Changes in regional cerebral blood flow during acute electroconvulsive therapy in patients with depression: positron emission tomographic study.

BACKGROUND: Although electroconvulsive therapy (ECT) is widely used to treat psychiatric disorders such as depression, its precise neural mechanisms remain unknown. AIMS: To investigate the time course of changes in cerebral blood flow during acute ECT. METHOD: Cerebral blood flow was quantified serially prior to, during and after acute ECT in six patients with depression under anaesthesia using [(15)O]H(2)O positron emission tomography (PET). RESULTS: Cerebral blood flow during ECT increased particularly in the basal ganglia, brain-stem, diencephalon, amygdala, vermis and the frontal, temporal and parietal cortices compared with that before ECT. The flow increased in the thalamus and decreased in the anterior cingulate and medial frontal cortex soon after ECT compared with that before ECT. CONCLUSIONS: These results suggest a relationship between the centrencephalic system and seizure generalisation. Further, they suggest that some neural mechanisms of action of ECT are mediated via brain regions including the anterior cingulate and medial frontal cortex and thalamus.

A comparison of the progression of early Parkinson's disease in patients started on ropinirole or L-dopa: an 18F-dopa PET study.

OBJECTIVE: To study the relative rates of progression of early Parkinson's disease (PD) in patients started on a dopamine agonist, ropinirole, or L-dopa. METHODS: A double-blind study of 45 early PD patients [mean age 61 +/- 9.8 SD and mean symptom duration, 26 +/- 16 SD months] randomized 2 : 1 (ropinirole : L-dopa). Supplementary L-dopa was allowed if, during the trial, there was lack of a therapeutic effect. (18)F-dopa PET scans were performed at baseline (n = 45) and 2 years (n = 37). RESULTS: At two years, the mean percentage reduction in putamen (18)F-dopa uptake (Ki(o)) was not significantly different between the two groups (13% ropinirole, n = 28 versus 18% L-dopa, n = 9). CONCLUSIONS: We found no significant overall difference in underlying PD progression, after two years treatment, between patients groups. In summary, (18)F-dopa PET can be employed to objectively evaluate the effect of potential neuroprotective agents on dopaminergic function.

Abnormal regional cerebral blood flow in childhood autism.

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Activity of midbrain reticular formation and neocortex during the progression of human non-rapid eye movement sleep.

To clarify the neural correlates and brain activity during the progression of human non-rapid eye movement (NREM) sleep, we examined the absolute regional cerebral blood flow (rCBF) during light and deep NREM sleep and during wakefulness in normal humans using positron emission tomography with H(2)(15)O. Relative changes in rCBF during light and deep NREM sleep in comparison to the rCBF during wakefulness were also analyzed. During light NREM sleep, the rCBF in the midbrain, in contrast to that in the pons and thalamic nuclei, did not decrease when compared to that during wakefulness, whereas rCBF decreased in the left medial frontal gyrus, left inferior frontal gyrus, and left inferior parietal gyrus of the neocortex. During deep NREM sleep, the rCBF in the midbrain tegmentum decreased, and there was a marked and bilateral decrease in the rCBF in all neocortical regions except for the perirolandic areas and the occipital lobe. There have been three groups of brain structures, each representing one type of deactivation during the progression of NREM sleep. The activity of the midbrain reticular formation is maintained during light NREM sleep and therefore represents a key distinguishing characteristic between light and deep NREM sleep. Selective deactivation of heteromodal association cortices, including those related to language, occurs with increasingly deep NREM sleep, which supports the recent theory that sleep is not a global, but it is a local process of the brain.

Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study.

We have studied focal changes in dopaminergic function throughout the brain volume in early and advanced Parkinson's disease by applying statistical parametric mapping (SPM) to 3D [(18)F]dopa-PET. Data from seven early hemi-Parkinson's disease and seven advanced bilateral Parkinson's disease patients were compared with that from 12 normal controls. Parametric images of [(18)F]dopa influx rate constant (K(i)(o)) were generated for each subject from dynamic 3D [(18)F]dopa datasets and transformed into standard stereotactic space. Significant changes in mean voxel [(18)F]dopa K(i)(o) values between the normal control group and each Parkinson's disease group were localized with SPM. Conventional region of interest analysis was also applied to comparable regions on the untransformed image datasets. In early left hemi-Parkinson's disease, significant extrastriatal increases in [(18)F]dopa K(i)(o) were observed in the left anterior cingulate gyrus and the dorsal midbrain region (P < 0.05, corrected) along with decreases in striatal [(18)F]dopa K(i)(o). In advanced Parkinson's disease, significant extrastriatal decreases in [(18)F]dopa K(i)(o) were observed in the ventral and dorsal midbrain regions (P < 0.05, corrected). No significant changes in [(18)F]dopa K(i)(o) were observed in the anterior cingulate region. In a direct comparison between the early and late Parkinson's disease groups, we observed relative [(18)F]dopa K(i)(o) reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal [(18)F]dopa K(i)(o) reductions. Similiar results were found with a region of interest approach, on non-transformed data, except for the focal midbrain [(18)F]dopa K(i)(o) increase seen in early Parkinson's disease. In conclusion, using SPM with [(18)F]dopa-PET, we have objectively localized changes in extrastriatal, pre-synaptic dopaminergic function in Parkinson's disease. The significance of the increased dopaminergic activity of anterior cingulate in early Parkinson's disease remains unclear, but may be compensatory. The [(18)F]dopa signal in dorsal midbrain and pontine regions suggests that [(18)F]dopa is taken up by serotonergic and noradrenergic neurons which also degenerate in advanced Parkinson's disease. This suggests, therefore, that Parkinson's disease is a monoaminergic neurodegenerative disorder.

Statistical parametric mapping with 18F-dopa PET shows bilaterally reduced striatal and nigral dopaminergic function in early Parkinson's disease.

OBJECTIVE: To apply statistical parametric mapping to 18F-dopa PET data sets, to examine the regional distribution of changes in dopaminergic metabolism in early asymmetric Parkinson's disease. METHODS: Thirteen normal volunteers (age 57.7 (SD 16.5) years; four women, nine men ) and six patients (age 50.3 (SD 13.5) years; three women, three men) with asymmetric (right sided) Parkinson's disease were studied. Images from each dynamic dopa PET dataset were aligned and parametric images of 18F-dopa influx (Ki) were created for each subject. The Ki images were transformed into standard stereotactic space. The Ki values of the caudate and putamen on spatially normalised images were compared with the Ki values before normalisation. The application of statistical parametric mapping (SPM) allowed statistical comparison of regional Ki values on a voxel by voxel basis between healthy volunteers and patients with Parkinson's disease. RESULTS: There was a strong correlation between the Ki values before and after spatial normalisation (r=0.898, p=0.0001). Significant decreases in the Ki values were found for the Parkinson's desease group throughout the entire left putamen (p< 0.001) and focally in the dorsal right putamen (p<0.001). Decreased Ki values were also shown bilaterally in the substantia nigra (p< 0.01). CONCLUSION: Using (SPM) and 18F-dopa PET, reductions in both striatal and nigral brain dopaminergic function could be demonstrated in early Parkinson's disease.

Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study.

Patients with Parkinson's disease have great difficulty in performing sequential and bimanual movements. We used H2(15)O PET to study the regional cerebral blood flow associated with performance of sequential finger movements made unimanually and bimanually in a group of Parkinson's disease patients and a group of control volunteers. In controls, sequential finger movements led to activation of the contralateral motor cortex and inferior parietal cortex (Brodmann area 40), the lateral premotor cortex and bilateral supplementary motor area. No prefrontal activation was seen. Sequential finger movements in the Parkinson's disease group were associated with a similar pattern of activation but there was relative impairment of activation in the mesial frontal and prefrontal areas. A novel finding was the presence of relative overactivity in the lateral premotor and inferolateral parietal regions. We conclude that in Parkinson's disease there is a switch from the use of striato-mesial frontal to parietal-lateral premotor circuits in order to facilitate performance of complex finger movements.

Prevalence of senile dementia in Okinawa, Japan. COSEPO Group. Study Group of Epidemiology for Psychiatry in Okinawa.

METHODS. The prevalence of dementia was investigated in Okinawa Prefecture, Japan. In all, 3524 subjects, > or = 65 years old, were sampled randomly (urban and rural populations 61.1% and 38.9% respectively). Phase 1 of the survey was carried out by specially trained students of the Faculty of Medicine who used the Mini-Mental State (MMS) scale (interview rate: 94.3%) to screen 522 (15.8%) of the 3312 subjects for the phase 2 survey. Phase 2, conducted by psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria, detected 172 cases of dementia. RESULTS. The estimated prevalence of dementia was 6.7%. For women, the rate increased sharply in the 90-99 year old group, and was 41.4%; for men in the 90-99 year old group prevalence was 21.2%. The ratio of Alzheimer-type dementia to multi-infarct dementia was 1.5:1 (men 1.2:1, women 1.7:1). The breakdown of the severity of dementia in the total cases was: mild 16.9%, moderate 30.8%, and severe 52.3%. The number of severe cases increased with age.

Correlation between event-related potentials and MR measurements in chronic alcoholic patients.

Event-related potentials were recorded in 25 abstinent alcoholics, and 25 gender- and age-matched controls during a two-tone discrimination (odd ball) task. All the subjects were free from medication and dextral. MR images were examined in the alcoholics. The amplitudes of N100, N200 and P300 in the alcoholics were reduced compared with those of the controls. In order to identify morphological changes responsible for ERP abnormalities, linear regression analyses were performed between ERP measures and MRI parameters. The amplitude of N100 was inversely correlated with ventricular size. The amplitudes of P300 were inversely correlated with both ventricular size and width of cortical sulci. It was suggested that the N100 abnormality was related to subcortical structure, and P300 alteration was related to both subcortical and cortical structures in the alcoholics.

Major depressive episode and low dose dexamethasone suppression test.

The authors studied the validity of a low dose (0.5 mg) dexamethasone suppression test (DST) in identifying depression. Nine patients who met the criteria of major depressive episode (MDE) in the Diagnostic and Statistical Manual of Mental Disorders, another nine psychiatric patients and one normal subject underwent the DST. At least one of the two blood samples obtained either at 8 a.m. or at 2 p.m. from each of the nine patients with MDE showed a cortisol concentration of over 5.0 micrograms/dl, while the cortisol concentration in the other 10 subjects was uniformly suppressed under this level. All the patients with MDE could be identified by nonsuppression of the cortisol secretion at 8 a.m. or at 2 p.m. An "early escape" phenomenon in depressed patients reported by Carroll et al. (1976) was absent in a 0.5 mg DST, and the blood samples at 8 p.m. were less useful for identifying the depressive patient. The reason why the one point sampling method used by previous investigators was insufficient to identify the depressed patient was discussed.