Symposium

Symposium 4 Current status of hallucination and delusion research シンポジウム4 幻覚・妄想研究の現在

SY4-1 Connectivity study of aberrant salience and delusion in schizophrenia 結合性解析から見た統合失調症における異常Salienceと妄想 Miyata Jun（宮田淳） Dept. of Psychiatry, Kyoto University 統合失調症では基底核におけるドーパミンの過剰により、日常の刺激に対して異常に高まったSalienceが帰属され、それが幻覚や妄想の基盤となると想定される（異常Salience仮説）。一方、ヒトの機能的MRI研究により、InsulaおよびAnterior cingulate cortex（ACC）よりなるSalience network（SN）が、刺激の性質に寄らずそのSalienceに反応することが知られているが、これら二つのSalienceの関係とその統合失調症における役割は分かっていない。発表者らは安静時機能的MRI（rsfMRI）を用いて機能的結合性解析を行い、ヒトでは基底核ネットワークとInsula-ACC SNとが結合しており、統合失調症ではその異常があること、またそれが陽性症状と相関することを明らかにした。一方、妄想の形成に関わる認知的バイアスとして、Jumping to conclusions（JTC）バイアスが知られている。これは統合失調症および妄想患者では、健常者に比べてより少ない情報に基づいて確率的判断をする、というものである。これは健常者における保守性バイアス（人は確率的判断の際、合理的と考えられるよりも多くの情報を要する）の異常と考えることが出来るが、これら認知的バイアスの神経相関は知られていない。発表者らは構造MRI、拡散テンソル画像、およびrsfMRIを用いて構造的・機能的結合性解析を行った。その結果、Default mode networkの中のPrecuneusにおける機能的結合性の強さが、健常者では保守性バイアスと、患者ではJTCバイアスと相関していることを明らかにした。結合性解析により、統合失調症および妄想のメカニズムが明らかになっていくことが期待される。		SY4-2 Neural basis of delusions in dementia 認知症における妄想の発現機序について Hashimoto Mamoru（橋本衛）¹，津野田尚子²，福原竜治¹ ¹Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan ²Mitsugumachi clinic, Kumamoto, Japan Delusional thoughts are common symptom in patients with dementia. Delusions reduce the individual well-being of the dementia sufferer and increase the burden of caregiver in the management of patients. However, little is known about the possible factors associated with development of delusions in patients with dementia. We examined the frequency of delusions in 578 outpatients with dementia, 326 patients with AD, 95 patients with dementia with Lewy bodies (DLB), 77 patients with vascular dementia (VaD), 42 subjects with frontotemporal lobar degeneration (FTLD), 19 subjects with corticobasal syndrome (CBS), and 19 patients with progressive supranuclear palsy (PSP). Using the Neuropsychiatric Inventory, delusions were identified in 26% of AD, 61% of DLB, 26% of VaD, 2.4% of FTLD, 11% of CBS and 11% of patients with PSP. The different prevalence of delusions among different types of dementia suggests that some neurobiological factors may be associated with delusions in dementia. In DLB, factor analysis revealed that delusions were classified under the same category as hallucinations. These results suggest that the disturbance of neuron systems such as dopamine or acetylcholine might be involved in delusions. On the other hand, FTLD may have resistance to delusions because of less disturbances of dopamine neurons and stronger frontal syndromes such as disinhibition or apathy. According to previous reports and our data, many factors other than dementia type seem to be involved in the development of delusions in dementia. They include the severity of dementia, the type of delusions such as misidentification delusion or persecutory delusion, cortical lesions such as frontal lobe or limbic system, psychosocial factors such as sex and the presence of loss experience, and so on.

SY4-3 Visual saliency in schizophrenia 統合失調症における視覚顕著性 Yoshida Masatoshi（吉田正俊）^1,2 ¹National Institute for Physiological Sciences ²The Grad. Univ. for Advanced Studies Aberrant salience hypothesis of psychosis proposes that an aberrant assignment of salience to the elements of one’s experience leads to delusion and hallucination. Patients with schizophrenia show abnormality in eye movements such as the shorter scanpath length during free-viewing of natural images. Here we examined whether such difference in eye movements arises from aberrant visual salience by which their attention is drawn to irrelevant features of the visual stimuli. Eye movements were measured from 83 patients and 252 healthy controls who viewed 56 natural and/or complex images. Itti-Koch’s saliency map was used for calculation of visual salience of these images. We found that the saliency values at the gaze were highest at initial fixation and went down during 8-sec viewing time in the control subjects while those were significantly higher during presentation in the patients. We examined contribution of visual features (color, luminance and orientation) to the saliency-guided eye movements and found that the orientation saliency at the gazes were higher in the patients than in the control subjects while the color saliency and the luminance saliency had no such difference between the subject groups. These results suggest aberrant processing of the orientation saliency in schizophrenic subjects, thereby supporting aberrant salience hypothesis of psychosis.		SY4-4 Evaluation for hallucinatory behavior by analysis of functional brain-connectivity in the recognition of emotional prosody in schizophrenia 統合失調症におけるプロソディー認知・脳内機能的結合を用いた幻覚妄想状態の評価 Koeda Michihiko（肥田道彦） Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan Human auditory hallucinations and thought disorders are the main symptoms of schizophrenia, and these symptoms profoundly affect the neural basis of social communications as well as behavior. In a previous study, by investigating the cerebral response to auditory attractiveness in schizophrenia, we demonstrated reduced activation at the left superior temporal gyrus (STG) and increased activation at the left middle temporal gyrus (MTG) (Koeda et al 2013). However, the frontotemporal functional connectivity in this brain network of social communication is unclear. In our present study, we aimed to investigate frontotemporal functional connectivity in the recognition of vocal attractiveness in schizophrenia. Cerebral activation was examined in 18 schizophrenia patients and 18 controls when performing Favorability Judgment Task (FJT) and Gender Differentiation Task (GDT) for pairs of greetings using event-related functional MRI. By analysis of variance, compared with controls, a significant hypo-connectivity was observed between the right anterior STG and cerebellum. Further, a significant negative correlation was observed between severity in the score of hallucinatory behavior and connectivity of two regions: 1) left planum temporale - right anterior STG, and 2) right triangular part of inferior frontal gyrus (IFG) - cerebellum. Based on these results, I would like to discuss the usefulness of evaluating brain activity and functional connectivity in STG-IFG in the recognition of vocal attractiveness in schizophrenia.

SY4-5 Neural basis of auditory hallucinations in neuroimaging/neurophysiology studies in patients with schizophrenia 神経画像・神経生理学からみた統合失調症の幻聴の神経基盤 Onitsuka Toshiaki（鬼塚俊明），平野羊嗣，平野昭吾 Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Schizophrenia is a severe mental disorder characterized by positive and negative symptoms, with cognitive dysfunction. Patients with schizophrenia have been hypothesized to have a functional impairment in filtering irrelevant sensory information, which may result in positive symptoms such as hallucinations or delusions. However, no clear association has yet been reported between the auditory gating deficits and positive symptoms like auditory hallucinations, exhibited in approximately 60-80% of patients with schizophrenia. I will review associations between electrophysiological (EEG)/magnetoencephalographic (MEG) signs and auditory hallucinations. In addition, magnetic resonance imaging (MRI) abnormalities and auditory hallucinations will be reviewed. Functionally, our data show significant associations between MEG auditory gating deficits in the left auditory cortex to human voices and the severity of auditory hallucinations in schizophrenia. Neuroanatomically, we found significant associations between the gray matter volume reduction of the left superior temporal gyrus (STG) and the severity of auditory hallucinations. These results provide evidence for deficits in auditory processing in schizophrenia, whose association with the left STG volume reduction points to the site of the anatomical substrate for auditory hallucinations.