A volumetric magnetic resonance imaging study of monozygotic twins discordant for bipolar disorder.

Six monozygotic (MZ) twin pairs discordant for bipolar disorder were compared with normal MZ twins with magnetic resonance imaging (MRI) on volumes of basal ganglia (BG), amygdala-hippocampus (AH), and cerebral hemisphere. Caudate nuclei were larger in both affected and unaffected bipolar twins than in normal MZ twins. The right hippocampus was smaller in the sick vs. well bipolar twins. The hippocampus was also less asymmetric in the affected bipolar twins than in the well cotwins and the normal MZ twins. These anatomical structures continue to be of interest in bipolar disorder research.

Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study.

OBJECTIVE: The temporal lobe and associated structures have been previously implicated in the neuroanatomy of schizophrenia. This study was designed to assess the potential influence of gender on the morphology of temporal lobe structures, including the superior temporal gyrus and the amygdala/hippocampal complex, in patients with schizophrenia and to examine whether schizophrenic patients differ morphologically in these structures from comparison subjects. METHOD: Magnetic resonance imaging was used to measure the volume of temporal lobe structures, including the superior temporal gyrus, the amygdala/hippocampal complex, and the temporal lobe (excluding the volumes of the superior temporal gyrus and amygdala/hippocampal complex), and two comparison areas--the prefrontal cortex and caudate--in 36 male and 23 female patients with schizophrenia and 19 male and 18 female comparison subjects. RESULTS: There was a significant main effect of diagnosis in the superior temporal gyrus and the amygdala/hippocampal complex, with smaller volumes in patients than in comparison subjects. There was a significant gender-by-diagnosis-by-hemisphere interaction for temporal lobe volume. Temporal lobe volume on the left was significantly smaller in male patients than in male comparison subjects. Female patients and female comparison subjects demonstrated no significant difference in temporal lobe volume. There were no statistically significant gender interactions for the superior temporal gyrus, the amygdala/hippocampal complex, or the comparison regions. CONCLUSIONS: These findings suggest that there may be a unique interaction between gender and the pathophysiologic processes that lead to altered temporal lobe volume in patients with schizophrenia.

Structural evaluation of the prefrontal cortex in schizophrenia.

OBJECTIVE: Altered prefrontal cortical function has been repeatedly implicated in the pathophysiology of schizophrenia. Attempts to determine whether this altered function is associated with structural changes in the prefrontal cortex have been hampered by the failure to examine more anatomically and functionally homogeneous regions. The authors have developed a reliable set of anatomical landmarks for subdividing the prefrontal cortex into superior, middle, inferior, and orbital regions, in order to determine whether patients with schizophrenia exhibit selective morphological abnormalities of the prefrontal cortex. METHOD: Magnetic resonance imaging (MRI) studies were obtained in 24 normal control subjects (14 men and 10 women) and 18 patients with schizophrenia (12 men and six women) by using a high-resolution thin spoiled-gradient recall acquisition in the steady-state protocol. The MRI images were used to determine prefrontal gray matter volumes for the four prefrontal regions and prefrontal total gray and white volumes. RESULTS: Patients with schizophrenia exhibited selective gray matter volume reductions in the right and left inferior prefrontal cortex. There were no significant group differences in the other prefrontal regions. Patients with schizophrenia also exhibited decreased prefrontal total white matter and total volumes; there was no significant difference in prefrontal total gray matter volume. CONCLUSIONS: Patients with schizophrenia are characterized by relatively selective reductions in inferior prefrontal cortex gray matter volumes.

Superior temporal gyrus volume in schizophrenia: a study using MRI morphometry assisted by surface rendering.

OBJECTIVE: Interpretation of the literature concerning superior temporal gyrus volume in patients with schizophrenia is complicated by methodological variation between studies and by the difficulty of identifying gyral boundaries in serial sections. METHOD: With the aid of three-dimensional cortical renderings, the authors developed a morphometric approach in which information from the cortical surface is incorporated into gyral boundary decisions. Using this technique, they assessed superior temporal gyrus volume in young, right-handed male patients with schizophrenia and in right-handed male comparison subjects. They also compared their technique with existing slice-based morphometric methods by using previously reported subcortical landmarks to define the gyral boundaries. RESULTS: There was no significant main effect of diagnosis and no significant diagnosis-by-hemisphere interaction. Significant leftward laterality was present only among comparison subjects. Leftward superior temporal gyrus laterality did not correlate with leftward laterality of the planum temporale. No significant reduction in superior temporal gyrus volume was revealed in the patients. No significant leftward laterality was detected with the slice-based technique, suggesting that a significant portion of superior temporal gyrus tissue is omitted with this approach. The lack of findings could not be explained by a general absence of morphometric abnormalities in this group of subjects because the patients had significantly larger lateral ventricles. CONCLUSIONS: Significant reduction in the superior temporal gyrus volume was not confirmed in this group of patients with schizophrenia, probably because of the small effect size of this finding. Methodological variation is an important factor in determining superior temporal gyrus volume on magnetic resonance imaging scans.

The functional neuroanatomy of Tourette's syndrome: an FDG-PET Study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness.

We analyzed F-18 fluoro-deoxyglucose PET scans carried out in 18 drug-free patients with Tourette's syndrome (TS) in order to evaluate relationships between cerebral metabolism and complex cognitive and behavioural features commonly associated with this disorder. These features (obsessions and compulsions, impulsivity, coprolalia, self-injurious behavior, echophenomena, depression, and measures of attentional and visuospatial dysfunction) were associated with significant increases in metabolic activity in the orbitofrontal cortices. Similar increases, although less robust, were observed in the putamen and, in the case of attentional and visuospatial measures, in the inferior portions of the insula. On the other hand, behavioral and cognitive features were not associated with metabolic rates in other subcortical (midbrain, ventral striatum), paralimbic (parahippocampal gyrus), or sensorimotor regions (supplementary motor area, lateral premotor or Rolandic cortices), in which metabolism had, in some cases more robustly, distinguished these TS patients from controls (Braun et al., 1993). These results suggest that a subset of regions in which metabolic activity appears to be associated with the diagnosis of TS per se, may be explicitly associated with the emergence of complex behavioral and cognitive features of the illness. This is most conspicuous in the orbitofrontal cortices, and it is consistent with the observation that these features resemble the elements of a behavioral syndrome typically seen in patients with lesions of the orbitofrontal cortex.

Normal asymmetry of the planum temporale in patients with schizophrenia. Three-dimensional cortical morphometry with MRI.

BACKGROUND: Abnormal cerebral anatomical lateralisation has been reported in schizophrenia and may implicate anomalous neurodevelopment in the aetiology of this disease. A popular recent hypothesis has predicted that such disturbances in normal lateralisation should be especially apparent in the morphology of the temporal lobes. METHOD: A temporal cortical region lying in the plane of the Sylvian fissure--known as the planum temporale--exhibits pronounced leftward asymmetry in normal right-handed males. We compared lateralisation of the planum temporale in schizophrenic and control males using MRI surface-rendering morphometry of the supratemporal cortex. RESULTS: Contrary to the lateralisation hypothesis, normal patterns of leftward planum asymmetry were detected in both the schizophrenic and control groups. Schizophrenics and controls also exhibited a predicted symmetry in the bilateral areas of Heschl's gyrus, a supratemporal cortical structure immediately anterior to the planum. CONCLUSION: These data do not support the notion that neurodevelopmental mechanisms of cerebral asymmetry are abnormal in schizophrenia.

Gender differences in the normal lateralization of the supratemporal cortex: MRI surface-rendering morphometry of Heschl's gyrus and the planum temporale.

Gender differences in hemispheric asymmetry for language functioning have been reported in the neuropsychological literature. Despite numerous reports of anatomic asymmetries in corresponding cortical regions, the possibility of gender dimorphism in the putative neuroanatomical substrate of language has not been systematically examined in vivo. We assessed asymmetry of the planum temporale (PT), a supratemporal region of auditory association cortex, in 12 normal, right-handed females and 12 age-matched right-handed males with the aid of MRI surface-rendering morphometry. Bilateral areas were also assessed for Heschl's gyrus (HG), a supratemporal region of primary auditory cortex where no asymmetry was anticipated. We found a significant interaction between gender and hemisphere for the PT, with males having significantly larger left versus right PTs. Left-right differences in PT area were not significant among females (10 of 12 males showed leftward lateralization of the PT, vs 5 of 12 females). No main effect of gender was found for total (left + right) PT area, and no asymmetries or gender effects were detected for HG. This finding of gender dimorphism in PT area is consistent with evidence for reduced asymmetry among females in the lateralization of language functions attributable to the supratemporal cortex. The implications for theories about interactions between sex hormones and the development of brain asymmetries are discussed.

The functional neuroanatomy of Tourette's syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls.

Regional metabolic rates for glucose estimated using [18F]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain. These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness.

Effects of ibotenic acid lesion of the medial prefrontal cortex on dopamine agonist-related behaviors in the rat.

Behavioral responses to apomorphine and to the selective D1 and D2 dopamine receptor agonists SK&F38393 and quinpirole were evaluated in rats following ibotenic acid (IA) or sham lesion of the medial prefrontal cortex (MPFC). IA-lesioned rats showed an increased responsiveness to the postsynaptic effects of all of the dopamine agonists. Patterns of the responses to the selective agonists administered alone and in combination suggest that these effects might be due to selective increases in the sensitivity of postsynaptic D1 receptor-associated mechanisms. In addition, IA-lesioned rats pretreated with saline were hyperactive in comparison to sham-lesioned rats when animals were exposed to a novel open field, but spontaneous motor activity did not differ between these two groups when animals were pretreated with low doses (0.03 mg/kg) of quinpirole. The fact that hyperreactivity observed in lesioned animals is inhibited by a dose of quinpirole that is felt to act presynaptically, selectively attenuating endogenous dopaminergic tone, suggests that effects of the MPFC lesion may be mediated presynaptically as well.

Three-dimensional surface rendering in MRI morphometry: a study of the planum temporale.

OBJECTIVE: The emergence of methodologies for accurately rendering cortical surfaces suggests possible quantitative applications of surface rendering to morphometry of the cerebral cortex. We examined this novel use of surface renderings in a study of the planum temporale, a neuroanatomical structure exhibiting well-documented normal asymmetry previously visible only in postmortem studies. MATERIALS AND METHODS: With the aid of three-dimensional renderings of the supratemporal cortex, the area of the planum temporal was analyzed in the volume MRIs of seven normal, strongly right-handed males. RESULTS: In comparison with areas derived from conventional measurements of serial MRI sections, planum temporale areas derived from supratemporal surface renderings offered far greater interrater reliability, and presumably improved validity as reflected by more consistent evidence of the anticipated planum asymmetry. CONCLUSION: Morphometry of the supratemporal cortex is enhanced by the use of three-dimensional surface renderings. Application of surface-rendering techniques to morphometry of other cortical regions is discussed.

Pimozide treatment for delusion of infestation.

Pimozide was tried in the treatment of delusion of parasitosis (a type of monosymptomatic hypochondriacal psychosis), a syndrome that is found with increasing frequency. Ten patients were selected on the basis of unambiguously defined psychopathological criteria. Pimozide therapy was assessed by means of placebo control and the double-blind method using a rating scale evolved for this particular therapy. The results have quite definitely proved the effect of small doses (two to eight mg per day) of pimozide compared to the administration of a placebo. The very few side-effects observed could easily be influenced. The dynamics of the regression of the psychopathological symptoms suggest that the efficacy of pimozide therapy is decisively linked to the central dopamine receptor blocking effect of the drug.