Biology subjects

Tremblay, L.

Publications and source records attributed to Tremblay, L..

5 recordsLinked to original sources

bioRxiv2026

CM/Pf contribution to mesocircuit dynamics underlying awareness in non-human primates

BackgroundIn acute disorders of consciousness following severe brain injury, the heterogeneity and multiplicity of brain lesions make it difficult to infer a direct causal link between lesion patterns and impaired consciousness. As a result, neuroimaging analyses performed in intensive care settings can inform theories of consciousness mainly through correlational, rather than causal, evidence. The mesocircuit hypothesis proposes that interactions between the thalamus, basal ganglia, and cortex support the neural mechanisms underlying awareness. Among its key components, the intralaminar thalamic nuclei are thought to play a central role, yet their respective contributions to mesocircuit dynamics remain poorly understood. MethodsIn two macaque monkeys, we combined causal perturbations of three thalamic nuclei (the centromedian-parafascicular complex (CM/Pf), central lateral nucleus (CL), and mediodorsal nucleus (MD)) with a cue-guided behavioural task requiring the processing of multisensory information. Electrical microstimulation was first used to compare the behavioural consequences of perturbing each target. Reversible pharmacological inactivation using muscimol was subsequently performed in the CM/Pf and CL. Finally, the large-scale metabolic effects of CM/Pf inactivation (muscimol) and disinhibition (bicuculline) were assessed using [18F]FDG PET imaging. ResultsPerturbation of the intralaminar nuclei disrupted behavioural performance, with the strongest and most reproducible effects observed following CM/Pf manipulation. CM/Pf inactivation reduced correct responses and increased omissions and wrong responses, particularly under conditions requiring greater behavioural engagement. Importantly, these deficits occurred without evidence of major wakefulness impairment, as animals remained responsive throughout testing and showed no substantial increase in eye-closure probability. In contrast, CL perturbation produced weaker behavioural effects, suggesting distinct functional contributions of the two intralaminar nuclei. [18F]FDG PET imaging revealed that CM/Pf disinhibition increased glucose metabolism across thalamic, striatal, pallidal, and frontal cortical territories, whereas CM/Pf inactivation induced a broadly reciprocal pattern of metabolic pattern. These findings identify the CM/Pf as a major modulator of both thalamo-striatal and thalamo-cortical components of the mesocircuit. ConclusionsOur results show that a unilateral intralaminar nucleus perturbation is not sufficient to affect wakefulness, suggesting that this function is mediated by a bilateral network at the thalamus level within the mesocircuit. The CM/Pf emerged as the intralaminar nucleus exerting the strongest influence on goal directed behaviours requiring the mesocircuit dynamics. Our findings also support the existence of partially distinct intralaminar pathways contributing differentially to global state regulation of awareness-related functions, and identify the CM/Pf as a key thalamo-striatal hub within the mesocircuit.

neuroscience↗

bioRxiv2026

The tilt board task as an internally valid practice-transfer paradigm for stabilometer balance assessments

Practice-transfer paradigms are central to motor learning research, yet dynamic balance lacks standardized, internally valid practice-transfer task pairings. This study evaluated whether a mediolateral tilt board can serve as a valid transfer task for stabilometer-based balance assessment. Sixteen healthy young adults (20-35 years) completed a single session consisting of two 40-second trials on a mediolateral stabilometer and two 40-second trials on a mediolateral tilt board. Participants aimed to keep each platform horizontal during each trial. Performance outcomes were derived from platform deviation angle. Neuromuscular outcomes were derived from surface EMG of bilateral gluteus medius, vastus lateralis, and vastus medialis, including muscle synergy structure, bilateral co-activation index, RMS amplitude of muscle activation, and strategy ratios (hip-to-knee and asymmetry metrics). Between-task associations were assessed using Spearman correlations. Cross-task muscle synergy similarity was high (mean cosine similarity = 0.915 {+/-} 0.044) and close to within-task trial-to-trial similarity, indicating preserved modular coordination across devices. Performance metrics were moderately to strongly correlated between tasks (RMS deviation angle: {rho} = 0.621, p = 0.0089; time-in-balance: {rho} = 0.668, p = 0.0036). EMG-derived strategy metrics also correlated significantly across tasks, including bilateral co-activation ({rho} = 0.688, p = 0.0023), hip-to-knee ratio ({rho} = 0.765, p = 0.0003), hip asymmetry ratio ({rho} = 0.688, p=0.0023), and knee asymmetry ratio ({rho} = 0.679, p = 0.0028). In contrast, EMG RMS amplitude did not correlate across tasks ({rho} = -0.044, p = 0.873), suggesting task-specific gain of activation magnitude. Stabilometer and tilt board tasks shared a similar coordination structure and showed a high correlation in balance performance and neuromuscular strategy, supporting the tilt board as an internally valid transfer task for stabilometer-based dynamic balance paradigms. Similarity of tasks appears strongest at the level of modular control and strategy organization, with device-specific gain scaling of activation amplitude.

neuroscience↗

bioRxiv2025

Determining perception thresholds of young adults to small continuous moving platform perturbations

Detecting external disturbances is vital for maintaining balance, as corrective actions are initiated to prevent falls. Quantifying peoples ability to perceive such disturbances improves our understanding of how balance is maintained. This study aims to: 1) quantify healthy young adults ability to perceive external perturbations while balancing on a stabilometer, and 2) understand the relationship between balance performance and perturbation magnitude relative to participants perception threshold. Participants (n=22; 20-35 years) completed a multiple staircase protocol. While standing on a stabilometer mounted on a moving platform, they attempted to keep it horizontal during 10-second trials with small continuous perturbations. After each trial, participants were asked whether they perceived the platform movement. Perturbation magnitudes were adjusted for the next trial based on their response. This process continued for each staircase until the termination criteria were met, at which point participants individual perception threshold was determined. Participants then performed ten 40-second trials on the stabilometer, two trials in each condition: without perturbation, perturbation at the 100%, 80%, and 50% of the individuals perception threshold, and the pilot studys minimum threshold. Balance performance was defined as time-in-balance ratio and RMS deviation angle from horizontal. Perception thresholds varied significantly between participants individuals, with an RMS acceleration ranging from 2.67 and 12.80 cm/s2. The results showed that perturbation magnitude has a significant correlation with variability in deviation angle (R=0.24, p=0.0038). The results suggest that some participants can perceive very small perturbations during a challenging balance task. Subthreshold perturbations, although very small, can influence balance performance. NEW & NOTEWORTHYTo our knowledge, this is the first study to quantitatively measure the conscious perception threshold of platform perturbations while doing a balancing task. We found that young healthy adults with little similar prior experience in tasks close to stabilameter balancing task can detect small platform perturbations while doing such challenging task. The results also showed that platform perturbations below conscious threshold can influence the balance performance on the stabilometer.

neuroscience↗

bioRxiv2019

The effects of postural threat induced by a virtual environment on performance of a walking balance task.

Rapid motor learning may occur in situations where individuals perceive a threat of injury if they do not perform a task well. This rapid motor learning may be facilitated by improved motor performance and, consequently, more errorless practice. As a first step towards understanding the role of perceived threat on rapid motor learning, the purpose of this study was to determine how performance of a motor task is affected in situations where perceived threat of injury is high. We hypothesized that perceived threat of injury in a virtual environment would result in improved performance of a walking task (i.e., walking on a narrow beam). Results demonstrated that increased perceived threat of injury yielded slightly greater, but not statistically significant, balance performance in virtual environments (median percentage of successful steps: 78.8%, 48.3%, and 55.2% in the real low-threat, virtual low-threat, and virtual high-threat environments, respectively). These results may be partially attributed to habituation to threat over time and practice. If implemented carefully, virtual reality technology can be an effective tool for investigating walking balance in environments that are perceived as threatening.

physiology↗

bioRxiv2017

Authentic Enzyme Intermediates Captured "on-the-fly" by Mix-and-Inject Serial Crystallography

Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases. Here, we demonstrate a general method for capturing enzyme catalysis in-action by mix-and-inject serial crystallography. Specifically, we follow the catalytic reaction of the Mycobacterium tuberculosis -lactamase with the 3rd generation antibiotic ceftriaxone by time-resolved serial femtosecond crystallography. The results reveal, in near atomic detail, antibiotic cleavage and inactivation on the millisecond to second time scales including the crossover from transition state kinetics to steady-state kinetics.\n\nSynopsisAn enzymatically catalyzed reaction is initiated by diffusion based mixing of substrate and followed at runtime by time-resolved serial crystallography using a free electron laser.

biophysics↗