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Biomedical subjects

Peter Brown

Publications and source records attributed to Peter Brown.

At least 19 recordsLinked to original sources
PubMed2004

Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat.

Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and "global activation". During SWA, there was coherence at approximately 1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at approximately 1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15-60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change.

Action Potentials↗
PubMed2004

Motor inhibition in patients with Gilles de la Tourette syndrome: functional activation patterns as revealed by EEG coherence.

There is considerable evidence that Gilles de la Tourette syndrome (TS) is due to frontal-striatal dysfunction. Here we determine whether adaptive cortical changes occur that might ameliorate the effects of this dysfunction. Specifically we test the hypothesis that increased interactions between selected cortical areas may help compensate through strengthened inhibition of inappropriate motor responses. To this end we recorded EEG in nine unmedicated patients with TS and nine age-matched healthy subjects during a variety of behavioural tasks related to motor inhibition. Functional connectivity between cortical areas was assessed by means of EEG coherence in the alpha frequency band (8-12 Hz). Elevated coherence was found between sensorimotor areas and the prefrontal and mesial frontal cortex during the acute voluntary suppression of tics. The same frontomesial network was overactive in TS patients compared with healthy subjects even when suppression of voluntary movement rather than tics was required during a Go-NoGo task. Behavioural performance in the Go-NoGo task was not different between patients and controls, confirming that the elevated frontomesial coherence in TS was likely to be adaptive rather than functionally disruptive. It is concluded that the gain in inhibitory frontomesial cortical networks is adaptively heightened in TS, and that the same network can also be engaged in the voluntary suppression of tics.

Acoustic Stimulation↗
PubMed2004

Online prediction of self-paced hand-movements from subthalamic activity using neural networks in Parkinson's disease.

The significance of local field potential (LFP) activity in the subthalamic nucleus (STN) of patients with Parkinson's disease is unclear. Here we show that it is possible to predict self-paced hand-movements from the oscillatory nature of the STN LFP on a trial-by-trial basis. To this end we used a neural networks' classification algorithm on features representing different measures of spectral activity. Our experiments were simulated to process online LFP signal recordings collected beforehand from macroelectrodes implanted in STN. With spectral features extracted via wavelet transformation, we were able to predict a voluntary hand-movement's onset with 95% sensitivity and 77% specificity. Most predictions were made over a second in advance of the movement. We conclude that oscillatory LFP activity in STN is directly or indirectly related to processes involved in motor preparation. The ability to predict movement in real-time may open up several experimental and therapeutic possibilities.

Action Potentials↗
PubMed2004

Changes in functional coupling patterns during bimanual task performance.

Functional interaction between cortical areas may involve synchronization of activities, manifest as coherence between EEG signals. However, although EEG-EEG coherence changes when motor tasks are compared to each other or rest, there is little evidence that coherence is modulated within an action. To address this issue we used a bimanual drawer-opening task necessitating asymmetrical hand actions and comprising distinct movement phases. Pronounced modulations in EEG-EEG coherence in the beta band (>12-24 Hz) occurred with movement phase. Differences in coherence due to a switch in role of the hands were mainly observed in the alpha band (8-12 Hz). These findings suggest that inter-regional synchronization changes dynamically across task execution in line with behavioral performance.

Cerebral Cortex↗
PubMed2004

Comparison of accelerator mass spectrometry with gas chromatography for the determination of pesticide residues in individual items in the diets of wild birds and mammals.

Methods to refine the assessment of exposure of wild birds and mammals to pesticides required measurement of pesticide residues in very small samples of their diets. Sample sizes were in the 1-100 mg range, and the target residue for measurement was 0.01 mg/kg. Gas chromatography-mass spectrometry (GC-MS) with large volume injection was compared with the use of an accelerator mass spectrometer (AMS) to measure residues of pesticide labeled at near-background levels with carbon-14. The GC-MS method was able to detect residues down to 0.1 ng per item of diet, and the AMS detected the radiolabel down to 1 mBq (0.06 disintegration per minute, 1 ng of pesticide at the specific activity used) per sample. The target residue level was achieved by the GC-MS method for samples down to 10 mg. The GC method appeared to be best suited to monitoring residues in field studies, and the AMS shows great potential for use in laboratory experiments concerning pesticide degradation.

Animals↗
PubMed2004

Brain state-dependency of coherent oscillatory activity in the cerebral cortex and basal ganglia of the rat.

The nature of the coupling between neuronal assemblies in the cerebral cortex and basal ganglia (BG) is poorly understood. We tested the hypothesis that coherent population activity is dependent on brain state, frequency range, and/or BG nucleus using data from simultaneous recordings of electrocorticogram (ECoG) and BG local field potentials (LFPs) in anesthetized rats. The coherence between ECoG and LFPs simultaneously recorded from subthalamic nucleus (STN), globus pallidus (GP), and substantia nigra pars reticulata (SNr) was largely confined to slow- ( approximately 1 Hz) and spindle- (7-12 Hz) frequency oscillations during slow-wave activity (SWA). In contrast, during cortical activation, coherence was mostly restricted to high-frequency oscillations (15-60 Hz). The coherence between ECoG and LFPs also depended on BG recording site. Partial coherence analyses showed that, during SWA, STN and SNr shared the same temporal coupling with cortex, thereby forming a single functional axis. Cortex was also tightly, but independently, correlated with GP in a separate functional axis. During activation, STN, GP, and, to a lesser extent, SNr shared the same coherence with cortex as part of one functional axis. In addition, GP formed a second, independently coherent loop with cortex. These data suggest that coherent oscillatory activity is present at the level of LFPs recorded in cortico-basal ganglia circuits, and that synchronized population activity is dynamically organized according to brain state, frequency, and nucleus. These attributes further suggest that synchronized activity should be considered as one of a number of candidate mechanisms underlying the functional organization of these brain circuits.

Action Potentials↗
PubMed2004

Synchronous unit activity and local field potentials evoked in the subthalamic nucleus by cortical stimulation.

The responses of single subthalamic nucleus (STN) neurons to cortical activation are complex and depend on the relative activation of several neuronal circuits, making theoretical extrapolation of single neuron responses to the population level difficult. To understand better the degree of synchrony imposed on STN neurons and associated neuronal networks by cortical activation, we recorded the responses of single units, pairs of neighboring neurons, and local field potentials (LFPs) in STN to discrete electrical stimulation of the cortex in anesthetized rats. Stimulation of ipsilateral frontal cortex, but not temporal cortex, generated synchronized "multiphasic" responses in neighboring units in rostral STN, usually consisting of a brief, short-latency excitation, a brief inhibition, a second excitation, and a long-duration inhibition. Evoked LFPs in STN consistently mirrored unit responses; brief, negative deflections in the LFP coincided with excitations and brief, positive deflections with inhibitions. This characteristic LFP was dissimilar to potentials evoked in cortex and structures surrounding STN and was resistant to fluctuations in forebrain activity. The short-latency excitation and associated LFP deflection exhibited the highest fidelity to low-intensity cortical stimuli. Unit response failures, which mostly occurred in caudal STN, were not associated with LFPs typical of rostral STN. These data suggest that local populations of STN neurons can be synchronized by both direct and indirect cortical inputs. Synchronized ensemble activity is dependent on topography and input intensity. Finally, the stereotypical, multiphasic profile of the evoked LFP indicates that it might be useful for locating the STN in clinical as well as nonclinical settings.

Action Potentials↗
PubMed2004

Motor cortex inhibition induced by acoustic stimulation.

The influence of the brainstem motor system on cerebral motor areas may play an important role in motor control in health and disease. A new approach to investigate this interaction in man is combining acoustic stimulation activating the startle system with transcranial magnetic stimulation (TMS) over the motor cortex. However, it is unclear whether the inhibition of TMS responses following acoustic stimulation occurs at the level of the motor cortex through reticulo-cortical projections or subcortically, perhaps through reticulo-spinal projections. We compared the influence of acoustic stimulation on motor effects elicited by TMS over motor cortical areas to those evoked with subcortical electrical stimulation (SES) through depth electrodes in five patients treated with deep brain stimulation for Parkinson's disease. SES bypasses the motor cortex, demonstrating any interaction with acoustic stimuli at the subcortical level. EMG was recorded from the contralateral biceps brachii muscle. Acoustic stimulation was delivered binaurally through headphones and used as a conditioning stimulus at an interstimulus interval of 50 ms. When TMS was used as the test stimulus, the area and amplitude of the conditioned motor response was significantly inhibited (area: 57.5+/-12.9%, amplitude: 47.9+/-7.4%, as percentage of unconditioned response) whereas facilitation occurred with SES (area: 110.1+/-4.3%, amplitude: 116.9+/-6.9%). We conclude that a startle-evoked activation of reticulo-cortical projections transiently inhibits the motor cortex.

Acoustic Stimulation↗
PubMed2004

Correlation of quantitative EEG in acute ischemic stroke with 30-day NIHSS score: comparison with diffusion and perfusion MRI.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) methods such as diffusion- (DWI) and perfusion-weighted (PWI) imaging have been widely studied as surrogate markers to monitor stroke evolution and predict clinical outcome. The utility of quantitative electroencephalography (qEEG) as such a marker in acute stroke has not been intensively studied. The aim of the present study was to correlate ischemic cortical stroke patients' clinical outcomes with acute qEEG, DWI, and PWI data. MATERIALS AND METHODS: DWI and PWI data were acquired from 11 patients within 7 and 16 hours after onset of symptoms. Sixty-four channel EEG data were obtained within 2 hours after the initial MRI scan and 1 hour before the second MRI scan. The acute delta change index (aDCI), a measure of the rate of change of average scalp delta power, was compared with the National Institutes of Health Stroke Scale scores (NIHSSS) at 30 days, as were MRI lesion volumes. RESULTS: The aDCI was significantly correlated with the 30-day NIHSSS, as was the initial mean transit time (MTT) abnormality volume (rho=0.80, P<0.01 and rho=0.79, P<0.01, respectively). Modest correlations were obtained between the 15-hour DWI lesion volume and both the aDCI and 30-day NIHSSS (rho=0.62, P<0.05 and rho=0.73, P<0.05, respectively). CONCLUSIONS: In this small sample the significant correlation between 30-day NIHSSS and acute qEEG data (aDCI) was equivalent to that between the former and MTT abnormality volume. Both were greater than the modest correlation between acute DWI lesion volume and 30-day NIHSSS. These preliminary results indicate that acute qEEG data might be used to monitor and predict stroke evolution.

Acute Disease↗
PubMed2004

Cortico-cortical coupling patterns during dual task performance.

We investigated the neural correlates of dual task performance using EEG coherence as a measure of the functional coupling between cortical regions. Nine healthy participants performed a rhythmical movement with the right hand and an isometric contraction with the left hand, either initiated simultaneously or successively. EEG data revealed that dual task performance was associated with stronger coherence in left hemispheric and mesial areas than the sum of the tasks performed separately in the beta (>12-30 Hz), but not alpha (8-12 Hz), band. This effect was more pronounced when the two assignments were initiated simultaneously, as opposed to successively. The data demonstrate that the pattern of cortico-cortical coupling during bimanual actions is not just the sum of that associated with its component parts, but is increased according to coordinative demands and processing load.

Arm↗
PubMed2004

Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance.

Although the basal ganglia play an important role in self-generated movement, their involvement in externally paced voluntary movement is less clear. We recorded local field potentials (LFPs) from the region of the subthalamic nuclei of eight patients with Parkinson's disease during the performance of a warned reaction time task in which an imperative cue instructed the subject to move or not to move. In 'go' trials, LFP activity in the beta frequency band ( approximately 20 Hz) decreased prior to movement, with an onset latency that strongly correlated with mean reaction time across patients. This was followed by a late post-movement increase in beta power. In contrast, in 'nogo' trials the beta power drop following imperative signals was prematurely terminated compared with go trials and reversed into an early beta power increase. These differences were manifest as power increases when go trials were subtracted from nogo trials. In six patients these relative beta power increases in nogo-go difference trials were of shorter latency than the respective reaction time. The findings suggest that, firstly, the subthalamic nucleus is involved in the preparation of externally paced voluntary movements in humans and, secondly, the degree of synchronization of subthalamic nucleus activity in the beta band may be an important determinant of whether motor programming and movement initiation is favoured or suppressed.

Aged↗
PubMed2004

Patterns of EMG-EMG coherence in limb dystonia.

Dystonia of the limbs may be due to a wide range of aetiologies and may cause major functional limitation. We investigated whether the previously described pathological 4 to 7 Hz drive to muscles in cervical dystonia is present in patients with aetiologically different types of dystonia of the upper and lower limbs. To this end, we studied 12 symptomatic and 4 asymptomatic carriers of the DYT1 gene, 6 patients with symptomatic dystonia due to focal basal ganglia lesions, and 11 patients with fixed dystonia, a condition assumed to be mostly psychogenic in aetiology. We evaluated EMG-EMG coherence in the tibialis anterior (TA) of these and 15 healthy control subjects. Ten of 12 (83%) of symptomatic DYT1 patients had an excessive 4 to 7 Hz common drive to TA, evident as an inflated coherence in this band. This drive also involved the gastrocnemius, leading to co-contracting electromyographic bursts. In contrast, asymptomatic DYT1 carriers, patients with symptomatic dystonia, patients with fixed dystonia, and healthy subjects showed no evidence of such a drive or any other distinguishing electrophysiological feature. Moreover, the pathological 4 to 7 Hz drive in symptomatic DYT1 patients was much less common in the upper limb, where it was only present in 2 of 6 (33%) patients with clinical involvement of the arms. We conclude that the nature of the abnormal drive to dystonic muscles may vary according to the muscles under consideration and, particularly, with aetiology.

Adult↗
PubMed2004

Natural history and syndromic associations of orthostatic tremor: a review of 41 patients.

Orthostatic tremor (OT) is a rare condition characterized by unsteadiness when standing still that is relieved when sitting or walking and is thought to arise from a central generator in the cerebellum or brainstem. OT is considered to be a distinct, discrete condition, and little is known about its demographic characteristics, natural history, associated features, and treatment response. We have reviewed these aspects in 41 OT patients fulfilling current diagnostic criteria, seen at our institution between 1986 and 2001. We classified 31 (75%) as having idiopathic "primary OT" either with (n = 24) or without an associated postural arm tremor. We found that 10 of 41 (25%) cases had additional neurological features, and we defined this group as having "OT plus" syndrome. Of these 10, 6 had parkinsonism; 4 of these had typical Parkinson's disease (PD), 1 had vascular and 1 had drug-induced parkinsonism. Among the remaining 4 patients, 2 had restless legs syndrome (RLS), 1 had tardive dyskinesia, and 1 orofacial dyskinesias of uncertain etiology. One patient with PD and the patient with vascular parkinsonism also had RLS. Age at onset was significantly earlier in the "primary OT" (mean +/- SD, 50.4 +/- 15.1) than in the "OT plus" (61.8 +/- 6.4; z = 2.7; P =.006) group. In 7 of the 10 "OT plus" patients, OT leg symptoms preceded the onset of additional neurological features. OT appeared to be underdiagnosed, and on average, it took 5.7 years from the initial complaints until a diagnosis was made. In general, treatment response to a variety of drugs such as clonazepam, primidone, and levodopa was poor. In most cases, OT symptoms remain relatively unchanged over the years, but in 6 of 41 cases (15%), the condition gradually worsened over the years, and in some of these cases, symptoms spread proximally to involve the trunk and arms. OT may not be a discrete disorder as commonly believed and associated features like parkinsonism present in nearly 25% of cases. Dopaminergic dysfunction may have a role in the pathophysiology of this disorder.

Aged↗
PubMed2004

A common N400 EEG component reflecting contextual integration irrespective of symbolic form.

OBJECTIVE: Electroencephalographic (EEG) waves modulated by context have been identified about 400 ms after presentation of a new semantic stimulus, such as a word or a number, within a prior context. However, it is not known if any component of these waves arises from a common brain system activated by different symbolic forms. METHODS: Multichannel EEG recordings were performed in 10 healthy subjects during the presentation of lexical and numerical series with congruent and incongruent endings. EEG was analysed using a combination of independent component and cluster analysis. RESULTS: Contextual integration of semantic stimuli elicited a negative independent component at around 400 ms that shared the same pattern of spatio-temporal covariation across numerical series and sentences within single subjects. This independent component was bigger following incongruent endings. CONCLUSIONS: These data provide evidence that one element of the activity contributing to the N400 is common to different symbolic forms. SIGNIFICANCE: One component of the brain systems evaluating the semantic inter-relationship of new stimuli with prior context may be common to different symbolic forms.

Acoustic Stimulation↗
PubMed2004

Effects of stimulation of the subthalamic area on oscillatory pallidal activity in Parkinson's disease.

The pattern of neuronal discharge within the basal ganglia is disturbed in Parkinson's disease (PD). In particular, there is a tendency for neuronal elements to synchronise at around 20 Hz in the absence of dopaminergic treatment, whereas this activity can be replaced by spontaneous synchronisation at much higher frequencies (>70 Hz) following dopaminergic treatment [J. Neurosci. 21 (2001) 1033; Brain 126 (2003) 2153]. In two PD patients (3 sides), we show that stimulating the subthalamic area at around 20 Hz exacerbates synchronisation at similar frequencies in the globus pallidus interna, the major output structure of the human basal ganglia. In contrast, stimulating the subthalamic area at >70 Hz suppresses pallidal activity at about 20 Hz. Clinically, stimulation of the subthalamic area at similar high frequencies reverses parkinsonism and forms the basis of therapeutic deep brain stimulation in PD. The results point to a possible common mechanism by which both dopaminergic treatment associated synchronisation of subthalamic activity at very high frequency and synchronisation imposed by therapeutic stimulation of the subthalamic area inhibit an abnormal and potentially deleterious synchronisation of basal ganglia output at around 20 Hz. If this activity is unchecked by synchronisation at higher frequency, then pathological 20-Hz oscillations may cascade through the basal ganglia, increasing at subsequent levels of processing.

Aged↗
PubMed2004

Functional significance of the ipsilateral hemisphere during movement of the affected hand after stroke.

Previous fMRI observations have suggested increased task-related activation of the ipsilateral cerebral motor cortex in patients recovering from stroke. This is generally taken to infer an increased output from this area, although the functional relevance of this has been questioned. Here, we use directed EEG coherence to reveal whether there is increased informational flow from the ipsilateral motor cortex following motor stroke, and through correlation with degree of recovery, establish that this pattern of activity is associated with limited functional improvement. Unrecovered (n = 14), recovered (n = 11) patients and healthy subjects (n = 16) performed an isometric grip task with either hand that corresponded to 25% of individual maximum force, while EEG was recorded. For unrecovered stroke patients, most task-related information flow between the sensorimotor cortices in the low beta band of the EEG came from the ipsilateral (undamaged) hemisphere during grip with the affected hand. This was not the case when they gripped with their unaffected hand, when cortical activity was driven from the contralateral sensorimotor cortex. The latter pattern was also seen in recovered patients and controls. These findings suggest a functional role for the ipsilateral hemisphere in organizing movement of the impaired limb following stroke, but only in those patients that do not make a good functional recovery. Patients making a fuller recovery organize movement-related cortical activity from the hemisphere contralateral to movement.

Adolescent↗
PubMed2004

Myoclonus: current concepts and recent advances.

Myoclonus presents as a sudden brief jerk caused by involuntary muscle activity. An organisational framework is crucial for determining the medical significance of the myoclonus as well as for its treatment. Clinical presentations of myoclonus are divided into physiological, essential, epileptic, and symptomatic. Most causes of myoclonus are symptomatic and include posthypoxia, toxic-metabolic disorders, reactions to drugs, storage disease, and neurodegenerative disorders. The assessment of myoclonus includes an initial screening for those causes that are common or easily corrected. If needed, further testing may include clinical neurophysiological techniques, enzyme activities, tissue biopsy, and genetic testing. The motor cortex is the most commonly shown myoclonus source, but origins from subcortical areas, brainstem, spinal, and peripheral nervous system also occur. If treatment of the underlying disorder is not possible, treatment of symptoms is worthwhile, although limited by side-effects and a lack of controlled evidence.

Animals↗