Biology subjects

Bernard, J. A.

Publications and source records attributed to Bernard, J. A..

28 records · Page 2Linked to original sources

bioRxiv2021

The influence of reproductive stage on cerebellar network connectivity across adulthood

Sex-specific differences in the aging cerebellum may be related to hormone changes with menopause. We evaluated the influence of reproductive stage on lobular cerebellar network connectivity using data from the Cambridge Centre for Ageing and Neuroscience repository. We used raw structural and resting state neuroimaging data and information regarding age, sex, and menopause-related variables. Crus I and II and Lobules V and VI were our cerebellar seeds of interest. We characterized reproductive stage using the Stages of Reproductive Aging Workshop criteria. Results show that postmenopausal females have lower cerebello-striatal and cerebello-cortical connectivity, particularly in frontal regions, along with lower connectivity within the cerebellum, compared to reproductive females. Postmenopausal females also exhibit greater connectivity in some brain areas as well. Differences begin to emerge across transitional stages of menopause. Further, results reveal sex-specific differences in connectivity between female reproductive groups and age-matched male control groups. This suggests that menopause may influence cerebellar network connectivity in aging females, and sex differences in the aging brain may be related to this biological process. HighlightsO_LILobular analysis of cerebellar network connectivity across reproductive stages C_LIO_LIPostmenopausal females show lower cerebellar connectivity, compared to reproductive C_LIO_LIConnectivity differences begin to emerge in transitional stages of menopause C_LIO_LIAge-matched male control groups show distinct patterns of cerebellar connectivity C_LIO_LIReproductive stage influences cerebellar network connectivity in aging females C_LI

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bioRxiv2021

Cerebello-Basal Ganglia Network Global Efficiency Predicts Cortical Network Global Efficiency

The cerebellum (CB) and basal ganglia (BG) each have topographically distinct functional subregions that are functionally and anatomically interconnected with cortical regions through discrete thalamic loops and with each other via disynaptic connections, with previous work detailing high levels of functional connectivity between these phylogenetically ancient regions. It was posited that this CB-BG network provides support for cortical systems processing, spanning cognitive, emotional, and motor domains, implying subcortical network measures are strongly related to cortical network measures (Bostan & Strick, 2018); however, it is currently unknown how network measures within distinct CB-BG networks relate to cortical network measures. Here, 122 regions of interest comprising cognitive and motor CB-BG networks and 7 canonical cortical resting-state were used to investigate whether the integration (quantified using global efficiency, GE) of cognitive CB-BG network (CCBN) nodes and their segregation from motor CB-BG network (MCBN) nodes is related to cortical network GE and segregation in 233 non-related, right- handed participants (Human Connectome Project-1200). CCBN GE positively correlated with GE in the default mode, motor, and auditory networks and MCBN GE positively correlated with GE in all networks except the default mode and emotional. MCBN segregation was related to MN segregation. These findings highlight the CB-BG networks role in executive function, task switching, and verbal working memory. This work has implications for understanding cortical network organization and cortical-subcortical interactions in healthy adults and may help in deciphering subcortical differences seen in disease states.

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bioRxiv2021

Cerebellar Dentate Connectivity Across Adulthood: A Large-Scale Resting State Functional Connectivity Investigation

Cerebellar contributions to behavior in advanced age are of interest and importance, given its role in motor and cognitive performance. There are differences and declines in cerebellar structure in advanced age and cerebellar resting state connectivity is lower. However, the work on this area to date has focused on the cerebellar cortex. The deep cerebellar nuclei provide the primary cerebellar inputs and outputs to the cortex, as well as the spinal and vestibular systems. Dentate networks can be dissociated such that the dorsal region is associated with the motor cortex, while the ventral aspect is associated with the prefrontal cortex. However, whether dentato-thalamo-cortical networks differ across adulthood remains unknown. Here, using a large adult sample (n=590) from the Cambridge Center for Ageing and Neuroscience, we investigated dentate connectivity across adulthood. We replicated past work showing dissociable resting state networks in the dorsal and ventral aspects of the dentate. In both seeds, we demonstrated that connectivity is lower with advanced age, indicating that connectivity differences extend beyond the cerebellar cortex. Finally, we demonstrated sex differences in dentate connectivity. This expands our understanding of cerebellar circuitry in advanced age and underscores the potential importance of this structure in age-related performance differences.

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bioRxiv2020

The polarity specific nature of single session high-definition transcranial direct current stimulation to the cerebellum and prefrontal cortex on motor and non-motor task performance

The cerebellum has an increasingly recognized role in higher order cognition. Advancements in noninvasive neuromodulation techniques allows one to focally create functional alterations in the cerebellum to investigate its role in cognitive functions. To this point, work in this area has been mixed, in part due to varying methodologies for stimulation, and it is unclear whether or not transcranial direct current stimulation (tDCS) effects on the cerebellum are task or load dependent. Here, we employed a between-subjects design using a high definition tDCS system to apply anodal, cathodal, or sham stimulation to the cerebellum or prefrontal cortex (PFC) to examine the role the cerebellum plays in verbal working memory, inhibition, motor learning, and balance performance, and how this interaction might interact with the cortex (i.e. PFC). We predicted performance decrements following anodal stimulation and performance increases following cathodal stimulation, compared to sham. Broadly, our work provides evidence for cerebellar contributions to cognitive processing, particularly in verbal working memory and sequence learning. Additionally, we found the effect of stimulation might be load specific, particularly when applied to the cerebellum. Critically, anodal simulation negatively impacted performance during effortful processing, but was helpful during less effortful processing. Cathodal stimulation hindered task performance, regardless of simulation region. The current results suggest an effect of stimulation on cognition, perhaps suggesting that the cerebellum is more critical when processing is less effortful but becomes less involved under higher load when processing is more prefrontally-dependent.

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bioRxiv2020

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.

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bioRxiv2019

Using high-definition transcranial direct current stimulation to elucidate the role of the cerebello-thalamo-prefrontal network 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.

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bioRxiv2019

Effects of prefrontal tDCS on dopamine-mediated behavior and psychophysiology

The ability to manipulate dopamine in vivo through non-invasive, reversible mechanisms has the potential to impact clinical, translational, and basic research. Recent PET studies have demonstrated increased dopamine release in the striatum after prefrontal transcranial direct current stimulation (tDCS). We sought to extend this work by examining whether prefrontal tDCS could demonstrate an effect on behavioral and physiological correlates of subcortical dopamine activity. We conducted a between-subjects study (n = 30) with active and sham tDCS and used spontaneous eye blink rate (EBR), facial attractiveness ratings, and greyscales orienting bias as indirect proxies for dopamine functioning. The initial design and analyses were pre-registered (https://osf.io/gmnpc). Stimulation did not significantly affect any of the three measures, though effect sizes were often moderately large and were all in the predicted directions. Additional exploratory analyses suggested that stimulations effect on EBR might depend on pre-stimulation dopamine levels. Our results shed light on the sensitivity of indirect measures of dopamine in humans and add to a growing body of work demonstrating the importance of examining individual differences in tDCS response.

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bioRxiv2019

The 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 non-motor behavior. Thus, this structure may contribute not only 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 (HD-tDCS) prior to 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.\n\nNew & NoteworthyThe 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 HD-tDCS, 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.

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bioRxiv2018

Dissociable Prefrontal-Cerebellar Networks Underlying Executive Function: Evidence from Resting State Functional Connectivity in the Human Connectome Project

To date, investigations of executive function (EF) have focused on the prefrontal cortex (PFC), and prominent theories of EF are framed with respect to this brain region. Multiple theories describe a hierarchical functional organization for the lateral PFC. However, recent evidence has indicated that the cerebellum (CB) also plays a role in EF. Posterior CB regions (Crus I & II) show structural and functional connections with the PFC, and CB networks are associated with individual differences in EF in healthy adults. However, it is unclear whether the cerebellum shows a similar functional gradient as does the PFC. Here, we investigated high-resolution resting-state data from 225 participants in the Human Connectome Project. We compared resting-state connectivity from posterior cerebellar ROIs, and examined functional data from several tasks that activate the lateral PFC. Demonstrating preliminary evidence for parallel PFC and CB gradients, Crus I was functionally connected with rostrolateral PFC, Crus II with middle and ventral PFC, and Lobule VI with posterior PFC. Contrary to previous work, the activation of the task thought to activate rostrolateral PFC resembled the connectivity maps of Crus II, not Crus I; similarly, the activation of the task thought to activate middle PFC resembled the connectivity maps of Crus I, not Crus II. Nevertheless, there was evidence for dissociable CB-PFC networks. Further work is necessary to understand the functional role of these networks.

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bioRxiv2018

Striatal-frontal network activation during voluntary task selection under conditions of monetary reward

During voluntary task selection there are a number of internal and external biases that may guide such a choice. However, it is not well understood how reward influences task selection when multiple options are possible. To address this issue, we examined brain activation in a voluntary task-switching paradigm while participants underwent fMRI (n=19). To reinforce the overall goal to choose the tasks randomly, participants were told of a large bonus they would receive at the end of the experiment for making random task choices. We also examined how occasional, random rewards influenced both task performance and brain activation. We hypothesized that these transient rewards would increase the value of the just-performed task and therefore bias participants to choose to repeat the same task on the subsequent trial. Contrary to expectations, transient reward had no consistent behavioral effect on subsequent task choice. Nevertheless, the receipt of such rewards did influence activation in brain regions associated with reward processing as well as those associated with goal-directed control. In addition, reward on a prior trial was found to influence activation during task choice on a subsequent trial, with greater activation in a number of executive function regions as compared to no-reward trials. We posit that both the random presentation of transient rewards and the overall task bonus for random task choices together reinforced the goal to choose the tasks randomly, which in turn influenced activation in both reward-related regions and those regions involved in abstract goal processing.

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