Biology subjects

Namburi, P.

Publications and source records attributed to Namburi, P..

5 recordsLinked to original sources

bioRxiv2026

Neuromuscular impairments alter energetic cost landscape curvature and stride speed variability in post-stroke locomotion

Neuromuscular impairments induce compensatory effects which alter the dynamics of human movement, but the mechanism linking specific impairments to post-stroke locomotion remains poorly understood. Here, we combine a predictive neuromusculoskeletal simulation framework with experimental gait observations in stroke survivors to test how two hemiparetic impairments, reduced muscle strength and increased baseline muscle activity, reshape the energetic cost landscape. We then evaluate whether impairment-dependent changes in the cost landscape curvature are associated with stride speed variability, which is experimentally observed to be higher after stroke. Using neuromusculoskeletal simulations, we show that increased paretic muscle activity reduces local curvature near the cost-minimized speed more than reduced paretic muscle strength and find that this predicts increases in stride speed variability observed in hemiparetic locomotion. These results support a mechanistic hypothesis that flatter cost landscapes reduce the relative cost of suboptimal behavior and, therefore, may contribute to increased motor variability after stroke. Author summaryMotor disorders, such as those caused by stroke, change the way humans walk and interact with the world, often reducing quality of life. Stroke affects millions of people each year and commonly causes unilateral motor impairment that requires substantial rehabilitation. In this study, we use simulations to understand how different impairments, specifically reduced muscle strength and increased muscle activity, alter movement behavior. By varying the severity of the impairment and the speed of walking, we show how different impairments lead to compensation strategies and influence sensitivity to speed fluctuations. These findings suggest that the energetic penalty incurred from suboptimal behavior changes with neuromuscular impairment and are predicted to contribute to increased variability after stroke.

neuroscience↗

bioRxiv2025

Efficient elastic tissue motions indicate general motor skill

Insights into the general nature of motor skill could fundamentally change how we develop movement abilities, with implications for musculoskeletal well-being and injury. Here, we sought to identify indicators of general motor skill-those shared by experts across disciplines (e.g., squash, ballet, volleyball) during non-specialized movements (e.g., reaching for water). Identifying such general indicators of motor skill has remained elusive. Using ultrasound imaging with deep learning and optical flow analysis, we tracked elastic tissues (muscles and associated connective tissues) during a simple reaching task performed similarly by world-class athletes and regional-level athletes drawn from diverse disciplines, as well as untrained non-experts. We analyzed previously unexamined inefficiencies: transverse elastic tissue motions orthogonal to muscle fiber direction and physiological tremors, which are oscillations that do not contribute to the net work done by muscles. We discovered that world-class experts minimize both these inefficient motions compared to regional level athletes and non-experts. While regional- level athletes surprisingly showed similar inefficiencies to non-experts, they used elastic tissues more effectively, achieving equivalent movements with smaller actuation-related tissue motions. We establish elastic tissue motion as a key indicator of general motor skill, expanding our understanding of elastic mechanisms and their role in general aspects of motor skill.

animal behavior and cognition↗

bioRxiv2023

Sexual dimorphism of insular cortex function in persistent alcohol drinking despite aversion in mice

One major hallmark of alcohol use disorder (AUD) is the persistence of drinking despite negative consequences. Among indicators of AUD vulnerability, binge drinking has been identified as one of the strongest risk factors. Although the lifetime prevalence of both binge drinking and AUD has historically been higher in men than women, this gap has dramatically narrowed in the last decade. Additionally, sex differences in AUD and binge drinking have been found in clinical and preclinical studies. At the neurobiological level, the insular cortex plays an important role in AUD, with the anterior (aIC) and posterior (pIC) divisions supporting different functions. However, the contributions of the aIC and pIC sections in sexual dimorphism of alcohol binge drinking and the persistence of alcohol drinking despite aversion remain to be uncovered. Using the drinking in the dark model in mice, we validated that female mice have a higher binge ethanol intake compared to males. To evaluate persistent ethanol consumption despite aversion, we supplemented ethanol with the bitter compound quinine, and found a higher persistent drinking in females compared to males. Using fiber photometry recordings, we revealed that aIC activity was increased during binge and persistent ethanol consumption independently of sex, whereas pIC glutamatergic neuron activity was higher during persistent ethanol drinking, specifically in female mice. Using chemogenetics, we revealed that inhibition of aIC glutamatergic neurons reduced intake of bitter solutions independently of the solvent (ethanol or water) in both sexes. In addition, inhibition of pIC glutamatergic neurons exclusively reduced persistent ethanol drinking in females, while decreasing quinine consumption only in males. These findings suggest a sex-dependent function of the pIC in the persistence of ethanol consumption, providing a starting point in understanding sex-specific functions of the insular cortex in the neurobiology of AUD.

neuroscience↗

bioRxiv2022

Thalamus sends information about arousal but not valence to the amygdala

RationaleThe basolateral amygdala (BLA) and medial geniculate nucleus of the thalamus (MGN) have both been shown to be necessary for the formation of associative learning. While the role that the BLA plays in this process has long been emphasized, the MGN has been less well-studied and surrounded by debate regarding whether the relay of sensory information is active or passive. ObjectivesWe seek to understand the role the MGN has within the thalamoamgydala circuit in the formation of associative learning. MethodsHere, we use optogenetics to dissect the MGN-BLA circuit and explore the specific subpopulations for evidence of learning and synthesis of information that could impact downstream BLA encoding. We employ various machine learning techniques to investigate function within neural subpopulations. We introduce a novel method to investigate tonic changes across trial-by-trial structure, which offers an alternative approach to traditional trial-averaging techniques. ResultsWe find that the MGN appears to encode arousal but not valence, unlike the BLA which encodes for both. We find that the MGN and the BLA appear to react differently to expected and unexpected outcomes; the BLA biased responses toward reward prediction error and the MGN focused on anticipated punishment. We uncover evidence of tonic changes by visualizing changes across trials during inter-trial intervals (baseline epochs) for a subset of cells. ConclusionWe conclude that the MGN-BLA projector population acts as both filter and transferer of information by relaying information about the salience of cues to the amygdala, but these signals are not valence-specified. PrefaceIn tribute to Nadia Chaudhri, and her discoveries regarding how contexts can modulate the representation of cues in the amygdala (Sciascia et al., 2015), and other mesolimbic circuit components (Chaudhri et al., 2009, 2008; Valyear et al., 2020), here we explore what information processing precedes entry into the basolateral amygdala (BLA) from the thalamus and develop visualization approaches for exploring across-trial temporal dynamics in addition to within-trial population activity.

neuroscience↗

bioRxiv2018

Acute Food Deprivation Rapidly Modifies Valence-Coding Microcircuits in the Amygdala

In the quest for food, we may expend effort and increase our vulnerability to potential threats. Motivation to seek food is dynamic, varying with homeostatic need. What mechanisms underlie these changes? Basolateral amygdala neurons projecting to the nucleus accumbens (BLA[->]NAc) preferentially encode positive valence, whereas those targeting the centromedial amygdala (BLA[->]CeM) preferentially encode negative valence. Longitudinal in vivo two-photon calcium imaging revealed that BLA[->]NAc neurons were more active, while BLA[->]CeM neurons were less active, following just 1 day of food deprivation. Photostimulating BLA[->]CeM neurons inhibited BLA[->]NAc neurons at baseline, but food deprivation rapidly converted this inhibition into facilitation, supporting a model wherein BLA[->]NAc excitability mediates invigorated food-seeking behavior after deprivation. Indeed, inhibiting BLA[->]NAc reduced motivation for a caloric reinforcer in food deprived animals. Taken together, negative valence overrides positive valence processing in satiety, but changing homeostatic needs alter reward value via a rapid shift in the balance between projection-defined populations of BLA neurons.

neuroscience↗