Neil M. Branston

Local Cerebral Blood Flow and Vascular Reactivity in a Chronic Stable Stroke in Baboons

Blood flow in the hemispheres of baboons three years after middle cerebral artery occlusion has been assessed by the hydrogen clearance technique. Blood flow in the infarct itself varied from very low (8 ml/100 gm per minute) to very high (89 ml/100 gm per minute) values and, averaging the values for the infarct as a whole, it was impossible to distinguish average flows in the infarct from those of the normal hemisphere. Flow values in surrounding zones of the infarct remained significantly lower than those of comparable normal hemispheres, and, excluding the infarct, the mean average hemispheral blood flow was 35.2 ml/100 gm per minute. This indicates a significant reduction in flow in the cortex, subsequently shown histologically to be normal, compared with normal blood flow values for the baboon hemisphere. Autoregulation was lost in the infarct and impaired in surrounding tissue. CO2 reactivity was grossly reduced in the hemisphere as a whole but was present in all areas, even occasionally in electrode placements within the infarct itself. After perfusion fixation of the head, pathological study of the area of infarction showed a fairly consistent distribution, the infarct itself consisting of many dilated blood vessels of non-capillary nature scattered among fibrous tissue in what was virtually a glial scar.

Changes in regional cortical tissue oxygen tension and cerebral blood flow during temporary middle cerebral artery occlusion in baboons

Cortical tissue oxygen measured by a platinum cathode, and cerebral blood flow recorded by a hydrogen clearance technique, were measured in 13 baboons before, during and after temporary occlusion of the middle cerebral artery. Mean control pO2 was 23.8 +/- 14 mm Hg and mean flow 51.3 +/- 12 ml/100g/min. During the occlusion, there was a gradation in pO2 from values in the opercular area of 3.6 +/- 5.9 mm Hg, to values in the high parietal area of 11.9 +/- 11.7, these being statistically different (P less than 0.05) from each other. The corresponding flow values were 5.5 +/- 7.5 (opercular) and 22.3 +/- 21.7 ml/100 g/min parietal (P less than 0.01). Following removal of the MCA clip, between 20% and 30% of the electrodes registered an early hyperoxia and hyperaemia, which lasted up to 5 min. A late and prolonged hyperoxia, with less evidence of hyperaemia, was also noted in about 20%. The mean tissue pO2, however, at 5-min intervals up to 40 min following the removal of the clip only reached 60-80% of control values in the most ischaemic areas. Only the parietal region showed a mean pO2 above control levels. The mean flow data were uniformly reduced in all regions to about 80% of control values. During and after a second occlusion in 6 animals, similar changes were noted but with even fewer instances of hyperoxia. The mean oxygen and flow results were lower than with the first occlusion, but the reduction was not significant. There was no overall effect of hypercapnia on cortical tissue pO2 during the control period, but there was a significant (P less than 0.05) reduction during the same procedure after the period of ischaemia. An increase in pO2 during hypercapnia could be observed if there were arousal responses of blood pressure spikes.

Firing patterns of pallidal cells in parkinsonian patients correlate with their pre-pallidotomy clinical scores

It is unclear how the disordered activity of cells in the basal ganglia contributes to the symptoms of Parkinsons disease (PD). We recorded from single neurons extracellularly in 3 regions of the globus pallidus (GPe, GPie and GPii) in patients undergoing pallidotomy for PD. Movement-related cell firing patterns, analysed using hidden Markov models, were significantly correlated with patients preoperative clinical scores (off drugs). Responses of cells in GPii correlated best with the scores for specific motor tasks, rather than general ones related to activities of daily living, but the reverse was true for responses from GPe. In both GPii and GPe, a higher score (i.e. greater parkinsonian severity) was associated with greater variability in cell firing rather than an increase in firing rate itself.

A model of selective experimental ischaemia in the primate thalamus.

A model for studying changes in local CBF and evoked potentials in selective thalamic ischaemia has been developed. The arterial supply to the posterior thalamus (mainly from the posterior choroidal arteries) was occluded in the baboon using a transorbital approach to the region of prepontine and ambient cisterns. Local CBF was measured by the hydrogen clearance method using electrodes introduced into the nucleus ventralis posterior lateralis of thalamus as well as cortex on both sides. The production of focal ischaemia was demonstrated by a significant decrease in thalamic CBF and confirmed by examination of the brain perfused with carbon particles.

Measurements of oxygen tension in the cerebral cortex of baboons

A polystyrene-covered platinum electrode (100-150 mum diameter) has been used to measure cortical tissue oxygen tension in baboon brains. The method of preparation, calibration, and the importance of small residual current (less than 40 nA) as an attribute of a reliable electrode, are described. With electrodes of this size, there was a large (16 +/- 12nA/torr) and linear current output with pO2 changes. The effect of avrious gases in addition to oxygen is described; halothane inhalation increases the apparent pO2 and hydrogen, used for blood flow estimations, reduces the recorded pO2. In 48 separate electrode placements in 13 baboons, the mean cortical qo2 was 23.8 +/- 12 mm Hg, with a range from 1-79 mm Hg; following occlusion of one middle cerebral artery, 37 electrodes recorded a pO2 of less then 5 mm Hg pO2 Oscillations were invariably noted in control conditions, independent of blood pressure; these waves disappeared during MCA occlusion and appeared to be augmented following release of the clip. Blood pressure spikes produce immediate and synchronous changes in all electrodes entirely different from the spontaneous waves. Such blood pressure changes may mask the true effect of hypercapnia on tissue pO2 and, if ignored, may lead to erroneous assumptions regarding local neural control of the circulation, the increased pO2 secondary to hypertension being regarded as evidence of regional vasodilation. A SUdden change in inspired pO2-the air test-was performed in control conditions and following the ischaemic insult, and the rate of change of cortical pO2 compared. The gradient was significantly greater (P less than 0.05) following ischaemia, suggesting a changed ratio in the tissues flow to oxygen requirements and/or a persisting vasodilatation.

Somatosensory Evoked Potentials in Experimental Brain Ischemia

Publisher Summary This chapter describes the experiments that are designed to clarify the question of the relative ischemic sensitivities among regions, extending the work to measure the somatosensory evoked potentials (SEPs) and cerebral blood flow (CBF) in thalamus and brainstem. The chapter presents the experimental data from primates on the relationships between features of early (

Changes in neural complexity of the EEG during a visual oddball task

OBJECTIVEnNeural complexity (C(N)) was introduced by Tononi et al. in an information-theoretic framework to capture the balance between functional specialisation and integration in the brain. We hypothesised that C(N) should vary during cognitive processing, specifically during an oddball task.nnnMETHODSnIn 11 normal human subjects, we recorded from groups of EEG electrodes in the frontal (F), central-parietal (CP) and occipito-temporal (OT) regions during a visual oddball reward conditioning task and calculated C(N) in each region. Three types of visual stimulus (abstract shapes, called neutral, reward and penalty) were presented randomly in three blocks of trials. During the first block, subjects did not know the significance of the stimulus shapes. For the subsequent (conditioning) blocks, subjects were informed that whenever they saw reward or penalty patterns, they would win or lose money, respectively.nnnRESULTSnIn regions CP and OT, C(N) was significantly larger in reward and penalty trials than in neutral during all blocks. During a trial, significant changes in C(N) occurred around the ERP peaks N1 and P300 and the effects of reward conditioning on C(N) could be distinguished from penalty.nnnCONCLUSIONSnOur findings support the above hypothesis, indicating that C(N) correlates with both the sensory and cognitive components of stimulus processing.nnnSIGNIFICANCEnThis study extends the scope of C(N) in the analysis of cognitive processing.

Visualisation of human basal ganglia neuron responses using the generative topographic mapping (GTM) algorithm

We present a data set obtained from neurophysiological recordings made from single neurons in the human basal ganglia in relation to movements of the limbs during surgical procedures for Parkinsons disease. Data from both the pre-movement (movement preparation) phase and the post-movement phase were recorded in 25 cells in 9 patients. Using the generative topographic mapping algorithm (GTM), we show that the data corresponding to individual cells cluster in different parts of the map, which suggests that different cells have their own distinct firing pattern. The self-organising map as implemented by GTM appears to be a useful tool for visualising the responses of these neurons in relation to movement.

Movement discrimination by single cells in the human pallidum characterised by hidden Markov models

Abstract. In patients undergoing pallidotomy for Parkinsons disease, we recorded extracellularly from single neurons in the two internal segments (GPii, GPie) and the external segment (GPe) of the globus pallidus (GP) in response to active (cued) movements of the contralateral wrist, elbow or ankle. The patterns of cell activity occurring both before and after movement onset were analysed using hidden Markov models (HMMs) and clustered by movement type using the generative topographical mapping algorithm. Cluster separation was quantified in order to measure a cells ability to discriminate between movements. Statistical analysis of variance indicated a significant regional gradient (GPii>GPie>GPe) of movement discrimination, while cells in all regions differentiated better between movements of different joints (wrist, elbow or ankle) than between flexion and extension of the same joint. We found that GP cells generally showed distinguishable firing patterns corresponding to more than one type of movement per cell, in support of the hypothesis that cells in these regions of the basal ganglia are not involved in preparation or execution of a single type of movement but participate in many different movements, analogous to the hidden units of a neural network. Our results also indicate that cell activity both preceding a movement and during its execution may be modelled by HMMs with only a small number of states.

Parameter selection and state dominance in hidden Markov models of neuronal activity

Hidden Markov model (HMM) analysis of single-neuron activity supports the concept that neural networks in the brain may operate by switching between a relatively small number of stable configurations of activity (attractors) in the processing of specific tasks. Here, we consider two problems: 1) how to estimate the true number of HMM states in the source (which is unknown) from the observed activity; and 2) how to decide whether the states are likely to be associated with a simple distribution such as the Poisson or a more complex one (Gaussian). We also show how state dominance (the observation that at any time one state is much more probable than all the others) depends on the source parameters. To do this, we deal with artificial data generated with known Markov statistics and resembling real neuronal activity.