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Low plasma iron status and akathisia.
Thirty patients were examined to test the hypothesis that a depletion of iron levels is associated with symptoms of akathisia. Fifteen akathisic patients were pair-matched with 15 non-akathisic patients. Plasma ferritin levels were significantly decreased in the akathisic patients, and there was a significant inverse correlation between plasma iron levels and akathisia rating. In addition, akathisia ratings were found to be correlated with a scale measuring symptoms of tardive dyskinesia.
Memory impairment in out-of-hospital cardiac arrest survivors is associated with global reduction in brain volume, not focal hippocampal injury.
BACKGROUND AND PURPOSE: More than 30% of out-of-hospital cardiac arrest (OHCA) survivors suffer significant memory impairment. The hippocampus may be vulnerable to hypoxic injury during cardiac arrest. The purpose of this study was to determine whether selective hippocampal injury is the substrate for this memory impairment. METHODS: Seventeen OHCA survivors and 12 patients with uncomplicated myocardial infarction were studied. OHCA survivors were divided into those with impaired and intact memory. Memory was assessed by use of the Rivermead Behavioural Memory Test and Doors and People Test. MRI was used to determine intracranial, whole-brain, amygdala-hippocampal complex, and temporal lobe volumes. Brain structure was also examined by statistical parametric mapping. RESULTS: Left amygdala-hippocampal volume was reduced in memory-impaired OHCA victims compared with control subjects (mean 3. 93 cm(3) and 95% CI 3.50 to 4.36 cm(3) versus mean 4.65 cm(3) and 95% CI 4.37 to 4.93 cm(3); P=0.002). Left temporal lobe and whole-brain volumes were also reduced. There were no differences in amygdala-hippocampal volume indexed against ipsilateral temporal lobe volume. Significant correlations were observed between total brain volume and Rivermead Behavioural Memory Test (r=0.56, P<0.05) and Doors and People Test (r=0.67, P<0.01) scores in OHCA survivors. Both recall and recognition were compromised in memory-impaired subjects. Statistical parametric mapping did not detect focal brain abnormalities in these subjects. Global cerebral atrophy was confirmed by qualitative assessment. CONCLUSIONS: Memory impairment in OHCA survivors is associated with global cerebral atrophy, not selective hippocampal damage. Rehabilitation protocols need to account for the global nature of the brain injury.
Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ('ecstasy') users.
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.
The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET).
Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.
Does idiopathic parkinsonism in Aberdeen follow intrauterine influenza?
A study is presented which fails to replicate a recent report that peak years of birth of patients later developing Parkinson's disease are related to the influenza pandemics of the period 1890-1930. The years of birth of a whole population cohort of 243 patients suffering from Parkinson's disease examined in Aberdeen in 1983 and reexamined in 1986/7 were compared with deaths due to influenza in the City of Aberdeen in the years 1900-1930. Although a significant peak of Parkinson births (compared with the age profile of the Aberdeen population in 1983) occurred in 1902, there appeared to be no systematic relationship between Parkinson births and influenza deaths. In addition, no season of birth effect could be detected in a comparison with 232 matched controls. The presence of peaks of birth years, for whatever aetiological reason, is of significance to epidemiological studies in that prevalence estimates may be influenced by the year of study relative to these mini-cohorts.
Left dorso-lateral repetitive transcranial magnetic stimulation affects cortical excitability and functional connectivity, but does not impair cognition in major depression.
PURPOSE: Transcranial magnetic stimulation (TMS) has been used for over a decade to investigate cortical function. More recently, it has been employed to treat conditions such as major depression. This study was designed to explore the effects of differential treatment parameters, such as stimulation frequency. In addition, the data were examined to determine whether a change in connectivity occurred following TMS. METHOD: Fifteen patients with major depression were entered into a combined imaging and treatment experiment with single photon emission computed tomography (SPECT) and repetitive transcranial magnetic stimulation (rTMS) over left dorso-lateral prefrontal cortex (DLPFC). Brain perfusion during a verbal fluency task was compared between pre- and poststimulation conditions. Patients were then treated with 80% of motor threshold for a total of 10 days, using 5000 stimuli at 5, 10 or 20 Hz. Tests of cortical excitability and neuropsychological tests were done throughout the trial. FINDINGS: Patients generally improved with treatment. There was no perceptible difference between stimulation frequencies, which may have reflected low study power. An increase in rostral anterior cingulate activation after the treatment day was associated with increased functional connectivity in the dorso-lateral frontal loop on the left and the limbic loop on both sides. No noticeable deterioration in neuropsychological function was observed. CONCLUSION: TMS at the stimulation frequencies used seems to be safe over a course of 5000 stimuli. It appears to have an activating effect in anterior limbic structures and increase functional connectivity in the neuroanatomical networks under the stimulation coil within an hour of stimulation.
Cerebral perfusion in chronic fatigue syndrome and depression.
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.
Executive function and uptake of 99mTc-exametazime shown by single photon emission tomography after oral idazoxan in probable Alzheimer-type dementia.
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.
Single photon emission computed tomography in long-term survivors of adult brain tumours.
Sixteen patients with primary brain tumours were examined on average eight years after treatment with surgery or whole brain irradiation using standard clinical assessment, CT, a neuropsychological test battery, and single photon emission CT (SPECT) with 99mTc-exametazime. Seventeen lesions were discovered on inspection of SPECT images, 11 with x-ray CT. Quantitative assessment of tracer uptake compared with 16 matched healthy volunteers was consistent with the presence of lesions. Measurement of uptake in brain regions of the hemisphere not containing the primary tumour still showed significant reductions in patients. This may be due to remote direct effects of the tumour or, more likely, to the whole brain irradiation received. Psychometric performance on most tests was significantly impaired in the patient group and was correlated with abnormalities of tracer uptake to relevant brain regions.
Chronic, treatment-resistant depression and right fronto-striatal atrophy.
BACKGROUND: Treatment-resistant depression (TRD) is relatively common but its neurobiological basis is poorly understood. Fronto-striatal structural brain changes have been reported in patients with depression but their association with treatment resistance and chronicity has not been established. METHOD: Magnetic resonance images of 20 patients with TRD were compared with images of 20 recovered patients and 20 healthy controls. Images were compared using a voxel-based analysis (VBA) method; the results were validated by conventional volumetric analysis. The clinical associations of magnetic resonance imaging (MRI) changes with illness duration and severity were examined by VBA. RESULTS: Only the TRD group exhibited right fronto-striatal atrophy, and subtle MRI changes in the left hippocampus on VBA. Atrophy was confirmed on volumetric analysis, the degree correlating with the cumulative number of electroconvulsive therapy (ECT) treatments received, suggesting an acquired deficit. CONCLUSIONS: This is the first study to demonstrate fronto-striatal atrophy in patients with depression with poor outcome; the atrophy is more marked in those with more severe illness.
Increased cortical inhibition in depression: a prolonged silent period with transcranial magnetic stimulation (TMS).
BACKGROUND: Motor slowing in depression may be associated with a relative dopaminergic (DA) deficit. Bradykinesia in Parkinson's syndrome is associated with an abnormally short silent period (SP) using transcranial magnetic stimulation (TMS). We hypothesized that depression would also be associated with a short SP. METHODS: Sixteen patients with DSM-IV depression and 19 matched controls participated. SPs were elicited by exercising the contralateral abductor policis brevis (APB) during TMS. RESULTS: The SP was significantly increased in the patient group. No correlation was found between SP and depression score. CONCLUSION: A long SP suggests increased motor cortical inhibition in depression. This finding is inconsistent with the hypothesis of behavioural motor slowing in depression being associated with Parkinsonian-like mechanisms including the dopaminergic deficit. There is a need for studies incorporating larger patient groups to investigate potential correlations between SP and depression indices.
Brain activation during an auditory 'oddball task' in schizophrenia measured by single photon emission tomography.
BACKGROUND: The study examines the effect of an auditory discrimination task on regional brain perfusion in schizophrenic patients. METHODS: Twenty patients were examined with single photon emission tomography (SPET), both resting and performing an auditory two-tone 'oddball' discrimination task. Statistical parametric mapping (SPM'95) was used to identify local activation effects and correlations between event related potential measures and regional perfusion. RESULTS: Compared with rest, patients activated left superior temporal gyrus during the task, together with right caudate. There was a (negative) correlation between P300-amplitude and perfusion during the activation procedure in both caudate nuclei and in the left lingual gyrus. No correlations were observed with P300-latency. Compared with healthy volunteers examined in earlier studies, our patients showed no frontal activation. This might be due to slightly different task demands in this study, but more likely to activation-hypofrontality in schizophrenic patients compared with controls. CONCLUSION: Auditory discrimination tasks can be used in schizophrenic patients to control their 'mental set' during brain perfusion studies with SPET. This approach can yield information about specific brain mechanisms associated with such tasks, and may make comparison with healthy volunteers easier.
Correlation of auditory 'oddball' P300 with verbal memory deficits in schizophrenia.
BACKGROUND: The study attempts to recruit well known 'cognitive' event related potential measures as an objective estimate of cognitive and specific memory impairment in schizophrenia. METHODS: We examined 19 schizophrenic patients and 28 healthy controls using an auditory discrimination task to elicit event related potentials, and a number of neuropsychological tests, including tests of general intellectual ability, putative frontal lobe function and verbal memory. RESULTS: The late positive deflection presumed to be associated with stimulus evaluation (P300) was of lower amplitude and had a longer latency in the patients compared with controls of similar age and sex. We found correlations between P300 amplitude and latency, and neuropsychological performance scores in patients. There were correlations between decreased P300 amplitude and lower IQ and poorer memory performance, in particular, abnormal semantic clustering, discriminability and intrusion errors. Increased P300 latency was correlated with lower pre-morbid IQ, poorer total memory scores and serial clustering, but paradoxically less relative retrieval deficit and fewer intrusion errors. CONCLUSIONS: These findings suggest that abnormal P300 is generally more likely to occur in patients with memory impairment.