Biomedical subjects

Peter Brown

Publications and source records attributed to Peter Brown.

At least 73 records · Page 4Linked to original sources

PubMed2004

Waiting time in relation to wait-list size at registration: statistical analysis of a waiting-list registry.

OBJECTIVE: To examine the relationship between the length of a waiting list for elective vascular surgery and the delay before undergoing the operation. METHODS: We undertook a prospective cohort study of patients registered on the waiting list for elective vascular surgery at an acute care hospital in Ontario. Regression analysis of wait times to express the admission rate in one group relative to another, with the ratio of rates being a measure of the difference between groups. RESULTS: List length at registration was associated with length of wait (log-rank test 596.4, p < 0.0001). Patients who were registered when the list length exceeded the weekly service capacity had 70% lower conditional probability of undergoing surgery than those on a list with fewer patients (rate ratio 0.30, 95% confidence interval [CI] 0.26-0.36) after adjustment for sex, age, procedure and period. Registering more than 5 patients when the list was short had an independent effect (rate ratio 0.61, CI 0.45-0.82). CONCLUSIONS: The number of registrants on a surgical wait list has an effect on the length of delay in providing necessary treatment. Our results suggest that a regulated list-length policy may contribute to reducing waiting times. Hospital managers may also use the findings to reduce uncertainty in reporting expected waits given the current list size, thereby improving resource planning.

Cohort Studies↗

PubMed2003

Influence of working memory on patterns of motor related cortico-cortical coupling.

Working memory is implicated in various higher-order cognitive operations. We hypothesized that the availability of a temporal representation in working memory would limit the extent of cortico-cortical coupling necessary to undertake a self-paced rhythmic movement. To this end we examined modulations in cortico-cortical interactions as determined by EEG coherence during a delay interval and subsequent movement reproduction. Right hand movement was initially paced by a metronome beat every 0.9 s, followed by a delay interval, after which hand movement was repeated in an unpaced manner. Movement reproduction after a long (22.5 s, corresponding to 25 movement cycles) compared to a short (5.4 s, corresponding to 6 movement cycles) delay interval was associated with an increased degree of functional coupling in the beta frequency band (12-30 Hz) of the left (movement-driving) hemisphere (F3-FC3, F3-C3 and F3-P3 connections) as well as mesial regions (FCz-FC3, FCz-C3 and Cz-FC3 connections) even though overall behavioral characteristics were not influenced. In addition, analysis of the EEG coherence in the delay period revealed a bilateral frontal network (F3-F4, F3-FC4, F4-FC3 and FC3-FC4 connections). Activity in the latter tended to be synchronized in the theta band (4-8 Hz) and was significantly less strong at 22.5 s than 5.4 s. These data suggest that working memory may be partly subserved by synchronization in a bilateral frontal network and may provide an intrinsic contextual influence that shapes the pattern of cortico-cortical interaction during a given task.

Biomechanical Phenomena↗

PubMed2003

Anticipatory cortico-cortical interactions: switching the task configuration between effectors.

Cognitive regulation enables a subject to plan actions according to context and to respond in a flexible manner to environmental conditions. This implies that foreknowledge about a change in system configuration will trigger preparatory activity in anticipation of the impending transformation. In the present study, we evaluate a unimanual task under two performance conditions that affected the cognitive context, and examine modulations in cortico-cortical interactions as determined by EEG coherence. The right hand movement was performed in an experimental paradigm that necessitated in some trials a voluntary and predictable switch towards a left hand movement, whereas in other trials no switch was required and movement of the right hand continued. The data showed that execution of the right hand movement was associated with an increased degree of task-related coherence in the alpha frequency band (8-12 Hz) in the switching as compared to the no switching condition, and this was most apparent for fronto-parietal connections of the movement-driving (left) as well as for the primed (right) hemisphere. For the primed hemisphere, we observed that the information flow was driven from the F4 electrode overlying the prefrontal area, which suggests that anticipatory preplanning occurred. These data indicate that higher-order cognitive operations bias cortico-cortical interactions in respect of an upcoming switch of the task settings between effectors by recruiting neural resources proactively. Dynamic adjustments in the alpha band suggest that low frequency activity is a characteristic of distributed information processing related to movement planning.

Adult↗

PubMed2003

Risk of emergency admission while awaiting elective cholecystectomy.

BACKGROUND: There is uncertainty regarding the frequency of adverse events while on a surgical waiting list. We assess the relationship between the duration of wait for cholecystectomy and the risk of emergency admission. METHODS: We analyzed time to emergency admission in a group of 761 patients who underwent cholecystectomy after being seen in clinic for biliary colic and placed on waiting lists at 2 acute care centres in Ontario, from 1997 to 2000. RESULTS: Emergency admissions due to worsening symptoms occurred in 51 patients (6.7%) waiting for elective cholecystectomy. The weekly rate of emergency admission was low during the first 19 weeks on the list, but increased almost by a factor of 3 after 20 weeks (rate ratio 2.7; 95% confidence interval 2.0-3.7). Relative to the first 4 weeks on the list, the rate was 1.6 times higher after 20 weeks, 2 times higher after 28 weeks and 7 times higher after 40 weeks. INTERPRETATION: The probability that a patient on a waiting list will be admitted for emergency cholecystectomy consistently increases with the duration of wait, particularly after 20 weeks.

Adult↗

PubMed2003

Transient increases of synchronized neural activity during movement preparation: influence of cognitive constraints.

The ability to prepare movement is an essential requirement for the control of goal-directed actions. It allows us to respond in an adaptable and swift manner to environmental conditions. In the present study, we manipulate cognitive context, by means of response probability, to modify the degree of movement preparation in a delayed cueing task performed with the right hand, and evaluate the neural dynamics (EEG coherence) and behavioural output (reaction time). Task-related coherence was stronger over the contralateral hemisphere. In particular, coherence between the left sensorimotor area and frontal (C3-F3, C3-FC3) and parietal (C3-P3) regions was increased during right-hand movement preparation as compared to rest in the alpha frequency band (8-12 Hz). Reducing response probability diminished the degree of functional coupling between C3-F3 and C3-FC3, and was associated with a prolonged reaction time. These findings suggest an association between neural dynamics and behavioural performance and emphasize that response predictability biases information processing in goal-oriented behaviour.

Adult↗

PubMed2003

Patterning of globus pallidus local field potentials differs between Parkinson's disease and dystonia.

Here we test the hypothesis that there are distinct temporal patterns of synchronized neuronal activity in the pallidum that characterize untreated and treated parkinsonism and dystonia. To this end we recorded local field potentials (LFPs) from the caudal and rostral contact pairs of macroelectrodes implanted into the pallidum of patients for the treatment of Parkinson's disease (12 cases recorded on and off medication, 17 macroelectrodes) and dystonia (10 cases, 19 macroelectrodes). Percentage LFP power in the 11-30 Hz band was decreased and that in the 4-10 Hz band increased across both contact pairs in treated Parkinson's disease compared with untreated Parkinson's disease. Dystonic patients had even less 11-30 Hz power and greater 4-10 Hz power compared with untreated or treated Parkinson's disease patients. The change in the 4-10 Hz band in patients with dystonia was particularly manifest in the more rostral contact pair, presumed to be within or bridging the globus pallidus externus. We conclude that untreated and treated Parkinson's disease and dystonia are characterized by different spatiotemporal patterns of activity in the human pallidum.

Adult↗

PubMed2003

Spectral phase estimates in the setting of multidirectional coupling.

In this paper we explore conventional techniques for estimating the time lag between two signals, using both time and frequency domain measures. We generate test signals to illustrate that in general, estimated temporal relationships between neural sites connected by multiple pathways are ambiguous except in special cases where multidirectional flow of information can be ruled out a priori. Signals are analyzed using the cross correlogram in the time domain, and coherence, phase and directed transfer function (DTF) in the frequency domain. In particular, we show how similar phase and DTF measures can be obtained from qualitatively different dynamical situations (uni and bi-directional flow), and argue that although the phase and DTF combined provide more directionality information than phase alone, one still needs to observe caution if one suspects multidirectional flow.

Models, Neurological↗

PubMed2003

The ipsilateral human motor cortex can functionally compensate for acute contralateral motor cortex dysfunction.

What promotes motor recovery from stroke? To date, studies of recovery from stroke have shown alterations in function in various cortical areas, including the contralesional (unaffected) motor cortex (M1). However, whether these changes contribute to recovery or are mere epiphenomena remains unclear. We therefore sought evidence that the ipsilateral M1 can compensate for dysfunction of the contralateral M1. We recorded the change in force production during a finger-tapping task in response to acute disruption of M1 function by repetitive transcranial magnetic stimulation (rTMS). Neither control (occipital) nor ipsilateral M1 rTMS lead to a change in tapping force. RTMS over contralateral M1 had a short-lived effect and induced changes in ipsilateral M1 excitability around the time that these behavioral effects abated, consistent with delayed compensation by the ipsilateral M1. Simultaneous bilateral M1 stimulation, designed to prevent compensation by the ipsilateral M1, had a large and prolonged effect on tapping force. This is the first demonstration that the ipsilateral primary motor cortex is capable of functionally significant compensation for focal contralateral cortical dysfunction in the adult human and provides a rational basis for interventional treatments aimed at promoting functional compensation in unaffected cortical areas after stroke.

Biomechanical Phenomena↗

PubMed2003

Behavioural cues are associated with modulations of synchronous oscillations in the human subthalamic nucleus.

The speed with which one reacts to an imperative signal depends on the extent to which preceding cues predict that command. When reliable warning cues are available, the processing of the imperative stimulus can be favoured and responses partially pre-prepared, leading to shorter reaction times. Here we seek evidence for involvement of the human basal ganglia in the exploitation of behaviourally relevant predictive cues. To this end, local field potentials (LFPs) were recorded in the region of the subthalamic nuclei of parkinsonian patients during the performance of a pre-cued reaction task in which the cue either predicted or failed to predict the demands of the imperative signal. We demonstrate that LFP activity in the beta frequency band ( approximately 20 Hz) is modulated by the behavioural relevance of the external cue. The findings suggest that, first, the subthalamic nucleus is involved in mediating or facilitating the response advantage derived from predictive cues in humans and, secondly, variations in synchronous neuronal activity in the beta band may contribute to this function in the subthalamic nucleus.

Aged↗

PubMed2003

Acoustic startle evokes bilaterally synchronous oscillatory EMG activity in the healthy human.

Despite animal evidence that the reticulospinal system is of major importance to movement, this motor pathway has remained relatively inaccessible to experimentation in the human. Consequently, little is known about its function in health and disease. Here, we use the acoustic startle response to demonstrate that one type of reticulospinal activity in the human is associated with a characteristic pattern of bilateral synchronization between motor units. Surface electromyography (EMG) was recorded from upper limb muscles in 15 healthy subjects during the reflex startle to unexpected acoustic stimulation, voluntary movements mimicking the startle and during sustained voluntary tonic contraction. Frequency analysis demonstrated autospectral peaks at approximately 14 Hz in deltoid and biceps muscles only during the startle reflex. Similarly, coherence spectra of the EMG recorded between homologous proximal upper limb muscles demonstrated a peak centered approximately 12-16 Hz during reflex startles. Coherence in the 10- to 20-Hz band was significantly greater in the startle reflex than during voluntary sham startles or voluntary tonic contraction for deltoid, but not first dorsal interosseous, muscles. The coherence at 10-20 Hz between EMGs from homologous muscles represents a potential surrogate measure of reticulospinal activity that may be useful in determining the contribution of the reticulospinal system to different types of movement in health and disease.

Acoustic Stimulation↗

PubMed2003

[123I]-FP-CIT-SPECT demonstrates dopaminergic deficit in orthostatic tremor.

There is increasing evidence of a potential role of the dopaminergic system in orthostatic tremor (OT): Association with parkinsonism and treatment effects of L-dopa and dopamine agonists have been reported. Eleven patients with isolated OT had single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123)I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) as dopamine transporter tracer. Results were compared with 12 age-matched normal controls and 12 patients with Parkinson's disease (PD). A marked reduction in striatal tracer binding was found in OT compared to normal controls (p < 0.001). Tracer uptake was significantly higher and more symmetrical than in PD, and caudate and putamen were equally affected. L-dopa challenges, performed in seven patients, showed a small but non-significant improvement on EMG and a small but significant improvement in clinical parameters on blinded video rating. Two-month open-label L-dopa treatment (600 mg/day) led to a small improvement in two of five patients but no significant overall change. Olfactory function on University of Pennsylvania Smell Identification Test was normal. Our finding of a marked tracer uptake reduction on dopamine transporter SPECT supports a role of the dopaminergic system in OT. Lack of evidence of a clinically relevant therapeutic response to L-dopa suggests that other mechanisms must also be involved in the pathogenesis.

Aged↗

PubMed2003

The importance of the dominant hemisphere in the organization of bimanual movements.

The successful control of upper limb movements is an essential skill of the human motor system. Yet, the neural organization of bimanual actions remains an issue of debate. Their control can be directed from both hemispheres, or, coordinated motion might be organized from the dominant (left) hemisphere. In order to unravel the neural mechanisms of bimanual behavior, we analyzed the standard task-related and directed coherence between EEG signals picked up over the primary sensorimotor cortices in right-handed subjects during unimanual as well as bimanual in-phase (symmetrical) and anti-phase (asymmetrical) movements. The interhemispheric coherence in the beta frequency band (>13-30 Hz) was increased in both unimanual and bimanual patterns, compared to rest. During unimanual actions, the drive in the beta band from one primary sensorimotor cortex to the other was greater during movement of the contralateral as opposed to ipsilateral hand. In contrast, during bimanual actions, the drive from the dominant to the non-dominant primary sensorimotor cortex prevailed, unless task constraints induced by an external perturbation resulted in a substantial uncoupling of the hand movements, when interhemispheric coherence would also drop. Together, these results suggest that the contralateral hemisphere predominantly organizes unimanual movements, whereas coupled bimanual movements are mainly controlled from the dominant hemisphere. The close association between changes in interhemispheric coupling and behavioral performance indicates that synchronization of neural activity in the beta band is exploited for the control of goal-directed movement.

Adult↗

PubMed2003

Primary orthostatic tremor is an exaggeration of a physiological response to instability.

Primary orthostatic tremor (POT) is a rare disorder characterised by an intense sense of unsteadiness upon standing and a 16-Hz tremor in which the timing between tremor bursts in different muscles (unilateral and bilateral) remains constant. Hitherto, similar EMG activity has not been described in healthy subjects and it has been postulated that the oscillations seen in POT are primarily pathological. In this study, EMG was recorded from tibialis anterior in healthy subjects who were made unsteady through vestibular galvanic stimulation or leaning backwards. Under these conditions, a peak at approximately 16 Hz was seen in the coherence between the left and right tibialis anterior. This bilateral coherence was absent when the subjects activated the same muscles when not unsteady. These data indicate the existence of a physiological system involved in organising postural responses under circumstances of imbalance and characterised by a highly synchronised output at approximately 16 Hz. In addition, the results suggest that the core abnormality in POT may be an exaggerated sense of unsteadiness when standing still, which then elicits activity from a 16-Hz oscillator normally engaged in postural responses.

Adult↗

PubMed2003

Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson's disease.

Alterations of basal ganglia physiology in parkinsonism may consist of two elements, an increase in the firing rate of neurones and a change in the pattern of synchronisation of discharges between neurones. Recent findings suggest the presence of two principal modes of synchronised activity within the human subthalamo-pallidal-thalamo-cortical circuit, at <30 Hz and >60 Hz. These oscillations are dynamically and systematically modulated by task, thereby suggesting a functional role in movement. More importantly, the two frequency modes are inversely affected by movement, consistent with opposing actions, and differentially expressed according to the prevailing level of dopaminergic activity. It is argued that the balance between these modes determines the effects of basal ganglia-thalamocortical projections on the motor areas of the cortex. The lower frequency oscillations facilitate slow idling rhythms in the motor areas of the cortex, whereas synchronisation at high frequency restores dynamic task-related cortical ensemble activity in the gamma band.

Basal Ganglia↗

PubMed2003

Coherence analysis in the myoclonus of corticobasal degeneration.

We investigated whether myoclonus in corticobasal degeneration (CBD) is cortical or subcortical in origin. Many authors have suggested that the myoclonus in CBD is a subtype of cortical myoclonus, despite the fact that back-averaging fails to detect a cortical correlate to spontaneous or action induced jerks and giant sensory evoked potentials are seldom found. Electroencephalographic-electromyographic (EEG-EMG) and EMG-EMG frequency analysis may be more sensitive to cortical drives when EMG bursts occur at a high frequency and at low amplitudes as in CBD. We evaluated EEG-EMG and EMG-EMG coherence and phase in 5 patients with clinically probable CBD and unilateral, action-induced and stimulus-sensitive myoclonus. We found negligible corticomuscular coherence despite a dramatically exaggerated EMG-EMG coherence. We conclude that an inflated EMG-EMG coherence is found in some patients with CBD and that this is unlikely to be due to an exaggerated cortical drive.

Aged↗

PubMed2003

Magnetic resonance spectroscopy of cerebral cortex is normal in hereditary hyperekplexia due to mutations in the GLRA1 gene.

Excessive startling and stiffness in hereditary hyperekplexia has been attributed to lack of inhibition at either the cortical or brainstem level. Six patients with hereditary hyperekplexia (HH) and a confirmed mutation in the gene encoding the alpha(1) subunit of the glycine receptor (GLRA1) underwent single voxel (1)H magnetic resonance spectroscopy (MRS) of the brainstem and an area of frontal cortex and white matter using a method that allows absolute quantification of metabolites. The results of MRS were within normal limits, although there was a tendency for the neuronal marker N-acetyl aspartate to be reduced in the brainstem of patients compared with that in controls. Thus, we found no evidence to support a deficit in the cerebral cortex in patients with hereditary hyperekplexia due to mutations in the GLRA1 gene.

Adolescent↗

PubMed2003

Mapping cerebral glutamate 13C turnover and oxygen consumption by in vivo NMR.

Regional rates of 13C incorporation from glucose to glutamate were detected in anesthetized rat brain in vivo at 7T with high temporal and spatial resolution using NMR method ICED PEPSI (in vivo carbon edited detection with proton echo planar spectroscopic imaging). Time courses of regional glutamate 13C turnover were fitted by a metabolic model to obtain regional tri-carboxylic acid (TCA) cycle flux and cerebral metabolic rate of oxygen consumption (CMRO2) in each voxel (8 microL) of rat cortex. CMRO2 maps obtained for rats under either alpha-chloralose or morphine anesthesia revealed average cortical values of 1.5 +/- 0.2 (n = 3) and 3.2 +/- 0.3 (n = 4) mumol/g/min, respectively. These values of CMRO2 are in good agreement with previous cortical measurements with coarser spatial resolution. The heterogeneity within each map, which depicted predominantly gray and white matter differences, was significantly greater under morphine (higher cortical activity) than under-alpha-chloralose (lower cortical activity) anesthesia. The regional variations in the basal awake state, which are expected to be even greater, should be considered to avoid partial-volume artifacts in functional activation studies of awake subjects.

Animals↗

PubMed2003

The integration of cortical and behavioural dynamics during initial learning of a motor task.

Here we test the hypothesis that frequency and topographically specific changes in the strength of functional cortico-cortical coupling occur during the acquisition of a completely new task. To this end we studied the behavioural and cortical dynamics of a bimanual multifrequency coordination pattern during which one hand moved at twice the frequency of the other hand. This pattern represents a noninherent assignment and necessitates training before appropriate interlimb decoupling takes place. Results showed that acquisition of the multifrequency task was associated with an improved behavioural output that matched specific changes in the electroencephalogram dynamics. In particular, practice of the coordination pattern was accompanied by a decrease in coherence between the primary sensorimotor regions, and over the midline area in the alpha and beta bands, respectively, along with an increase in functional interhemispheric coupling between the prefrontal areas in the gamma band. These data suggest that the strength of cortico-cortical connectivity is adaptively modified across regions and across frequencies during early learning as the functional couplings are created and optimized for the purpose of movement execution.

Cerebral Cortex↗