Hippocampal Subfield Volumes and Cognitive Function in Schizophrenia and Mood Disorders.

INTRODUCTION: The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD). METHODS: The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group. RESULTS: The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score. CONCLUSION: Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.

Reduction of cortical excitability and increase of thalamic activity in a low-frequency rTMS treatment for chronic tinnitus.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) has received increasing attention for the treatment of tinnitus, but its therapeutic mechanisms are unclear. We performed low-frequency rTMS treatment for a patient with chronic tinnitus and examined changes of cortical excitability and cerebral blood flow using paired-pulse TMS and single-photon emission computed tomography. After the rTMS treatment, tinnitus loudness was decreased, cortical excitability was reduced, and blood flow in the thalamus was increased. Our results suggest that low-frequency rTMS treatment reduces tinnitus loudness by an inhibitory effect on the cortical excitability and a remote activation effect on the thalamus through the corticothalamic networks.

Female sex and age-based advantage of simulated electric field in TMS to the prefrontal cortex in schizophrenia and mood disorders.

This study investigates computational models of electric field strength for transcranial magnetic stimulation (TMS) of the left dorsolateral prefrontal cortex (DLPFC) based on individual MRI data of patients with schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BP), and healthy controls (HC). In addition, it explores the association of electric field intensities with age, gender and intracranial volume. The subjects were 23 SZ (12 male, mean age = 45.30), 24 MDD (16 male, mean age = 43.57), 23 BP (16 male, mean age = 39.29), 23 HC (13 male, mean age = 40.91). Based on individual MRI sequences, electric fields were computationally modeled by two independent investigators using SimNIBS ver. 2.1.1. There was no significant difference in electric field strength between the groups (HC vs SZ, HC vs MDD, HC vs BP, SCZ vs MDD, SCZ vs BP, MDD vs BP). Female subjects showed higher electric field intensities in widespread areas than males, and age was positively significantly associated with electric field strength in the left parahippocampal area as observed. Our results suggest differences in electric field strength of left DLPFC TMS for gender and age. It may open future avenues for individually modeling TMS based on structural MRI data.

Cerebral blood flow in the subgenual anterior cingulate cortex and modulation of the mood-regulatory networks in a successful rTMS treatment for major depressive disorder.

The subgenual anterior cingulate cortex (Cg25) has been reported to be a node of mood-regulatory networks. Using a responder and a non-responder of repetitive transcranial magnetic stimulation (rTMS) for depression, we examined pre/post-treatment cerebral blood flow (CBF) in the Cg25 and treatment-related CBF changes in cortical/subcortical regions. In the responder, pre-treatment Cg25 perfusion was higher and was decreased after treatment, in addition, CBF was increased in the frontal and parietal regions and decreased in the hippocampus and basal ganglia. Our results suggest that rTMS treatment response may be related to pre-treatment Cg25 activity and modulation of the Cg25 and mood-regulatory networks.

Prospective multicenter cohort study of possible psychogenic nonepileptic seizure cases-Results at 1-year follow-up examinations.

OBJECTIVE: The primary purpose of this prospective multicenter study was to examine clinical and demographic feature differences according to the diagnostic level of psychogenic nonepileptic seizures (PNES) and then clarify whether prognosis may also differ accordingly. METHODS: Two hundred forty-two consecutive patients strongly suspected of having PNES attacks were invited to participate, of whom 52 did not consent or contact was lost. At the 1-year follow-up examination, PNES diagnosis was reconsidered in nine patients. In 96 patients, the diagnostic level remained the same (P-group), with that in 43 considered to be clinically established (CE-group) and in 42 documented (D-group). The Qolie-10 and NDDI-E questionnaires were examined at both the study entry and the follow-up examination. RESULTS: Multiple regression analysis of quality of life (QoL) score (n = 173; R2  = 0.374; F = 7.349; P < 0.001) revealed NDDI-E score (t = -6.402; P < 0.001), age of PNES onset (t = -3.026; P = 0.003), and ethnic minority status (t = 3.068; P = 0.003) as significant contributors. At entry, the P-group showed the lowest PNES attack frequency (P < 0.000), the lowest rate of antiseizure, antidepressant, and antipsychotic medication (P < 0.000; P = 0.031; P = 0.013, respectively), and the lowest proportion of psychosis (P = 0.046). At follow-up, PNES attack frequency (P < 0.000), number of admittances to emergency room (P < 0.000), and scores for QoL (P < 0.000) as well as depression (P = 0.004) were found to be significantly improved together with other collateral indicators, such as rate of antiseizure medication prescription (P = 0.001) and psychiatric symptoms (P = 0.03). Multiple regression analysis of a sample limited to patients with intellectual disability (ID) (n = 44; R2  = 0.366; F = 4.493; P = 0.002) revealed continued psychotherapy at follow-up (t = 2.610, P = 0.013) and successful reduction in antiseizure medication (t = 2.868; P = 0.007) as positively related with improved QoL. SIGNIFICANCE: Clinical and the socio-psychological constellation of possible, clinically established, and documented PNES were found to differ greatly. Unexpectedly, significant effects of the continuous psychotherapeutic intervention were confirmed in PNES patients with ID.

Structural connectivity between the hippocampus and cortical/subcortical area relates to cognitive impairment in schizophrenia but not in mood disorders.

Cognitive impairment in schizophrenia and other psychiatric disorders is a challenge to be overcome in order to maintain patients' quality of life and social function. The neurological pathogenesis of cognitive impairment requires further elucidation. In general, the hippocampus interacts between the cortical and subcortical areas for information processing and consolidation and has an important role in memory. We examined the relationship between structural connectivity of the hippocampus and cortical/subcortical areas and cognitive impairment in schizophrenia, major depressive disorder and bipolar disorder. Subjects comprised 21 healthy controls, 19 patients with schizophrenia, 20 patients with bipolar disorder and 18 patients with major depressive disorder. Diffusion-weighted tensor images data were processed using ProbtrackX2 to calculate the structural connectivity between the hippocampus and cortical/subcortical areas. Cognitive function was assessed using the Brief Assessment of Cognition in schizophrenia composite score. Hippocampal structural connectivity index was significantly correlated with composite score in the schizophrenia group but not in the healthy control, major depressive disorder or bipolar disorder groups. There were no statistically significant differences in hippocampal structural connectivity index between the four groups. Structural connectivity between the hippocampus and cortical/subcortical areas is suggested to be a pathophysiological mechanism of comprehensive cognitive impairment in schizophrenia.

Probable progressive supranuclear palsy in a patient with chronic schizophrenia: A case report.

Rare neurodegenerative disorders may be considered in the differential diagnosis of Parkinsonism in patients with schizophrenia who show worsening signs of Parkinsonism under treatment with antipsychotics. To the best of our knowledge, the present study is the first report describing probable progressive supranuclear palsy (PSP) in a patient with chronic schizophrenia. A 64-year-old man presented with hallucinations, delusions and asociality. He had received treatment with both typical and atypical antipsychotics for ~13 years. He began experiencing short-term memory impairment and bradykinesia two years before presentation, and then showed increased dysphagia, upper-limb muscle rigidity, extrapyramidal symptoms, vision loss and photophobia. Psychological manifestations included chronic depression, irritability and, occasionally, euphoria. His gait worsened, leading to repeated falls. Antipsychotics were discontinued, and the patient was almost completely dependent on a wheelchair in daily life. In a neurology consultation, he was diagnosed with probable progressive supranuclear palsy-Richardson's syndrome presenting as vertical supranuclear gaze palsy and prominent postural instability with falls. Brain magnetic resonance imaging (MRI) revealed atrophy of the mesencephalic tegmentum, and 123I-ioflupane single-photon emission computed tomography (SPECT) revealed reduced bilateral striatal reuptake. Overall, PSP should be considered in patients with schizophrenia with worsening Parkinsonism, especially when it is accompanied by supranuclear ophthalmoplegia, pseudobulbar palsy, dysarthria and dystonic stiffness of the neck and upper body. In the present case, the combination of brain MRI and 123I-ioflupane SPECT helped to discriminate PSP from other Parkinsonian syndromes, including drug-induced Parkinsonism, in the differential diagnosis.

Two cases of steroid dementia showing partial recovery during 2-year follow-up.

Background: Steroid dementia has been reported since the 1970s. In the current super-aged society, it increasingly receives attention because of the growing number of elderly people that are medicated with steroids for systemic rheumatic disease. Case Presentation: We report two cases of steroid dementia that were diagnosed as a result of careful observation of clinical symptoms and biological examination, including nuclear medicine tests. Cognitive and daily living functions were partially recovered in both cases after decrease or discontinuance of steroid medication in 2-year follow-up, but their daily living function could not be totally restored to premorbid level. Conclusion: Cognitive dysfunction caused by steroids is suggested by these cases, although definitive diagnosis in these cases is not possible. It was partially reversible over the course of a few years, but some functional loss remains. Cognitive function should be assessed appropriately before, during, and after steroid treatment. Detailed differential diagnosis of neurodegenerative disorders and longitudinal follow-up is required when cognitive dysfunction is observed after initiation of steroid therapy.

Computational modeling of electric fields for prefrontal tDCS across patients with schizophrenia and mood disorders.

This cross-diagnostic study aims to computationally model electric field (efield) for prefrontal transcranial direct current stimulation in mood disorders and schizophrenia. Enrolled were patients with major depressive disorder (n = 23), bipolar disorder (n = 24), schizophrenia (n = 23), and healthy controls (n = 23). The efield was simulated using SimNIBS software (ver.2.1.1). Electrodes were placed at the left and right prefrontal areas and the current intensity was set to 2 mA intensity. Schizophrenia and major depressive disorder groups showed significantly lower 99.5th percentile efield strength than healthy controls. In voxel-wise analysis, patients with schizophrenia showed a significant reduction of simulated efield strength in the bilateral frontal lobe, cerebellum and brain stem compared with healthy controls. Among the patients with schizophrenia, reduction of simulated efield strength was not significantly correlated with psychiatric symptoms or global functioning. The patients with bipolar disorder showed no significant difference in simulated efield strength compared with healthy controls, and there was no significant difference between the clinical groups. Our results suggest attenuated electrophysiological response to transcranial direct current stimulation to the prefrontal cortex in patients with schizophrenia, and to some extent in patients with major depressive disorder.

Brain activity during the Clock-Drawing Test: multichannel near-infrared spectroscopy study.

The Clock-Drawing Test (CDT) is widely used in clinical practice for the screening of dementia. However, neural activity during real clock drawing has not been investigated due to motion artifacts. In the present study, we examined brain activity during real clock drawing using multichannel near-infrared spectroscopy (NIRS). We measured hemoglobin concentration changes in the prefrontal and temporal surface areas during clock drawing using 52-channel NIRS. Data obtained from 37 right-handed healthy volunteers were analyzed. We found significant increases in oxy-Hb in more than 96.2% of the channels (false-discovery rate corrected, p < .025). The time required for CDT performance showed a negative correlation with changes in oxy-Hb in the prefrontal region (r = -.529, p = .002). The mean value for oxy-Hb changes was higher in the left hemisphere in 20 subjects (54%) and in the right hemisphere in 17 subjects (46%). The NIRS/CDT combination is acceptable as a clinical tool, as the method has the advantages of direct measurement of cortical activation with high temporal resolution. Our results confirm the aspects of the CDT involving the frontal-lobe battery.

Evaluation of regional cerebral blood flow in a patient with musical hallucinations.

A 52-year-old woman with musical hallucinations was examined using brain single photon emission computed tomography (SPECT) with 99mTc-ECD. Changes in regional cerebral blood flow (rCBF) after carbamazepine treatment were assessed using a three-dimensional stereotaxic ROI template. Following treatment, rCBF was decreased in the subcortical structures and increased in the global cortical regions. From our findings, we propose that rCBF values in subcortical structures represent abnormalities similar to those reported in previous reports or other psychiatric disorders, while those in cortical regions suggest background brain dysfunctions that result in generation of musical hallucinations.

A case of autoimmune autonomic ganglionopathy with prolonged delirium.

Autoimmune autonomic ganglionopathy (AAG) is a rare acquired immune-mediated disorder that leads to autonomic failure. It is sometimes complicated by mental and behavioral symptoms. We report a case of 72-year-old male with AAG who was admitted to the psychiatric department for prolonged severe delirium. Repeated loss of consciousness attributed to severe orthostatic hypotension disturbed recovery from delirium. In addition, intracerebral hemorrhage occurred during hospitalization, and this cerebrovascular event may have been substantially affected by unstable blood pressure due to AAG. This case suggests importance of differential diagnosis of AAG in patients with mental and behavioral symptoms accompanying severe autonomic failure.

Microstructural abnormalities in callosal fibers and their relationship with cognitive function in schizophrenia: A tract-specific analysis study.

INTRODUCTION: The corpus callosum serves the essential role of relaying cognitive information between the homologous regions in the left and the right hemispheres of the brain. Cognitive impairment is a core dysfunction of schizophrenia, but much of its pathophysiology is unknown. The aim of this study was to elucidate the association between microstructural abnormalities of the corpus callosum and cognitive dysfunction in schizophrenia. METHODS: We examined stepwise multiple regression analysis to investigate the relationship of the fractional anisotropy (FA) of callosal fibers in each segment with z-scores of each brief assessment of cognition in schizophrenia subtest and cognitive composite score in all subjects (19 patients with schizophrenia [SZ group] and 19 healthy controls [HC group]). Callosal fibers were separated into seven segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. RESULTS: The FA of callosal fibers in the temporal segment was significantly associated with z-scores of token motor test, Tower of London test, and the composite score. In the SZ group, the FA of callosal fibers in the temporal segment was significantly associated with the z-score of the Tower of London test. In addition, the FA of callosal fibers in temporal segment showed significant negative association with the positive and negative syndrome scale negative score in the SZ group. Compared to the HC group, the FA in temporal segment was significantly decreased in the SZ group. CONCLUSION: Our results suggest that microstructural abnormalities in the callosal white matter fibers connecting bilateral temporal lobe cortices contribute to poor executive function and severe negative symptom in patients with schizophrenia.

Widespread abnormalities in white matter integrity and their relationship with duration of illness in temporal lobe epilepsy.

OBJECTIVE: Elucidation of abnormal connections throughout the whole brain is necessary to understand temporal lobe epilepsy (TLE). We examined abnormalities in whole-brain white matter integrity and their relationship with duration of illness in patients with TLE. METHODS: The subjects were 15 patients with TLE and 17 healthy controls. Mean duration of illness in the TLE group was 21.6 years. Tract-based spatial statistics (TBSS) were used for diffusion tensor imaging (DTI) analysis. Four diffusion tensor metrics, that is, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and then examined for differences between the TLE and healthy control groups. We also examined for correlations between DTI parameters and duration of illness in the TLE group. RESULTS: In the TLE group, compared with the healthy control group, FA was reduced, and MD and RD were increased, not only in the limbic and temporal lobe regions and their directly connecting regions in both hemispheres, but also in remote white matter regions. Duration of illness showed a significant negative correlation with mean whole-brain FA and a significant positive correlation with both mean whole-brain MD and RD. Brain regions showing correlation between disease duration and DTI metrics also extended to the limbic area and its connecting regions, and to remote white matter regions. SIGNIFICANCE: The results of this study suggest that widespread abnormalities in white matter integrity in patients with TLE are associated with long-term disease.

Hepatic encephalopathy with status epileptics: a case report.

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epilepticus. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy (phenytoin sodium) and treatment for hepatic encephalopathy (Branched chain amino acids). The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: a tract-specific analysis study.

BACKGROUND: The corpus callosum modulates interhemispheric communication and cognitive processes. It has been suggested that white matter abnormalities in the corpus callosum are related to the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). The aim of this study was to examine microstructural abnormalities in callosal fibers separated by their connection to functional brain regions and determine the relationship of these abnormalities with cognitive function in MDD and BD. METHODS: The subjects were 18 patients with MDD, 20 patients with BD, and 21 healthy controls. The callosal fibers were divided into 6 segments based on their cortical projection using tract-specific analysis of diffusion tensor imaging. We examined differences in the fractional anisotropy (FA) of callosal fibers in six segments among the three subject groups and examined the correlation between the FA in each segment and cognitive performance in the 3 groups. RESULTS: The FA of anterior callosal fibers were reduced significantly in the MDD and BD groups compared to those in the HC group, and the FA of anterior callosal fibers correlated significantly with the raw scores of the digit sequencing task and symbol coding in the MDD group. LIMITATIONS: The patients were medicated at the time of scanning, and the MDD and BD groups were not matched for symptom severity. CONCLUSIONS: Our results suggest that MDD and BD have similar microstructural abnormalities in anterior callosal fibers connecting bilateral frontal cortices, and these abnormalities may be related to impairment of working memory and attention in MDD.

Re-examination of the value of localising aura sensations and lateralising interictal epileptiform discharges in view of structural lesions demonstrated by MRI.

We examined the relationship between MRI lesions and electro-clinical findings with special attention to the localising value of aura sensations and the sides of interictal epileptiform discharges in 327 patients with symptomatic localisation-related epilepsy. As a result, while autonomic as well as psychic auras were correlated with temporal lesions, simple motor seizures were associated with extra-temporal ones. Within the group of patients with temporal lobe epilepsy, autonomic but not psychic auras concurred significantly more often with medial temporal structural lesions. Furthermore, there was a significant difference between concordance rates between sides of MRI lesions and EEG foci as a function of laterality: while the right-sided MRI lesions constantly showed ipsilateral EEG foci, EEG foci concurring with the left-sided MRI lesions proved to be often falsely lateralising. From these results, we assumed that lateral as well as medial temporal involvement is needed in the genesis of the psychic aura in contrast to the autonomic aura, which could be induced without lateral temporal involvement, and lesions in the left hemisphere are more apt to induce secondarily epileptogenic than those in the right hemisphere.

Reduction of cortical GABAergic inhibition correlates with working memory impairment in recent onset schizophrenia.

BACKGROUND: Cognitive impairments are present during the early course of schizophrenia, and the contribution of GABAergic dysfunction to these cognitive impairments has received increasing attention. Cortical GABAergic inhibition can be assessed using short-interval intracortical inhibition (SICI) in a paired-pulse transcranial magnetic stimulation (ppTMS). The aim of this study was to examine the relationship between cortical GABAergic inhibition and cognitive function in recent onset schizophrenia patients using ppTMS and a neuropsychological battery. METHODS: The subjects were 20 healthy controls (HC group) and 20 patients with schizophrenia whose duration of illness was less than three years (SZ group). All subjects underwent ppTMS measurements of SICI and intracortical facilitation (ICF), and cognitive performance of the SZ group was assessed using the Brief Assessment of Cognition in Schizophrenia Japanese-language version. We examined group differences in ppTMS measurements (resting motor threshold, SICI, and ICF). In the SZ group, we assessed the relationship between SICI and cognitive performance, and the relationships between SICI and age, duration of illness, medications, and psychopathology. RESULTS: The SZ group showed a significant reduction of SICI compared to the HC group, and demonstrated a significant correlation between the reduction of SICI and impaired performance of a working memory task. The HC and the SZ groups did not differ significantly in resting motor threshold and ICF. The SZ group did not show any significant correlations between SICI and age, duration of illness, medications, or psychopathology. CONCLUSIONS: Our results suggest that the reduction of cortical GABAergic inhibition is related to impairment of working memory in patients with recent onset schizophrenia.