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Khajehnejad, M.

Publications and source records attributed to Khajehnejad, M..

3 recordsLinked to original sources

A Computational Perspective on the No-Strong-Loops Principle in Brain Networks

Cerebral cortical networks in the mammalian brain exhibit a non-random organization in which reciprocal projections, although widespread, are systematically asymmetric in strength: feedforward connections are consistently stronger than their feedback counterparts, particularly in sensory cortices. This "no-strong-loops" principle is thought to prevent runaway excitation and maintain stability, yet its actual computational impact remains unclear. Here, we use computational analysis and modeling to show that connectivity asymmetry supports high working-memory capacity, whereas increasing reciprocity reduces memory capacity and representational diversity in reservoir-computing models of recurrent neural networks. We systematically examine synthetic architectures inspired by mammalian cortical connectivity and find that sparse, modular, and hierarchical networks achieve superior performance, relative to random, small-world, or core-periphery graphs, but only when reciprocity is constrained. Validated on directed mammalian (macaque, marmoset, rat, and mouse) connectomes, these results indicate that restricting reciprocal motifs yields functional benefits in sparse networks, consistent with an evolutionary strategy for stable, efficient information processing in the brain. These findings suggest a biologically-inspired design principle for artificial neural systems.

neuroscience↗

Psychedelics Align Brain Activity with Context

Psychedelics can profoundly alter consciousness by reorganising brain connectivity; however, their effects are context-sensitive. To understand how this reorganisation depends on context, we collected and comprehensively analysed the largest psychedelic neuroimaging dataset to date. Sixty-two adults were scanned with functional MRI and EEG during rest and naturalistic stimuli (meditation, music, and movie), before and after ingesting 19 mg of psilocybin (functional MRI {approx}80 min post-dose; EEG {approx}150 min post-dose). Half the participants ranked the experience among the most meaningful of their lives. Under psilocybin, functional MRI and EEG signals recorded during eyes-closed conditions became similar to those recorded during an eyes-open condition. Global functional connectivity increased in associative regions and decreased in sensory areas. Using machine learning to represent neural activity as low-dimensional trajectories, we found that psilocybin reorganised these into structured, context-sensitive patterns of brain activity that reflected both experimental condition and the quality of subjective experience, revealing an organisation that was missed by time-averaged connectivity measures. Under psilocybin, brain networks that ordinarily segregate internal and external processing coherently integrated and aligned neural dynamics with context. This context-alignment manifested as distinct and cohesive neural trajectories in participants reporting positively felt self- and boundary-dissolving effects, corresponding to the felt experience of being part of the environment, which we refer to as embeddedness--the subjective experience of being continuous with, rather than separate from, the surrounding environment. The strength of this context-alignment was associated with next-day mindset change, bridging the neural, experiential, and therapeutic dimensions of the psychedelic state. These findings show that the organisation of brain activity covaries with the experiential coherence of the psychedelic state, and provide a systems-level framework for how context-sensitive brain dynamics link neurobiology to subjective experience and behavioural change.

neuroscience↗

Drug treatment alters performance in a neural microphysiological system of information processing

Assessment of pharmacological intervention on in vitro neural systems often emphasizes molecular and structural changes. However, neural systems fundamentally process and act on information. For preclinical assays to predict drug efficacy, they must model these physiological functions. DishBrain, an in vitro synthetic biological intelligence (SBI) assay embodying a neural system in a simulated game-world, enables the quantification of this information-processing capacity, however the question remains whether such a system permits classical pharmacological interrogation and dose-response profiling. Hyperactive glutamatergic dysregulation is linked to neurological disorders including epilepsy, and inducible overexpression of neurogenin 2 (NGN2) in human induced pluripotent stem cells (hiPSCs) generates glutamatergic cultures with dysregulated hyperactivity. We therefore tested three anti-seizure medications (ASMs), phenytoin, perampanel, and carbamazepine, on NGN2 neurons from day 21 of differentiation in this system. The key finding was that, while all compounds altered spontaneous firing, carbamazepine 200 {micro}M significantly improved gameplay metrics. This marks the first demonstration of altered SBI following exogenous drug treatment. Notably, only inhibitory compounds enhanced goal-directed activity, linking glutamatergic attenuation to performance. Neurocomputational analysis revealed nuanced pharmacological responses during closed-loop stimulation, highlighting insights beyond spontaneous activity metrics.

neuroscience↗