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D J Brooks

Publications and source records attributed to D J Brooks.

At least 91 records · Page 5Linked to original sources
PubMed1999

Temporally-specific retrograde amnesia in two cases of discrete bilateral hippocampal pathology.

The role of the hippocampus in retrograde amnesia remains controversial and poorly understood. Two cases are reported of discrete bilateral hippocampal damage, one of which was a rare case of limbic encephalitis secondary to the human herpes virus 6. Detailed memory testing showed marked anterograde memory impairment, but only mild, temporally-limited retrograde amnesia that covered a period of several years in both autobiographical and factual knowledge domains. The absence of extensive retrograde amnesia in these two cases points to a time-limited role for the hippocampus in the retrieval of retrograde memories, and suggests that entorhinal, perirhinal, parahippocampal, or neocortical areas of the temporal lobe may be more critical than the hippocampus proper for long-term retrograde memory functioning. Our findings offer general support to theories of memory consolidation that propose a gradual transfer of memory from hippocampal to neocortical dependency.

Adult↗
PubMed1999

The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins.

Despite the major finding of a genetic defect being responsible for the Parkinson's disease (PD) phenotype in some kindreds with dominantly transmitted PD, the role of inheritance in the cause of the more widespread sporadic form of the disease is still unclear. Twin studies are a classic tool for assessing the influence of hereditary factors in diseases; however, the application of this approach to late-onset illnesses, like PD, poses some problems because of the identification of subclinical cases. In the present longitudinal study we have used [18F]dopa and positron emission tomography to study dopaminergic function in twin pairs at baseline clinically discordant for PD. At baseline, the concordance for subclinical striatal dopaminergic dysfunction was found to be significantly higher in 18 monozygotic than in 16 dizygotic twin pairs (55% vs 18%, respectively). The asymptomatic monozygotic cotwins all showed progressive loss of dopaminergic function over 7 years and 4 developed clinical PD. None of the dizygotic twin pairs became clinically concordant. At follow-up, the combined concordance levels for subclinical dopaminergic dysfunction and clinical PD were 75% in the 12 monozygotic and 22% in the 9 dizygotic twin pairs evaluated twice. Our findings suggest a substantial role for inheritance in sporadic PD.

Aged↗
PubMed1999

Functional imaging of Parkinson's disease: is it possible to detect brain areas for specific symptoms?

H2(15)O PET activation studies enable the brain systems involved in controlling different aspects of motor function to be defined. In Parkinson's disease (PD) freely chosen limb movements are performed slowly. This bradykinesia is associated with selective underactivity of the supplementary motor area and dorsal prefrontal cortex, frontal association areas that receive subcortical input principally from the basal ganglia. At the same time there is compensatory overactivity of the lateral premotor and parietal cortex, areas that have a primary role in facilitating motor responses to visual and auditory cues. This finding explains why PD patients find it easier to perform cued as opposed to freely chosen actions. Levels of activation of the supplementary motor area and dorsal prefrontal cortex in PD can be restored with dopaminergic medication, implants of fetal mesencephalic tissue, internal pallidotomy or high frequency electrical subthalamic stimulation. Activation studies suggest that Parkinsonian rest tremor arises from a combination of inappropriate overactivity of cerebellar connections and loss of dopaminergic function. When tremor is relieved by ventral thalamotomy or thalamic stimulation this cerebellar overactivity is corrected but at the expense of reducing levels of primary motor cortex activation. It has been hypothesised that dyskinesias in PD arise due to altered dopamine receptor binding following chronic exposure to levodopa stimulation. Functional imaging findings, however, are against this hypothesis and rather suggest that downstream increases in basal ganglia opioid neurotransmission are more likely to be relevant.

Brain↗
PubMed1999

A proton magnetic resonance spectroscopy study of the striatum and cerebral cortex in Parkinson's disease.

Animal studies have suggested an increased striatal glutamate activity in Parkinson's disease models, although this has not been substantiated in magnetic resonance spectroscopy studies in patients. Our initial aim was to assess glutamate and glutamine levels in the striatum of patients with idiopathic Parkinson's disease, using multivoxel proton magnetic resonance spectroscopy techniques. Since data were collected from other areas of the brain without a priori selection, information on the cortex was also obtained. Twelve healthy volunteers, seven dyskinetic and five non-dyskinetic patients were studied. Peak area ratios of choline-containing compounds (Cho), glutamine and glutamate (Glx) and N-acetyl moieties including N-acetylaspartate (NAx), relative to creatine (Cr) were calculated. Spectra were analysed from the corpus striatum, the occipital cortex and the temporo-parietal cortex. The median Glx/Cr ratio was unaltered in the striatal spectra of Parkinson's disease patients compared to healthy controls. However, the more severely affected patients had significantly reduced NAx/Cr ratios in spectra localised to the temporo-parietal cortex, compared to healthy controls. Furthermore, the entire patient population had significantly reduced Cho/Cr ratios in spectra from the temporo-parietal cortex, compared to the reference population. We found no evidence of increased striatal glutamate in either dyskinetic or non-dyskinetic Parkinson's disease. However, the low NAx/Cr and Cho/Cr ratios in the temporo-parietal cortex may indicate the presence of subclinical cortical dysfunction.

Aged↗
PubMed1999

Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient.

Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.

Aged↗
PubMed1999

Mapping the network for planning: a correlational PET activation study with the Tower of London task.

We used the Tower of London task (TOL) and H(2)(15)O-PET to map the network of brain structures involved in planning. Six healthy right-handed subjects had 12 measurements of relative regional cerebral blood flow (rrCBF) during six conditions, each performed twice. There was one rest condition, and five sets of TOL problems at different complexity levels, performed on a touch-sensitive computer monitor with the right arm. Complexity was defined as the number of moves required to solve each problem. Activation was analysed in two ways: a category analysis comparing levels of rrCBF during rest and task was done to identify all structures involved in performance of the TOL; and a correlation analysis was carried out to delineate a subset of structures where the levels of rrCBF correlated with task complexity. Activated brain areas in which rrCBF increases did not correlate with complexity could be grouped into: (i) regions belonging to the dorsal stream of visual input processing, namely visual cortical areas 17, 18 and 19, and posterior parietal cortical areas 7 and 40; and (ii) regions involved in the execution and sequencing of arm movements (right cerebellum, left primary motor cortex and supplementary motor area). Brain regions where levels of rrCBF correlated with task complexity included lateral premotor cortex (area 6), rostral anterior cingulate cortex (areas 32 and 24), dorsolateral prefrontal cortex (areas 9 and 46) bilaterally, and right dorsal caudate nucleus. We propose that dorsolateral prefrontal, lateral premotor, anterior cingulate and caudate areas form a network for the planning of movement that interacts with brain areas primarily involved in visual processing and movement execution.

Aged↗
PubMed1999

Huntington's disease progression. PET and clinical observations.

Using serial [(11)C]SCH 23390- and [11C]raclopride-PET, we have measured the rate of loss of striatal dopamine D1 and D2 receptor binding over a mean of 40 months in nine asymptomatic adult Huntington's disease mutation carriers, four patients with symptomatic disease, seven mutation-negative controls and three subjects at risk for the disease. Eight of the nine asymptomatic Huntington's disease mutation carriers had serial [11C]raclopride-PET and showed a mean annual loss of striatal D2 binding of 4.0%. Only five of these eight, however, showed active progression, and they had a mean annual loss of D2 binding of 6.5%. All nine asymptomatic mutation carriers had serial [11C]SCH 23390-PET and showed a mean annual loss of striatal D1 binding of 2. 0%. Four of these subjects demonstrated active progression and they had a mean annual loss of 4.5%. Our four symptomatic Huntington's disease patients showed a mean annual loss of D2 binding of 3.0% and of D1 binding of 5.0%. Loss of striatal D1 and D2 binding was significantly greater in the known mutation carriers than in the combined at-risk and gene-negative groups (P < 0.05). At follow-up PET all subjects were clinically assessed using the Unified Huntington's Disease Rating Scale. Scores for motor function and total functional capacity correlated with PET measures of striatal dopamine receptor binding both in the asymptomatic mutation carriers (D1, P < 0.01) and across the combined asymptomatic and clinically affected Huntington's disease mutation carrier group (D1 and D2, P < 0.001). We conclude that PET measures of striatal D1 and D2 dopamine binding can be used to identify asymptomatic Huntington's disease mutation carriers who are actively progressing and who would thus be suitable for putative neuroprotective therapies. Measures of disease progression rates in Huntington's disease patients and asymptomatic mutation carriers will be of critical importance in future trials of experimental restorative treatments.

Adult↗
PubMed1999

Sequential bilateral transplantation in Parkinson's disease: effects of the second graft.

Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.

Adult↗
PubMed1999

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.

Biological Transport↗
PubMed1999

The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study.

Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some results in animal models have failed to confirm this finding, and the validity of extrapolation to man from animal data is uncertain. To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative H2(15)O positron emission tomography (PET) studies before and after administration of the non-isoform-specific NO synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), in 10 healthy male volunteers. Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determined. Resting global CBF fell from 33.3 +/- 5.3 mL x 100 g(-1) x min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL x 100 g(-1) x min(-1) after L-NMMA (P = 0.001). This fall was reversed by L-arginine administration. Learning sequential finger movements induced increases in rCBF in the left motor, right prefrontal, and bilateral premotor cortices. After NO synthase inhibition with L-NMMA, there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.

Adult↗
PubMed1999

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.

Adult↗
PubMed1999

Evidence for cortical dysfunction in clinically non-demented patients with Parkinson's disease: a proton MR spectroscopy study.

OBJECTIVES: To investigate whether proton magnetic resonance spectroscopy (1H MRS) can detect cortical dysfunction in non-demented patients with Parkinson's disease, and to correlate changes with cognitive function on formal neuropsychological testing. METHODS: Multivoxel 1H MRS was performed in 17 patients with levodopa treated idiopathic Parkinson's disease with out clinical dementia, and 10 age match ed control subjects. Measurements of N-acetylaspartate (NAA)/choline (Cho), NAA/creatine+phosphocreatine (Cr), and Cho/Cr were obtained from right and left temporoparietal cortex and occipital cortex. Fourteen patients with Parkinson's disease underwent a full battery of neuropsychological testing including performance and verbal subtests of the WAIS-R, Boston naming test, FAS test, and California verbal learning test. RESULTS: There were significant temporoparietal cortex reductions in NAA/Cr ratios in right and left averaged spectra of the patients with Parkinson's disease (p=0.012 after Bonferroni correction) and in spectra contralateral to the worst clinically affected limbs of the patients with Parkinson's disease compared with controls (p = 0.003 after Bonferroni correction). There was a significant correlation between reduction in NAA/Cr ratios and measures of global cognitive decline, occurring independently of motor impairment (p=0.019). CONCLUSIONS: This study suggests that 1H MRS can detect temporoparietal cortical dysfunction in non-demented patients with Parkinson's disease. Further longitudinal studies are needed to investigate whether these 1H MRS changes are predictive of future cognitive impairment in the subset of patients with Parkinson's disease who go on to develop dementia, or occur as part of the normal Parkinson's disease process.

Aged↗
PubMed1999

Unilateral pallidotomy for Parkinson's disease: results after more than 1 year.

OBJECTIVE: To examine follow up results of unilateral ventral medial pallidotomy in 22 patients with advanced Parkinson's disease more than 1 year after the operation in comparison with their results (previously reported) at 3 months. METHODS: Twenty patients who had undergone unilateral pallidotomy were assessed with the core assessment programme for intracerebral transplantation (CAPIT) protocol preoperatively, at 3 months postoperatively, and again after a median postoperative follow up of 14 months. Two further patients had only one evaluation 3 months postoperatively. RESULTS: The reduction of contralateral dyskinesias (median 67%) at 3 months was slightly attenuated after 1 year to 55% (both p<0.001 compared with baseline). A less pronounced effect on ipsilateral and axial dyskinesias decreased from 39% to 33% (p<0.005 and p<0.01), and from 50% to 12.5% (p<0.001 and p<0.01), respectively. However, there was no significant change between the 3 month and the follow up assessment. The modest improvement of the contralateral unified Parkinson's disease rating scale (UPDRS) motor score in the "off" state remained improved compared with preoperative levels, but less significantly (26%, p<0.001, and 18%, p<0.01). The activities of daily living (ADL) subscore of the UPDRS in the off state remained improved with median changes of 23% and 22% at follow up (both p<0. 005). There was no significant improvement of "on" state or ipsilateral off state motor scores. Median modified Hoehn and Yahr scores in off and on state were unchanged, as was the time spent off. Speech in off had significantly deteriorated by 1 year after the operation. CONCLUSIONS: The beneficial effects of unilateral pallidotomy persist for at least 12 months and, dyskinesias are most responsive to this procedure.

Adult↗
PubMed1999

Identification of the cerebral loci processing human swallowing with H2(15)O PET activation.

Lesional and electrophysiological data implicate a role for the cerebral cortex in the initiation and modulation of human swallowing, and yet its functional neuroanatomy remains undefined. We therefore conducted a functional study of the cerebral loci processing human volitional swallowing with 15O-labeled water positron emission tomography (PET) activation imaging. Regional cerebral activation was investigated in 8 healthy right handed male volunteers with a randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually cued and monitored with submental electromyogram (EMG). Group and individual linear covariate analyses were performed with SPM96. In five of eight subjects, the cortical motor representation of pharynx was subsequently mapped with transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate findings of hemispheric differences in sensorimotor cortex activation seen with PET. During swallowing, group PET analysis identified increased regional cerebral blood flow (rCBF) (P < 0.001) within bilateral caudolateral sensorimotor cortex [Brodmann's area (BA) 3, 4, and 6], right anterior insula (BA 16), right orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left superiomedial cerebellum, and dorsal brain stem. Decreased rCBF (P < 0.001) was also observed within bilateral posterior parietal cortex (BA 7), right anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42). Individual PET analysis revealed asymmetric representation within sensorimotor cortex in six of eight subjects, four lateralizing to right hemisphere and two to left hemisphere. TMS mapping in the five subjects identified condordant interhemisphere asymmetries in the motor representation for pharynx, consistent with the PET findings. We conclude that volitional swallowing recruits multiple cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex, cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of interhemispheric asymmetry, further substantiated with TMS. Such findings may help explain the variable nature of swallowing disorders after stroke and other focal lesions to the cerebral cortex.

Adult↗
PubMed1998

Selection of a cDNA clone for chicken high-mobility-group 1 (HMG1) protein through its unusually conserved 3'-untranslated region, and improved expression of recombinant HMG1 in Escherichia coli.

Screening of cDNA libraries for the homologous vertebrate proteins high mobility group (HMG) 1 and 2 using DNA probes based on the coding sequences is likely to result in isolation of both HMG1 and HMG2 clones, as well as pseudogenes, which may be transcribed at low levels. However, the 3'-untranslated regions (UTRs) of HMG1 and 2 are quite distinct, and unusually conserved across species. We have used this property to select the true chicken HMG1 cDNA clone from a chicken lymphocyte cDNA library in lambdagt11, using a probe based on the 3'-UTR of rat HMG1 cDNA. The chicken HMG1 cDNA clone is very similar to all the complete HMG1 cDNA clones isolated so far. We suggest that the sequence designated chicken HMG1 in the GenBank Data Library (Accession number D14314) is, in fact, that of HMG2a [and moreover that the recently reported mouse clone (Accession number AF022465), proposed to encode a new HMG protein, HMG4, is also likely to encode an HMG2a, based on the translated amino-acid sequence and 3'-UTR]. We also report much improved expression of intact recombinant HMG1 in Escherichia coli by the use of chloramphenicol rather than ampicillin selection and conditions that limit cell growth. This should be general for all members of the HMG1 (and 2) family which may be toxic to cells (possibly because of the long acidic tail), and may also prove useful in the production of other such proteins.

3' Untranslated Regions↗
PubMed1998

Cerebral control of unimanual and bimanual movements: an H2(15)O PET study.

We measured regional cerebral blood flow (rCBF) during unimanual and bimanual movements using H2(15)O PET. Six healthy volunteers performed unimanual, bimanual-symmetric and bimanual-asymmetric ballistic finger movements. The study was designed to minimize anticipation and preparation of movements. Data were analysed using SPM. Unpredictably paced unimanual movements resulted in significant activation of contralateral primary motor-somatosensory cortex (M1-S1) and mesial frontal cortex (p < 0.001). Performance of symmetric bimanual movements resulted in bilateral activation, but no additional activation of mesial frontal cortex was shown. Comparison of asymmetric with symmetric bimanual movements revealed additional recruitment of mesial frontal cortex (p< 0.001). We suggest that rostral mesial frontal cortex facilitates asymmetric non-mirrored bimanual finger movements.

Aged↗
PubMed1998

Focal cortical release of endogenous opioids during reading-induced seizures.

BACKGROUND: Studies in animals implicate endogenous release of opioid peptides as a mechanism for terminating partial and generalised seizures. To localise dynamic changes in opioid neurotransmission associated with partial seizures and higher cognitive function, we investigated the release of endogenous opioids in patients with reading-induced seizures compared with healthy controls. METHODS: Five patients who had reading epilepsy and six controls had 11C-diprenorphine (DPN) positron-emission-tomography (PET) scans while reading a string of symbols (baseline) or a scientific paper (activation). Statistical parametric mapping was used to find areas with differences in opioid-receptor binding. FINDINGS: On activation scans mean 11C-DPN binding to opioid receptors was significantly lower (p<0.05 corrected for multiple non-independent comparisons) in the left parieto-temporo-occipital cortex (Brodmann area 37) in reading-epilepsy patients compared with controls. INTERPRETATION: These findings suggest that opioid-like substances are involved in the termination of reading-induced seizures.

Adult↗