We have used positron emission tomography to study the functional anatomy of motor sequence learning. Subjects learned sequences of keypresses by trial and error using auditory feedback. They were scanned with eyes closed under three conditions: at rest, while performing a sequence that was practiced before scanning until overlearned, and while learning new sequences at the same rate of performance. Compared with rest, both sequence tasks activated the contralateral sensorimotor cortex to the same extent. Comparing new learning with performance of the prelearned sequence, differences in activation were identified in other areas. (1) Prefrontal cortex was only activated during new sequence learning. (2) Lateral premotor cortex was significantly more activated during new learning, whereas the supplementary motor area was more activated during performance of the prelearned sequence. (3) Activation of parietal association cortex was present during both motor tasks, but was significantly greater during new learning. (4) The putamen was equally activated by both conditions. (5) The cerebellum was activated by both conditions, but the activation was more extensive and greater in degree during new learning. There was an extensive decrease in the activity of prestriate cortex, inferotemporal cortex, and the hippocampus in both active conditions, when compared with rest. These decreases were significantly greater during new learning. We draw three main conclusions. (1) The cerebellum is involved in the process by which motor tasks become automatic, whereas the putamen is equally activated by sequence learning and retrieval, and may play a similar role in both. (2) When subjects learn new sequences of motor actions, prefrontal cortex is activated. This may reflect the need to generate new responses. (3) Reduced activity of areas concerned with visual processing, particularly during new learning, suggests that selective attention may involve depressing the activity of cells in modalities that are not engaged by the task.

Background: Brain abscesses and ischaemic strokes complicate pulmonary arteriovenous malformations (PAVMs). At risk individuals are poorly recognised. Stroke/ abscess risk factors have not been defined. Methods: A cohort study of 323 consecutive individuals with PAVMs (n = 219) and/or the commonly associated condition hereditary haemorrhagic telangiectasia (HHT, n = 305) was performed. Most of the 201 individuals with PAVMs and HHT had no respiratory symptoms, and were unaware they had HHT. Anderson-Gill models assessed constant and time dependent potential predictive variables for stroke/abscess, and rate reduction by PAVM embolisation. Results: 57 individuals with PAVMs and HHT experienced brain abscess or ischaemic stroke, usually prior to the diagnosis of underlying PAVMs/HHT. The primary determinants of stroke and abscess risks were unrelated to severity of PAVMs. Males had higher brain abscess rates (hazard ratio 3.61 (95% CI 1.58, 8.25), p = 0.0024); interventional histories and bacteriological isolates suggested dental sources. Once adjusted for gender, there was a marginal association between brain abscess and low oxygen saturation. For ischaemic stroke, there was no association with any marker of PAVM severity, or with conventional neurovascular risk factors. Surprisingly, low mean pulmonary artery pressure was strongly associated with ischaemic stroke (hazard ratio 0.89 (95% CI 0.83, 0.95) per mm Hg increase; p = 6.2610 25 ). PAVM embolisation significantly reduced ischaemic stroke rate (p = 0.028); no strokes/abscesses occurred following obliteration of all angiographically visible PAVMs. The mean PAVM diagnosis-treatment interval was longer, however, when neurological risks were unrecognised. Conclusions: Ischaemic strokes and brain abscesses occur commonly in undiagnosed HHT patients with PAVMs. Risk reduction could be improved.Pulmonary arteriovenous malformations (PAVMs) are abnormal dilated vessels which provide a rightto-left (R-L) shunt between the pulmonary arterial and venous circulations.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.