Search PubMed⌕ Search

Biomedical subjects

D J Brooks

Publications and source records attributed to D J Brooks.

At least 145 records · Page 8Linked to original sources
PubMed1997

Cortical control of movement in Huntington's disease. A PET activation study.

Regional cerebral blood flow was measured with H2(15)O PET in seven patients with choreic Huntington's disease and seven age-matched control subjects. Subjects were scanned at rest and when performing paced joystick movements, in freely chosen directions, with the dominant arm. During movement, the patients showed impaired activation of contralateral primary motor, medial premotor, bilateral parietal and bilateral prefrontal areas along with increased activation of bilateral insular areas. The underactivity of frontal areas in Huntington's disease is similar to the pattern of impaired activation in Parkinson's disease and is likely to result from degeneration of basal ganglia to frontal projections. Primary motor underactivity may explain the bradykinesia that these patients exhibit and, if inhibitory neurons are involved, also their chorea.

Adult↗
PubMed1997

11C-diprenorphine binding in Huntington's disease: a comparison of region of interest analysis with statistical parametric mapping.

We compare region of interest (ROI) analytical approaches with statistical parametric mapping (SPM) of 11C-diprenorphine positron emission tomography findings in five patients with Huntington's disease (HD) and nine age-matched controls. The ROI were placed on caudate, putamen, and an occipital reference area. Ratios of striatal-occipital uptake from averaged static images centered at 60 minutes showed a mean 20% reduction in caudate (P = 0.034) and 15% reduction in putamen (P = 0.095) receptor binding in the HD patients. Dynamic data from caudate and putamen ROI, together with a plasma tracer input function, were analyzed using spectral analysis to give regional impulse response functions. Regional data at 60 minutes after impulse showed a mean 29% decrease in caudate (P = 0.006) and 23% decrease in putamen (P = 0.029) opioid binding in the HD cohort. Parametric images of tracer binding also were produced with spectral analysis on a voxel basis. The images of the unit impulse response function at 60 minutes showed a mean 31% decrease in caudate (P = 0.005) and a 26% decrease in putamen binding (P = 0.011) in HD. The voxel-based parametric images were transformed into standard stereotactic space, and a between-group comparison (patient versus controls) was performed with SPM. This approach revealed symmetrical decreases in caudate (peak 40% decrease, z score = 4.38) and putamen opioid binding (peak 24% decrease, z score = 4.686) with additional nonhypothesized changes in cingulate, prefrontal, and thalamic areas. The significance and precision of changes measured with spectral analysis applied to dynamic data sets were superior to ROI-based ratio analysis on static images. The SPM replicated the striatal reductions in opioid binding in HD and detected additional nonpredicted changes. This study suggests that SPM is a valid alternative to conventional ROI analytical approaches for determining binding changes with positron emission tomography and may have advantages over region-based analyses in exploratory studies.

Adult↗
PubMed1997

Advances in imaging Parkinson's disease.

Positron emission tomography and single photon emission computed tomography both now provide an objective means of quantitating loss of striatal dopaminergic terminal function in Parkinson's disease and of following disease progression. 18F-dopa positron emission tomography can also detect frontal changes in Parkinson's disease and preclinical disease in 30% of asymptomatic adult relatives of familial cases. Positron emission tomography, single photon emission computed tomography and proton magnetic resonance spectroscopy are all useful for distinguishing Parkinson's disease from atypical syndromes where diagnostic doubt exists.

Brain Mapping↗
PubMed1997

Central benzodiazepine/gamma-aminobutyric acid A receptors in idiopathic generalized epilepsy: an [11C]flumazenil positron emission tomography study.

PURPOSE: Previous [11C]flumazenil (FMZ) positron emission tomography (PET) investigations in patients with idiopathic generalized epilepsy (IGE) have demonstrated nonsignificant global cortical decreases in central benzodiazepine gamma-aminobutyric acid A (GABA[A]) receptor (cBZR) binding or focal decreases in the thalamus and increases in the cerebellar nuclei with no changes in cerebral cortex. We previously reported lower [11C]FMZ binding in cerebral cortex of IGE patients treated with valproate (VPA) than in cerebral cortex of controls. We now report high-resolution three-dimensional [11C]FMZ PET studies in a larger number of subjects using an improved method to detect differences in cBZR between IGE patients and controls and a more powerful longitudinal design to determine the functional effect of VPA. METHODS: We compared parametric images of [11C]FMZ volume of distribution (FMZVD) in 10 IGE patients before and after addition of VPA and in 20 normal subjects. RESULTS: Mean FMZVD was significantly higher in the cerebral cortex (11%, p = 0.009), thalamus (14%, p = 0.018), and cerebellum (15%, p = 0.027) of the 10 IGE patients as compared with that of 20 normal controls. Using statistical parametric mapping, no significant areas of focal abnormality of FMZVD were detected. Addition of VPA was not associated with a significant change in mean FMZVD in any brain area. CONCLUSIONS: Our finding of increased FMZVD in IGE could reflect microdysgenesis or a state of cortical hyperexcitability. Our data suggest that short-term VPA therapy does not affect the number of available cBZR in patients with IGE.

Adult↗
PubMed1997

Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis.

OBJECTIVES: To examine the relation between cognitive dysfunction and pseudobulbar features in patients with amyotrophic lateral sclerosis (ALS). METHODS: The performance of two patient groups, ALS with pseudobulbar palsy (n = 24) and ALS without pseudobulbar palsy (n = 28), was compared with 28 healthy age matched controls on an extensive neuropsychological battery. Tests used were the national adult reading test, short form of the WAIS-R, recognition memory test, Kendrick object learning test, paired associate learning, Wisconsin card sorting test, verbal fluency, Stroop and negative priming tests, a random movement joystick test, and a computerised Tower of Hanoi test. RESULTS: Tests of executive function showed a pronounced deficit on written verbal fluency in both ALS groups in comparison to controls, which tended to be more prominent in patients with ALS with pseudobulbar palsy. The random movement joystick test (a non-verbal test of intrinsic movement generation) showed an impairment in the generation of random sequences in patients with pseudobulbar palsy only. The computerised Tower of Hanoi showed a subtle planning impairment (shorter planning times) in all the patients with ALS compared with controls on trials requiring more complex solutions. In addition the pseudobulbar patients displayed shorter planning times on complex trials, and tended to solve these trials less accurately. There was also evidence of a deficit for all patients with ALS in comparison with controls on total errors and number of categories achieved on the Wisconsin card sorting test and a strong tendency towards an impairment on a task of selective attention and cognitive inhibition (negative priming). A word recognition memory deficit was showed across both ALS groups. CONCLUSIONS: This study elicited cognitive deficits (involving predominantly executive processes, with some evidence of memory impairment) in patients with ALS and further strengthened the link between ALS and frontal lobe dysfunction, this being more prominent in patients with pseudobulbar palsy. However, cognitive impairments suggestive of extramotor cortical involvement were not exclusive to this subgroup.

Adult↗
PubMed1997

Anatomy of motor learning. I. Frontal cortex and attention to action.

We used positron emission tomography to study new learning and automatic performance in normal volunteers. Subjects learned sequences of eight finger movements by trial and error. In a previous experiment we showed that the prefrontal cortex was activated during new learning but not during during automatic performance. The aim of the present experiment was to see what areas could be reactivated if the subjects performed the prelearned sequence but were required to pay attention to what they were doing. Scans were carried out under four conditions. In the first the subjects performed a prelearned sequence of eight key presses; this sequence was learned before scanning and was practiced until it had become overlearned, so that the subjects were able to perform it automatically. In the second condition the subjects learned a new sequence during scanning. In a third condition the subjects performed the prelearned sequence, but they were required to attend to what they were doing; they were instructed to think about the next movement. The fourth condition was a baseline condition. As in the earlier study, the dorsal prefrontal cortex and anterior cingulate area 32 were activated during new learning, but not during automatic performance. The left dorsal prefrontal cortex and the right anterior cingulate cortex were reactivated when subjects paid attention to the performance of the prelearned sequence compared with automatic performance of the same task. It is suggested that the critical feature was that the subjects were required to attend to the preparation of their responses. However, the dorsal prefrontal cortex and the anterior cingulate cortex were activated more when the subjects learned a new sequence than they were when subjects simply paid attention to a prelearned sequence. New learning differs from the attention condition in that the subjects generated moves, monitored the outcomes, and remembered the responses that had been successful. All these are nonroutine operations to which the subjects must attend. Further analysis is needed to specify which are the nonroutine operations that require the involvement of the dorsal prefrontal and anterior cingulate cortex.

Adult↗
PubMed1997

Anatomy of motor learning. II. Subcortical structures and learning by trial and error.

We used positron emission tomography to study motor learning by trial and error. Subjects learned sequences of eight finger movements. Tones generated by a computer told the subjects whether any particular move was correct or incorrect. A control condition was used in which the subjects generated moves, but there was no feedback to indicate success or failure, and so on learning occurred. In this condition (free selection) the subjects were required to make a finger movement on each trial and to vary the movements randomly over trials. The subjects had a free choice of which finger to move on any one trial. On this task there was no systematic change in responses over trials and no change in the response times. Two other conditions were included. In one the subjects repetitively moved the same finger on all trials and in a baseline condition the subjects heard the pacing tones and auditory feedback but made no movements. Comparing new learning with the free selection task, there was a small activation in the right prefrontal cortex. This may reflect the fact that in new learning, but not free selection, the subject rehearse past moves and adapt their responses accordingly. The caudate nucleus was strongly activated during new learning. It is suggested that this activity may be related either to mental rehearsal or to reinforcement of the movements as a consequence of the outcomes. The putamen was activated anteriorly on the free selection task and more posteriorly when the subjects repetitively made the same movement. It is suggested that the differences in the location of the peak activation in the striatum may represent the operation of different corticostriatal loops. The cerebellar nuclei (bilaterally) and vermis were more active in the new learning condition than during the performance of the free selection task. There was no difference in the activation of the cerebellum when the free selection task was compared with repetitive performance of the same movement. We tentatively suggest that the basal ganglia may be involved in the specification of movement on the basis of memory of either the movements or the outcomes, but that the cerebellum may be more directly involved in changes in the parameters of movement execution.

Acoustic Stimulation↗
PubMed1997

Abnormal access of axial vibrotactile input to deafferented somatosensory cortex in human upper limb amputees.

We studied two human subjects with total deafferentation of one upper limb secondary to traumatic multiple cervical root avulsions. Both subjects developed a phantom limb and underwent elective amputation of the paralyzed, deafferentated limb. Psychophysical study revealed in each subject an area of skin in the pectoral region ipsilateral to the amputation where vibrotactile stimulation (VS) elicited referred sensations (RS) in the phantom limb. Positron emission tomography was then used to measure regional cerebral blood flow changes during VS of the pectoral region ipsilateral to the amputation with RS and during VS of a homologous part of the pectoral region adjacent to the intact arm without RS. A voxel-based correlation analysis was subsequently used to study functional connectivity. VS of the pectoral region adjacent to the intact arm was associated with activation of the dorsal part of the contralateral primary somatosensory cortex (S1) in a position consistent with the S1 trunk area. In contrast, VS of the pectoral region ipsilateral to the amputation with RS was associated with activation of the contralateral S1 that extended from the level of the trunk representation ventrally over distances of 20 and 12 mm, respectively, in the two subjects. The area of S1 activated during VS of the digits in a normal control subject was coextensive with the ventral S1 region abnormally activated during VS of the ectopic phantom representation in the two amputees, suggesting that the deafferented digit or hand/arm area had been activated by sensory input from the pectoral region. Correlation analysis showed an abnormal pattern of intrinsic connectivity within the deafferented S1 hand/arm area of both amputees. In one subject, the deafferented S1 was functionally connected with 3 times as many S1 voxels as the normally afferented S1. This abnormal functional connectivity extended in both the rostrocaudal and ventrodorsal dimensions. The results demonstrate that sensory input delivered to the axial body surface may gain access to the S1 hand/arm area in some humans who have suffered extensive deafferentation of this area. The findings are consistent with the hypothesis that deafferentation of an area of S1 may result in activation of previously dormant inputs from body surfaces represented in immediately adjacent parts of S1. The results also provide evidence that changes in functional connectivity between these adjacent areas of the cortex play a role in the somatotopic reorganization.

Adult↗
PubMed1997

Motor disturbance and brain functional imaging in Parkinson's disease.

18F-Dopa positron emission tomography (PET) provides a sensitive means of quantitating the loss of nigrostriatal dopaminergic fibres in Parkinson's disease and so can be used to diagnose its presence and to objectively follow the rate of disease progression. It can also be used, in principle, to determine the efficacy of putative neuroprotective agents and has already been extensively used to monitor the viability of striatal transplants of fetal mesencephalic tissue. Loss of dopaminergic projections produces significant changes in the patterns of both resting and activated cortical function. H2(15)O PET activation studies have suggested that the akinesia of Parkinson's disease is associated with failure to activate the supplementary motor and dorsal prefrontal areas, brain regions particularly involved in motor preparation and decision making. Activation of these cortical areas can be restored by administering dopaminergic medication, implanting the striatum with fetal mesencephalic tissue, and by pallidotomy. This article reviews the insight that PET studies have provided into the pathophysiology of Parkinson's disease.

Brain↗
PubMed1997

Dopaminergic function in patients with posttraumatic parkinsonism: an 18F-dopa PET study.

Posttraumatic encephalopathy (PTE) is characterized by a combination of upper motor neuron, basal ganglia, cerebellar, and psychiatric disturbances. A "striatal" variant, with predominant posttraumatic parkinsonism (PTP), is uncommon and may be difficult to distinguish from idiopathic Parkinson's disease (PD). We report the clinical characteristics of six patients clinically presumed to have PTP who were investigated with 18F-dopa PET. We compared their findings with those of age-matched controls and a group of idiopathic PD patients without a history of head trauma. The PTP patients showed a uniform 40% reduction (p < 0.0001) of mean 18F-dopa uptake in caudate and putamen compared with controls. Their mean putamen uptake was significantly higher than that seen in the PD group (p < 0.004) while mean caudate uptake was lower. The PTP mean caudate:putamen Ki ratio (0.97) was similar to that of controls (1.10) but significantly lower than that of the PD group (1.90) (p < 0.0001). These results suggest that although PTP may appear clinically similar to PD, 18F-dopa PET may help to differentiate it in vivo by demonstrating uniform nigrostriatal involvement as opposed to relative sparing of caudate function. These data also provide support for the view that delayed neurologic sequelae may follow cumulative head trauma.

Aged↗
PubMed1997

In vivo studies on striatal dopamine D1 and D2 site binding in L-dopa-treated Parkinson's disease patients with and without dyskinesias.

Dyskinesias are usually seen in Parkinson's disease (PD) patients after several years of L-dopa therapy. Their presence has been attributed to supersensitivity of striatal D1 and D2 receptors. We have used PET to assess striatal D2 receptor binding in untreated PD patients and striatal D1 and D2 binding in L-dopa-treated PD patients. Untreated patients showed a 14% increase in mean D2 receptor binding in the putamen contralateral to the more affected limbs (p < 0.02). Treated patients were segregated into subgroups according to the presence or absence of dyskinesias. There were no differences in mean caudate and putamen D1 and D2 binding between dyskinetic and nondyskinetic patients, matched for duration of clinical disease. Both dyskinetic and nondyskinetic PD subgroups showed a similar 16% reduction of mean caudate D2 binding (p < 0.01) with normal D2 binding in putamen. Mean caudate and putamen D1 binding potentials of both subgroups were reduced by 10% compared with those of controls, though this trend did not reach significance. Putamen D1 binding, however, showed a negative correlation with duration and L-dopa treatment (p < 0.03). These findings suggest that, while exposure of PD patients to L-dopa may be associated with reductions in caudate D2 and caudate and putamen D1 receptor, dyskinesias are unlikely to result from alterations in striatal dopamine receptor binding.

Adult↗
PubMed1997

11C-flumazenil PET, volumetric MRI, and quantitative pathology in mesial temporal lobe epilepsy.

BACKGROUND: Using statistical parametric mapping and 11C-flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy (mTLE) due to hippocampal sclerosis (HS). The limited spatial resolution of PET, however, results in partial-volume averaging that affects quantitative analysis of cBZR density. METHOD: We determined hippocampal volume loss and reduction in cBZR binding using an MRI-based method for partial-volume effect correction of 11C-FMZ volume of distribution (FMZ-Vd) in 17 patients with refractory mTLE and an MRI diagnosis of HS that was subsequently histologically verified in all cases. Quantitative neuropathology was performed with assessment of neuron density in 14 of the 17 patients. Absolute FMZ-Vd and asymmetry indices (FMZ-AI) were compared before and after partial-volume effect correction with MRI-determined hippocampal volumes (HCV), hippocampal T2 measurements, and, if available, neuronal cell densities. RESULTS: Compared with 15 age-matched healthy volunteers, significant reductions of absolute hippocampal FMZ-Vd were found before correction for partial-volume effects in 11 of 17 patients (65%) and only abnormal FMZ-AI in the other six patients. After partial-volume effects correction all 17 patients (100%) showed both significant unilateral reduction of absolute FMZ-Vd and abnormal FMZ-AI. There was no correlation between corrected absolute FMZ-Vd and HCV or neuronal cell density. After correction for partial-volume effect we found a mean 38% reduction of FMZ-Vd in the sclerosed hippocampus, over and above the reduction of HCV. CONCLUSION: Correction for partial-volume effect allows absolute quantitation of FMZ-PET and increases its sensitivity for detecting abnormalities in TLE due to HS. The lack of correlation between cBZR binding and neuronal density implies that atrophy with neuron loss is not the sole determinant of reduced cBZR binding in patients with mTLE and hippocampal sclerosis.

Adult↗
PubMed1997

PET and SPECT studies in Parkinson's disease.

Positron emission tomography (PET) and single photon emission tomography (SPECT) provide sensitive means for quantifying the loss of nigrostriatal dopaminergic fibres in Parkinson's disease and for detecting the presence of dopaminergic dysfunction in asymptomatic at-risk relatives and patients with isolated tremor. Functional imaging can also be used to follow the rate of disease progression objectively, determine the efficacy of putative neuroprotective agents, and monitor the viability of transplants of fetal tissue. Additionally, in vivo pharmacological changes associated with development of treatment complications (fluctuations, dyskinesias) can be studied. Loss of dopaminergic projections produces profound changes in resting and activated brain metabolism. PET and SPECT activation studies have suggested that the akinesia of Parkinson's disease is associated with failure to activate the supplementary motor and dorsal pre-frontal areas. Activation of these cortical areas is restored towards normal by the use of dopaminergic medication, striatal transplantation with fetal mesencephalic tissue, and pallidotomy. The aim of this chapter is to review the insight which functional imaging has given us into the pathophysiology of parkinsonism.

Brain↗
PubMed1996

The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study.

We used H2 15O positron emission tomography (PET) to investigate the effect of ethyl alcohol on regional cerebral blood flow in 6 patients with alcohol-responsive essential tremor and 6 age-matched control subjects. The patients were scanned while at rest and during involuntary postural tremor of the extended right arm. Normal control subjects were scanned at rest and during passive wrist oscillation of the right arm at tremor frequency. Regional cerebral blood flow associated with these conditions was measured before and after oral administration of 2 to 3 units of alcohol. The mean blood alcohol level was 35.3 +/- 20.0 mg/dl in the patient group and caused marked suppression of tremor; it was 33.9 +/- 12.9 mg/dl in the control group. Similar to previous PET studies on essential tremor patients, tremor compared with rest was associated with bilateral cerebellar activation including the cerebellar vermis. This pattern of activation differed from passive wrist oscillation where ipsilateral cerebellar activation was observed. Ethanol ingestion led to bilateral decreases of cerebellar blood flow in both tremor patients and normal subjects, and this was associated with suppression of tremor in the patients. Alcohol-associated increases of regional cerebral blood flow were observed in the inferior olivary nuclei in the patients but not in the control subjects. We conclude that alcohol-induced suppression of essential tremor is mediated via a reduction of cerebellar synaptic overactivity resulting in increased afferent input to the inferior olivary nuclei.

Adult↗
PubMed1996

Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington's disease.

We have investigated striatal dopamine D1 and D2 receptor binding in asymptomatic subjects from Huntington's disease (HD) families using positron emission tomography. Nineteen adult subjects at risk of developing HD were scanned with 11C-SCH 23390 and 11C-raclopride to calculate the D1 and D2 receptor binding potential, respectively. Eight of the 19 were shown to have the HD mutation; of these, 4 subjects had significant reductions in striatal dopamine receptor binding. Abnormalities were more common in older subjects and were not correlated with the size of the HD mutation. There was a strong coefficient of correlation between individual levels of striatal D1 and D2 binding in subjects with the mutation. Of 6 other cases with a 50% risk of carrying the HD gene, 1 showed subclinical loss of caudate and putamen D2 binding. Our study suggests that both striatal D1 and D2 dopamine receptors are lost in parallel from both caudate and putamen in presymptomatic HD and that dopamine receptor binding provides a sensitive means of detecting subclinical striatal dysfunction.

Adult↗
PubMed1996

Benzodiazepine receptors in focal epilepsy with cortical dysgenesis: an 11C-flumazenil PET study.

Previous imaging studies using 11C-flumazenil in patients with mesial temporal lobe epilepsy and neocortical partial seizure disorders have found focal decreases in gamma-aminobutyric acid type A/benzodiazepine receptor binding. These studies used subjective visual assessment and a region of interest approach to quantitation. We performed three-dimensional, 11C-flumazenil positron emission tomography in 12 patients with cortical dysgenesis identified by high-resolution volumetric magnetic resonance imaging and in 26 normal subjects. Spectral analysis was used to produce a parametric image of 11C-flumazenil volume of distribution for each subject. Using volumetric normalization and statistical parametric mapping, we compared the entire brain volume of each patient with the brains of the normal group to produce maps of regions of abnormal 11C-flumazenil binding which were then rendered into the volumetric magnetic resonance images. This allowed a correlation of structure and function to be made. Of the 12 patients, 10 showed at least one region of abnormal 11C-flumazenil binding; the abnormal regions were frequently more extensive than were the lesions seen with magnetic resonance imaging. 11C-Flumazenil binding abnormalities were frequently seen in regions of cortex that had a normal magnetic resonance appearance. Lesions were characterized by increases in gamma-aminobutyric acid type A/benzodiazepine receptor availability, and by the decreases found in previous studies. These findings have implications for the neurobiology of seizure disorders associated with cortical dysgenesis and for the management of such patients if surgery is contemplated.

Adult↗