Publications

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.

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 gamma band (30-100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use gamma-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 gamma-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.

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.

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.

A high prevalence of abnormal cavum septi pellucidi (CSP) in schizophrenia may reflect neurodevelopmental abnormalities in midline structures of the brain. The relationship, however, between abnormal CSP and clinical symptoms, and with abnormalities in other limbic structures remains unclear, as does the question of whether a similar abnormality is present in affective psychosis. Seventy-four patients at their first hospitalization, 33 with schizophrenia and 41 with affective (mainly manic) psychosis, and 56 healthy control subjects underwent high-spatial-resolution magnetic resonance imaging (MRI). CSP on six slices or more on 0.9375-mm resampled coronal images was categorized as abnormal. The prevalence of abnormal CSP in both schizophrenic patients (26.1%) and affective psychosis patients (18.2%) was significantly higher than was observed in control subjects (8.2%). In schizophrenic patients only, larger CSP was significantly associated with more severe thinking disturbance and smaller left parahippocampal gyrus gray matter volumes. While the relationships between CSP ratings and clinical symptoms did not significantly differ between the two psychosis groups as assessed by the comparison of regression slopes, the association with limbic volumes appeared to be specific to schizophrenic patients. These results suggest that psychosis associated with schizophrenia and affective disorder share, at least to some extent, neurodevelopmental abnormalities involving midline structures and associated psychopathological consequences. However, the association between abnormal CSP and limbic systems may be more specific to schizophrenia.

In NMR diffusometry, one often uses the short gradient pulse (SGP) limit approximation in the interpretation of data from systems with restricted diffusion. The SGP limit approximation means that the gradient pulse length, delta, is so short that the spins do not diffuse during the pulse duration, but this condition is rarely met. If the length scale of the pores corresponds to the molecular mean square displacement during the gradient pulse, the measured echo intensities become a function of the gradient pulse length. Here, we have studied highly concentrated emulsions to show how the length of the gradient pulse influences NMR diffusion experiments. We have focused on molecules confined to one pore and molecules that can migrate through the porous system. For the former the echo decays give smaller pores than the actual case and for the latter we show large changes in echo decay depending on the gradient pulse length, everything else being equal.

OBJECTIVE: The P300 event-related potential shows anterior P300 increases on NoGo tasks (target stimulus=withhold response) relative to Go tasks (target stimulus=commit response). This ’NoGo anteriorization’ has been hypothesized to reflect response inhibition. However, silent-count tasks show similar P300 anteriorization. The P300 anteriorization on silent-count tasks relative to Go tasks cannot reflect inhibition-related processes, and questions the degree to which anteriorization observed on NoGo trials can be ascribed to response inhibition. Comparison of anteriorization between the silent-count and NoGo tasks is thus essential. P300 topography on NoGo and silent-count tasks has not been previously compared. METHODS: P300 on Go, NoGo, and silent-count auditory oddball tasks were compared. If the NoGo P300 anteriorization reflects response inhibitory processes, the NoGo P300 should be larger anteriorly than the Go P300 (overt responses) and the silent-count P300s (covert responses). If anteriorization primarily reflects negative voltage Go task motor activity that reduces the normal frontal P300 amplitude, then the Go task P300 should be smaller than both the NoGo and silent-count P300s, which should not differ from one another. RESULTS: The Go task elicited a bilaterally reduced frontal P300 and asymmetrical frontal P300 relative to both the NoGo and silent-count tasks. The NoGo task P300 and silent-count task P300 showed similar amplitude and topography. P300 and slow wave on the NoGo task were not asymmetrical. CONCLUSIONS: The increased frontal P300 in NoGo tasks cannot be attributed solely to a positive-going inhibitory process, but likely reflects negative voltage response execution processes on Go trials. However, the alternative explanation that memory-related processes increase the silent-count P300 anteriorly to the same degree as NoGo inhibitory processes cannot be ruled out.

The reaction of Ln(BH(4))(3)(THF)(3) or LnCl(3)(THF)(3) with 1 equiv of KCp*’ ligand (Cp’ = C(5)Me(4)n-Pr) afforded the new monocyclopentadienyl complexes Cp*’LnX(2)(THF)(n) (X = BH(4), Ln = Sm, n = 1, 1a, Ln = Nd, n = 2, 1b; X = Cl, Ln = Sm, n = 1, 3a) and [Cp*’LnX(2)](n’) (X = BH(4), n’ = 6, Ln = Sm, 2a, Ln = Nd, 2b; X = Cl, Ln = Nd, 4b). All these compounds were characterized by elemental analysis and (1)H NMR. Crystals of mixed borohydrido/chloro-bridged [Cp*’(6)Ln(6)(BH(4))(12-x))Cl(x)(THF)(n’)] (x = 10, n’ = 4, Ln = Sm, 2a’, Ln = Nd, 2b’; x = 5, n = 2, Ln = Sm, 2a’ ’) were also isolated. Compounds 2a, 2b, 2a’, 2b’, and 2a’’ were structurally characterized; they all exhibit a hexameric structure in the solid state containing the [Cp*(3)Ln(3)X(5)(THF)] building block. The easy clustering of THF adducts first isolated is illustrative of the well-known bridging ability of the BH(4) group. Hexameric 2a was found to be unstable in the presence of THF vapors; this may be correlated to the opening of unsymmetrical borohydride bridges observed in the molecular structure.

The goal of this study is to assess the predictive capacity of computational models of transvenous defibrillation by comparing the results of patient-specific simulations to clinical defibrillation thresholds (DFT). Nine patient-specific models of the thorax and in situ electrodes were created from segmented CT images taken after implantation of the cardioverter-defibrillator. The defibrillation field distribution was computed using the finite volume method. The DFTs were extracted from the calculated field distribution using the 95% critical mass criterion. The comparison between simulated and clinical DFT energy resulted in a rms difference of 12.4 J and a 0.05 correlation coefficient (cc). The model-predicted DFTs were well matched to the clinical values in four patients (rms = 1.5 J; cc = 0.84). For the remaining five patients the rms difference was 18.4 J with a cc = 0.85. These results suggest that computational models based soley on the critical mass criterion and a single value of the inexcitability threshold are not able to consistently predict DFTs for individual patients. However, inspection of the weak potential gradient field in all nine patients revealed a relationship between the degree of dispersion of the weak field and the clinical DFT, which may help identify high DFT patients.