Hiroto Hokama

Abnormalities of the left temporal lobe and thought disorder in schizophrenia : a quantitative magnetic resonance imaging study

BACKGROUND Data from postmortem, CT, and magnetic resonance imaging (MRI) studies indicate that patients with schizophrenia may have anatomical abnormalities of the left temporal lobe, but it is unclear whether these abnormalities are related to the thought disorder characteristic of schizophrenia. METHODS We used new MRI neuroimaging techniques to derive (without knowledge of the diagnosis) volume measurements and three-dimensional reconstructions of temporal-lobe structures in vivo in 15 right-handed men with chronic schizophrenia and 15 matched controls. RESULTS As compared with the controls, the patients had significant reductions in the volume of gray matter in the left anterior hippocampus-amygdala (by 19 percent [95 percent confidence interval, 3 to 36 percent]), the left parahippocampal gyrus (by 13 percent [95 percent confidence interval, 3 to 23 percent], vs. 8 percent on the right), and the left superior temporal gyrus (by 15 percent [95 percent confidence interval, 5 to 25 percent]). The volume of the left posterior superior temporal gyrus correlated with the score on the thought-disorder index in the 13 patients evaluated (r = -0.81, P = 0.001). None of these regional volume decreases was accompanied by a decrease in the volume of the overall brain or temporal lobe. The volume of gray matter in a control region (the superior frontal gyrus) was essentially the same in the patients and controls. CONCLUSIONS Schizophrenia involves localized reductions in the gray matter of the left temporal lobe. The degree of thought disorder is related to the size of the reduction in volume of the left posterior superior temporal gyrus.

Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder

This study used quantitative volumetric magnetic resonance imaging techniques to explore the neuroanatomic correlates of chronic, combat-related posttraumatic stress disorder (PTSD) in seven Vietnam veterans with PTSD compared with seven nonPTSD combat veterans and eight normal nonveterans. Both left and right hippocampi were significantly smaller in the PTSD subjects compared to the Combat Control and Normal subjects, even after adjusting for age, whole brain volume, and lifetime alcohol consumption. There were no statistically significant group differences in intracranial cavity, whole brain, ventricles, ventricle:brain ratio, or amygdala. Subarachnoidal cerebrospinal fluid was increased in both veteran groups. Our finding of decreased hippocampal volume in PTSD subjects is consistent with results of other investigations which utilized only trauma-unexposed control groups. Hippocampal volume was directly correlated with combat exposure, which suggests that traumatic stress may damage the hippocampus. Alternatively, smaller hippocampi volume may be a pre-existing risk factor for combat exposure and/or the development of PTSD upon combat exposure.

A digital brain atlas for surgical planning, model-driven segmentation, and teaching

We developed a three-dimensional (3D) digitized atlas of the human brain to visualize spatially complex structures. It was designed for use with magnetic resonance (MR) imaging data sets. Thus far, we have used this atlas for surgical planning, model-driven segmentation, and teaching. We used a combination of automated and supervised segmentation methods to define regions of interest based on neuroanatomical knowledge. We also used 3D surface rendering techniques to create a brain atlas that would allow us to visualize complex 3D brain structures. We further linked this Information to script files in order to preserve both spatial information and neuroanatomical knowledge. We present here the application of the atlas for visualization in surgical planning far model-driven segmentation and for the teaching of neuroanatomy. This digitized human brain has the potential to provide important reference information for the planning of surgical procedures. It can also serve as a powerful teaching tool, since spatial relationships among neuroanatomical structures can be more readily envisioned when the user is able to view and rotate the structures in 3D space. Moreover, each element of the brain atlas is associated with a name tag, displayed by a user controlled pointer. The atlas holds a major promise as a template for model-driven segmentation. Using this technique, many regions of interest can be characterized simultaneously on new brain images.

Volumetric Evaluation of the Thalamus in Schizophrenic Male Patients Using Magnetic Resonance Imaging

BACKGROUND The thalamus, an important subcortical brain region connecting limbic and prefrontal cortices, has a significant role in sensory and cortical processing. Although inconsistently, previous studies have demonstrated neuroanatomical abnormalities in the thalamus of schizophrenic patients. METHODS This structural magnetic resonance imaging study, based on segmentation of contiguous coronal 1.5-mm images, compared thalamic brain volumes of 15 chronic, male schizophrenic patients with 15 normal controls matched on age, sex, handedness, and parental socioeconomic status. RESULTS There were no significant differences between patients and controls in thalamic volumes, right or left, adjusted for total brain volume; however, there were significantly different correlations of thalamic volumes with prefrontal white matter and lateral ventricles among patients, but not among controls. Thalamic volumes among patients were also significantly correlated with bizarre behavior, hallucinations, and thought disorder. CONCLUSIONS Findings suggest that connectivity between thalamic nuclei and prefrontal cortical areas are abnormal in chronic male schizophrenic patients. In addition, ventricular enlargement may be, in part, due to subtle reduction in thalamic volume and/or in volume of thalamocortical and corticothalamic fibers secondary to thalamic abnormalities. Finally, correlations with positive symptomatology underscore the role of the thalamus in gating or filtering of sensory information and coordination of cortical processing.

Caudate, putamen, and globus pallidus volume in schizophrenia: a quantitative MRI study.

Basal ganglia structures have been reported to be abnormal in schizophrenia. However, while component structures of the basal ganglia are functionally differentiated, there have been no evaluations of their separate magnetic resonance imaging (MRI) volumes with small voxel (1.5 mm3) spoiled gradient-recalled acquisition in steady state techniques and multi-plane assessments. We examined MRI scans from 15 male, right-handed, neuroleptic-medicated schizophrenic patients and 15 age-, handedness-, and gender-matched normal volunteers. Compared with normal subjects, schizophrenic patients showed enlarged volumes: 14.2% for total basal ganglia, 27.4% for globus pallidus, 15.9% for putamen, and 9.5% for caudate. Increased volumes, especially of the caudate, were associated with poorer neuropsychological test performance on finger tapping and Hebbs Recurring Digits. These findings indicate abnormalities throughout all basal ganglia structures in at least a subgroup of schizophrenic patients.

A topographic study of ERPs elicited by visual feature discrimination.

The functional properties and topographic distribution of event-related potential (ERP) components elicited by visual discrimination of orientation, spatial frequency, spatial location, and color were investigated. ERPs were recorded from 28 electrode sites from 16 adult subjects. Five ERP components were measured: N1 (peak latency = 160 ms), P2 (250 ms), anterior N2 (260 ms), posterior N2 (280 ms), and P3 (400 ms). N1 and P2 were more negative when a stimulus was a target, showing the selection negativity effect. Feature-specific effects on component amplitude or topography varied by component. N1 and P2 were sensitive to stimulus orientation and location. Anterior or posterior N2 was sensitive to orientation, spatial frequency, and location. P3 varied with orientation, but not with other stimulus features. Cross-task comparisons of ERPs to vertical line segments in the color, orientation, and location discrimination tasks indicated that P2 and N2, but not N1 and P3, were sensitive to changes in task-demand. These data provide topographic evidence that ERP components in the 160-400 ms time domain can be differentiated on the basis to processing of specific visual features, and reflect neurophysiologically distinct visual pathways in the human cortex.

Temporal lobe sulco-gyral pattern anomalies in schizophrenia: an in vivo MR three-dimensional surface rendering study

Neuroanatomical and histological findings from post-mortem brains, as well as in vivo findings from magnetic resonance imaging (MRI) studies, suggest the presence of morphologic temporal lobe abnormalities in schizophrenia. To determine whether or not sulco-gyral pattern abnormalities in the temporal lobe could be detected in vivo, we applied computerized surface rendering techniques to MR data sets in order to make both qualitative and quantitative analyses of three-dimensional reconstructions of the temporal and frontal cortex in 15 schizophrenic patients and 15 normal controls. The qualitative analysis, based on a visual classification of the temporal lobe sulco-gyral pattern by 4 raters blind to diagnosis, showed that in schizophrenics there was a more vertical orientation to the sulci in the left temporal lobe, with an interrupted course of sulci due to gyri coursing across the sulci. Normal controls, in contrast, showed a more horizontal orientation with no interruptions. These findings were supported by the quantitative analysis, where more sulcal lines, representing an interrupted course of sulci, were observed in the temporal lobes (more pronounced on the left) in schizophrenics than in normal controls. These data suggest that some of the abnormalities observed in schizophrenia may have their origin in alterations occurring during the course of neurodevelopment when the sulco-gyral pattern is determined.

Auditory ERPs to non-target stimuli in schizophrenia: relationship to probability, task-demands, and target ERPs

The effects of task demands and stimulus probability on the N1 and P2 components of the auditory event-related potential (ERP) to non-target stimuli were investigated in normal and medicated schizophrenic subjects. Subjects either read a book while tones were presented, or counted the rare (low probability) tones in an auditory oddball paradigm. The mismatch negativity to rare tones in the reading condition was present, and did not differ between groups. N1 amplitude was smaller in schizophrenic patients in all conditions. When subjects counted the rare tones, the amplitude and latency of P2 increased. This task-related effect on P2 was much greater in control than in schizophrenic subjects. Difference ERPs were used to better characterize the effect of task demands by subtracting the ERP in the reading condition from the ERP in the counting condition. The difference ERP consisted of a negative deflection at 182 ms, and a positive deflection at 276 ms, which were both reduced in schizophrenic subjects. N2 and P3 amplitude to target stimuli were reduced in patients as well, but these abnormalities were uncorrelated with N1 and P2 abnormalities to non-target stimuli. Despite automatic registration of stimulus mismatch, and normal processing speed, patients showed deficient task-related modulation of processing to both non-target and target stimuli. Reduction of N1 amplitude in schizophrenia occurs regardless of task demands, and may reflect a chronic, early-stage disturbance in information processing.

Abnormalities of auditory event-related potentials in schizophrenia prior to treatment.

BACKGROUND P300 amplitude reduction is a consistent finding in schizophrenic patients, but it is unclear if this abnormality predates neuroleptic treatment or is present at onset of illness. METHODS Auditory event-related potentials (ERPs), during a standard oddball paradigm, were recorded from 45 neuroleptic-naive schizophrenics, 56 drug-free, previously treated schizophrenics, and 73 healthy normal controls. Forty-seven of the schizophrenic subjects had their first episode within the past year. RESULTS N200 amplitude did not differ among groups. P300 amplitude was significantly smaller in both neuroleptic-naive and previously treated schizophrenic groups compared to the control groups. There were no significant differences between the two schizophrenic groups in P300 amplitude. N200 and P300 latency were prolonged in previously treated schizophrenics compared to neuroleptic-naive schizophrenics and normal controls. CONCLUSIONS The present study suggests that ERP abnormalities, especially P300 amplitude reduction, are already present prior to the administration of neuroleptic medication in the earliest stage of schizophrenia.

The N400 component of event-related potentials in schizophrenic patients: a preliminary study.

ERPs were recorded during a word recognition task to investigate cognitive dysfunction in schizophrenia. Thirteen medicated schizophrenics and 26 normal controls were tested. In each trial a pair of stimuli, S1 (a word) and S2 (a word or a non-word), were presented. The subjects were required to discriminate between a word and a non-word for S2 (lexical decision task). In a related (R) condition, S2 was the antonym of S1 (e.g., brother-sister); in an unrelated (U) condition, S1 and S2 were semantically unrelated (e.g., brother-drive); in the non-word (N) condition, S2 was a non-word (e.g., brother-grofe). The ERPs for S2 were analyzed, and the contextual effects on the ERPs for S2 observed for both the patients and controls. For both groups, in the U and N conditions S2 elicited a large negative-trending deflection (N370). In contrast, in the R condition it elicited only a small negative-trending notch. There was no difference in the amplitude of N370 between the groups, but its latency was more prolonged or its wave shape more extended for the schizophrenics than for the controls. The N400 amplitude is concluded to remain unchanged in schizophrenics.