Biology subjects

Markov, N. T.

Publications and source records attributed to Markov, N. T..

5 recordsLinked to original sources

bioRxiv2026

Decoherence via Demyelination Hypothesis (DDH): A Mechanism of Cognitive Decline During Aging

Progressive cognitive decline and loss of white matter integrity are observed during aging, but whether these two processes are connected remains unclear. We propose the Decoherence via Demyelination Hypothesis (DDH) as a mechanism linking non-uniform, tract-specific myelin loss during aging, which results in the degradation of conduction timing that is required to coordinate long-range neuronal assemblies. This impairs the dynamic assembly of task-dependent functional networks and promotes age-associated cognitive change. Axonal myelination determines conduction velocity as well as signal transmission fidelity, properties essential for phase-locked integration of long-distance inputs with local oscillations and for the assembly of mesoscale functional brain networks. If myelin loss is heterogeneous across tracts, the resulting timing perturbations should be heterogeneous as well, with disproportionate impact on networks supporting higher-order cognition. To test this, we analyzed structural and microstructural MRI in 638 individuals aged 40-99, quantifying fasciculation in different white matter pathways as well as neurite orientation dispersion and density imaging (NODDI) to the gray-white matter interface beneath cortical regions. We observed tract-specific, non-uniform myelin decline, with significant nonlinear losses in tracts serving high order cognition and memory (uncinate fasciculus, fornix, corpus callosum), consistent with accelerated late-life vulnerability in pathways implicated in cognitive aging and increased risk for neurodegenerative diseases. Tract-level degeneration tracked with age-related shifts in network organization and cognition. These findings may support DDH as a framework for age-associated cognitive change. Particularly, tract-specific timing perturbations drive the breakdown of coordinated network activity in aging.

neuroscience↗

bioRxiv2024

Building compositional tasks with shared neural subspaces

Cognition is remarkably flexible; we are able to rapidly learn and perform many different tasks1. Theoretical modeling has shown artificial neural networks trained to perform multiple tasks will re-use representations2 and computational components3 across tasks. By composing tasks from these sub-components, an agent can flexibly switch between tasks and rapidly learn new tasks4. Yet, whether such compositionality is found in the brain is unknown. Here, we show the same subspaces of neural activity represent task-relevant information across multiple tasks, with each task compositionally combining these subspaces in a task-specific manner. We trained monkeys to switch between three compositionally related tasks. Neural recordings found task-relevant information about stimulus features and motor actions were represented in subspaces of neural activity that were shared across tasks. When monkeys performed a task, neural representations in the relevant shared sensory subspace were transformed to the relevant shared motor subspace. Subspaces were flexibly engaged as monkeys discovered the task in effect; their internal belief about the current task predicted the strength of representations in task-relevant subspaces. In sum, our findings suggest that the brain can flexibly perform multiple tasks by compositionally combining task-relevant neural representations across tasks.

neuroscience↗

bioRxiv2023

Learning attentional templates for value-based decision-making

Attention filters sensory inputs to enhance task-relevant information. It is guided by an attentional template that represents the stimulus features that are relevant for the current task. To understand how the brain learns and uses new templates, we trained monkeys to perform a visual search task that required them to repeatedly learn new attentional templates. Neural recordings found templates were represented across prefrontal and parietal cortex in a structured manner, such that perceptually neighboring templates had similar neural representations. When the task changed, a new attentional template was learned by incrementally shifting the template towards rewarded features. Finally, we found attentional templates transformed stimulus features into a common value representation that allowed the same decision-making mechanisms to deploy attention, regardless of the identity of the template. Altogether, our results provide new insight into the neural mechanisms by which the brain learns to control attention and how attention can be flexibly deployed across tasks.

neuroscience↗

bioRxiv2019

Unique Features of Sub-Cortical Circuits in A Macaque Model of Congenital Blindness

There is extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of the congenital blindness in macaque resulting from the removal of the retina during in utero development. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced hybrid cortex (HC) combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas including hybrid cortex reveals a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the hybrid cortex, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the inter-areal cortical network and the ascending visual pathways.

neuroscience↗

bioRxiv2017

Cortical Connectivity In A Macaque Model Of Congenital Blindness

AbstractBrain-mapping of the congenitally blind human reveals extensive plasticity(1). The visual cortex of the blind has been observed to support higher cognitive functions including language and numerical processing(2, 3). This functional shift is hypothesized to reflect a metamodal cortical function, where computations are defined by the local network. In the case of developmental deafferentation, local circuits are considered to implement higher cognitive functions by accommodating diverse long-distance inputs(4-7). However, the extent to which visual deprivation triggers a reorganization of the large-scale network in the cortex is still controversial(8). Here we show that early prenatal ablation of the retina, an experimental model of anophthalmia in macaque, leads to a major reduction of area V1 and the creation of a default extrastriate cortex (DEC)(9, 10). Anophthalmic and normal macaques received retrograde tracer injections in DEC, as well as areas V2 and V4 post-natally. This revealed a six-fold expansion of the spatial extent of local connectivity in the DEC and a surprisingly high location of the DEC derived from a computational model of the cortical hierarchy(11). In the anophthalmic the set of areas projecting to the DEC, area V2 and V4 does not differ from that of normal adult controls, but there is a highly significant increase in the relative cumulative weight of the ventral stream areas input to the early visual areas. These findings show that although occupying the territory that would have become primary visual cortex the DEC exhibits features of a higher order area, thus reflecting a combination of intrinsic and extrinsic factors on cortical specification. Understanding the interaction of these contributing factors will shed light on cortical plasticity during primate development and the neurobiology of blindness.

neuroscience↗