Using high-definition transcranial direct current stimulation to investigate the role of the dorsolateral prefrontal cortex in explicit sequence learning.

Though we have a general understanding of the brain areas involved in motor sequence learning, there is more to discover about the neural mechanisms underlying skill acquisition. Skill acquisition may be subserved, in part, by interactions between the cerebellum and prefrontal cortex through a cerebello-thalamo-prefrontal network. In prior work, we investigated this network by targeting the cerebellum; here, we explored the consequence of stimulating the dorsolateral prefrontal cortex using high-definition transcranial direct current stimulation (HD-tDCS) before administering an explicit motor sequence learning paradigm. Using a mixed within- and between- subjects design, we employed anodal (n = 24) and cathodal (n = 25) HD-tDCS (relative to sham) to temporarily alter brain function and examine effects on skill acquisition. The results indicate that both anodal and cathodal prefrontal stimulation impedes motor sequence learning, relative to sham. These findings suggest an overall negative influence of active prefrontal stimulation on the acquisition of a sequential pattern of finger movements. Collectively, this provides novel insight on the role of the dorsolateral prefrontal cortex in initial skill acquisition, when cognitive processes such as working memory are used. Exploring methods that may improve motor learning is important in developing therapeutic strategies for motor-related diseases and rehabilitation.

Cerebellar and prefrontal-cortical engagement during higher-order rule learning in older adulthood.

To date most aging research has focused on cortical systems and networks, ignoring the cerebellum which has been implicated in both cognitive and motor function. Critically, older adults (OA) show marked differences in cerebellar volume and functional networks, suggesting it may play a key role in the behavioral differences observed in advanced age. OA may be less able to recruit cerebellar resources due to network and structural differences. Here, 26 young adults (YA) and 25 OA performed a second-order learning task, known to activate the cerebellum in the fMRI environment. Behavioral results indicated that YA performed significantly better and learned more quickly compared to OA. Functional imaging detailed robust parietal and cerebellar activity during learning (compared to control) blocks within each group. OA showed increased activity (relative to YA) in the left inferior parietal lobe in response to instruction cues during learning (compared to control); whereas, YA showed increased activity (relative to OA) in the left anterior cingulate to feedback cues during learning, potentially explaining age-related performance differences. Visual interpretation of effect size maps showed more bilateral posterior cerebellar activation in OA compared to YA during learning blocks, but early learning showed widespread cerebellar activation in YA compared to OA. There were qualitatively large age-related differences in cerebellar recruitment in terms of effect sizes, yet no statistical difference. These findings serve to further elucidate age-related differences and similarities in cerebellar and cortical brain function and implicate the cerebellum and its networks as regions of interest in aging research.

Shaky scaffolding: Age differences in cerebellar activation revealed through activation likelihood estimation meta-analysis.

Cognitive neuroscience research has provided foundational insights into aging, but has focused primarily on the cerebral cortex. However, the cerebellum is subject to the effects of aging. Given the importance of this structure in the performance of motor and cognitive tasks, cerebellar differences stand to provide critical insights into age differences in behavior. However, our understanding of cerebellar functional activation in aging is limited. Thus, we completed a meta-analysis of neuroimaging studies across task domains. Unlike in the cortex where an increase in bilateral activation is seen during cognitive task performance with advanced age, there is less overlap in cerebellar activation across tasks in older adults (OAs) relative to young. Conversely, we see an increase in activation overlap in OAs during motor tasks. We propose that this is due to inputs for comparator processing in the context of control theory (cortical and spinal) that may be differentially impacted in aging. These findings advance our understanding of the aging mind and brain.

Single session high definition transcranial direct current stimulation to the cerebellum does not impact higher cognitive function.

The prefrontal cortex is central to higher order cognitive function. However, the cerebellum, generally thought to be involved in motor control and learning, has also been implicated in higher order cognition. Recent work using transcranial direct current stimulation (tDCS) provides some support for right cerebellar involvement in higher order cognition, though the results are mixed, and often contradictory. Here, we used cathodal high definition tDCS (HD-tDCS) over the right cerebellum to assess the impact of HD-tDCS on modulating cognitive performance. We predicted that stimulation would result in performance decreases, which would suggest that optimal cerebellar function is necessary for cognitive performance, much like the prefrontal cortex. That is, it is not simply a structure that lends support to complete difficult tasks. While the expected cognitive behavioral effects were present, we did not find effects of stimulation. This has broad implications for cerebellar tDCS research, particularly for those who are interested in using HD-tDCS as a way of examining cerebellar function. Further implications, limitations, and future directions are discussed with particular emphasis on why null findings might be critical in developing a clear picture of the effects of tDCS on the cerebellum.