The brain localization of motor sequence learning was studied in norma
l subjects with positron emission tomography. Subjects performed a ser
ial reaction time (SRT) task by responding to a series of stimuli that
occurred at four different spatial positions. The stimulus locations
were either determined randomly or according to a 6-element sequence t
hat cycled continuously The SRT task was performed under two condition
s. With attentional interference from a secondary counting task there
was no development of awareness of the sequence. Learning-related incr
eases of cerebral blood flow were located in contralateral motor effec
tor areas including motor cortex, supplementary motor area, and putame
n, consistent with the hypothesis that nondeclarative motor learning o
ccurs in cerebral areas that control limb movements. Additional cortic
al sites included the rostral prefrontal cortex and parietal cortex. T
he SRT learning task was then repeated with a new sequence and no atte
ntional interference. In this condition, 7 of 12 subjects developed aw
areness of the sequence. Learning-related blood flow increases were pr
esent in right dorsolateral prefrontal cortex, right premotor cortex,
right ventral putamen, and biparieto-occipital cortex. The right dorso
lateral prefrontal and parietal areas have been previously implicated
in spatial working memory and right prefrontal cortex is also implicat
ed in retrieval tasks of verbal episodic memory. Awareness of the sequ
ence at the end of learning was associated With greater activity in bi
lateral parietal, superior temporal, and right premotor cortex. Motor
learning can take place in different cerebral areas, contingent on the
attentional demands of the task.