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1. Emergent Low-Frequency Activity in Cortico-Cerebellar Networks with Motor Skill Learning

   https://doi.org/10.1523/ENEURO.0011-23.2023  

   Fleischer, Pierson; Abbasi, Aamir; Fealy, Andrew W.; Danielsen, Nathan P.; Sandhu, Ramneet; Raj, Philip R.; Gulati, Tanuj (February 2023, eneuro)

   Abstract The motor cortex controls skilled arm movement by recruiting a variety of targets in the nervous system, and it is important to understand the emergent activity in these regions as refinement of a motor skill occurs. One fundamental projection of the motor cortex (M1) is to the cerebellum. However, the emergent activity in the motor cortex and the cerebellum that appears as a dexterous motor skill is consolidated is incompletely understood. Here, we report on low-frequency oscillatory (LFO) activity that emerges in cortico-cerebellar networks with learning the reach-to-grasp motor skill. We chronically recorded the motor and the cerebellar cortices in rats, which revealed the emergence of coordinated movement-related activity in the local-field potentials as the reaching skill consolidated. Interestingly, we found this emergent activity only in the rats that gained expertise in the task. We found that the local and cross-area spiking activity was coordinated with LFOs in proficient rats. Finally, we also found that these neural dynamics were more prominently expressed during accurate behavior in the M1. This work furthers our understanding on emergent dynamics in the cortico-cerebellar loop that underlie learning and execution of precise skilled movement. 

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2. Mental Visualization in the Cerebellum: Rapid Non-motor Learning at Sub-Lobular and Causal Network Levels

   https://doi.org/10.3389/fnsys.2021.655514  

   Likova, Lora T.; Mineff, Kristyo N.; Nicholas, Spero C. (September 2021, Frontiers in Systems Neuroscience)

   It is generally understood that the main role of the cerebellum is in movement planning and coordination, but neuroimaging has led to striking findings of its involvement in many aspects of cognitive processing. Mental visualization is such a cognitive process, extensively involved in learning and memory, artistic and inventive creativity, etc. Here, our aim was to conduct a multidimensional study of cerebellar involvement in the non-motor cognitive tasks. First, we used fMRI to investigate whether the cognitive task of visualization from an immediate memory of complex spatial structures (line drawings) engages the cerebellum, and identified a cerebellar network of both strongly activated and suppressed regions. Second, the task-specificity of these regions was examined by comparative analysis with the task of perceptual exploration and memorization of the drawings to be later visualized from memory. BOLD response patterns over the iterations of each task differed significantly; unexpectedly, the suppression grew markedly stronger in visualization. Third, to gain insights in the organization of these regions into cerebellar networks, we determined the directed inter-regional causal influences using Granger Causal Connectivity analysis. Additionally, the causal interactions of the cerebellar networks with a large-scale cortical network, the Default Mode Network (DMN), were studied. Fourth, we investigated rapid cognitive learning in the cerebellum at the level of short-term BOLD response evolution within each region of interest, and at the higher level of network reorganization. Our paradigm of interleaved sequences of iteration between two tasks combined with some innovative analyses were instrumental in addressing these questions. In particular, rapid forms of non-motor learning that strongly drive cerebellar plasticity through mental visualization were uncovered and characterized at both sub-lobular and network levels. Collectively, these findings provide novel and expansive insights into high-order cognitive functions in the cerebellum, and its macroscale functional neuroanatomy. They represent a basis for a framework of rapid cerebellar reorganization driven by non-motor learning, with implications for the enhancement of cognitive abilities such as learning and memory. 

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3. Postural mechanisms in moderate-to-severe cerebral palsy

   https://doi.org/10.1152/jn.00549.2020  

   Goodworth, Adam; Saavedra, Sandra (May 2021, Journal of Neurophysiology)

   null (Ed.)

   People with moderate-to-severe cerebral palsy (CP) have the greatest need for postural control research yet are usually excluded from research due to deficits in sitting ability. We use a support system that allows us to quantify and model postural mechanisms in nonambulatory children with CP. A continuous external bench tilt stimulus was used to evoke trunk postural responses in seven sitting children with CP (ages 2.5 to 13 yr) in several test sessions. Eight healthy adults were also included. Postural sway was analyzed with root mean square (RMS) sway and RMS sway velocity, along with frequency response functions (FRF, gain and phase) and coherence functions across two different stimulus amplitudes. A feedback model (including sensorimotor noise, passive, reflexive, and sensory integration mechanisms) was developed to hypothesize how postural control mechanisms are organized and function. Experimental results showed large RMS sway, FRF gains, and variability compared with adults. Modeling suggested that many subjects with CP adopted “simple” control with major contributions from a passive and reflexive mechanism and only a small contribution from active sensory integration. In contrast, mature trunk postural control includes major contributions from sensory integration and sensory reweighting. Relative to their body size, subjects with CP showed significantly lower damping, three to five times larger corrective torque, and much higher sensorimotor noise compared with the healthy mature system. Results are the first characterization of trunk postural responses and the first attempt at system identification in moderate-to-severe CP, an important step toward developing and evaluating more targeted interventions. NEW & NOTEWORTHY Cerebral palsy (CP) is the most common cause of motor disability in children. People with moderate-to-severe CP are typically nonambulatory and have major impairments in trunk postural control. We present the first systems identification study to investigate postural responses to external stimulus in this population and hypothesize at how the atypical postural control system functions with use of a feedback model. People with moderate-to-severe CP may use a simple control system with significant sensorimotor noise. 

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4. The relationship between birth timing, circuit wiring, and physiological response properties of cerebellar granule cells

   https://doi.org/10.1073/pnas.2101826118  

   Shuster, S. Andrew; Wagner, Mark J.; Pan-Doh, Nathan; Ren, Jing; Grutzner, Sophie M.; Beier, Kevin T.; Kim, Tony Hyun; Schnitzer, Mark J.; Luo, Liqun (June 2021, Proceedings of the National Academy of Sciences)

   Cerebellar granule cells (GrCs) are usually regarded as a uniform cell type that collectively expands the coding space of the cerebellum by integrating diverse combinations of mossy fiber inputs. Accordingly, stable molecularly or physiologically defined GrC subtypes within a single cerebellar region have not been reported. The only known cellular property that distinguishes otherwise homogeneous GrCs is the correspondence between GrC birth timing and the depth of the molecular layer to which their axons project. To determine the role birth timing plays in GrC wiring and function, we developed genetic strategies to access early- and late-born GrCs. We initiated retrograde monosynaptic rabies virus tracing from control (birth timing unrestricted), early-born, and late-born GrCs, revealing the different patterns of mossy fiber input to GrCs in vermis lobule 6 and simplex, as well as to early- and late-born GrCs of vermis lobule 6: sensory and motor nuclei provide more input to early-born GrCs, while basal pontine and cerebellar nuclei provide more input to late-born GrCs. In vivo multidepth two-photon Ca 2+ imaging of axons of early- and late-born GrCs revealed representations of diverse task variables and stimuli by both populations, with modest differences in the proportions encoding movement, reward anticipation, and reward consumption. Our results suggest neither organized parallel processing nor completely random organization of mossy fiber→GrC circuitry but instead a moderate influence of birth timing on GrC wiring and encoding. Our imaging data also provide evidence that GrCs can represent generalized responses to aversive stimuli, in addition to recently described reward representations. 

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5. Cortico-cerebellar coordination facilitates neuroprosthetic control

   https://doi.org/10.1126/sciadv.adm8246  

   Abbasi, Aamir; Rangwani, Rohit; Bowen, Daniel W; Fealy, Andrew W; Danielsen, Nathan P; Gulati, Tanuj (April 2024, Science Advances)

   Temporally coordinated neural activity is central to nervous system function and purposeful behavior. Still, there is a paucity of evidence demonstrating how this coordinated activity within cortical and subcortical regions governs behavior. We investigated this between the primary motor (M1) and contralateral cerebellar cortex as rats learned a neuroprosthetic/brain-machine interface (BMI) task. In neuroprosthetic task, actuator movements are causally linked to M1 “direct” neurons that drive the decoder for successful task execution. However, it is unknown how task-related M1 activity interacts with the cerebellum. We observed a notable 3 to 6 hertz coherence that emerged between these regions’ local field potentials (LFPs) with learning that also modulated task-related spiking. We identified robust task-related indirect modulation in the cerebellum, which developed a preferential relationship with M1 task–related activity. Inhibiting cerebellar cortical and deep nuclei activity through optogenetics led to performance impairments in M1-driven neuroprosthetic control. Together, these results demonstrate that cerebellar influence is necessary for M1-driven neuroprosthetic control. 

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