysis of rapidly changing EEGs before generalized spike and wave complexes

Ten epileptic patients who had absence and tonic-clonic seizures were examined. They showed almost generalized 2-5 Hz spike and wave complexes (SWCs) with maxima at the frontal or central locations. Their EEGs were recorded from F3, F4, C3, C4, P3, P4, O1 and O2. One 15 sec EEG epoch, which included the background activity followed by SWCs, was divided into 20 segments. On the basis of Akaikes information criterion obtained from an AR model fitted to each segment by the least squares method, a distance measure between segments was obtained. The 20 segments were classified according to the distance measure with the combined use of both cluster analysis and multidimensional scaling. The power spectrum was also obtained for each segment. There were 2-6 clusters at some locations, always including the largest amplitude locations of the SWCs (the frontal or central locations). The clusters could be grouped into 3 major types, each forming a period: (1) one large cluster distant from the SWCs (the period of background activity); (2) small clusters just before the SWCs (the period just before the SWCs); (3) small clusters during the SWCs (the period of the SWCs). The period just before the SWCs, which occurred earliest at the largest amplitude location, may be a transition state of the background activity to the SWCs. A few segments remote from the SWCs belonged to the small cluster just before or during the SWCs in some patients, thus suggesting that an EEG event similar to EEG changes just before or during the SWCs occurred. The EEG event buried within the background can be considered as a poorly developed epileptiform discharge. A gradual increase or decrease in alpha frequency before the SWCs was found in most patients; this suggests that changes in the level of vigilance occur before SWCs.

Brain Regions Responsible for Tinnitus Distress and Loudness: A Resting-State fMRI Study

Subjective tinnitus is characterized by the perception of phantom sound without an external auditory stimulus. We hypothesized that abnormal functionally connected regions in the central nervous system might underlie the pathophysiology of chronic subjective tinnitus. Statistical significance of functional connectivity (FC) strength is affected by the regional autocorrelation coefficient (AC). In this study, we used resting-state functional MRI (fMRI) and measured regional mean FC strength (mean cross-correlation coefficient between a region and all other regions without taking into account the effect of AC (rGC) and with taking into account the effect of AC (rGCa) to elucidate brain regions related to tinnitus symptoms such as distress, depression and loudness. Consistent with previous studies, tinnitus loudness was not related to tinnitus-related distress and depressive state. Although both rGC and rGCa revealed similar brain regions where the values showed a statistically significant relationship with tinnitus-related symptoms, the regions for rGCa were more localized and more clearly delineated the regions related specifically to each symptom. The rGCa values in the bilateral rectus gyri were positively correlated and those in the bilateral anterior and middle cingulate gyri were negatively correlated with distress and depressive state. The rGCa values in the bilateral thalamus, the bilateral hippocampus, and the left caudate were positively correlated and those in the left medial superior frontal gyrus and the left posterior cingulate gyrus were negatively correlated with tinnitus loudness. These results suggest that distinct brain regions are responsible for tinnitus symptoms. The regions for distress and depressive state are known to be related to depression, while the regions for tinnitus loudness are known to be related to the default mode network and integration of multi-sensory information.

Potential flow of frontal midline theta activity during a mental task in the human electroencephalogram

The movement of potential field (potential flow) of frontal midline theta activity (Fm theta) as well as its potential distribution was examined in 7 subjects by using optical flow detection techniques in image processing. Electroencephalograms (EEGs) over the fronto-central region were recorded from 13 electrodes near the frontal midline (Fz) while the subjects were performing a mental task. The potential flow of Fm theta was estimated on a frame consisting of a square grid with Fz at its center. In regions anterior to Fz, the direction of potential flow was from lateral to medial, whereas it was from medial to lateral in regions posterior to Fz. The peak-to-trough amplitude distribution was round or oval with a maximum just anterior to Fz. The source density distribution showed the greatest potential along the midline in the frontal region and bilaterally symmetric smaller maximum areas mostly in the prefrontal regions. Our findings suggested the presence of 2 different source areas of opposite direction in each hemisphere in spite of a round or oval amplitude distribution.

Neurobiological basis of behavioral and psychological symptoms in dementia of the Alzheimer type

Abstract Recent dementia studies indicate that behavioral and psychological symptoms of dementia (BPSD) are not merely an epiphenomenon of cognitive impairment, but could be attributed to specific biological brain dysfunction. We describe findings from different research modalities related with BPSD (psychopathological, neuropsychological, neurochemical, and psychophysiological strategies), and attempt to reconcile them into the more integrated form. Characteristics of delusions in dementia patients should be studied in more detail from a psychopathological aspect, aiming for the integration of psychopathology and neurobiology. Imperfect integration of memory function and cognitive function, assigned to the limbic systems and association areas, respectively, may result in BPSD. More intimate collaboration of psychopathological and neurobiological study would be fruitful to promote the research in psychological basis of BPSD. Neurochemical studies indicated that density of extracellular tangles and/or PHF‐tau protein have relationships with delusion or misidentification. These changes in neurochemical parameters should be the key to understanding the pathogenesis of BPSD. More importantly, neurochemical and psychological study could be linked by the research in psychophysiology. Computer‐assisted electroencephalogram analysis suggests that the right posterior hemisphere shows significant age‐associated change earlier than the left in the elderly. Cerebral metabolic rate by positron emission tomography study indicates that paralimbic, left medial temporal, and left medial occipital area are involved in pathogenesis of BPSD in some dementia patients.