1. Two experiments were aimed at investigating the functional organization of the human anterior cingulate cortex (ACC) in relation to higher-order motor control. 2. The 15O-labeled H2O bolus method was used to measure relative changes of regional cerebral blood flow (rCBF) in 18 healthy human subjects as they performed oculomotor, manual, or speech tasks. 3. Task-specific rCBF changes were obtained in distinct subregions of the ACC, depending on the output system employed. The oculomotor and the manual task-related foci were found in the rostral and caudal regions of the ACC, respectively, whereas the speech foci were localized within two cingulate subregions, the intermediate dorsal and the rostral ACC. 4. In the manual tasks, two groups of activation foci could be distinguished, one just behind and the other just in front of the vertical plane traversing the anterior commissure. 5. The above pattern of rCBF changes was observed only if there was concomitant activation within the lateral prefrontal cortex (except for the posterior group of foci obtained in the manual tasks). 6. The localization of output-specific rCBF changes within the human ACC is consistent with the known somatotopic organization of the cingulate cortex in the monkey. 7. It is tentatively proposed that the ACC participates in motor control by facilitating the execution of the appropriate responses and/or suppressing the execution of the inappropriate ones. Such a modulatory effect would be of particular importance when behavior has to be modified in new and challenging situations.

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Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.

Fluorescein angiography and xenon-133 (133Xe) clearance studies were performed during surgery on 15 patients who were undergoing superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis. Fourteen patients had occlusive disease of the internal carotid artery (ICA), and one patient had severe stenosis of the MCA. Before anastomosis, fluorescein angiography showed slow filling of the MCA branches through collateral channels. Focal areas of impaired microcirculatory filling and washout were seen in the territory of severely sclerotic cortical arteries. The findings of preanastomotic 133Xe clearance studies were variable and a uniform pattern of regional cerebral blood flow (rCBF) changes was not defined. In 55% of the patients, rCBF was reduced to 25 ml/100 gm/min or less at one or more detector sites. Fluorescein angiography provided an immediate assessment of anastomotic patency and clearly displayed the distribution of blood entering the epicerebral circulation through the STA. In 67% of patients, multiple MCA cortical branches filled with fluorescein, whereas in 33% filling was restricted to the receptor artery territory. An immediate, substantial (greater than or equal to 15 ml/100 gm/min) increase in rCBF was demonstrated in 73% of patients after anastomosis. The rCBF changes were consistently better in patients with donor and receptor arteries greater than 1 mm in diameter. Redistribution of collateral input acted to increase rCBF in areas distant from the anastomotic site. Some improvement in fluorescein circulation and rCBF also was seen in cortex supplied by sclerotic MCA branches.