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Biomedical subjects

Peter Brown

Publications and source records attributed to Peter Brown.

At least 37 records · Page 2Linked to original sources
PubMed2005

Existing motor state is favored at the expense of new movement during 13-35 Hz oscillatory synchrony in the human corticospinal system.

Oscillations in local field potentials in the beta-frequency band (13-35 Hz) are a pervasive feature of human and nonhuman primate motor cortical areas. However, the function of such synchronous activity across populations of neurons remains unknown. Here, we test the hypothesis that beta activity may promote existing motor set and posture while compromising processing related to new movements. Three experiments were performed. First, healthy subjects were instructed to make reaction time movements of the outstretched index finger in response to imperative cues triggered by transient increases in corticospinal synchrony, as evidenced by phasic elevations of beta-frequency band microtremor and intermuscular synchrony. Second, healthy subjects were instructed to resist a stretch to the index finger triggered in the same way. Finger acceleration in the reaction time task and transcortical components of the stretch reflex were measured and compared with those elicited by random cue or stretch presentation. Finally, we sought a correlation between finger acceleration in the reaction time task and cortical synchrony directly measured from the electrocorticogram in two patients undergoing functional neurosurgery. We demonstrate that movements are slowed and transcortical responses to stretch are potentiated during periods of elevated beta-band cortical synchrony. The results suggest that physiological periods of beta synchrony are associated with a cortical state in which postural set is reinforced, but the speed of new movements impaired. The findings are of relevance to Parkinson's disease, in which subcortical and cortical beta-band synchronization is exaggerated in the setting of increased tone and slowed movements.

Adult↗
PubMed2005

Basal ganglia local field potential activity: character and functional significance in the human.

Functional neurosurgery in patients with movement disorders has provided a unique opportunity to record directly form the human basal ganglia (BG) and to thereby further our understanding of these 'dark basements of the mind.' Two possibilities exist: either single unit and local field potential (LFP) recordings can be made intra-operatively through microelectrodes, or LFPs may be recorded directly from the deep brain stimulation electrode in the peri-operative period. The LFPs so recorded in the BG of patients are pleomorphic, oscillatory, focal and the product of synchronised current changes in local neuronal elements. They are presently most simply classified by frequency into activities at <8, 8-30 and >60 Hz, although such a schema is unlikely to capture the full complexity of rhythmic synchronisation with respect to behavioural and disease dependency. The best characterised group of LFP oscillations is that at 8-30 Hz. This activity is prominent in the subthalamic nucleus and globus pallidus of Parkinsonian patients withdrawn from their dopaminergic medication. Dopaminergic treatments, behaviourally relevant stimuli and voluntary movement suppress it. The available evidence points to the 8-30 Hz activity being essentially antikinetic in character and inversely related to motor processing. Its exaggeration may therefore contribute to the bradykinesia of Parkinson's disease.

Action Potentials↗
PubMed2005

Different functional loops between cerebral cortex and the subthalmic area in Parkinson's disease.

We investigate the extent to which functional circuits coupling cortical and subthalamic activity are multiple and segregated by frequency in untreated Parkinson's disease (PD). To this end, we recorded EEG and local field potentials (LFPs) from macroelectrodes inserted into the subthalamic nucleus area (SA) in nine awake patients following functional neurosurgery for PD. Patients were studied after overnight withdrawal of medication. Coherence between EEG and SA LFPs was apparent in the theta (3-7 Hz), alpha (8-13 Hz), lower beta (14-20 Hz) and upper beta (21-32 Hz) bands, although activity in the alpha and upper beta bands dominated. Theta coherence predominantly involved mesial and lateral areas, alpha and lower beta coherence the mesial and ipsilateral motor areas, and upper beta coherence the midline cortex. SA LFPs led EEG in the theta band. In contrast, EEG led the depth LFP in the lower and upper beta bands. SA LFP activity in the alpha band could either lead or lag EEG. Thus there are several functional sub-loops between the subthalamic area and cerebral cortical motor regions, distinguished by their frequency, cortical topography and temporal relationships. Tuning to distinct frequencies may provide a means of marking and segregating related processing, over and above any anatomical segregation of processing streams.

Brain Mapping↗
PubMed2005

The brain of LB1, Homo floresiensis.

The brain of Homo floresiensis was assessed by comparing a virtual endocast from the type specimen (LB1) with endocasts from great apes, Homo erectus, Homo sapiens, a human pygmy, a human microcephalic, specimen number Sts 5 (Australopithecus africanus), and specimen number WT 17000 (Paranthropus aethiopicus). Morphometric, allometric, and shape data indicate that LB1 is not a microcephalic or pygmy. LB1's brain/body size ratio scales like that of an australopithecine, but its endocast shape resembles that of Homo erectus. LB1 has derived frontal and temporal lobes and a lunate sulcus in a derived position, which are consistent with capabilities for higher cognitive processing.

Animals↗
PubMed2005

Cortico-cortical coupling in Parkinson's disease and its modulation by therapy.

The role of changes in inter-regional cortical synchronization in the pathophysiology of Parkinson's disease and the mechanism of action of dopaminergic therapy and high frequency subthalamic nucleus (STN) stimulation is unclear. We hypothesized that synchronization between distributed cortical areas would correlate with parkinsonism and that changes in synchronization with treatment would correlate with improvements in parkinsonism. To this end, we recorded scalp EEG in parkinsonian patients off treatment (16 patients, 31 sides) and then separately during high frequency stimulation (HFS) of the STN (16 patients, 31 sides) and following drug treatment (12 patients, 24 sides). All recordings were made at rest to avoid the confounding effects of differences in task performance. The motor Unified Parkinson's Disease Rating Scale (UPDRS) score was determined in each state. We found that EEG-EEG coherence over approximately 10-35 Hz correlated with the severity of parkinsonism, and reductions in cortical coupling over this frequency range with both l-dopa and STN stimulation correlated with clinical improvement. These results suggest that both dopaminergic therapy and STN stimulation may support the restoration of normal cortico-cortical interactions in the frequency domain. This mechanistic similarity may underscore the strong clinical correlation between the therapeutic effects of these treatment modalities.

Adult↗
PubMed2005

Frequency dependent effects of subthalamic nucleus stimulation in Parkinson's disease.

Excessive synchronisation of basal ganglia activity at frequencies < 30 Hz is a hallmark of the parkinsonian state, and may contribute to bradykinesia. Accordingly, we electrically stimulated chronically implanted subthalamic macroelectrodes in 10 Parkinson's disease patients, after overnight withdrawal of anti-parkinsonian medication. We compared the effects of stimulation at 0, 5, 10, 15, 20, 25, 30, and ca. 130 Hz by measuring kinesia time (KT) in a tapping task. Although the effects of direct stimulation were small, frequency-response curves demonstrated local peaks at 5-10 Hz and at 20-25 Hz, superimposed upon an overall tendency for KT to reduce with increasing stimulation frequency. This is consistent with the hypothesis that spontaneous activities in these bands might promote bradykinesia.

Aged↗
PubMed2005

Alkane oxidation by osmium tetroxide.

Aqueous alkaline OsO4 at 85 degrees C oxidizes saturated alkanes, including primary, secondary, and tertiary C-H bonds. Isobutane affords tert-butanol in quantitative yield based on consumed OsO4. Cyclohexane is oxidized to a mixture of adipate and succinate. Ethane and propane are oxidized to acetate, which itself is further oxidized under the reaction conditions. A few turnovers of isobutane oxidation have been accomplished using NaIO4 as the terminal oxidant. The alkane oxidation is an example of ligand accelerated catalysis, as hydroxide binding to OsO4 is required for reaction. A concerted mechanism involving [3+2] addition of a C-H bond to two oxo groups of OsO4(OH)- is suggested, analogous to the pathways for dihydroxylation of alkenes by OsO4(L) and for addition of H2 to OsO4(L).

Alcohols↗
PubMed2005

Lateralization of event-related beta desynchronization in the EEG during pre-cued reaction time tasks.

OBJECTIVE: Here, we investigate whether the event-related desynchronization (ERD) of spectral components of the cortical EEG in the beta (13-30 Hz) frequency range may, in part, index motor selection processes. Specifically, we sought evidence for a contralaterally dominant component of the beta ERD that is limited to trials in which motor selection is possible prior to any imperative cue to move, with attendant behavioural advantage. METHODS: We measured reaction time and assessed the lateralization of beta ERD in 12 healthy volunteers as they performed pre-cued choice reaction time tasks, in which warning S1 cues were either fully predictive about the laterality of a subsequent imperative S2 signal or provided no laterality information. We calculated 'lateralized ERD index' (LERDI), a parallel measure to the lateralized readiness potential in the time domain. RESULTS: Trials with 100% S1-S2 congruency produced significantly shorter reaction times than trials with 50% S1-S2 congruency, where laterality information was unreliable. Beta LERDI indicated significantly greater lateralisation of the ERD in the warning-go interval and of event-related synchronization (ERS) following movement in the 100% condition than in the 50% condition. The lateralization of the beta ERD with respect to hand persisted, even when subjects were instructed to make movements of opposite laterality to those prompted. CONCLUSIONS: Lateralized EEG changes occur in the beta band in the S1-S2 interval prior to movement, but only when informative warning cues allow early motor selection, as suggested by the shortening of reaction time. Furthermore, the enhanced contralateral ERS with 100% S1-S2 congruency suggests that this phenomenon is at least partly independent of afferent feedback, as the same movement was made in the 100 and 50% conditions. SIGNIFICANCE: Lateralized suppression of beta power prior to externally generated movements is associated with motor selection.

Adult↗
PubMed2005

The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson's disease.

Depth recordings in patients with Parkinson's disease (PD) have demonstrated prominent oscillatory activity in the beta frequency (13-35 Hz) band in local field potentials (LFPs) recorded from the region of the subthalamic nucleus (STN). Although this activity has been hypothesized to contribute to bradykinesia, it is unclear to what extent the LFP oscillations arise in the STN and are synchronous with local neuronal discharge. We therefore recorded both LFPs and multi-neuronal activity from microelectrodes inserted into STN in six PD patients (8 sides) during functional neurosurgery. As microelectrodes passed from above STN into STN, there was a pronounced increase in beta frequency band LFP activity. Furthermore, spike-triggered averages of LFP activity suggested that the discharges of neurons in STN were locked to beta oscillations in the LFP. The LFP is therefore likely to represent synchronous activity in populations of neurons in the STN of patients with PD.

Action Potentials↗
PubMed2005

Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease.

Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = -0.65, P < 0.001 and r = -0.33, P < 0.001 for activities over 13-30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.

Action Potentials↗
PubMed2005

Oral L-arginine improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men.

When administered intravenously, L-arginine substantially reduces blood pressure (BP) and peripheral vascular resistance in healthy adults and in patients with vascular disease. Oral L-arginine has been shown to improve endothelial function; however, it is not clear whether oral administration has significant effects on systemic hemodynamics. In a randomized, placebo-controlled, crossover study we tested whether oral L-arginine (12 g/d for 3 wk) affected hemodynamics, glucose, insulin, or C-reactive protein in 16 middle-age men with hypercholesterolemia. After each treatment, hemodynamic variables were measured at rest and during 2 standardized stressor tasks (a simulated public-speaking task and the cold pressor). Regardless of treatment, the stressor tasks increased BP and heart rate (P < or = 0.02). Relative to placebo, L-arginine changed cardiac output (-0.4 L/m), diastolic BP (-1.9 mm Hg), pre-ejection period (+3.4 ms), and plasma homocysteine (-2.0 micromol/L) (P < or = 0.03). The change in plasma L-arginine was inversely correlated with the change in plasma homocysteine (r = -0.57, P = 0.03). Contrary to the results of previous studies of L-arginine administered intravenously, oral administration did not affect total peripheral resistance or plasma insulin. Oral L-arginine also did not affect plasma glucose, C-reactive protein, or lipids. This pattern of findings is consistent with the hypothesis that oral L-arginine reduces BP. This study is the first to describe a hemodynamic mechanism for the hypotensive effect of oral L-arginine and the first to show substantial reductions in homocysteine with oral administration.

Administration, Oral↗
PubMed2005

The relationship between oscillatory activity and motor reaction time in the parkinsonian subthalamic nucleus.

Averaging techniques have demonstrated that movement preparatory cues and movement itself are associated with marked reductions in the oscillatory synchrony of local neuronal populations in the area of the human parkinsonian subthalamic nucleus (STN), as indexed by 8-30 Hz local field potential (LFP) activity. In order to examine the detailed nature and strength of the relationship between reductions in oscillatory activity and movement we examined single-trial LFP activity recorded from the STN area of parkinsonian subjects engaged in a choice reaction task. In this task an initial warning cue was either fully predictive or non-predictive of the hand required to make a later motor response. This motor response was elicited by a second go cue to which data were aligned. We observed a significant linear relationship between the onset time of oscillation reduction after go cues and subsequent motor response time across single trials within subjects. Consistent with this observation we also found a positive correlation of power with response time following go cues. In addition, we observed shorter durations of suppression in fully predictive trials where selection of the response could precede go cue presentation. The results are consistent with the hypothesis that reductions in 8-30 Hz population synchrony in the STN area are related to the processing required for motor preparation, particularly response selection.

Aged↗
PubMed2005

Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat.

Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) of untreated patients implanted with stimulation electrodes for the treatment of Parkinson's disease (PD) demonstrate strong coherence with the cortical electroencephalogram over the beta-frequency range (15-30 Hz). However, studies in animal models of PD emphasize increased temporal coupling in cortico-basal ganglia circuits at substantially lower frequencies, undermining the potential usefulness of these models. Here we show that 6-hydroxydopamine (6-OHDA) lesions of midbrain dopamine neurons are associated with significant increases in the power and coherence of beta-frequency oscillatory activity present in LFPs recorded from frontal cortex and STN of awake rats, as compared with the healthy animal. Thus, the pattern of synchronization between population activity in the STN and cortex in the 6-OHDA-lesioned rodent model of PD closely parallels that seen in the parkinsonian human. The peak frequency of coherent activity in the beta-frequency range was increased in lesioned animals during periods of spontaneous and sustained movement. Furthermore, administration of the dopamine receptor agonist apomorphine to lesioned animals suppressed beta-frequency oscillations, and increased coherent activity at higher frequencies in the cortex and STN, before producing the rotational behaviour indicative of successful lesion. Taken together, these results support a crucial role for dopamine in the modulation of population activity in cortico-basal ganglia circuits, whereby dopaminergic mechanisms effectively filter out synchronized, rhythmic activity at beta-frequencies at the systems level, and shift temporal couplings in these circuits to higher frequencies. These changes may be important in regulating movement.

Adrenergic Agents↗
PubMed2005

Reciprocal interactions between oscillatory activities of different frequencies in the subthalamic region of patients with Parkinson's disease.

Synchronization of neuronal activity evident in the local field potential (LFP) recorded in the subthalamic region of patients with Parkinson's disease occurs at low frequencies (< 30 Hz) and, in some patients following treatment with levodopa, at high frequencies between 65 and 85 Hz. Here we investigate the functional relationship between these different activities by determining whether spontaneous fluctuations in their strength are correlated across time. To this end, we analysed recordings of LFPs from macroelectrodes inserted in the subthalamic area of 16 patients with Parkinson's disease, after treatment with anti-parkinsonian medication. Time-evolving autospectra of LFPs with significant 65-85 Hz peaks (from 21 sides) were computed and correlations between frequency components determined over time. LFP activity in the 5-32 Hz band was significantly negatively correlated with that in the 65-85 Hz band in data averaged across all 21 sides, as well as in 15 (71%) of the individual records. Negative correlations were relatively selective for interactions between these frequency bands and occurred over time epochs of as little as 40 s. They occurred about 50 min after levodopa and were recorded concurrently with contralateral levodopa-induced dyskinesias in all but four cases. Positive correlations were not seen between activities in the 5-32 Hz and 65-85 Hz bands. The spontaneous negative correlations suggest a reciprocal relationship between population synchrony in the high- and low-frequency ranges, and raise the possibility that spontaneous fluctuations in the balance between these activities may contribute to levodopa-induced dyskinesias.

Action Potentials↗
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↗