Melissa Frumin

DTI and MTR abnormalities in schizophrenia: Analysis of white matter integrity

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Cingulate fasciculus integrity disruption in schizophrenia: a magnetic resonance diffusion tensor imaging study

Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.

White matter hemisphere asymmetries in healthy subjects and in schizophrenia: a diffusion tensor MRI study

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 limbs 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 neurodevelopmental abnormalities in schizophrenia.

Fornix Integrity and Hippocampal Volume in Male Schizophrenic Patients

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 (D(m)), 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. D(m) was significantly increased, whereas hippocampal volume was bilaterally reduced in patients. Reduced hippocampal volume was correlated with increased mean D(m) 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.

Neuropsychological Correlates of Diffusion Tensor Imaging in Schizophrenia

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.

Occipital lobe gray matter volume in male patients with chronic schizophrenia: A quantitative MRI study

Schizophrenia is characterized by deficits in cognition as well as visual perception. There have, however, been few magnetic resonance imaging (MRI) studies of the occipital lobe as an anatomically defined region of interest in schizophrenia. To examine whether or not patients with chronic schizophrenia show occipital lobe volume abnormalities, we measured gray matter volumes for both the primary visual area (PVA) and the visual association areas (VAA) using MRI based neuroanatomical landmarks and three-dimensional information. PVA and VAA gray matter volumes were measured using high-spatial resolution MRI in 25 male patients diagnosed with chronic schizophrenia and in 28 male normal controls. Chronic schizophrenia patients showed reduced bilateral VAA gray matter volume (11%), compared with normal controls, whereas patients showed no group difference in PVA gray matter volume. These results suggest that reduced bilateral VAA may be a neurobiological substrate of some of the deficits observed in early visual processing in schizophrenia.

Dissociable contributions of MRI volume reductions of superior temporal and fusiform gyri to symptoms and neuropsychology in schizophrenia

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.

Observations on evoked dendritic potentials of human cortex.

Abstract 1. 1. Stimulation of the exposed human cortex evokes a 15–20 msec. surface negative response which is identical to the synaptic potential of apical dendrites as recorded in the cat. 2. 2. The conduction velocity of horizontal fibers in the molecular layer is 0.5 m/sec. A central synaptic delay of 1 msec. is determined from conduction velocity studies with paired recording leads. 3. 3. Whereas human dendritic synapses are relatively resistant to locally injected d-tubocurarine, LSD inhibits dendritic activity in a manner similar to that observed in the cat. 4. 4. Variations in activity cycles of apical dendrites are believed to be accounted for by the interaction of opposing excitatory and inhibitory synaptic processes which determine overall dendritic responsiveness. 5. 5. Discussion has focused on the significance of the suggestive differences in the pharmacological and physiological organization of cortical synapses in man and cat as they relate to hypotheses of drug actions determined solely in the latter species.

A MRI study of fusiform gyrus in schizotypal personality disorder.

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.

PSYCHIATRIC AND BEHAVIORAL PROBLEMS

In an emergency setting, many neurologic conditions present with psychiatric and behavioral symptoms. These symptoms may either be the first manifestation of the neurologic illness or a later occurrence in the progression of the disease. It is important for clinicians evaluating patients with psychiatric symptoms to identify the signs indicating associated neurologic illness and to have strategies for managing the acute, potentially dangerous, neuropsychiatric manifestations of the disease. This article addresses emergency evaluation and management of depression, anxiety, psychosis, mania, suicide attempts, neuroleptic malignant syndrome and other hypermetabolic and amnestic syndromes, somatoform disorders, aggression, and legal issues, such as capacity to accept or refuse treatment.