Person:

Kikinis, Ron

We introduce an algorithm for segmenting brain magnetic resonance (MR) images into anatomical compartments such as the major tissue classes and neuro-anatomical structures of the gray matter. The algorithm is guided by prior information represented within a tree structure. The tree mirrors the hierarchy of anatomical structures and the sub-trees correspond to limited segmentation problems. The solution to each problem is estimated via a conventional classifier. Our algorithm can be adapted to a wide range of segmentation problems by modifying the tree structure or replacing the classifier. We evaluate the performance of our new segmentation approach by revisiting a previously published statistical group comparison between first-episode schizophrenia patients, first-episode affective psychosis patients, and comparison subjects. The original study is based on 50 MR volumes in which an expert identified the brain tissue classes as well as the superior temporal gyrus, amygdala, and hippocampus. We generate analogous segmentations using our new method and repeat the statistical group comparison. The results of our analysis are similar to the original findings, except for one structure (the left superior temporal gyrus) in which a trend-level statistical significance (p=0.07) was observed instead of statistical significance.

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.

Objective: The middle temporal gyrus and inferior temporal gyrus subserve language and semantic memory processing, visual perception, and multimodal sensory integration. Functional deficits in these cognitive processes have been well documented in patients with schizophrenia. However, there have been few in vivo structural magnetic resonance imaging (MRI) studies of the middle temporal gyrus and inferior temporal gyrus in schizophrenia. Method: Middle temporal gyrus and inferior temporal gyrus gray matter volumes were measured in 23 male patients diagnosed with chronic schizophrenia and 28 healthy male subjects by using high-spatial-resolution MRI. For comparison, superior temporal gyrus and fusiform gyrus gray matter volumes were also measured. Correlations between these four regions and clinical symptoms were also investigated. Results: Relative to healthy subjects, the patients with chronic schizophrenia showed gray matter volume reductions in the left middle temporal gyrus (13% difference) and bilateral inferior temporal gyrus (10% difference in both hemispheres). In addition, the patients showed gray matter volume reductions in the left superior temporal gyrus (13% difference) and bilateral fusiform gyrus (10% difference in both hemispheres). More severe hallucinations were significantly correlated with smaller left hemisphere volumes in the superior temporal gyrus and middle temporal gyrus. Conclusions: These results suggest that patients with schizophrenia evince reduced gray matter volume in the left middle temporal gyrus and bilateral reductions in the inferior temporal gyrus. In conjunction with findings of left superior temporal gyrus reduction and bilateral fusiform gyrus reductions, these data suggest that schizophrenia may be characterized by left hemisphere-selective dorsal pathophysiology and bilateral ventral pathophysiology in temporal lobe gray matter.

We introduce a method for combining fiber tracking from diffusion-tensor (DT) imaging with cortical gray matter parcellation from structural high-spatial-resolution 3D spoiled gradient-recalled acquisition in the steady state images. We applied this method to a tumor case to determine the impact of the tumor on white matter architecture. We conclude that this new method for combining structural and DT imaging data is useful for understanding cortical connectivity and the localization of fiber tracts and their relationship with cortical anatomy and brain abnormalities.

Voxel-based morphometry (VBM) may afford a more rapid and extensive survey of gray matter abnormalities in schizophrenia than manually drawn region of interest (ROI) analysis, the current gold standard in structural MRI. Unfortunately, VBM has not been validated by comparison with ROI analyses, nor used in first-episode patients with schizophrenia or affective psychosis, who lack structural changes associated with chronicity. An SPM99-based implementation of VBM was used to compare a group of 16 patients with first-episode schizophrenia and a group of 18 normal controls and, as a further comparison, 16 first-episode patients with affective psychosis. All groups were matched for age and handedness. High spatial resolution structural images were normalized to the SPM99 template and then segmented, smoothed, and subjected to an ANCOVA. Schizophrenia vs control group comparisons: Voxel-by-voxel comparison of gray matter densities showed that only the left STG region was significantly different when corrected for multiple comparisons P < .05), consistent with our previously reported manual ROI results. Analysis of the extent of voxel clusters, replicated with permutation analyses, revealed group differences in bilateral anterior cingulate gyri and insula (not previously examined by us with manually drawn ROI) and unilateral parietal lobe, but not in medial temporal lobe (where our ROI analysis had shown differences). However, use of a smaller smoothing kernel and a small volume correction revealed left-sided hippocampal group differences. Affective psychosis comparisons: When the same statistical thresholding criteria were used, no significant differences between affective psychosis patients and controls were noted. Since a major interest was whether patients with affective psychosis shared some anatomical abnormalities with schizophrenia, we applied a small volume correction and searched within the regions that were significantly less dense in schizophrenia compared to control subjects. With this statistical correction, the insula showed, bilaterally, the same pattern of differences in affective disorder subjects as that in schizophrenic subjects, whereas both left STG and left hippocampus showed statistical differences between affectives and schizophrenics, indicating the abnormalities specific to first-episode schizophrenia. These findings suggest both the promise and utility of VBM in evaluating gray matter abnormalities. They further suggest the importance of comparing VBM findings with more traditional ROI analyses until the reasons for the differences between methods are determined.

Objective: “Cognitive” circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. Method: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. Results: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. Conclusions: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.

Objective: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. Method: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. Results: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. Conclusions: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.

Background: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the “endophenotype” common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. Methods: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. Results: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. Conclusions: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum “endophenotype.” It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.

Objective: Previous research has noted functional and structural temporal lobe abnormalities in schizophrenia that relate to symptoms such as auditory hallucinations and thought disorder. The goal of the study was to determine whether the functional abnormalities are present in schizophrenia at early stages of auditory processing. Method: Functional magnetic resonance imaging activity was examined during the presentation of the mismatch stimuli, which are deviant tones embedded in a series of standard tones. The mismatch stimuli are used to elicit the mismatch negativity, an early auditory event-related potential. Ten patients with schizophrenia and 10 comparison subjects were presented the mismatch stimuli condition and a control condition in which only one tone was presented repeatedly. Results: The superior temporal gyrus showed the most prevalent and consistent activation. The superior temporal gyrus showed less activation in the schizophrenic subjects than in the comparison subjects only during the mismatch stimuli condition. Conclusions: This result is consistent with those of mismatch negativity event-related potential studies and suggests that early auditory processing is abnormal in chronic schizophrenia.

Objective: Recent evidence suggests that the cerebellum may play a role in higher cognitive functions and, therefore, may play an important role in schizophrenia. Method: The authors used magnetic resonance imaging to measure cerebellum and vermis volume in 15 patients with schizophrenia and 15 normal comparison subjects. Results: They found that 1) vermis volume was greater in patients with schizophrenia than in normal subjects, 2) greater vermis white matter volume in the patients with schizophrenia significantly correlated with severity of positive symptoms and thought disorder and with impairment in verbal logical memory, and 3) patients with schizophrenia showed a trend for more cerebellar hemispheric volume asymmetry (left greater than right). Conclusions: These data suggest that an abnormality in the vermis may contribute to the pathophysiology of schizophrenia.