Person:

Frumin, Melissa

We sought to identify the functional correlates of reduced magnetic resonance imaging (MRI) volumes of the superior temporal gyrus (STG) and the fusiform gyrus (FG) in patients with chronic schizophrenia. MRI volumes, positive/negative symptoms, and neuropsychological tests of facial memory and executive functioning were examined within the same subjects. The results indicated two distinct, dissociable brain structure-function relationships: (1) reduced left STG volume-positive symptoms-executive deficits; (2) reduced left FG-negative symptoms-facial memory deficits. STG and FG volume reductions may each make distinct contributions to symptoms and cognitive deficits of schizophrenia.

Background: The hippocampus has been shown to be abnormal in schizophrenia. The fornix is one of the main fiber tracts connecting the hippocampus with other brain regions. Few studies have evaluated the fornix in schizophrenia, however. A focus on fornix abnormalities and their association with hippocampal abnormalities might figure importantly in our understanding of the pathophysiology of schizophrenia. Methods: Line-scan diffusion tensor imaging (DTI) was used to evaluate diffusion in the fornix in 24 male patients with chronic schizophrenia and 31 male control subjects. Maps of fractional anisotropy (FA) and mean diffusivity (Dm), which are indices sensitive to white-matter integrity, were generated to quantify diffusion within the fornix. We used high spatial resolution magnetic resonance imaging (MRI) to measure hippocampal volume. Results: FA and cross-sectional area of the fornix were significantly reduced in patients compared with control subjects. Dm was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean Dm and reduced cross-sectional area of the fornix for patients. Patients also showed a significant correlation between reduced scores on neuropsychologic measures of declarative-episodic memory and reduced hippocampal volumes. Conclusions: These findings demonstrate a disruption in fornix integrity in patients with schizophrenia.

Objective: The authors examined the association between volume of the fusiform gyrus, a region involved in face processing, and the personality trait of extraversion in patients with schizophrenia. Method: Male patients (N=24) and age-matched male comparison subjects (N=26) completed NEO Five-Factor Inventory personality measures of extraversion and underwent high-spatial-resolution magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter. Results: Low extraversion scores were significantly correlated with gray matter volume reductions in the right posterior fusiform gyrus for patients but not comparison subjects. Conclusions: Reduced right posterior fusiform gyrus volume may contribute to disease-related social disturbances, characterized by both low extraversion and reduced sensitivity to human faces.

Hemisphere asymmetry was explored in normal healthy subjects and in patients with schizophrenia using a novel voxel-based tensor analysis applied to fractional anisotropy (FA) of the diffusion tensor. Our voxel-based approach, which requires precise spatial normalization to remove the misalignment of fiber tracts, includes generating a symmetrical group average template of the diffusion tensor by applying nonlinear elastic warping of the demons algorithm. We then normalized all 32 diffusion tensor MRIs from healthy subjects and 23 from schizophrenic subjects to the symmetrical average template. For each brain, six channels of tensor component images and one T2-weighted image were used for registration to match tensor orientation and shape between images. A statistical evaluation of white matter asymmetry was then conducted on the normalized FA images and their flipped images. In controls, we found left-higher-than-right anisotropic asymmetry in the anterior part of the corpus callosum, cingulum bundle, the optic radiation, and the superior cerebellar peduncle, and right-higher-than-left anisotropic asymmetry in the anterior limb of the internal capsule and the anterior limb’s prefrontal regions, in the uncinate fasciculus, and in the superior longitudinal fasciculus. In patients, the asymmetry was lower, although still present, in the cingulum bundle and the anterior corpus callosum, and not found in the anterior limb of the internal capsule, the uncinate fasciculus, and the superior cerebellar peduncle compared to healthy subjects. These findings of anisotropic asymmetry pattern differences between healthy controls and patients with schizophrenia are likely related to neuro-developmental abnormalities in schizophrenia.

Accumulating evidence suggests that schizophrenic patients do not use context efficiently. Also, studies suggest similarities in clinical and cognitive profiles between schizophrenic and schizotypal personality disorder (SPD) individuals, and epidemiological studies point to a genetic link between the two disorders. This study examined electrophysiological correlates of processing sentence context in a group of SPD women in a classical N400 sentence paradigm. The study assessed if the dysfunction in context use found previously in schizophrenia and male SPD also exists in female SPD. We tested 17 SPD and 16 matched normal control women. The results suggest the presence of abnormality in context use in female SPD similar to that previously reported for male schizophrenic and SPD individuals, but of lesser degree of severity. In SPD women, relative to their comparison group, a more negative N400 was found only to auditory congruent sentences.

Objective: An abnormal superior temporal gyrus has figured prominently in schizophrenia research, and left superior temporal gyrus volume has been shown to be smaller in male subjects with schizotypal personality disorder. This is the first structural magnetic resonance imaging study to examine a group of female subjects with schizotypal personality disorder. Method: The superior temporal gyrus was drawn on coronal images acquired from female subjects recruited from the community (schizotypal personality disorder group: N=21, comparison group: N=29). Results: There were no gray matter volume differences in the left or right superior temporal gyrus between the subjects with schizotypal personality disorder and the comparison subjects. Within the schizotypal personality disorder group, however, there was an interaction between hemisphere and family history of mental illness. Moreover, subjects with schizotypal personality disorder did demonstrate formal thought disorder and a negative correlation between left superior temporal gyrus volume and odd speech. Conclusions: This study of female subjects with schizotypal personality disorder showed no superior temporal gyrus volume differences, but preliminary findings indicate that among female subjects with schizotypal personality disorder, there is a left–right difference in those who have a family history of mental illness relative to those who do not. These data also suggest an association between abnormal speech and left superior temporal gyrus volume, a finding similar to that found in schizophrenia. Results from this study thus clearly reinforce the importance of studying female subjects separately.

The fusiform gyrus is important for face and object recognition, is abnormal in schizophrenia, but has not been studied in schizotypal personality disorder (SPD). Thin-slice MR images showed no differences, either in right, left or total fusiform gyri volumes, between subjects with SPD (N = 21) and normal controls (N = 19). However, there was a correlation between severity of illusions and magical thinking suffered by the SPD subjects and smaller right fusiform gyrus volumes. This suggests that future studies may be useful in determining the functional competence of this gyrus in SPD.

Objective: This study examined whether early or late processes in semantic networks were abnormal in women with a diagnosis of schizotypal personality disorder. The N400 component of the EEG event-related potentials was used as a probe of semantic processes. Method: Word pairs were presented with short and long stimulus-onset asynchronies to investigate, respectively, early and late semantic processes in 16 women with schizotypal personality disorder and 15 normal female comparison subjects. Event-related potentials were recorded in response to the last words in a pair. Results: With the short stimulus-onset asynchrony, the N400 amplitude was less negative in the schizotypal personality disorder group than in the normal comparison group. No group differences were found with the long stimulus-onset asynchrony. Conclusions: The finding of a less negative than normal N400 amplitude with the short stimulus-onset asynchrony in women with schizotypal personality disorder supports the hypothesis that persons with this disorder evince an overactivation of semantic networks. The absence of group differences with the long stimulus-onset asynchrony, which is primarily sensitive to processes involved in context integration, suggests that in this group of schizotypal personality disorder subjects, additional demands on working memory may be necessary to bring out the semantic dysfunction.

Patients with schizophrenia (n = 41) and healthy comparison participants (n = 46) completed neuropsychological measures of intelligence, memory, and executive function. A subset of each group also completed magnetic resonance diffusion tensor imaging (DTI) studies (fractional anisotropy and cross-sectional area) of the uncinate fasciculus (UF) and cingulate bundle (CB). Patients with schizophrenia showed reduced levels of functioning across all neuropsychological measures. In addition, selective neuropsychological–DTI relationships emerged. Among patients but not controls, lower levels of declarative–episodic verbal memory correlated with reduced left UF, whereas executive function errors related to performance monitoring correlated with reduced left CB. The data suggested abnormal DTI patterns linking declarative–episodic verbal memory deficits to the left UF and executive function deficits to the left CB among patients with schizophrenia.

Current views of schizophrenia suggest that it results from abnormalities in neural circuitry, but empirical evidence in the millisecond range of neural activity has been difficult to obtain. In pursuit of relevant evidence, we previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phaselocking of the electroencephalogram in the γ band (30–100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use γ-band oscillations as a mechanism for synchronization. Here, we report the unique finding that, in both healthy controls and schizophrenia patients, visual Gestalt stimuli elicit a γ-band oscillation that is phase-locked to reaction time and hence may reflect processes leading to conscious perception of the stimuli. However, the frequency of this oscillation is lower in schizophrenics than in healthy individuals. This finding suggests that, although synchronization must occur for perception of the Gestalt, it occurs at a lower frequency because of a reduced capability of neural networks to support high-frequency synchronization in the brain of schizophrenics. Furthermore, the degree of phase locking of this oscillation is correlated with visual hallucinations, thought disorder, and disorganization in the schizophrenia patients. These data provide support for linking dysfunctional neural circuitry and the core symptoms of schizophrenia.