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.

Supplementary motor area and other cortical areas in organization of voluntary movements in man

The characteristic form and development of sensory disturbances during migraine auras suggests that the underlying mechanism is a disturbance of the cerebral cortex, probably the cortical spreading depression (CSD) of Leao. The demonstration of unique changes of brain blood flow during attacks of migraine with aura, which have been replicated in animal experiments during CSD, constitutes another important line of support for the 'spreading depression' theory, which may be a key to an understanding of the migraine attack. Cortical spreading depression is a short-lasting depolarization wave that moves across the cortex at a rate of 3-5 mm/min. A brief phase of excitation heralds the reaction which is immediately followed by prolonged nerve cell depression synchronously with a dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells and enhanced energy metabolism. Recent experimental work has shown that CSD in the neocortex of a variety of species including man is dependent on activation of a single receptor, the N-methyl-D-aspartate receptor, one of the three subtypes of glutamate receptors. The combined experimental and clinical studies point to fruitful areas in which to look for migraine treatments of the future and provide a framework within which important aspects of the migraine attack can be modelled.

Pathophysiology of the migraine aura. The spreading depression theory.

The "hypofrontality hypothesis" has been supported by many neuroimaging studies, but not all, perhaps because of heterogeneity of samples. The present study examined three different samples that permitted assessment of a variety of confounders, such as effects of long-term treatment, chronicity of illness, and presenting phenomenology: (1) 13 neuroleptic-naive schizophrenic patients, (2) 23 nonnaive schizophrenic patients who had been relatively chronically ill but were medication free for at least 3 weeks, and (3) 15 healthy normal volunteers. Regional cerebral blood flow was measured using single-photon emission computed tomography with xenon 133 as the tracer. The control condition consisted of looking at undulating colored shapes on a video monitor, while the experimental task was the Tower of London. We observed the Tower of London to be a relatively specific stimulant of the left mesial frontal cortex (probably including parts of the cingulate gyrus) in healthy normal volunteers. Both the neuroleptic-naive and the nonnaive patients lacked this area of activation, as well as a related one in the right parietal cortex (representing the circuitry specifically activated by the Tower of London). Decreased activation occurred only in the patients with high scores for negative symptoms. These results suggest that hypofrontality is related to negative symptoms and is not a long-term effect of neuroleptic treatment or of chronicity of illness.

Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Assessment with xenon 133 single-photon emission computed tomography and the Tower of London.

Regional cerebral blood flow (rCBF) was measured in 254 areas of a hemisphere with the xenon 133 intraarterial injection method. Six cases of classic migraine were followed from the normal state into the prodromal phase, and in 3 cases further into the headache phase. One patient with common migraine was similarly followed during his only classic attack. The attacks were initiated by focal hyperemia in 3 patients. During prodromes all patients displayed occipitoparietal rCBF reduction (oligemia), but in only 1 case did the reduction approach critical values. Oligemia gradually spread anteriorly in the course of 15 to 45 minutes. In 4 patients a global oligemia was observed. In 4 patients severe headache was present concomitantly with oligemia and with no sign of hyperemia or nonhomogeneous brain perfusion. The normal rCBF increase during cortical activity (hand movement, speech, and similar activities) was impaired in 6 patients. The results indicate that the vasospastic model of the migraine attack is too simplistic.

Focal hyperemia followed by spreading oligemia and impaired activation of rcbf in classic migraine

These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flo...

Localization of cortical areas activated by thinking

A single-photon emission tomograph has been designed and built for regional studies of brain blood flow using 133Xe or 127Xe. The dynamic computer assisted tomograph (DCAT) features fast rotation of a square array of detectors enabling the collection of data in 5 sec, simultaneous recording

A single photon dynamic computer assisted tomograph (DCAT) for imaging brain function in multiple cross sections.

A computer-based scintillation camera has been designed for both dynamic and static radionuclide studies. The detecting head has 254 independent sodium iodide crystals, each with a photomultiplier and amplifier. In dynamic measurements simultaneous events can be recorded, and 1 million total counts per second can be accommodated with less than 0.5% loss in any one channel. This corresponds to a calculated deadtime of 5 nsec. The multidetector camera is being used for 133Xe dynamic studies of regional cerebral blood flow in man and for 99mTc and 197 Hg static imaging of the brain.

http://jnm.snmjournals.org/content/18/2/168.full.pdf

A Multidetector Scintillation Camera with 254 Channels

A fast moving single photon emission tomograph for regional cerebral blood flow studies in man

Dynamic functional brain studies with a single photon computerized tomography (SPECT) can only provide detailed and reliable information when the studies are performed with a single photon tomograph designed exclusively for the brain investigations.

Per Rommer

Papers

A single photon dynamic computer assisted tomograph (DCAT) for imaging brain function in multiple cross sections.

A Multidetector Scintillation Camera with 254 Channels

A fast moving single photon emission tomograph for regional cerebral blood flow studies in man

High Efficiency Multislice Approach for Single Photon Tomography of the Brain