Person:

Whitford, T

Background—Abnormalities within language-related anatomical structures have been associated with clinical symptoms and with language and memory deficits in schizophrenia. Recent studies suggest disruptions in functional connectivity within the Inferior Frontal Gyrus (IFG) network in schizophrenia. However, due to technical challenges, anatomical connectivity abnormalities within this network and their involvement in clinical and cognitive deficits have not been studied. Material and Methods—Diffusion and anatomical scans were obtained from 23 chronic schizophrenia patients and 23 matched controls. The IFG was automatically segmented, and its white matter connections extracted and measured with newly-developed stochastic tractography tools. Correlations between anatomical structures and measures of semantic processing were also performed. Results—White Matter connections between the IFG and posterior brain regions followed two distinct pathways: dorsal and ventral. Both demonstrated left lateralization, but ventral pathway abnormalities were only found in schizophrenia. IFG volumes also showed left lateralization andabnormalities in schizophrenia. Further, despite similar laterality and abnormality patterns, IFG volumes and white matter connectivity were not correlated with each other in either group. Interestingly, measures of semantic processing correlated with white matter connectivity in schizophrenia and with gray matter volumes in controls. Finally, hallucinations were best predicted by both gray matter and white matter measures together. Conclusions—Our results suggest abnormalities within the ventral IFG network in schizophrenia, with white matter abnormalities better predicting semantic deficits. The lack of a statistical relationship between coexisting gray and white matter deficits might suggest their different origin and the necessity for a multimodal approach in future schizophrenia studies.

It has been suggested that some cases of schizophrenia may be caused by an interaction between physiological risk factors and exposure to certain neurotropic infectious agents such as Herpes Simplex Virus type 1 (HSV1). This study investigated whether HSV1 exposure was associated with structural brain abnormalities in individuals who, because of genetic or other factors, were deemed at ultra high risk (UHR) of developing psychosis. Twenty-five UHR individuals with a history of HSV1 exposure (HSV1+), 33 UHR participants without a history of HSV1 exposure (HSV1-) and 19 healthy controls participated in the study. All participants underwent a T1- weighted structural MRI scan, and HSV1 exposure was determined based on the presence of IgG class antibodies in the blood serum. Voxel based morphometry revealed that the HSV1+ participants exhibited volumetric gray matter reductions in the cuneus, relative to both the HSV1- and healthy control participants (p<0.05, small volume corrected for familywise error). The results of the study suggest that a history of HSV1 infection is associated with volumetric gray matter reductions in individuals at ultra-high risk for developing psychosis, and are consistent with previous studies that have identified structural gray matter abnormalities in HSV1-infected patients with established schizophrenia.

Introduction—The Middle Longitudinal Fascicle (MdLF) is a long association fiber connecting the superior temporal gyrus (STG) and temporal pole with the angular gyrus through the white matter of the STG, structures which are known to play a crucial role in the pathology of schizophrenia. Functions of MdLF are thought to be related to language and thought processing in the left hemisphere, and with attention in the right hemisphere. While deficits of these functions are core clinical features of schizophrenia, no study has investigated structural abnormalities of MdLF in schizophrenia. Method—3T diffusion tensor data was acquired from twenty-six patients with schizophrenia and twenty-five healthy control subjects. Streamline tractography technique was used to extract MdLF. Fractional Anisotropy (FA) was compared between two groups. In addition, relationships were investigated between FA in the left MdLF and the Disorganized Thought Factor derived from the Positive and Negative Symptom Scale five factor model, and between FA in the right MdLF and the Poor Attention. Result—Relative to control subjects, the patients with chronic schizophrenia showed significant mean FA reductions in the bilateral MdLF. The FA of the left MdLF demonstrated a significant negative association with the Disorganized thoughts factor, and the FA of the right MdLF showed a significant negative relationship with the Poor Attention. Conclusions—This study provides new evidence for structural deficits in the bilateral MdLF in patients with chronic schizophrenia. It further demonstrates contribution of these abnormalities to the core clinical features - especially to disorganization and attention deficit.

Background—Whilst the neuroanatomical underpinnings of the functional brain disconnectivity observed in patients with schizophrenia remain elusive, white matter fiber bundles of the brain are a likely candidate given that they represent the infrastructure for long-distance neural communication. Methods—This study investigated for diffusion abnormalities in 19 patients with chronic schizophrenia (SZ), relative to 19 matched controls, across tractography-defined segments of the Corpus Callosum. Diffusion-weighted images were acquired with 51 non-collinear gradients on a 3T scanner (1.7mm isotropic voxels). The Corpus Callosum was extracted by means of whole-brain tractography and automated fiber-clustering, and was parcellated into six segments on the basis of fiber trajectories. The diffusion indices of Fractional Anisotropy (FA) and Mode were calculated for each segment. Results—Relative to the healthy controls, the SZ patients exhibited Mode increases in the Parietal fibers, suggesting a relative absence of crossing fibers. SZ patients also exhibited FA reductions in the Frontal fibers, which were underpinned by increased in Radial Diffusivity, consistent with myelin abnormalities. Significant correlations were observed between patients' degree of Reality Distortion and their FA and Radial Diffusivity, such that the most severely psychotic patients were the least abnormal in terms of their Frontal fiber diffusivity. Conclusions—The SZ patients exhibited a variety of diffusion abnormalities in the Corpus Callosum, which were related to the severity of their psychotic symptoms. To the extent that diffusion abnormalities influence axonal transmission velocities, these results provide support for those theories that emphasize neural timing abnormalities in the etiology of schizophrenia.

Background—Delusions of control are among the most distinctive and characteristic symptoms of schizophrenia. Several theories have been proposed that implicate aberrant communication between spatially disparate brain regions in the etiology of this symptom. Given that white matter fasciculi represent the anatomical infrastructure for long-distance communication in the brain, the present study investigated whether delusions of control were associated with structural abnormalities in four major white matter fasciculi. Methods—Ten schizophrenia patients with current delusions of control, 13 patients with no clinical history of delusions of control, and 12 healthy controls underwent a Diffusion-Tensor Imaging (DTI) scan. Deterministic tractography was used to extract the corpus callosum, superior longitudinal fasciculus, arcuate fasciculus and cingulum bundle. The structural integrity of these four fasciculi were quantified with Fractional Anisotropy (FA), and compared between groups. Results—The patients with delusions of control exhibited significantly lower FA in all four fasciculi, relative to the healthy controls. Furthermore, the patients with delusions of control also exhibited significantly lower FA in the cingulum bundle relative to patients without a history of this symptom, and this difference remained significant when controlling for between-group differences in global SAPS score and medication dosage. Conclusions—The results suggest that structural damage to the cingulum bundle may be involved in the etiology of delusions of control, possibly because of its role in connecting the action initiation areas of the premotor cortex with the cingulate gyrus.