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2-Deoxyglucose autoradiography and repeated electroconvulsive shock in rats
Semiquantitative autoradiography with tritiated deoxyglucose was performed on rats after a series of 10 electro-convulsive shocks (ECS) administered over 10 days. The purpose of the study was to identify changes in cerebral glucose uptake after ECS. Glucose uptake over a large number of grey and white matter structures cannot be differentiated between rats receiving real and sham ECS. Various behavioral parameters measured in activity boxes do not show significant differences between the two groups.
The validity of the national adult reading test in estimating premorbid intellectual ability in long‐term survivors of hemispheric glioma and whole brain irradiation—a pilot study
We have examined the validity of using the National Adult Reading Test (NART) to estimate premorbid intellectual levels in long‐term survivors of glioma who had received whole brain prophylactic irradiation. Sixteen controls matched for age, sex, education and social class were compared with 16 patients. Patients made significantly more errors in the NART than controls, even after controlling for demographic variables. NART errors were compared with demographically predicted NART errors and NART‐predicted Wechsler Adult Intelligence Scale‐Revised (WAIS‐R) with pro‐rated WAIS‐R scores. While predicted and measured error scores were similar for the controls, for patients NART errors were higher than those predicted by demographic variables, while NART‐predicted WAIS‐R scores were higher than pro‐rated WAIS‐R. NART performance, therefore, appears to be detrimentally affected by brain changes due to the primary tumour or received treatment. This conclusion was supported by the finding that, in patients, NART errors were correlated with current IQ, but not with IQ predicted by socio‐demographic variables. After excluding four demented patients, this pattern of results was largely preserved. After excluding four patients with left temporal lobe involvement, the correlation of NART errors with current IQ disappeared, whereas that with NART errors predicted by socio‐demographic variables became significant. These results suggest that the NART can only be used with caution in survivors of malignant primary brain tumors, particularly if left temporal lobe structures are involved. Copyright © 1993 John Wiley & Sons, Ltd
Automatic classification of SPECT images of Alzheimer's disease patients and control subjects
In this article we study the use of SPECT perfusion imaging for the diagnosis of Alzheimer's disease. We present a classifier based approach that does not need any explicit knowledge about the pathology. We directly use the voxel intensities as features. This approach is compared with three classical approaches: regions of interests, statistical parametric mapping and visual analysis which is the most commonly used method. We tested our method both on simulated and on real data. The realistic simulations give us total control about the ground truth. On real data, our method was more sensitive than the human experts, while having an acceptable specificity. We conclude that an automatic method can be a useful help for clinicians. © Springer-Verlag Berlin Heidelberg 2004.
SPECT in dementia
This book is essential reading for all scientists, economists and clinicians in geriatric medicine, neurology and psychiatry, neuro-radiology and nuclear ...
Right and left prefrontal transcranial magnetic stimulation at 1 Hz does not affect mood in healthy volunteers.
BACKGROUND: Prefrontal repetitive transcranial magnetic stimulation (rTMS) has been used to induce side-specific mood changes in volunteers and patients. To clarify inconsistencies between reports that used different stimulation frequencies, we conducted a controlled study with a low (1 Hz) frequency, comparing left with right-sided stimulation METHODS: Nineteen healthy volunteers received randomised left or right prefrontal rTMS at a frequency of 1 Hz and 100% of motor threshold in two sessions two weeks apart. RESULTS: There were significant improvements with TMS for performance in the digit symbol substitution and verbal fluency tests, but no change of mood on a number of measures. There was also a reduction of pulse rate after TMS. The only side-specific TMS-effect was on mean arterial pressure, which decreased pressure after left, but not after right prefrontal TMS. CONCLUSIONS: Apart from the unexpected and so far unreplicated effect on mean arterial pressure, there were no side-specific effects on mood in volunteers. It is unlikely that a simple laterality model of mood together with the assumed activating effect of higher and 'quenching' effect of lower stimulation frequency can account for the effects of TMS on mood.
Mood and cerebral perfusion revisited.
Twenty patients with major depression and observed diurnal variations of mood were examined using clinical and neuropsychological measures and perfusion HMPAO-SPECT at 8 a.m. and 8 p.m. In thirteen patients depression scores varied more than 15% although 4 patients with reverse diurnal variation caused mean group depression scores to be not different between morning and evening. There was an overall trend for higher depression scores to be associated with higher perfusion in posterior cingulate. This was mainly accounted for by significant positive correlations in the morning scan in posterior, but also anterior cingulate and medial prefrontal cortex compared with evening scans. This means that morning regression slopes were steeper than evening slopes. This result is discussed with regard to possible interpretations, such as adaptive or habituating changes during the day that may occur in depressed patients.
Memory for emotional material: a comparison of central versus peripheral beta blockade.
The connection between affect and memory is poorly understood. A possible psychopharmacological linking mechanism is the sympathetic arousal that occurs in response to threatening or emotive material. Cahill et al. (1994) reported that a single administration of 40 mg propranolol hydrochloride, a non-selective beta-adrenergic blocker, to healthy young adults significantly reduced delayed recall of emotive material, with recall of matched neutral material unaffected. This study differed importantly from the original Cahill et al. (1994) procedure in that only the emotionally arousing narrative was employed. Using the same slide presentation as Cahill et al. (1994), an experiment was carried out in order to determine whether beta-adrenergic blockade significantly reduces recall of emotive material via a central or peripheral mode of action. Thirty-six healthy young adults were recruited as subjects. Subjects were randomly allocated to three groups: (a) placebo (b) 40 mg propranolol hydrochloride (a beta blocker which readily crosses the blood brain barrier) and (c) 40 mg nadolol (a beta blocker which does not cross the blood-brain barrier). The three groups were matched for age, sex, intelligence, personality factors, and general memory functioning. Subjects viewed a series of 11 slides accompanied by a narrative, divisible into three phases. The emotionally arousing component of the narrative was introduced during phase II. Both central and peripheral beta blockade produced the expected effects on the sympathetic nervous system, as demonstrated by reliable reductions in systolic and diastolic blood pressure. In a surprise memory test 1 week later, subjects were asked to recall as much as possible of the story and slides, and also completed a forced choice recognition memory test. All three groups showed heightened recall and recognition for the central (emotive) section of the story. There was no differential effect of beta blockade (either central or peripheral) relative to placebo. Beta blockade markedly reduced systolic and diastolic blood pressure, but resulted in no significant effect on memory for both emotional and neutral material.
New models for depression
Ebert D, Ebmeier KP (eds): New Models for Depression. Adv Biol Psychiatry. Basel , Karger, 1998, vol 19, pp 1–33 ............................ Cognitive ...
Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer's disease.
The effects of a single oral dose of the acetylcholinesterase inhibitor velnacrine maleate on word and object recognition memory and regional uptake of 99mTc-exametazime were examined in patients with Alzheimer's disease. Word recognition memory was marginally improved 2 h after 75 mg velnacrine. With the same dose of velnacrine a relative increase in superior frontal uptake of 99mTc-exametazime was shown with single photon emission computed tomography (SPECT). This suggests increased regional perfusion and metabolism as a consequence of cholinergic stimulation. The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients.
A comparison of Tc-99m HM-PAO and I-123 IMP cerebral SPECT images in Alzheimer's disease and multi-infarct dementia.
SPECT images of the brain can be obtained using either 123I labelled amines or 99mTc-hexamethylpropyleneamineoxime (HM-PAO). Both materials produce images which are blood flow dominated and so appear similar in normal subjects, although the respective mechanisms of uptake are not yet finally established. It seems likely, however, that the different mechanisms of uptake are responsible for recent reports of some differences seen in images obtained with the two types of agent in patients with cerebral pathology, mainly cerebrovascular disease. In this study, 12 demented patients, 6 with dementia of the Alzheimer type (DAT) and 6 with multi infarct dementia (MID), were imaged with 123I-isopropylamphetamine (IMP) and 99mTc-HM-PAO and the images compared. Significantly more lesions were seen with IMP than HM-PAO (P less than 0.02); out of a possible 120 sites, 41 lesions were seen with IMP compared to 28 with HM-PAO, 23 being seen with both agents. However, it is concluded that either agent can be used for the differential diagnosis of dementia, a task for which the new cerebral blood flow agents seem well suited.
Neuropsychological function and diurnal variation in depression.
Twenty-six patients suffering from DSM-III-R major depressive episode with diurnal variation of mood were examined at approximately 8 AM and 8 PM, using a neuropsychological test battery. We found that tests of executive function, especially the verbal fluency test, were sensitive measures of diurnal variation, but that personality measures were relatively robust in that they were not significantly affected by diurnal variations of mood. The relevance of detecting and assessing diurnal changes of mood with reliable, objective measures of performance is discussed.
Cognitive brain potentials and regional cerebral blood flow equivalents during two- and three-sound auditory "oddball tasks".
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.
Diurnal variation of mood and neuropsychological function in major depression with melancholia.
20 DSM-III-R melancholics with clinically evident diurnal symptoms and 20 controls were assessed with a battery of neuropsychological tests, a test of maximum voluntary hand-grip, and neuroendocrine measures of hypothalamic-pituitary-adrenal axis function morning and evening in a 24-h period, using a balanced design. The morning pattern of neuropsychological impairment in the melancholics was comprehensive, affecting attention and concentration/working memory, episodic memory, reaction time and, strikingly, the speed of simultaneous match to sample, which was performed more slowly than the version of the task delayed to 0 or 4 s. The melancholics were significantly weaker than controls, on a measure of maximal voluntary contraction. Significantly improved neuropsychological function was seen in the melancholic patients in the evening, in line with diurnal improvement in mood; there was also a large increase in strength. Slowing on the digit symbol substitution test, the simultaneous match to sample task, total errors on the match to sample and hand-grip remained impaired in the evening compared to controls; other neuropsychological measures were no longer statistically different from control values which were often worsened. Neuroendocrine measures showed significantly raised levels of cortisol and ACTH morning and evening in the melancholics. Morning cortisol in the melancholics correlated with the diurnal improvement in neuropsychological functioning. The results have implications for the timing of neuropsychological assessment in major depression. Indices of neuropsychological and motor function may be as reliable quantitative estimates of illness severity as subjective estimates of mood.
State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment.
Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.