Tsechung Wei

d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered patients in metabolite and pharmacologic challenge studies. This study used positron emission tomography to explore whether reduced serotonergic function occurs in critical brain regions such as orbital frontal and cingulate cortex that may play a role in modulating aggression. Six impulsive-aggressive patients and five healthy volunteers were evaluated for changes in regional glucose metabolism after administration of the serotonergic releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers demonstrated increases in orbital frontal and adjacent ventral medial frontal cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive patients showed no significant increases in glucose metabolism after fenfluramine in any region. Compared with volunteers, patients showed significantly blunted metabolic responses in orbital frontal, adjacent ventral medial and cingulate cortex, but not in inferior parietal lobe. These results are consistent with reduced serotonergic modulation of orbital frontal, ventral medial frontal, and cingulate cortex in patients with impulsive-aggressive personality disorders.

Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder

The size and shape of the corpus callosum were assessed on sagittal section magnetic resonance images in 27 patients with schizophrenia, 13 patients with schizotypal personality disorder (SPD), and 30 healthy volunteers. High-resolution 1.2mm axial SPGR images were acquired and resectioned so that the sagittal plane passed through the anterior and posterior commissures and was parallel to the interhemispheric fissure. The corpus callosum and the whole brain were traced on midsagittal section slices of each brain, and the callosum was divided into 30 anteroposterior sectors. Pixel-by-pixel chi-square and thin-plate spline analyses were used to assess between-group shape differences. Size of the corpus callosum was smaller anteriorly in the genu of the corpus callosum and posteriorly in the splenium in schizophrenic patients than in normal controls. The genu of the corpus callosum was larger in SPD patients than in schizophrenic patients or normal controls. The posterior corpus callosum was largest in normal controls, smaller in SPD patients, and smallest in schizophrenic patients. Shape analysis was consistent with these size comparisons, and suggested a downward bowing of the corpus callosum in schizophrenic and SPD patients. SPD patients also had a region of the callosum just posterior to the genu that was narrower than in the other two groups. The decreases in corpus callosal size in schizophrenia varied directly with length of illness, perhaps indicative of a progressive process. The patient-control differences in callosal size and shape are consistent with a hypothesis of decreased connectivity between the left and the right hemispheres in schizophrenia and SPD.

Whole-brain diffusion MR histograms differ between MS subtypes

Objective: To determine whether quantitative whole-brain MR diffusion histograms in patients with MS differ from those of normal control subjects. Background: MRI detects macroscopic cerebral lesions in MS, but the white matter lesion burden on MRI correlates imperfectly to clinical disability. Previous reports have further suggested abnormalities in white matter of MS patients with no visible lesions on conventional MRI. Methods: A total of 25 subjects (13 with MS [9 relapsing–remitting, 4 secondary progressive] and 12 healthy control subjects) underwent diffusion-weighted echoplanar MRI encompassing the entire brain. The average apparent diffusion coefficient (ADCave, or diffusion trace) was calculated on a pixel-by-pixel basis after segmentation of intracranial space from calvarium and extracranial soft tissues. Whole-brain ADCave histograms were calculated and plotted for statistical comparison. Results: Mean whole-brain MR ADCave in MS patients was elevated and histograms were shifted to higher values compared with normal control subjects. Mean whole-brain ADCave of secondary progressive patients was shifted to higher values compared with relapsing–remitting patients. Whole-brain ADCave histograms of relapsing–remitting patients showed no significant difference from normal control subjects. Conclusion: Whole-brain MR diffusion histograms may quantitate overall cerebral lesion load in patients with MS and may be able to discern differences between clinical subgroups.

Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging

Magnetic resonance imaging (MRI) was performed in 12 patients with schizotypal personality disorder (SPD), 11 patients with chronic schizophrenia, and 23 age- and sex-matched normal volunteers. MRI slices were acquired in the axial plane at 1.2-mm intervals, and the ventricles were traced on every other slice. The lateral ventricular system was divided into the anterior horn, temporal horn, and dorsal lateral ventricle. Schizophrenic patients had larger left anterior and temporal horns than the normal volunteers. Size of the left anterior and temporal horn in SPD patients was intermediate between those of normal volunteers and schizophrenic patients and differed significantly from schizophrenic patients. The left-minus-right difference was larger in schizophrenic patients than in normal volunteers or SPD patients. Thus, in their structural brain characteristics, as well as in their clinical symptomatology, SPD patients evidence, in attenuated form, abnormalities resembling those found in full-fledged schizophrenia. The findings suggest that decreased left hemispheric volume, in frontal and temporal regions, may characterize both psychotic and non-psychotic disorders of the schizophrenia spectrum.

Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study

BACKGROUND Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. METHODS Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. RESULTS Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. CONCLUSIONS These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia.

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.

Visualizing fronto-striatal circuitry and neuroleptic effects in schizophrenia.

Disturbances in fronto‐striatal circuitry have been postulated to be important in schizophrenia. Positron emission tomography typically shows decreased metabolic rates in these areas relative to other brain areas in schizophrenia. After treatment with typical neuroleptics, striatal metabolic rates are increased, but other brain areas tend not to show significant changes. Atypical neuroleptics less markedly affect striatal metabolic rates, but show wider cortical effects. In order to examine fronto‐striatal circuitry, a technique for visualizing the correlations between metabolic rates in all brain areas was applied in 33 controls and 27 unmedicated schizophrenic patients. Correlation images revealed strong fronto‐striatal connections in controls, but weak fronto‐striatal links in schizophrenic patients. Changes in striatal circuits, also reflected in recent anatomical studies, may be important for understanding antipsychotic effects.

Hemispheric asymmetry for selective attention

A letter-identification task, previously demonstrated to show activation of the pulvinar nucleus of the thalamus with fluodeoxyglucose position emission tomography, was administered to 20 normal volunteers. The letter to be detected could appear alone as a big stimulus or as a small one stimulus surrounded by flanking letters. To test for a hemispheric specialization for filtering processes, the stimuli were displayed horizontally, either in the left or in the right hemifield, or vertically, either above or below the fixation point. In addition, to study the effect of cognitive processes on selective attention resources, we varied the feedback conditions, by delivering or not delivering a blue flash in cases of misses or mistakes. The results show a significant interaction between the type of stimulus (alone or surrounded by flankers) and the hemifield of presentation (left or right) only in the condition where the subjects were presented stimuli horizontally without any feedback. In this condition, reaction times (RTs) were shorter in the left hemifield than in the right hemifield for single stimuli, whereas for stimuli surrounded by flankers, the opposite pattern was observed, that is, shorter RT in the right hemifield than in the left one. The present findings suggest a hemispheric specialization for selective attention, in particular at the subcortical level.

Kraepelinian and non-Kraepelinian schizophrenia subgroup differences in cerebral metabolic rate

We studied two subtypes of schizophrenia. the Kraepelinian subtype (n = 10) characterized by an unremitting and severe course and the non-Kraepelinian subtype (n = 17) characterized by a remitting course and some periods of self-care. Patients were assessed with positron emission tomography (PET) with 18F-deoxyglucose (FDG) and high-resolution magnetic resonance imaging (MRI). A group of 32 age- and sex-matched normal volunteers served as comparison subjects. During the FDG tracer uptake period, patients performed a serial verbal learning task. MR images were segmented into gray, white and cerebrospinal fluid regions, and warped to average normal coordinates. PET images were coregistered to the MR images and similarly warpedfor analysis. Kraepelinian subtype patients were characterized by lower metabolic rates in the temporal lobe and cingulategyrus. and lower fronto/occipital ratios than non-Kraepelinian subtype patients. Exploratory statistical probability mapping alsorevealed lower metabolic rates in the right striatum in Kraepelinian versus non-Kraepelinian patients. These differences couldnot be attributed to differences in age, symptom severity, task performance during FDG uptake, or severity of involuntary movements. Factor analysis of the cortical surface identified significantly lower temporal lobe metabolic rates in Kraepelinian patients than non-Kraepelinian patients. A combined frontal/temporal deficit or greater cortical change may be associated with poorer longitudinal course.

A method of basal forebrain anatomical standardization for functional image analysis

Functional as well as structural assessment of the basal forebrain has mostly focused on the dorsal caudate and putamen in axial slices where they are easily outlined or their centers located with stereotaxic methods. The more ventral extent of the basal forebrain, where the irregular form and indistinct boundaries of the nucleus accumbens and substantia innominata are difficult to trace and where the brains ventral surface may contribute partial volume artifacts to measurement, has been less studied. We present a method based on coronal sections, landmarks placed on clearly visible anchor points, and the computational technique of thin-plate spline warping which allows the alignment of groups of individuals to common coordinates for pixel-by-pixel statistical mapping. The reliability of the landmarks across independent raters yields a median absolute difference of 1.3-1.6 mm. The validity of the method is confirmed by variance maps which reveal significant decreases in variance over spindle and bounding box alignment.