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Background: Patients with chronic fatigue syndrome (CFS) and depressive illness share many, but not all, features.Aims: To test the hypothesis that patients with CFS have abnormal cerebral perfusion, that differs from that in patients with depressive illness.Method: We recruited 30 patients with CFS who were not depressed, 12 depressed patients and 15 healthy volunteers. Regional cerebral perfusion at rest was assessed using region of interest (ROI) and voxel-based statistical parametric mapping (SPM) techniques.Results: On SPM analysis there was increased perfusion in the right thalamus, pallidum and putamen in patients with CFS and in those with depressive illness. CFS patients also had increased perfusion in the left thalamus. Depressed patients differed from those with CFS in having relatively less perfusion of the left prefrontal cortex. The results were similar on ROI analysis.Conclusions: Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to those in patients with depressive illness. Thalamic overactivity may be a correlate of increased attention to activity in CFS and depression; reduced prefrontal perfusion in depression may be associated with the greater neuropsychological deficits in that disorder. [ABSTRACT FROM AUTHOR]

Background: Imaging studies in depression of the elderly are often small and highly selective.Aims: To investigate a large group of elderly depressed patients in order to assess changes in clinical, imaging and neuropsychological variables at follow-up.Method: Patients (n = 175, age range 65-91 years) with clinical depression were identified from consecutive local referrals. Clinical interviews, neuropsychological tests and SPECT scans were carried out at referral and at two-year follow-up.Results: Of 84 re-examined patients, 46.5% were well, 9.5% were ill, 33% partially recovered and 11% had developed dementia. Duration of illness before index assessment was the only factor to predict outcome. Thirty-nine patients could be scanned and followed up. There were no differences between patients with good or poor depressive outcome on SPECT. Ten clinically improved patients could be re-examined with SPECT. There were relative increases in right cingulate gyrus and right cerebellum at follow-up.Conclusions: The patients group was comparable with other studies showing high levels of residual depressive symptoms. Activity changes in limbic cortex are implicated in depression of old age. [ABSTRACT FROM AUTHOR]

Background: The use of MDMA ('ecstasy') is common among young people in Western countries. Animal models of MDMA toxicity suggest a loss of serotonergic neurons, and potentially implicate in the development of significant psychiatric morbidity in humans.Aims: To test whether long-term use of MDMA can produce abnormalities in cerebral serotonin, but not dopamine, transporter binding measured by single photon emission computed tomography (SPECT).Method: Ten male regular ecstasy users and 10 well-matched controls recruited from the same community sources participated in SPECT with the serotonin transporter (SERT) ligand [123I] beta-CIT. Dopamine transporter binding was determined from scans acquired 23 hours after injection of the tracer.Results: Ecstasy users showed a cortical reduction of SERT binding, particularly prominent in primary sensory-motor cortex, with normal dopamine transporter binding in lenticular nuclei.Conclusions: This cross-sectional association study provides suggestive evidence for specific, at least temporary, serotonergic neurotoxicity of MDMA in humans. [ABSTRACT FROM AUTHOR]

Background: The aetiology of treatment-resistant major depression is little understood; its apparent intractability may reflect brain abnormality.Method: Magnetic resonance images of the brains of 20 subjects with major depression lasting for two years or more were compared with 20 healthy control subjects and 20 other subjects who had completely recovered from depression. Subjects were individually matched for age, gender, years of education and premorbid IQ. Grey matter was segmented from the images, and compared between groups on a voxel-by-voxel basis.Results: Subjects with chronic depression showed reduced grey matter density in the left temporal cortex including the hippocampus. There was also a trend for reduction in the right hippocampus. Left hippocampal grey matter density was correlated with measures of verbal memory, supporting the functional significance of the observed magnetic resonance imaging changes.Conclusions: Our results potentially challenge the accepted view of depression as a functional and fully reversible illness, implying instead that more permanent brain changes may be associated with chronicity. Confirmatory longitudinal and prospective studies are required to determine whether these differences pre-date the onset of depression or are the result of the chronic illness process or its treatment. [ABSTRACT FROM AUTHOR]

Background: The spontaneous diurnal variation of mood and other symptoms provides a substrate for the examination of the relationship between symptoms and regional brain activation in depression.Method: Twenty unipolar depressed patients with diurnal variation of mood were examined at 8 a.m. and 8 p.m. with neuropsychological measures, clinical ratings and single photon emission tomography (SPET). Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric (correlational) analysis was used to examine the relationship between symptom severity and brain perfusion, both between and within subjects.Results: Global depression severity and an independent 'vital' depression factor were associated in subjects with increased perfusion in cingulate and other paralimbic areas. In addition there was a probable association between an increase in an anxious-depression factor and reduced frontal neocortical perfusion.Conclusions: Depressive symptom changes are associated with metabolic changes in the cingulate gyrus and associated paralimbic structures. [ABSTRACT FROM AUTHOR]

Signal averaging to detect abnormalities in the terminal phase of ventricular depolarization has been performed in several groups of patients with various manifestations of ischaemic heart disease. Late potentials were common in patients with VT and in a group of patients having cardiac surgery. Findings in the surgical group highlighted the close correlation of late potentials with delayed, fragmented epicardial activation supporting the hypothesis that late potentials reflect a myocardial substrate which would support re-entrant VT. The findings in the surgical group allowed a definition of late potentials which could be applied to other patients in the study, and also demonstrated a spectrum of late depolarization abnormalities. Signal averaging is technically feasible in the noisy CCU environment but late potentials were detected in few patients early in AMI. Late potentials were also rarely seen in patients with VF and therefore cannot be construed as a predictive index of this arrhythmia. [ABSTRACT FROM PUBLISHER]

The grey matter (GM) segments from T1 structural magnetic resonance (MR) images of the brain in subjects at high risk of schizophrenia (n=146) were compared with normal control subjects (n=36) and first episode schizophrenic subjects (n=34) using automated voxel-based morphometry (VBM). The subjects were recruited for the Edinburgh High Risk Study (EHRS) and regional brain volumes had previously been measured using a semi-automated volumetric region of interest (ROI) method of analysis. For the current report, the images were processed using a study specific template and statistically analysed using the SPM99 program. The small volume correction tool in SPM was also used to restrict the analyses to specific voxels. Reductions in the probability of grey matter (GM) density were seen bilaterally in the anterior cingulate, and as a trend in the left parahippocampal gyrus for the high-risk vs. control subjects. In contrast, first episode schizophrenia subjects had less GM than high-risk subjects in several frontal and temporal regions. These results are compatible with the findings of our previous volumetric ROI analysis.

This study tests the hypothesis that administration of an oral amino acid load mimicking hemoglobin in patients with cirrhosis of the liver causes deterioration in neuropsychological function and a reduction in regional cerebral perfusion. Eight overnight fasted, metabolically stable cirrhotic patients with no evidence of overt hepatic encephalopathy were studied prior to and 4 h after simulating an upper gastrointestinal bleed by oral administration of 75 g of a solution mimicking the amino acid composition of hemoglobin. Neuropsychological function was measured using a test battery. Peripheral venous blood was collected for the measurement of ammonia and amino acid concentrations. Regional cerebral perfusion was measured using a head SPECT scanner following intravenous administration of technetium-99m hexamethyl propylamineoxime. The amino acid solution resulted in significant deterioration in the immediate and delayed story recall tests. Ammonia concentration increased from a median of 87 (range 67-94) micromol/L to 105 (98-112) micromol/L at 4 h after the simulated bleed (p < 0.01). The concentration of almost all amino acids increased; only isoleucine levels decreased following the upper gastrointestinal bleed. SPECT analysis showed a significant reduction in cerebral perfusion after the simulated bleed in both temporal lobes, left superior frontal gyrus, and right parietal and cingulate gyrus. An oral amino acid load mimicking hemoglobin in cirrhotic patients produces hyperammonemia and hypoisoleucinemia and causes a significant deterioration in memory tests, probably due to a reduction in regional cerebral perfusion. The model of simulating the metabolic effects of an upper gastrointestinal bleed in patients with cirrhosis of the liver seems to be useful in studying the metabolism of hepatic encephalopathy.

The aim of this study was to compare the gray matter segments from T1 structural MR images of the brain in first-episode schizophrenic subjects (n = 34) and normal control subjects (n = 36) using automated voxel-based morphometry (VBM). This study is novel in that few studies have examined subjects in their first episode of schizophrenia. The subjects were recruited for the Edinburgh High Risk project and regional brain volumes were previously measured using a semi-automated volumetric region of interest (ROI) method of analysis. The primary interest was to compare the results from the compatible parts of the ROI study and the primary VBM approach. Our secondary interest was to compare the results of a study-specific template that was constructed from the control group to those using the generic T1 template (152 Montreal Neurological Institute brains) supplied with SPM99 (statistical parametric mapping). The images were processed and statistically analyzed using the SPM99 program. VBM analysis identified significant decreases in gray matter in the schizophrenics relative to the normal control group at the corrected voxel level (P < 0.05) in the right anterior cingulate, right medial frontal lobe, left middle temporal gyrus, left postcentral gyrus, and the left limbic lobe. There were no increases in gray matter in the schizophrenics relative to the control group. The construction of a customized template appeared to improve the detection of structural abnormalities. The analyses were subsequently restricted to voxels within the amygdala-hippocampal complex using the SPM small-volume correction. This identified gray matter decreases in the schizophrenics, at the corrected voxel level (P < 0.05), in the left and right uncus and parahippocampal gyri and the right amygdala. These results are compatible with and extend the relevant findings of the previous volumetric ROI analysis, when allowing for the differences between the methods and interpretation of their results.

Objective: Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects., Method: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping., Results: Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF., Conclusions: rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed.

Several functional imaging studies have reported abnormalities of the orbitofrontal and anterior cingulate cortices, striatum and thalamus in obsessive-compulsive disorder (OCD). These studies have often been limited by small patient samples and image analysis methods that rely on region-of-interest (ROI) approaches. We have assessed resting regional cerebral blood flow with 99mTc-ECD SPECT in 26 unmedicated OCD patients and 22 healthy control subjects using the voxel-based Statistical Parametric Mapping method for data analysis. We found a significantly reduced ECD uptake in OCD patients relative to the control subjects in the right lateral orbitofrontal cortex, and in the left dorsal anterior cingulate cortex (P<0.001 two-tailed, uncorrected for multiple comparisons). There were significant positive correlations in the OCD group between the ECD uptake in the left lateral orbitofrontal cortex and ratings for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms. There were also unpredicted significant ECD uptake increases in the cerebellum in OCD patients, as well as a negative correlation between posterior cingulate ECD uptake and OCS severity (P<0.05, corrected for multiple testing). These results implicate specific subregions of the orbitofrontal and anterior cingulate cortices in the pathophysiology of OCD, as well as suggesting the involvement of other areas not usually included in ROI-based imaging studies. With the incorporation of voxel-based methods and the use of large patient samples, rCBF-SPECT studies may continue to provide valuable information about the functional anatomy of OCD.

Simulated abnormalities were introduced in a normal SPECT with known and controllable characteristics (abnormality size and depth) in an attempt to provide validation for the analysis of SPECT lesion studies using SPM. Two simulations were carried out. The first determined the minimum hypoperfusion depth detectable using SPM by altering mean local intensity while keeping the size of the lesion constant. This was done by changing the mean local intensity in percentile increments of 10 down to -100 and up to 50. The second simulation determined the cluster size that SPM can detect by keeping the mean intensity of the lesion constant while altering its size from 4 voxels to 63,000 voxels in a total brain volume of 300, 000 voxels. Both simulations determined which method of normalization is most appropriate, what level of grey matter thresholding should be used, and at what statistical probability peak threshold (u) the results should be determined. Proportional scaling was found to be the most appropriate normalization method. ANCOVA was useful where very large abnormalities were present and normalization external to SPM was not available. In those cases, ANCOVA was used in conjunction with measurement of an unaffected part of the brain (in this case medial occipital lobe). For better results statistical probability peak threshold was set to p(u) = 0. 01 and grey matter threshold was set to a value below 0.5. SPM produced best results when the abnormality represented a decrease of about -50% from the normal or more and detected other decreases in an acceptable manner., (Copyright 1999 Academic Press.)

Thirty-nine elderly depressed patients as well as 15 demented patients with Alzheimer's disease and 11 healthy volunteers were imaged at rest with a high resolution single-slice 12-detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-Exametazime (HM-PAO). Statistical parametric maps were computed to compare early- and late-onset depressed, Alzheimer patients and healthy volunteers and to examine associations between regional perfusion and clinical and MRI variables. Patients with late-onset depression showed reductions in temporal lobe perfusion compared with early-onset depression and controls. Alzheimer patients had the expected reduced perfusion in temporoparietal and prefontal cortex, as well as basal ganglia, compared with healthy controls. Compared with depressed patients, they showed a relative reduction in temporoparietal cortex, only. This difference was more pronounced between Alzheimer patients and early onset, compared to late-onset patients with depression. Periventricular white matter changes on MRI were associated with temporal lobe reductions of tracer uptake in depression. In the Alzheimer group, deep white matter MRI changes were associated with frontal perfusion deficits. Our results support a vulnerability hypothesis, which predicts that patients with late-onset depression will show more brain changes than patients with an early onset of their illness. Statistical parametric mapping in patients with organic psychiatric brain syndromes is feasible and promising as a clinical and research method.

Preliminary reports suggest improved executive function in patients with lobar dementia after treatment with single doses of the alpha 2 adrenoceptor antagonist, idazoxan. The potential for use in probable Alzheimer-type dementia prompted the present study. Fifteen patients with probable Alzheimer-type dementia were examined twice with neuropsychological measures and 14 also with single photon emission tomography (SPET) after a single double blind oral administration of 40 mg idazoxan or placebo in a balanced cross-over design. Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric analysis was used to examine the relationship between the drug effect, verbal fluency and brain perfusion. Two to 3 h after idazoxan, measures of reaction time, Stroop test, category fluency and anxiety were unchanged. Verbal fluency (letter) and spatial working memory were impaired and performance on the Tower of London test in a sub-set of patients showed a trend to impairment in the idazoxan condition. Idazoxan produced a modest relative activation in left thalamus and inferior occipital cortex: decreases occurred in inferior anterior cingulate and left insular cortex. There were significant correlations on both days between measures of fluency and brain perfusion in left lateral prefrontal cortex. The reduced performance with idazoxan was directly correlated with reduced perfusion in left lateral prefrontal cortex, supporting an important interaction between drug and task performance. The imaging component of the study therefore suggested that activation of frontal networks is necessary for performing fluency tasks in Alzheimer-type dementia. Brain networks involving prefrontal cortex are the locus for the primary cognitive effects of noradrenergic drugs. The direction of the effect of any dose of agonist or antagonist may depend critically upon the age and pathology of the experimental subjects and the relationship between performance, noradrenergic drive and task difficulty.

Ten healthy volunteers were examined with single photon emission tomography and 99mTc-exametazime. They were studied on 2 occasions, during a 2- and a 3-sound auditory discrimination (oddball) task. Twenty healthy volunteers were used as controls, studied once at rest. During the 2-tone task there was a bilateral posterior (occipito-) temporal and medial frontal activation, a left pericentral increase, and posterior cingulate suppression. During the 3-sound task activation was again found in posterior (occipito-) temporal, medial frontal cortex, left pericentral, with a small non-significant reduction in posterior cingulate uptake. Compared with the 2-tone task, there was a trend towards higher activity in left medial frontal, right posterior temporal and posterior cingulate cortex in the 3-sound task. P3b amplitudes were negatively correlated with posterior cingulate tracer uptake during both tasks. Positive correlations with P3b amplitudes were found in various frontal and temporal regions. These results are consistent with more invasive localisation studies of P3b. Posterior cingulate cortex appears to be inhibited during the oddball tasks, the more so, the more restricted the range of stimuli, and the greater the task-related recruitment of neurones (P3b amplitude). As expected from its more frontal distribution, P3a amplitude was positively correlated with anterior cingulate tracer uptake, and negatively correlated with temporal cortical activity.

Twenty-three schizophrenic patients and 26 age-matched control subjects were studied using the P300 recorded during the auditory oddball task, with counting. Our aim was to assess the most suitable method of measurement and analysis of P300 amplitude and latency for use in clinical studies of schizophrenia. The effect of high-pass filtering, peak definition method and recording electrode site were all investigated. We have developed a technique, based on a least-mean-squares approximation to data, which seems particularly well suited to dealing with multi-peak P300 complexes. We have also investigated the spectral composition of the P300 and have found some evidence to support a proposed 2-frequency model of the P300 complex.