Biology subjects

Cook, D. J.

Publications and source records attributed to Cook, D. J..

8 recordsLinked to original sources

bioRxiv2025

Repeated subconcussive head impacts compromise white matter integrity: A longitudinal DTI and NODDI study in collegiate football players

ObjectivesTo determine whether repetitive subconcussive impacts in collegiate football are associated with altered white matter microstructure, motor control deficits, and changes in concussion symptoms across a single season. DesignCohort study with non-contact controls and stratification of contact athletes by head-impact exposure. MethodTwenty-two male varsity football players and 27 non-contact controls underwent pre-season diffusion tensor imaging. Tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were derived from commissural and association tracts using probabilistic tractography. Helmet-mounted accelerometers quantified head-impact frequency and gForce over the season, classifying athletes into high (HE) and low-exposure (LE) groups. Football players completed the Kinarm Ball-on-Bar bimanual coordination task and SCAT3 symptom checklist pre- and post-season. ResultsAt pre-season, contact athletes showed altered white matter microstructure versus controls, with higher FA and predominantly lower MD across most tracts. Over the season, HE athletes sustained more total impacts and gForce than LE athletes and showed declining bimanual coordination on the Ball-on-Bar motor task. SCAT3 symptom and severity scores were low and showed no differences in change. ConclusionsRepetitive subconcussive exposure in collegiate football is associated with persisting white matter differences and subtle bimanual motor coordination deficits that are not detected by routine symptom-based tools, supporting the use of advanced neuroimaging and robotic motor assessment to monitor athlete brain health.

neuroscience↗

bioRxiv2024

Brain Charts for the Rhesus Macaque Lifespan

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

neuroscience↗

bioRxiv2022

Spontaneous behavioural recovery following stroke relates to the integrity of sensory and association cortices

Stroke is a devastating disease that results in neurological deficits and represents a leading cause of death and disability worldwide. Following a stroke, there is a degree of spontaneous recovery of function, the neural basis of which is of great interest among clinicians in their efforts to reduce disability following stroke and enhance rehabilitation. Conventionally, work on spontaneous recovery has tended to focus on the neural reorganization of motor cortical regions, with comparably little attention being paid to changes in non-motor regions and how these relate to recovery. Here we show, using structural neuroimaging in a macaque stroke model and by exploiting individual differences in spontaneous behavioural recovery, that the preservation of regions in the sensory and association cortices predict animal recovery. To characterize recovery, we performed a clustering analysis using Non-Human Primate Stroke Scale (NHPSS) scores and identified a good versus poor recovery group. By comparing the preservation of brain volumes in the two groups, we found that brain areas in integrity of brain areas in parietal, temporal and somatosensory cortex were associated with better recovery. In addition, a decoding approach performed across all subjects revealed that the preservation of specific brain regions in the parietal, somatosensory and medial frontal cortex predicted recovery. Together, these findings highlight the importance of the sensory and association regions in spontaneous behavioural recovery, supporting the notion that the sensory retraining of impairments following stroke is critical to recovery and motor function.

neuroscience↗

bioRxiv2021

Convergence of proprioceptive and visual feedback on neurons in primary motor cortex

An important aspect of motor function is our ability to rapidly generate goal-directed corrections for disturbances to the limb or behavioural goal. Primary motor cortex (M1) is a key region involved in feedback processing, yet we know little about how different sources of feedback are processed by M1. We examined feedback-related activity in M1 to compare how different sources (visual versus proprioceptive) and types of information (limb versus goal) are represented. We found sensory feedback had a broad influence on M1 activity with [~]73% of neurons responding to at least one of the feedback sources. Information was also organized such that limb and goal feedback targeted the same neurons and evoked similar responses at the single-neuron and population levels indicating a strong convergence of feedback sources in M1.

neuroscience↗

bioRxiv2021

Comparison of cerebrospinal fluid biomarkers relevant to neurodegenerative diseases in healthy cynomolgus and rhesus macaque monkeys

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSNon-human primates are important translational models of neurodegenerative disease. We characterized how species, sex, age, and site of sampling affected concentrations of key biomarkers of neurodegeneration. METHODSAmyloid-beta (A{beta}40, A{beta}42), tau (tTau, pTau), and neurofilament light (NFL) in CSF were measured in 82 laboratory-housed naive cynomolgus and rhesus macaques of both sexes. RESULTSA{beta}40, A{beta}42, and NFL were significantly higher in rhesus compared with cynomolgus macaques. tTau and NFL were higher in males. pTau was not affected by species or sex. Site of acquisition only affected NFL, with NFL being higher in CSF acquired from lumbar compared with cisterna magna puncture. DISCUSSIONNormative values for key neurodegeneration biomarkers were established for laboratory housed cynomolgus and rhesus macaque monkeys. Differences were observed as a function of species, sex and site of CSF acquisition that should be considered when employing primate models. Research In ContextO_LISystematic review: We reviewed reports characterizing CSF biomarkers of neurodegenerative diseases in non-human primates - an increasingly important model of disease - revealing that studies with laboratory housed macaque monkeys were of small sample size, with a paucity of data about how biomarkers varied as a function of species, sex, age, and site of acquisition. C_LIO_LIInterpretation: To address this gap, we collected CSF from 82 naive laboratory housed male and female macaques of two species and measured A{beta}40, A{beta}42, tTau, pTau, and NFL. In addition to providing normative statistics for concentrations of these biomarkers, we revealed various species and sex differences. C_LIO_LIFuture directions: Establishing normative values of biomarkers is an important step to the efficient development of cynomolgus and rhesus macaques as models of neurodegenerative disorders such as Alzheimers disease. Reference values reduce the need for large control groups by which to compare with disease model animals. C_LI

neuroscience↗

bioRxiv2020

Causal roles of frontoparietal cortical areas in feedback control of the limb

Goal-directed motor corrections are surprisingly fast and complex, but little is known on how they are generated by the central nervous system. Here we show that temporary cooling of dorsal premotor cortex (PMd) or parietal area 5 (A5) in behaving monkeys caused impairments in corrective responses to mechanical perturbations of the forelimb. Deactivation of PMd impaired both spatial accuracy and response speed, whereas deactivation of A5 impaired spatial accuracy, but not response speed. Simulations based on optimal feedback control demonstrated that deactivation of the control policy (reduction of feedback gain) impaired both spatial accuracy and response speed, whereas deactivation in state estimation (reduction of Kalman gain) impaired spatial accuracy but not response speed, paralleling the impairments observed from deactivation of PMd and A5, respectively. Furthermore, combined deactivation of both cortical regions led to additive impairments of individual deactivations, whereas reducing the amount of cooling (i.e. milder cooling) to PMd led to impairments in response speed, but not spatial accuracy, both also predicted by the model simulations. These results provide causal support that higher order motor and somatosensory regions beyond primary somatosensory and primary motor cortex are involved in generating goal-directed motor responses. As well, the computational models suggest that the distinct patterns of impairments associated with these cortical regions reflect their unique functional roles in goal-directed feedback control.

neuroscience↗

bioRxiv2020

Maintained representations of the ipsilateral and contralateral limbs during bimanual control in primary motor cortex.

Primary motor cortex (M1) almost exclusively controls the contralateral side of the body. However, M1 activity is also modulated during ipsilateral body movements. Previous work has shown that M1 activity related to the ipsilateral arm is independent of the M1 activity related to the contralateral arm. How do these patterns of activity interact when both arms move simultaneously? We explored this problem by training two monkeys (male, Macaca mulatta) in a postural perturbation task while recording from M1. Loads were applied to one arm at a time (unimanual) or both arms simultaneously (bimanual). We found 83% of neurons were responsive to both the unimanual and bimanual loads. We also observed a small reduction in activity magnitude during the bimanual loads for both limbs (25%). Across the unimanual and bimanual loads, neurons largely maintained their preferred load directions. However, there was a larger change in the preferred loads for the ipsilateral limb (~25%) than the contralateral limb (~9%). Lastly, we identified the contralateral and ipsilateral subspaces during the unimanual loads and found they captured a significant amount of the variance during the bimanual loads. However, the subspace captured more of the bimanual variance related to the contralateral limb (97%) than the ipsilateral limb (66%). Our results highlight that even during bimanual motor actions, M1 largely retains its representations of the contralateral and ipsilateral limbs. Significance StatementPrevious work has shown that primary motor cortex (M1) reflects information related to the contralateral limb, its downstream target, but also reflects information related to the ipsilateral limb. Can M1 still reflect both sources of information when performing simultaneous movements of the limbs? Here we use a postural perturbation task to show that M1 activity maintains a similar representation for the contralateral limb during bimanual motor actions, while there is only a modest change in the representation of the ipsilateral limb. Our results indicate that two orthogonal representations can be maintained and expressed simultaneously in M1.

neuroscience↗

bioRxiv2019

Keep your hands apart: independent representations of ipsilateral and contralateral forelimbs in primary motor cortex

It is generally accepted that each cortical hemisphere primarily drives the opposite side of the body. Yet, primary motor cortical (M1) activity has been robustly correlated with both contralateral and ipsilateral arm movements. It has remained unanswered as to why ipsilaterally-related activity does not cause contralateral motor activity. Here we apply multi-joint elbow and shoulder loads to the left or right arms of monkeys during a postural perturbation task. We show that many M1 neurons respond to mechanical disturbances applied to either the contra- or ipsilateral arms. More neurons respond to loads applied to the contralateral arm with response magnitudes that were ~2x as large and had onset times that were ~10ms earlier. However, in some cases, neurons exhibited large and earlier responses to loads applied to the ipsilateral arm than loads applied to the contralateral arm. Similar effects were observed when the monkeys were maintaining postural control well after the load had been applied. Importantly, we show that the load preference to one arm has little predictive power on a neurons preference in the opposite arm. Furthermore, we found contralateral and ipsilateral neural activity resided in orthogonal subspaces allowing for a weighted sum of neural responses to extract the contralateral activity without interference from the ipsilateral activity, and vice versa. These data show how activity in M1 unrelated to downstream motor targets can be segregated from downstream motor output.

neuroscience↗