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Rajeswaran, P.

Publications and source records attributed to Rajeswaran, P..

5 recordsLinked to original sources

Changes to task relevance in redundant motor environments distinguish structure learning from adaptation

Motor actions often exceed the dimensionality of task feedback, which creates control redundancy that requires learners to identify which movement dimensions influence task outcomes. The computations that shape learning in redundant tasks, especially when task-relevant spaces change, remain unclear. We studied this by combining established visuomotor perturbation approaches with a redundant motor interface reaching task. Two monkeys learned a 3D hand position to 2D cursor position mapping that allowed us to define and manipulate the task-relevant space. After animals learned an initial task-relevant space, we introduced two types of perturbations: Relevance Preserving (RP), which rotated hand-cursor relationships within the learned task relevant space, and Relevance Altering (RA), which altered the task relevant space. We hypothesized that RP perturbations would engage error-based adaptation (observed in non-redundant tasks), whereas RA perturbations would engage additional learning mechanisms associated with acquiring new skills. RP perturbations were learned rapidly during training (online) and generalized to the initial learned mapping, consistent with error-based adaptation. In contrast, adapting to the first RA perturbation took longer, engaged learning outside of training (offline), and did not generalize to the initial learned mapping. Animals also adapted faster across repeated exposures to new RA mappings and changed how they generated movements to learn each new mapping, consistent with computations associated with structure learning. These findings suggest that changing task relevance shifts motor learning from adaptation toward structure learning, which has implications for models of motor learning and sensorimotor therapies like brain-computer interfaces.

neuroscience↗

Combining phase analysis and causal stimulation enables longitudinal mesoscale connectivity mapping

Uncovering the circuit mechanisms of flexible behavior requires characterizing how neural signals propagate across large-scale networks and tracking how those networks evolve over time. Signal propagation through networks can be characterized by injecting activity and analyzing signals propagation, thereby measuring "causal connectivity". However, current techniques cannot measure causal connectivity at centimeter scales over weeklong periods of time, especially in non-human primates. Here, we present a stimulation and recording method to longitudinally measure causal connectivity across centimeter-scale cortical networks in macaques. We combined multi-site optogenetic stimulation with micro-electrocorticography using a semi-chronic implant approach that enables stable daily measurements over weeks-long periods spanning years. Stimulation evoked activity reflected a mixture of local, stimulation-driven responses and secondary, delayed activity presumably driven through connections. We applied phase-based spectral analysis to disentangle stimulation-driven and secondary activity related to causal connections. We validated this approach by tracking connectivity across weeks. We demonstrated improved stability over long durations while preserving sensitivity to eyes-open vs. closed behavioral states. This platform provides a robust means to investigate the large-scale circuit dynamics underlying complex behavior in the primate brain.

neuroscience↗

Mapping eye, arm, and reward information in frontal motor cortices using electrocorticography in non-human primates

Goal-directed reaches give rise to dynamic neural activity across the brain as we move our eyes and arms, and process outcomes. High spatiotemporal resolution mapping of multiple cortical areas will improve our understanding of how these neural computations are spatially and temporally distributed across the brain. In this study, we used micro-electrocorticography ({micro}ECoG) recordings in two male monkeys performing visually guided reaches to map information related to eye movements, arm movements, and receiving rewards over a 1.37 cm2 area of frontal motor cortices (primary motor cortex, premotor cortex, frontal eye field, and dorsolateral pre-frontal cortex). Time-frequency and decoding analyses revealed that eye and arm movement information shifts across brain regions during a reach, likely reflecting shifts from planning to execution. We then used phase-based analyses to reveal potential overlaps of eye and arm information. We found that arm movement decoding performance was impacted by task-irrelevant eye movements, consistent with the presence of intermixed eye and arm information across much of motor cortices. Phase-based analyses also identified reward-related activity primarily around the principal sulcus in the pre-frontal cortex as well as near the arcuate sulcus in the premotor cortex. Our results demonstrate {micro}ECoGs strengths for functional mapping and provide further detail on the spatial distribution of eye, arm, and reward information processing distributed across frontal cortices during reaching. These insights advance our understanding of the overlapping neural computations underlying coordinated movements and reveal opportunities to leverage these signals to enhance future brain-computer interfaces. Significance statement Picking up your coffee mug requires coordinating movements of your eyes and hand and processing the outcomes of those movements. Mapping how neural activity relates to different functions helps us understand how the brain performs these computations. Many mapping techniques have limited spatial or temporal resolution, restricting our ability to dissect computations that overlap closely in space and time. We used micro-electrocorticography recordings to map neural activity across multiple cortical areas while monkeys made goal-directed reaches. These measurements revealed high spatial and temporal resolution maps of neural activity related to eye, arm, and reward information processing. These maps reveal overlapping neural computations underlying movement and open opportunities to use eye and reward information to improve therapies to restore motor function.

neuroscience↗

Selective inflammation of the tumor microenvironment and invigorated T cell-mediated tumor control upon induced systemic inactivation of TREX1

Therapeutic innate immune stimulation within the tumor microenvironment can potentiate endogenous antitumor T cell immunity. DNase 3-repair exonuclease 1 (TREX1) is essential for cellular DNA disposal which prevents autoimmunity ensuing from cGAS/STING activation by endogenous DNA. Optimal strategies to therapeutically leverage cGAS/STING signalling for cancer therapy are highly sought after. TREX1-deficient tumor cells elicit enhanced protective immunity in syngeneic models. Here we show that induced inactivation of the Trex1 gene in (non-malignant) host cells is well tolerated and yields improved type I IFN- and T cell-dependent control of established TREX1-competent tumors with selective immune cell infiltration of tumor, but not other tissues. Intra-tumoral T cell proliferation and numbers of effector and effector-like exhausted cells massively increased, enabling complete rejection in synergy with checkpoint inhibition. We conclude that systemic TREX1 inhibition is a promising approach to boost anti-tumor immunity, that can overcome immune evasion by cancer cell- intrinsic cGAS/STING inactivation.

immunology↗

Assistive sensory-motor perturbations influence learned neural representations

Task errors are used to learn and refine motor skills. We investigated how task assistance influences learned neural representations using Brain-Computer Interfaces (BCIs), which map neural activity into movement via a decoder. We analyzed motor cortex activity as monkeys practiced BCI with a decoder that adapted to improve or maintain performance over days. Over time, task-relevant information became concentrated in fewer neurons, unlike with fixed decoders. At the population level, task information also became largely confined to a few neural modes that accounted for an unexpectedly small fraction of the population variance. A neural network model suggests the adaptive decoders directly contribute to forming these more compact neural representations. Our findings show that assistive decoders manipulate error information used for long-term learning computations like credit assignment, which informs our understanding of motor learning and has implications for designing real-world BCIs.

neuroscience↗