Niels A. Lassen

1. Previous studies in man have revealed a coupling between the regional cerebral blood flow (rCBF) and the regional cerebral metabolic rate for oxygen. In normal man, increases in the regional cerebral metabolic rate for oxygen leads to proportional increases in the rCBF(34). We have measured the rCBF as an expression of the level of cortical activity simultaneously from 254 cortical regions in 28 patients with no major neurological defects, during rest and during planning and execution of a few types of learned voluntary movements with the hand. 2. We found that the rCBF increases exclusively in the supplementary motor area while subjects were programming a sequence of fast isolated movements of individual fingers, without actually executing it. 3. During execution of the same motor sequence, there were equivalent increases of the rCBF in both supplementary motor areas, but only in the contralateral primary motor area. In addition, there were more modest rCBF increases in the contralateral sensory hand area, the convexity part of the premotor area, and bilaterally in the inferior frontal region. 4. Repetitive fast flexions of the same finger or a sustained isometric muscular contraction raise the blood flow in the contralateral primary motor and sensory hand area. 5. A pure somatosensory discrimination of the shapes of objects, without any concomitant voluntary movements, also leaves the supplementary motor areas silent. 6. We conclude that the primary motor area and the part of the motor system it projects to by itself can control ongoing simple ballistic movements with the self-same body part. A sequence of different isolated finger movements requires programming in the supplementary motor areas. We suggest that the supplementary motor areas are programming areas for motor subroutines and that these areas form a queue of time-ordered motor commands before voluntary movement are executed by way of the primary motor area.

As shown previously, the electrical function of the brain is critically dependent on cerebral blood flow in the sense that reduction beyond an ischemic threshold of approximately 15 ml/100 gm per minute (approximately 35% of control) in the baboon leads to complete failure of the somatosensory evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as well as evoked potential were made in the baboon neocortex. Reductions in blood flow were obtained by occlusion of the middle cerebral artery and depression beyond the ischemic threshold of electrical function achieved by a reduction of systemic blood pressure which, in the ischemic zones, changed local cerebral blood flow proportionally. Abolition of evoked response could not be explained by depolarization by release of intracellular K+, nor was it critically dependent on cortical pH. However, the massive release of intracellular K+ was by itself critically dependent on cortical blood flow and occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support the concept of an ischemic penumbra during which the neurons remain structurally intact but functionally inactive. That neurons can survive for some time in this state of lethargy is evidenced by the observations that an increase in rCBF, if sufficient, can restore evoked potential and normalize extracellular K+ activity as well as pH.

Cerebral blood flow was studied by the arteriovenous oxygen difference method in patients with severe hypertension and in normotensive controls. The blood pressure was lowered to study the lower limit of autoregulation (the pressure below which cerebral blood flow decreases) and the pressure limit of brain hypoxia. Both limits were shifted upwards in the hypertensive patients, probably as a consequence of hypertrophy of the arteriolar walls. These findings have practical implications for antihypertensive therapy.When the blood pressure was raised some patients showed an upper limit of autoregulation beyond which an increase of cerebral blood flow above the resting value was seen without clinical symptoms. No evidence of vasospasm was found in any patient at high blood pressure. These observations may be of importance for the understanding of the pathogenesis of hypertensive encephalopathy.