Hidehisa Yamashita

Brain activity during expectancy of emotional stimuli : An fMRI study

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.

Post-stroke affective or apathetic depression and lesion location: left frontal lobe and bilateral basal ganglia

This study was designed to examine the correlation between damage to the basal ganglia or frontal lobe and depression status (both affective and apathetic dimensions) in 243 stroke patients. We assessed the affective dimension in post-stroke depression (PSD) using the Zung Self-rating Depression Scale (SDS) and the apathetic dimension in PSD using the apathy scale (AS). We classified basal ganglia or frontal lobe damage into four groups: no damage, damage to the left side only, damage to the right side only, and damage to both sides. Affective and/or apathetic PSD was found in 126 patients (51.9%). The severity of affective depression (SDS score) was associated with left frontal lobe (but not basal ganglia) damage, and that of apathetic depression (AS score) was related to damage to the bilateral basal ganglia (but not to the frontal lobe). The anatomical correlates of PSD differ depending on the PSD dimension (affective or apathetic) and may explain interstudy differences regarding the association between lesion location and type of PSD.

Post-stroke depression and apathy: Interactions between functional recovery, lesion location, and emotional response.

Depression and apathy are often observed after stroke and are often confused with one another. In the present review, we argue that the current concept of ‘post‐stroke depression’ (PSD) in fact consists of two core symptoms or syndromes: (i) affective (depressive) PSD; and (ii) apathetic PSD. We argue that these two core symptoms are each associated with a different underlying neuroanatomical mechanism, a pattern that influences functional recovery. Post‐stroke disabilities can provoke several distinct emotional responses, some of which are associated with severe depression. We examined one of these emotional responses previously, namely ‘insistence on recovery’, which was believed to be a negative indicator of functional improvement in disabled stroke patients. However, an appropriate level of insistence on recovery may, in fact, be associated with reduced depression and apathy, resulting in enhanced recovery from stroke‐related disabilities. Improvements in physical disabilities (trunk stability or activities of daily living, such as walking) also reduce depression and apathy. Therefore, the experience of PSD/apathy may be intertwined with various initial emotional responses and improvements in physical functioning. Effective treatment of PSD/apathy requires a multidisciplinary approach, such that neuroanatomical/neurobiological, emotional, and physical (rehabilitation) domains are all addressed.

Effect of risperidone on sleep in schizophrenia: a comparison with haloperidol

The aim of the present study is to determine the effect of the atypical antipsychotic drug, risperidone on sleep measures in patients with schizophrenia by polysomnography. Sleep measures were compared in five schizophrenic patients who were receiving risperidone alone and five schizophrenic patients who were receiving haloperidol alone. There were no differences between these two groups in their demographic characteristics or doses of antipsychotic medication. The slow wave sleep period was significantly longer in the risperidone-treated group than in the haloperidol-treated group. There were, however, no other significant differences in sleep variables between these groups. This difference in the effect on sleep between risperidone and haloperidol may be due to their differential actions on serotonin (5-HT2) receptors. Risperidone, which is known to be a serotonin-dopamine antagonist, has the potential to improve the quality of sleep in schizophrenic patients.

Anterior cingulate cortex modulates preparatory activation during certain anticipation of negative picture

We studied the neural activation associated with anticipations of emotional pictures using functional magnetic resonance imaging (fMRI) by directly comparing certain with uncertain anticipation conditions. While being scanned with fMRI, healthy participants (n=18) were cued to anticipate and then perceive emotional stimuli having predictable (i.e., certain) emotional valences (i.e., positive and negative), given a preceding cue, as well as cued stimuli of uncertain valence (positive or negative). During anticipation of pictures with certain negative valence, activities of supracallosal anterior cingulate cortex, ventrolateral prefrontal cortex, insula, and amygdala were enhanced relative activity levels that for the uncertain emotional anticipation condition. This result suggests that these brain regions are involved in anticipation of negative images, and that their activity levels may be enhanced by the certainty of anticipation. Furthermore, the supracallosal anterior cingulate cortex showed functional connectivity with the insula, prefrontal cortex, and occipital cortex during the certain negative anticipation. These findings are consistent with an interpretation that top-down modulation, arising from anterior brain regions, is engaged in certain negative anticipation within the occipital cortex. It is thought that the limbic system involving the amygdala, ACC, and insula, engaged emotional processes, and that the input system involving the visual cortex entered an idling state.

Anticipation of affective images and event-related desynchronization (ERD) of alpha activity : An MEG study

We investigated the event-related power decrease (event-related desynchronization: ERD) of the alpha bands associated with the anticipation of affective images. Participants (n=19) were presented with emotionally positive or negative images under different anticipatory conditions, and their brain responses were recorded using magnetoencephalography (MEG). In the Affective Cue conditions, the cue stimulus indicated the emotional valence (positive or negative) of the image. In the Null Cue condition, the cue stimulus did not include any information about the valence of the image, and in the No Cue condition, the affective image was presented without a preceding cue. The cues in the affective and null conditions were followed by emotional images. During the anticipation period for the affective image, the alpha ERD preceding an anticipated negative image was larger than that preceding an anticipated positive image; this effect had an occipital dominance. Furthermore, during the anticipation period, the lower-2-alpha ERD of the right frontal area showed the same result. These results demonstrate that anticipation of negative stimuli induced alpha ERD in both the visual and the right frontal cortex, indicating that top-down modulation may be provided by the right frontal cortex to the visual cortex.

Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia.

While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone.

Neuroanatomic Pathways Associated with Poststroke Affective and Apathetic Depression

OBJECTIVES Our goal was to localize lesions in poststroke depression patients using magnetic resonance imaging, based on the statistical parametric maps image analysis technique that can be used to combine image data from multiple participants and correlate these images with other data sets. METHODS Magnetic resonance imaging acquisitions were obtained from 149 poststroke patients, who were assessed for affective and apathetic symptoms using the Hospital Anxiety and Depression Scale and the Apathy Scale, respectively. We created a statistical parametric map that displayed an association between lesion location and affective and apathetic symptoms. RESULTS Among the patients with higher depressive scores, the lesion overlap centered on the brainstem, left basal ganglia, and left frontal cortex. Among the patients with higher apathy scores, the lesion overlap centered on the brainstem and bilateral striatum. The overlap lesion for both affective and apathetic depression centered mainly on the brainstem; however, the two types of depression often did not overlap. CONCLUSIONS Two core symptoms that can occur after stroke, affective and apathetic symptoms, appear to be associated with different monoaminergic neuroanatomic pathways (serotonergic and dopaminergic).

Quetiapine Treatment for Behavioral and Psychological Symptoms in Patients with Senile Dementia of Alzheimer Type

The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25– 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles.

Attenuated prefrontal activation during a verbal fluency task in remitted major depression

The aim of the present study was to investigate whether a functional abnormality in the left prefrontal cortex observed in patients with major depression performing a verbal fluency task is present after remission of depression. Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in eight remitted patients with major depression and 10 healthy control subjects during a verbal fluency task. Compared to the control subjects, the patients had a reduced response in the left prefrontal cortex (middle frontal gyrus, Brodmann area 10). These findings suggest the presence of dysfunction in the left prefrontal cortex during remission in major depression.