Sequence learning in the human brain: A functional neuroanatomical meta-analysis of serial reaction time studies

Sequence learning underlies numerous motor, cognitive, and social skills. Previous models and empirical investigations of sequence learning in humans and non-human animals have implicated cortico-basal ganglia-cerebellar circuitry as well as other structures. To systematically examine the functional neuroanatomy of sequence learning in humans, we conducted a series of neuroanatomical meta-analyses. We focused on the serial reaction time (SRT) task. This task, which is the most widely used paradigm for probing sequence learning in humans, allows for the rigorous control of visual, motor, and other factors. Controlling for these factors (in sequence-random block contrasts), sequence learning yielded consistent activation only in the basal ganglia, across the striatum (anterior/mid caudate nucleus and putamen) and the globus pallidus. In contrast, when visual, motor, and other factors were not controlled for (in a global analysis with all sequence-baseline contrasts, not just sequence-random contrasts), premotor cortical and cerebellar activation were additionally observed. The study provides solid evidence that, at least as tested with the visuo-motor SRT task, sequence learning in humans relies on the basal ganglia, whereas cerebellar and premotor regions appear to contribute to aspects of the task not related to sequence learning itself. The findings have both basic research and translational implications.