Chihiro Namiki

Anterior and posterior cingulum abnormalities and their association with psychopathology in schizophrenia: A diffusion tensor imaging study

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus may play a role in the pathophysiology of schizophrenia. The cingulum bundles (CBs; posterior and anterior) are the most prominent white matter tracts in the limbic system, furnishing both input and output to the cingulate gyrus . In previous diffusion tensor imaging (DTI) studies, abnormal integrity has been demonstrated in the anterior CB portion, but not the posterior, in schizophrenia. As well, the relationships between the abnormalities of CB integrity and the psychopathology of schizophrenia remain to be elucidated. Using DTI acquired on a 3 T MRI machine, we examined fractional anisotropy (FA) in the anterior and posterior CBs of 42 patients with schizophrenia and 24 group-matched controls. Moreover, we investigated the relationships between CB abnormalities and the psychopathology of schizophrenia. Bilaterally reduced FA was demonstrated in both anterior and posterior CBs in schizophrenia patients. However, the pattern of FA reduction was different between anterior and posterior CBs: the reduction in FA was left-accentuated in anterior CBs, while no such lateralized abnormality was found in posterior ones. Finally, FA in posterior CBs correlated with positive symptom scores in patients with schizophrenia. These findings suggest that CB abnormalities in schizophrenia are not restricted to the anterior CB, but include the posterior as well. Pathology in the posterior CB would be one of the possible neural underpinnings of positive symptoms in schizophrenia.

Social cognition and frontal lobe pathology in schizophrenia: A voxel-based morphometric study

Impaired social cognition in schizophrenia is considered as the core contributor in the poor psychosocial functioning of schizophrenic patients. In this study, in order to better understand the neurobiological processes underlying social dysfunction in schizophrenia, we investigated regional structural brain abnormalities and emotion-attribution abilities in these patients. Twenty schizophrenic patients and 20 group-matched healthy comparison participants underwent magnetic resonance imaging (MRI) and were examined for emotion-attribution abilities by using the Perception of Affect Task (PAT). Voxel-based morphometry (VBM) was applied to investigate regional brain structural alterations. Relative to the healthy participants, the schizophrenic patients exhibited reduced gray matter concentrations in the left superior temporal gyrus, the medial prefrontal cortex (MPFC), right anterior cingulate gyrus, bilateral ventrolateral prefrontal cortex, and right insula. The schizophrenic patients performed poorly on emotion-attribution tasks. Importantly, poor performance on emotion attribution to protagonists in social situations was found to be associated with reductions in gray matter in the MPFC of the patient group. This preliminary result suggests that in schizophrenia, difficulties in understanding the emotional experiences of others are possible manifestations of structural abnormalities in the MPFC. This study provides the neurobiological correlates of social dysfunction in schizophrenia and links structural abnormalities with impaired social cognitive abilities.

Anterior cingulate pathology and social cognition in schizophrenia: a study of gray matter, white matter and sulcal morphometry.

The anterior cingulate gyrus (ACG) is a critical structure for social cognitive processing; the pathology of this structure might be a major source of social dysfunction in schizophrenia. Multiple structural abnormalities of the ACG have been demonstrated in schizophrenia including changes in gray matter volume, white matter microstructures and macroscopic sulcal morphology. However, the interrelationships among these different abnormalities have not been investigated. Thus, the relationship between structural abnormalities in the ACG and social cognition in schizophrenia remains to be elucidated. Magnetic resonance imaging data were acquired at 3.0 T from 26 schizophrenic patients and 20 healthy participants. We performed anterior cingulate cortex (ACC) volumetry, evaluated diffusion tensor imaging of the anterior cingulum, analyzed paracingulate/cingulate sulcus (PCS/CS) morphology and investigated the interrelationships among these measures. We also investigated the association between ACG structural abnormalities and psychopathology, and the social cognition ability of schizophrenic patients as estimated by emotion attribution tasks. Compared with healthy subjects, schizophrenic patients exhibited reduced ACC volume, decreased fractional anisotropy in the anterior cingulum bilaterally and a poorly developed PCS/CS in the left hemisphere. No interrelationship was identified among these measures in the schizophrenic group. Schizophrenic patients performed poorly on emotion attribution tasks. Importantly, clinical symptoms and performance on emotion attribution subtasks were associated with ACC volumes and left PCS/CS variation in different ways. These results suggested that pathology of the ACC, anterior cingulum and PCS/CS is, at least partially, independent and has differential impacts on psychopathology and social cognitive impairment in schizophrenia.

The Role of the Uncinate Fasciculus in Memory and Emotional Recognition in Amnestic Mild Cognitive Impairment

Background: The putative neural bases of affected episodic memory and emotional recognition in early Alzheimer’s disease are suspected to be limbic and paralimbic pathological processes. The uncinate fasciculus (UF) is especially considered to be a critical structure. In the present study, we investigated microstructural UF pathology by diffusion tensor imaging in the subjects with amnestic mild cognitive impairment (aMCI), and its association with memory and emotional processing impairment. Methods: Subjects included 16 patients with aMCI and 16 healthy individuals. Diffusion tensor images were acquired and the fractional anisotropy (FA) of the UF was calculated. In addition, its association with verbal memory and emotional facial recognition was investigated. Results: The FA values of the left UF were significantly lower in aMCI, and strongly correlated with episodic memory performance in aMCI. For the emotional recognition task, the aMCI subjects performed worse in negative emotion recognitions. The FA values of the left UF were correlated with the performance of fearful facial expression recognition in aMCI. Conclusion: These results indicated that microstructural alterations of the UF had already occurred in aMCI. In addition, these alterations could be one of the causes of memory and emotional processing impairment in aMCI.

Prediction of psychiatric response to donepezil in patients with mild to moderate Alzheimer's disease

Donepezil is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderate Alzheimers disease (AD). Since behavioral symptoms severely affect quality of life for AD patients and their caregivers, predicting behavioral responses to donepezil will be useful in managing patients with AD. In this study, we analyzed 70 consecutive cases with mild to moderate AD. Caregivers were interviewed with the Neuropsychiatric Inventory for behavioral assessment and 4-point improvement at week 12 was accepted as a treatment response. Twenty-one (30.0%) patients showed a behavioral response, while 42 (60.0%) showed no behavioral change and 7 (10.0%) worsened. Dysphoria, anxiety and apathy significantly improved after treatment among the responder group. The baseline profile including age, sex, Mini-Mental State Examination (MMSE), the Alzheimers Disease Assessment Scale (ADAS-cog) and the Geriatric Depression Scale did not differ significantly among the three groups. Statistical Parametric Mapping analysis of single photon emission computed tomography (SPECT) images at baseline showed that cerebral blood flow in the premotor and parietotemporal cortices was significantly higher in the responder group than in the worse group. The present study suggested usefulness of SPECT imaging in the prediction of behavioral response to donepezil among AD patients even with similar psychiatric symptoms and cognitive functions.

Insular volume reduction in schizophrenia

Structural and functional abnormalities of the insular cortex have been reported in patients with schizophrenia. Most studies have shown that the insular volumes in schizophrenia patients are smaller than those of healthy people. As the insular cortex is functio-anatomically divided into anterior and posterior subdivisons, recent research is focused on uncovering a specific subdivisional abnormality of the insula in patients with schizophrenia. A recent ROI-based volumetric MRI study demonstrated specific left anterior insular volume reduction in chronic schizophrenia patients (Makris N, Goldstein J, Kennedy D, Hodge S, Caviness V, Faraone S, Tsuang M, Seidman L (2006) Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophr Res 83:155–171). On the other hand, our VBM-based volumetric study revealed a reduction in right posterior insular volume (Yamada M, Hirao K, Namiki C, Hanakawa T, Fukuyama H, Hayashi T, Murai T (2007) Social cognition and frontal lobe pathology in schizophrenia: a voxel-based morphometric study. NeuroImage 35:292–298). In order to address these controversial results, ROI-based subdivisional volumetry was performed using the MRI images from the same population we analyzed in our previous VBM-study. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. Patients with schizophrenia showed a global reduction in insular gray matter volumes relative to healthy comparison subjects. In a simple comparison of the volumes of each subdivision between the groups, a statistically significant volume reduction in patients with schizophrenia was demonstrated only in the right posterior insula. This study suggests that insular abnormalities in schizophrenia would include anterior as well as posterior parts. Each subdivisional abnormality may impact on different aspects of the pathophysiology and psychopathology of schizophrenia; these relationships should be the focus of future research.

Brain volume and dysexecutive behavior in schizophrenia

OBJECTIVE Behaviors associated with frontal/executive impairments are common in patients with schizophrenia. Our aim was to reconfirm that morphological brain abnormalities in schizophrenia patients would overlap the areas underpinning frontal systems behavior, and examine whether any specific association exists between abnormalities of brain structures and frontal behavioral deficits in schizophrenia patients. METHOD Twenty-six schizophrenia patients and 26 matched healthy controls underwent structural magnetic resonance imaging and their frontal function was assessed by a self-rating questionnaire, Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry (VBM) to investigate regional brain volume alternations. RESULT Compared with healthy controls, schizophrenia patients showed reduced gray matter volume in multiple frontal and temporal structures, namely, the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral medial prefrontal cortices, left ventrolateral prefrontal cortex, bilateral anterior cingulate cortices, and bilateral superior temporal gyri. The scores on the executive dysfunction subscale of the FrSBe were correlated with volume reduction in the bilateral DLPFC in the patient group. CONCLUSION Our result suggests that pathology of the DLPFC could be the neural basis of real-life dysexecutive behaviors in schizophrenia patients.

Structural abnormalities of the adhesio interthalamica and mediodorsal nuclei of the thalamus in schizophrenia

OBJECTIVE Several studies have suggested the existence of thalamic volume reduction in patients with schizophrenia. However, the precise locus of volume reduction within the thalamus has scarcely been investigated. On the other hand, underdevelopment of the adhesio interthalamica [AI; Danos, P., Baumann, B., Kramer, A., Bernstein, H.G., Stauch, R., Krell, D., Falkai, P., Bogerts, B., 2003. Volumes of association thalamic nuclei in schizophrenia: a post-mortem study. Schizophrenia Res. 60 141-155], which bridges bilateral medial edges of the thalamus, has been reported in patients with schizophrenia. We assessed the volumes of mediodorsal nuclei (MDN) of thalami, level of AI development, and their interrelationship, in patients with schizophrenia. METHOD A sample of 58 patients with schizophrenia and 44 matched healthy volunteers underwent assessment with high-resolution 1-mm-thick anatomical MRI. Volume measurements of the MDN of the thalamus and whole thalamus were performed by manual tracing. The level of AI development was quantitatively defined as the maximal anterior-to-posterior length of the AI. RESULTS Schizophrenia patients had significantly smaller volumes of bilateral MDN. AI ratings were twice as high in women than in men among the control subjects; however, no gender difference emerged in the schizophrenia group due to reduced ratings in female patients. No significant correlation was found between MDN volumes and AI ratings among both groups. CONCLUSIONS These results provide evidence of volume reduction of the MDN, and female-specific underdevelopment of the AI in schizophrenia. As we did not demonstrate a relationship between MDN volume and AI ratings, it is suggested that these two measures of medial thalamic abnormality are manifestations of different neuropathological processes in schizophrenia patients.

Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT

BACKGROUND Although the clinical efficacy of electroconvulsive therapy (ECT) has been well established in patients with pharmacotherapy-resistant depression, the physiological mechanism and changes in regional cerebral function after ECT are unclear. METHODS We recruited 16 depressed patients who underwent ECT, and 11 healthy controls. The change in cerebral glucose metabolism was evaluated before and after a series of ECT using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). RESULTS Before ECT, the patient group showed significant hypometabolism in the superior frontal gyrus, and hypermetabolism in the inferior temporal gyri compared with healthy controls, and these abnormalities remained after ECT. Comparisons between pre- and post-ECT metabolic activity revealed decreased regional metabolism in the frontotemporal neocortical areas after ECT, while increased metabolism was found in the right medial temporal structures including amygdala and pons. In addition, a decrease in glucose metabolism in the fronto-temporo-parietal regions correlated with an increase in glucose metabolism in the right medial temporal regions across subjects. LIMITATIONS There was considerable variability in the interval between the last ECT and FDG-PET scan. Depressed subjects were maintained on medication. The subjects included both major depressive disorder and bipolar disorder patients, as well as both ECT responders and non-responders. CONCLUSION Depression refractory to pharmacotherapy might have functional deficits in specific circumscribed frontal and temporal structures. ECT resolves the clinical symptoms without largely affecting these brain metabolic abnormalities. In contrast, ECT shifts the balance of corticolimbic function, which might explain how ECT ameliorates symptoms of depression in patients.

Interfrontal commissural abnormality in schizophrenia: Tractography-assisted callosal parcellation

Previous studies have indicated abnormal fiber connectivity of the corpus callosum (CC) in schizophrenia. This study investigated whether the interfrontal commissural region of the CC is decreased in schizophrenia, by partitioning the CC using a function-anatomically relevant internal landmark derived from tractographic analysis of diffusion tensor imaging (DTI). T1 weighted and DTI images were acquired by 3T-MRI. Using tractography, the interfrontal commissural region (anterior part) was partitioned from the rest of the CC in 40 schizophrenia patients and 36 healthy controls. Schizophrenia patients showed smaller anterior/total CC length and area rates. These results suggested interfrontal hypoconnectivity in schizophrenia.