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Biomedical subjects

R G Brown

Publications and source records attributed to R G Brown.

At least 37 records · Page 2Linked to original sources
PubMed2000

The impact of deep brain stimulation on executive function in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi) improves Parkinson's disease and increases frontal blood flow. We assessed the effects of bilateral DBS on executive function in Parkinson's disease patients, seven with electrodes implanted in the STN and six in the GPi. Patients were assessed off medication with stimulators off, on and off again. The groups showed differential change with stimulation on the Reitan Trail-Making test (TMT B) (STN more improved) and on some measures of random number generation and Wisconsin Card Sorting (STN improved, GPi worse with stimulation). Across the groups, stimulation speeded up responding (Stroop control trial, TMT A) and improved performance on paced serial addition and missing digit tests. Conversely, conditional associative learning became more errorful with stimulation across the two groups. In general, change in performance with stimulation was significant for the STN but not the GPi group. These results support two opposite predictions. In support of current models of Parkinson's disease, 'releasing the brake' on frontal function with DBS improved aspects of executive function. Conversely, disruption of basal ganglia outflow during DBS impaired performance on tests requiring changing behaviour in novel contexts as predicted by Marsden and Obeso in 1994.

Association Learning↗
PubMed1999

Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease.

Recent pathophysiological models of Parkinson's disease have led to new surgical approaches to treatment including deep brain stimulation (DBS) and lesioning of basal ganglia structures. Various measures of upper limb akinesia were assessed in 6 patients with bilateral DBS of the internal pallidum and 6 with DBS of the subthalamic nucleus. Stimulation improved a number of aspects of motor function, and particularly movement time, and force production. Time to initiate movements, and to perform repetitive movements also improved but less dramatically. Processes indicating preparatory motor processes showed no significant change. Few significant differences were found between the internal pallidum and subthalamic nucleus groups. In general, the effects of DBS closely parallel previous reports of the effects of dopaminergic medication. It is suggested that disrupted pallidal output in Parkinson's disease interferes with the rate, level, and coordination of force production but has little effect on preparatory processes. The similarity of the effects of subthalamic nucleus and internal pallidum stimulation suggests this disrupted outflow is the most important determinant of upper limb akinesia in Parkinson's disease. The effects of DBS were similar to the effects of unilateral pallidal lesions reported elsewhere.

Brain↗
PubMed1999

The effects of posteroventral pallidotomy on the preparation and execution of voluntary hand and arm movements in Parkinson's disease.

We studied the effect of posteroventral pallidotomy on movement preparation and execution in 27 parkinsonian patients using various motor tasks. Patients were evaluated after overnight withdrawal of medication before and 3 months after unilateral pallidotomy. Surgery had no effect on initiation time in unwarned simple and choice reaction time tasks, whereas movement time measured during the same tasks was improved for the contralesional hand. Movement times also improved for isometric and isotonic ballistic movements. In contrast, repetitive, distal and fine movements measured in finger-tapping and pegboard tasks were not improved after pallidotomy. Preparatory processes were investigated using both behavioural and electrophysiological measures. A precued choice reaction time task suggested an enhancement of motor preparation for the contralesional hand. Similarly, movement-related cortical potentials showed an increase in the slope of the late component (NS2) when the patients performed joystick movements with the contralesional hand. However, no significant change was found for the early component (NS1) or when the patient moved the ipsilesional hand. The amplitude of the long-latency stretch reflex of the contralesional hand decreased after surgery. In summary, the data suggest that pallidotomy improved mainly the later stages of movement preparation and the execution of proximal movements with the contralesional limb. These results provide detailed quantitative data on the impact of posteroventral pallidotomy on previously described measures of upper limb akinesia in Parkinson's disease.

Electroencephalography↗
PubMed1998

Relation of coagulation parameters to patency and recurrent ischemia in the Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial.

Current protocols for use of tissue-type plasminogen activator in acute myocardial infarction include heparin estimated by the activated partial thromboplastin time (aPTT). Recent reports indicate a risk of recurrent ischemic events with long aPTT values. Longer aPTT values in the Thrombolysis in Myocardial Infarction-II (TIMI II) Trial, obtained within the first 48 hours, were associated with patency at 18 to 48 hours and better left ventricular function at discharge (average 9.6 days), but also with emergency catheterizations within the first 48 hours and, weakly, with recurrent ischemia during the first 18 hours. A moderate decrease in fibrinogen, compared with a "small" decrease, was also associated with patency, but a "large" decrease was associated with hemorrhagic events. Patency was associated with higher fibrinogen values and higher plasminogen values at baseline. The aPTT results support frequent monitoring during the first 24 to 48 hours to ensure optimal clinical outcome. The coagulation factor results suggest that there may be an optimum window for fibrinogenolysis in this setting.

Fibrinogen↗
PubMed1998

Executive processes in Parkinson's disease--random number generation and response suppression.

In producing random numbers, subjects typically deviate systematically from statistical randomness. It is considered that these biases reflect constraints imposed by underlying structures and processes, rather than a deficient concept of randomness. Random number generation (RNG) places considerable demands on executive processes, and provides a possibly useful tool for their investigation. A group of patients with Parkinson's disease (PD) and a group of controls were tested on a RNG task, both alone and with a concurrent attention-demanding task (manual tracking). Both groups showed the biases in RNG described previously, including a strong counting tendency and repetition avoidance. Overall RNG performance did not differ between the groups, although differences were found in the counting biases in the patient and control groups, with the controls showing a bias towards counting in twos, and the patients a bias towards counting in ones. The secondary task reversed the bias shown by controls and exacerbated the bias in the patients. A network modulation model may help explain many of the features of RNG. We suggest that naturally biased output from an associative network must be actively suppressed by an attention-demanding, limited-capacity process. This suppression may be disrupted by the pathophysiology of PD and by concurrent tasks. Convergent evidence from various sources is discussed which supports a role of the dorsolateral prefrontal cortex (DLPFC) in this process.

Aged↗
PubMed1998

Training improves the speed of aimed movements in Parkinson's disease.

In this study, the extent to which bradykinesia in patients with idiopathic Parkinson's disease can be influenced by practice and by specific training strategies was investigated. Fifteen patients with Parkinson's disease tested after withdrawal of anti-Parkinson medication, and 15 matched control subjects, practised a ballistic aiming task. Performance was tested before, during and after training and again 1 h later. The Parkinson's disease patients and control subjects were randomly assigned to one of two training schedules, practising with or without rhythmic auditory cues. At baseline, the Parkinson's disease patients showed longer movement times, with a marked decrease in maximum acceleration and deceleration in the initial open-loop phase compared with those of the control subjects. With training, they were able to make significant improvement in the speed of aimed movements, particularly in the early movement phase, without any deterioration in accuracy. These effects transferred to an untrained limb and were at least partially maintained after a 1-h delay. While patients remained impaired relative to control subjects at all phases of training and follow-up, the patients' performance at the end of training did not differ significantly from the control subjects' baseline function. Contrary to expectation, rhythmic auditory cues did not enhance improvement in the speed of aimed movements in either patients or control subjects. If anything, less improvement was shown in the cued groups, although there were suggestions that the aiming skill was retained better over the delay period. The results demonstrate preserved abilities to improve speed of single ballistic aiming movements in Parkinson's disease patients and the possibility of reducing bradykinesia by training.

Aged↗
PubMed1998

The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation.

Random number generation is an attention-demanding task that engages working memory and executive processes. Random number generation requires holding information 'on line', suppression of habitual counting, internally driven response generation and monitoring of responses. Evidence from PET studies suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in the generation of random responses. We examined the effects of short trains of transcranial magnetic stimulation (TMS) over the left or right DLPFC or medial frontal cortex on random number generation in healthy normal participants. As in previous evidence, in control trials without stimulation participants performed poorly on the random number generation task, showing repetition avoidance and a tendency to count. Brief disruption of processing with TMS over the left DLPFC changed the balance of the individuals' counting bias, increasing the most habitual counting in ones and reducing the lower probability response of counting in twos. This differential effect of TMS over the left DLPFC on the balance of the subject's counting bias was not obtained with TMS over the right DLPFC or the medial frontal cortex. The results suggest that, with disruption of the left DLPFC with TMS, habitual counting in ones that has previously been suppressed is released from inhibition. From these findings a network modulation model of random number generation is proposed, whereby suppression of habitual responses is achieved through the modulatory influence of the left DLPFC over a number-associative network in the superior temporal cortex. To allow emergence of appropriate random responses, the left DLPFC inhibits the superior temporal cortex to prevent spreading activation and habitual counting in ones.

Adult↗
PubMed1998

Phytochrome regulation and differential expression of gibberellin 3beta-hydroxylase genes in germinating Arabidopsis seeds.

Despite extensive studies on the roles of phytochrome in photostimulated seed germination, the mechanisms downstream of the photoreceptor that promote germination are largely unknown. Previous studies have indicated that light-induced germination of Arabidopsis seeds is mediated by the hormone gibberellin (GA). Using RNA gel blot analyses, we studied the regulation of two Arabidopsis genes, GA4 and GA4H (for GA4 homolog), both of which encode GA 3beta-hydroxylases that catalyze the final biosynthetic step to produce bioactive GAs. The newly isolated GA4H gene was expressed predominantly during seed germination. We show that expression of both GA4 and GA4H genes in imbibed seeds was induced within 1 hr after a brief red (R) light treatment. In the phytochrome B-deficient phyB-1 mutant, GA4H expression was not induced by R light, but GA4 expression still was, indicating that R light-induced GA4 and GA4H expression is mediated by different phytochromes. In contrast to the GA4 gene, the GA4H gene was not regulated by the feedback inhibition mechanism in germinating seeds. Our data demonstrate that expression of GA 3beta-hydroxylase genes is elevated by R light, which may result in an increase in biosynthesis of active GAs to promote seed germination. Furthermore, our results suggest that each GA 3beta-hydroxylase gene plays a unique physiological role during light-induced seed germination.

Amino Acid Sequence↗
PubMed1998

An unusual enhancement of motor performance during bimanual movement in Parkinson's disease.

In both clinical and laboratory tests, patients with Parkinson's disease have considerable difficulty in performing different manual tasks simultaneously with the two hands. The present study reports on an unusual enhancement in performance under such conditions in a substantial proportion of patients tested. When performed at the same time as repetitive tapping tasks, the ability to rapidly place pegs in holes improved in almost half of the patients compared with unimanual performance of the peg task. Various possible explanations are considered for this unusual finding. The two most plausible, and testable, relate to either the withdrawal of attention from the task permitting a more automatic mode of execution, or a facilitation provided by sensory feedback from the simultaneous tapping task.

Adult↗
PubMed1997

Evidence for a long-lasting single administration contraceptive vaccine in wild grey seals.

A single-administration birth control vaccine based on liposome delivery of porcine zona pellucida antigens reduced pup production in grey seals (Halichoerus grypus) by about 90%. Anti-porcine zona pellucida titers of individual seals with two or more recaptures were variable but without a diminishing trend during the 5 year post-immunization period. Seals that produced at least one or more pups during the 2-5 year post-immunization period when the vaccine is fully effective, had an average anti-porcine zona pellucida titer of 5% of the reference serum. In contrast, the subset of seals that did not reproduce but were recaptured during the breeding season had an average titer of 31% of the reference serum. As measured by antibody titers and pup production, there were no differences in efficacy of the vaccine in 14-, 20- and 21-year-old female grey seals.

Age Factors↗
PubMed1997

Temporal trends in antibody production in captive grey, harp and hooded seals to a single administration immunocontraceptive vaccine.

The temporal production of antibody to a single-administration immunocontraceptive vaccine, known to be immunocontraceptive in free-ranging female grey seals (Halichoerus grypus), was studied in captive grey seals, harp seals (Phoca groenlandica) and hooded seals (Cystophora cristata). The vaccine is based on liposome delivery of porcine zona pellucida antigens. When measured by antigen capture, the response of hooded and harp seals to the vaccine was similar to the response of grey seals. Determination of antibody production by ELISA with protein A, ELISA with rabbit anti-seal immunoglobulin sera and SDS-PAGE after affinity chromatography confirmed the similarity in response to the vaccine by grey and harp seals, but suggested lower titers in hooded seals. The vaccine produced titers in captive, juvenile grey and harp seals known to be immunocontraceptive in wild, adult grey seals.

Animals↗
PubMed1997

Rapid rate transcranial magnetic stimulation--a safety study.

We assessed the safety of repeated short trains (4 stimuli) of rapid-rate transcranial magnetic stimulation (rrTMS) over the left motor cortex in 6 healthy normal subjects. rrTMS involved two separate blocks of 50 consecutive trains of 4 stimuli at a frequency of 20 Hz and an intensity of 5-10% above active motor threshold. We monitored EEG, and assessed aspects of neurological (balance, gait, two-point discrimination, blood pressure, pulse rate), cognitive (attention, memory, executive function) and motor function (speed of movement initiation and execution and manual dexterity) before and after the two blocks of rrTMS. EMG was also recorded from a number of hand, forearm and arm muscles contralateral to the site of stimulation. Two blocks of repeated rrTMS at 20 Hz and 5-10% above active motor threshold did not produce any adverse effects. Measures of neurological, cognitive and motor function showed no change following rrTMS. From the EMG recording there was evidence of increase in the amplitude of the motor evoked potentials (MEPs) recorded from the biceps in one subject during the first block of rrTMS, but this did not occur in the second block. A similar magnification of MEPs was also observed in another subject only during the second block of stimulation. When applied using parameters falling within published guidelines (Pascual-Leone et al., 1993; Pascual-Leone et al., 1994), repeated rrTMS is a relatively safe technique in healthy normal subjects. As rrTMS allows disruption of cortical function for a longer period, it has the potential of becoming a particularly useful tool for the study of cognitive function as well as sensory or motor function.

Adult↗
PubMed1997

Learning manual pursuit tracking skills in patients with Parkinson's disease.

Evidence from a number of sources identifies the putamen and its ultimate cortical projection sites as forming a possible substrate for motor learning. The present paper describes two experiments which explored motor learning of a pursuit tracking task under first (position) and second (velocity) order control dynamics, in patients with Parkinson's disease on and off (experiment 2 only) their normal dopaminergic medication. In neither experiment did the medicated patients show evidence of significant impairment in learning the tasks. In the velocity tracking task, however, the patients off medication showed significantly less improvement in performance with practice. The discussion considers a number of possible interpretations of this finding. Contemporary cognitive theories of motor learning consider behavioural change with practice to be the combined action of an automatic procedural system, together with input from a conscious declarative system. Development of declarative knowledge about the task may have changed the nature of the process involved, from a visually guided task to a more predictive one based upon an internal representation. Evidence from various sources suggests that patients with Parkinson's disease have particular problems with this mode of control, thus making the task more difficult. It is suggested that motor control deficits have not been adequately considered in previous studies on motor learning, and that the evidence from clinical studies for a role of the putamen/supplementay motor area in motor learning remains equivocal.

Aged↗
PubMed1997

A comparison of certified and noncertified pet foods.

The market presents the buyer with a wide array of pet food choices. Marketing pet foods has changed in the last decade and today foods may be bought at a variety of outlets. The present study compares nutrient composition, digestibility, and effect on urine pH (cat foods only) of selected certified and noncertified pet foods from different outlets. The selected foods were considered analogous in terms of declared ingredients and macronutrient profiles. The analytical methods used were those of the Association of Official Analytical Chemists as described in the Pet Food Certification Protocol of the Canadian Veterinary Medical Association. The test foods were sampled 4 times from August 1994 to July 1995. Both certified and noncertified products met the nutritional requirements on a consistent basis, although 1 of the noncertified dog foods consistently failed to meet the zinc requirements. This same product also failed to meet the Canadian Veterinary Medical Association's standards for concentrations of protein, calcium, and phosphorus. One of the noncertified cat foods failed to meet the recommended calcium level. With the exception of fat digestion in 1 noncertified food, there were no statistically significant differences in major nutrient digestibility between certified and noncertified pet foods. There were some statistically significant differences in digestibility within both the certified and noncertified groups of foods. The practical significance of any of the statistical differences in digestibility is uncertain. Urine pH observed in cats fed noncertified test diets was variable, with some values greater than 7.0 as a maximum or 6.5 as an average. The general conclusion of this study was that the commonly available certified products were the nutritional equal of those foods that position themselves as "premium."

Animal Feed↗