From Synchrony to Asynchrony: Cerebellar-Basal Ganglia Functional Circuits in Young and Older Adults.

Resting state functional magnetic resonance imaging (rs-fMRI) has indicated disruptions in functional connectivity in older adults (OA) relative to young adults (YA). While age differences in cortical networks are well studied, differences in subcortical networks are poorly understood. Both the cerebellum and the basal ganglia are of particular interest given their role in cognitive and motor functions, and work in nonhuman primates has demonstrated direct reciprocal connections between these regions. Here, our goal was twofold. First, we were interested in delineating connectivity patterns between distinct regions of the cerebellum and basal ganglia, known to have topologically distinct connectivity patterns with cortex. Our second goal was to quantify age differences in these cerebellar-striatal circuits. We performed a targeted rs-fMRI analysis of the cerebellum and basal ganglia in 33 YA and 31 OA individuals. In the YA, we found significant connectivity both within and between the cerebellum and basal ganglia, in patterns supporting semi-discrete circuits that may differentially subserve motor and cognitive performance. We found a shift in connectivity, from one of synchrony in YA, to asynchrony in OA, resulting in substantial age differences. Connectivity was also associated with behavior. These findings significantly advance our understanding of cerebellar-basal ganglia interactions in the human brain.

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.

Effects of cerebellar transcranial direct current stimulation on the cognitive stage of sequence learning.

Though the cerebellum has been previously implicated in explicit sequence learning, the exact role of this structure in the acquisition of motor skills is not completely clear. The cerebellum contributes to both motor and nonmotor behavior. Thus, this structure not only may contribute to the motoric aspects of sequence learning but may also play a role in the cognitive components of these learning paradigms. Therefore, we investigated the consequence of both disrupting and facilitating cerebellar function using high-definition transcranial direct current stimulation (tDCS) before the completion of an explicit motor sequence learning paradigm. Using a mixed within- and between-subjects design, we employed cathodal (n = 21) and anodal (n = 23) tDCS (relative to sham), targeting the lateral posterior cerebellum, to temporarily modulate function and investigate the resulting effects on the acquisition of a sequential pattern of finger movements. Results indicate that cathodal stimulation has a positive influence on learning while anodal stimulation has the opposite effect, relative to sham. Though the cerebellum is presumed to be primarily involved in motor function and movement coordination, our results support a cognitive contribution that may come into play during the initial stages of learning. Using tDCS targeting the right posterior cerebellum, which communicates with the prefrontal cortex via closed-loop circuits, we found polarity-specific effects of cathodal and anodal stimulation on sequence learning. Thus, our results substantiate the role of the cerebellum in the cognitive aspect of motor learning and provide important new insights into the polarity-specific effects of tDCS in this area.NEW & NOTEWORTHY The cerebellum contributes to motor and cognitive processes. Investigating the cognitive contributions of the cerebellum in explicit sequence learning stands to provide new insights into this learning domain, and cerebellar function more generally. Using high-definition transcranial direct current stimulation, we demonstrated polarity-specific effects of stimulation on explicit sequence learning. We speculate that this is due to facilitation of working memory processes. This provides new evidence supporting a role for the cerebellum in the cognitive aspects of sequence learning.

A case for motor network contributions to schizophrenia symptoms: Evidence from resting-state connectivity.

Though schizophrenia (SCZ) is classically defined based on positive symptoms and the negative symptoms of the disease prove to be debilitating for many patients, motor deficits are often present as well. A growing literature highlights the importance of motor systems and networks in the disease, and it may be the case that dysfunction in motor networks relates to the pathophysiology and etiology of SCZ. To test this and build upon recent work in SCZ and in at-risk populations, we investigated cortical and cerebellar motor functional networks at rest in SCZ and controls using publically available data. We analyzed data from 82 patients and 88 controls. We found key group differences in resting-state connectivity patterns that highlight dysfunction in motor circuits and also implicate the thalamus. Furthermore, we demonstrated that in SCZ, these resting-state networks are related to both positive and negative symptom severity. Though the ventral prefrontal cortex and corticostriatal pathways more broadly have been implicated in negative symptom severity, here we extend these findings to include motor-striatal connections, as increased connectivity between the primary motor cortex and basal ganglia was associated with more severe negative symptoms. Together, these findings implicate motor networks in the symptomatology of psychosis, and we speculate that these networks may be contributing to the etiology of the disease. Overt motor deficits in SCZ may signal underlying network dysfunction that contributes to the overall disease state. Hum Brain Mapp 38:4535-4545, 2017. © 2017 Wiley Periodicals, Inc.

Age Differences in the Subcomponents of Executive Functioning.

OBJECTIVES: Across the life span, deficits in executive functioning (EF) are associated with poor behavioral control and failure to achieve goals. Though EF is often discussed as one broad construct, a prominent model of EF suggests that it is composed of three subdomains: inhibition, set shifting, and updating. These subdomains are seen in both younger (YA) and older adults (OA), with performance deficits across subdomains in OA. Therefore, our goal was to investigate whether subdomains of EF might be differentially affected by age, and how these differences may relate to broader global age differences in EF. METHODS: To assess these age differences, we conducted a meta-analysis at multiple levels, including task level, subdomain level, and of global EF. Based on previous work, we hypothesized that there would be overall differences in EF in OA. RESULTS: Using 1,268 effect sizes from 401 articles, we found overall differences in EF with age. Results suggested that differences in performance are not uniform, such that variability in age effects emerged at the task level, and updating was not as affected by age as other subdomains. DISCUSSION: These findings advance our understanding of age differences in EF, and stand to inform early detection of EF decline.

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.

Patients with schizophrenia show aberrant patterns of basal ganglia activation: Evidence from ALE meta-analysis.

The diverse circuits and functional contributions of the basal ganglia, coupled with known differences in dopaminergic function in patients with schizophrenia, suggest they may be an important contributor to the etiology of the hallmark symptoms and cognitive dysfunction experienced by these patients. Using activation-likelihood-estimation meta-analysis of functional imaging research, we investigated differences in activation patterns in the basal ganglia in patients with schizophrenia, relative to healthy controls across task domains. This analysis included 42 functional neuroimaging studies, representing a variety of behavioral domains that have been linked to basal ganglia function in prior work. We provide important new information about the functional activation patterns and functional topography of the basal ganglia for different task domains in healthy controls. Crucially however, we demonstrate that across task domains, patients with schizophrenia show markedly decreased activation in the basal ganglia relative to healthy controls. Our results provide further support for basal ganglia dysfunction in patients with schizophrenia, and the broad dysfunction across task domains may contribute to the symptoms and cognitive deficits associated with schizophrenia.