Wilson, M. N., Kharitonova, E. K., Yeh, J. et al. · neuroscience
Methods 96%
Abstract
The balance between excitatory and inhibitory (E/I) neurons is fundamental to cortical function, and its disruption underlies a wide range of neurological disorders, including epilepsy, Alzheimers disease and autism spectrum disorder. Cortical organoids offer a promising model to study this balance, as they recapitulate key features of brain development, including the emergence of E/I circuitry. However, no existing technology can simultaneously resolve neuronal identity, spatial organization, and dynamic network activity within intact organoids, limiting precise interrogation of E/I circuit function. Here, we report INFORM, an INtegrated Flexible Organoid Recording Multimodal neural interface that conformally wraps organoids of any size and shape, enabling long-term recordings over 371 days with above 90% of channels detecting spikes. INFORM interface combines four distinct modalities; electrophysiology, two-photon calcium imaging, targeted electrical microstimulation, and chemical intervention to monitor and modulate neural activity across multiple spatial and temporal scales spanning from action potentials from single neurons to synchronized bursts from large-scale populations. Such high-resolution interrogation enables probing of emergence of functional connectivity in fusing assembloids and resolves spatially discrete functional subnetworks that can be selectively recruited and modulated by INFORM. Neurotransmission blockade confirms that stimulus-evoked suppression of neuronal spiking is mediated by GABAergic inputs providing direct functional evidence of the presence of inhibitory signaling in organoids. This work allows single-cell dissection of functional networks in brain organoids, providing a powerful platform for modelling and studying cortical development, neurological diseases, and the E/I imbalances underlying circuit dysfunction.
Deng, Q., Chen, C., Zikopoulos, B. et al. · neuroscience
Computational models 94%Neural coding 64%
Abstract
INTRODUCTION: Alzheimer's disease (AD) involves early sensory and perceptual changes that can precede memory decline. We developed a two-layer rate-based neural model of early and higher visual areas with feedforward, feedback, and recurrent connections to examine how excitatory/inhibitory (E/I) balance shapes visual motion perception in AD. METHODS: Using Motion-Induced Position Shift and Altered Motion Repulsion stimuli, we factorially manipulated excitatory (E) and inhibitory (I) subfield power and connectivity to examine their effects on illusion representation across visual layers. RESULTS: Increased E, decreased I, and increased E/I reduced illusion representation, consistent with reduced illusion susceptibility in AD, whereas the converse increased illusion representation, reflecting neurotypical processing. Higher-level layer 2 representations were more resistant to E/I perturbations than lower-level layer 1. Illusion representation was less affected by E/I increases in intra-areal (recurrent) connectivity than in inter-areal (feedforward/feedback) connectivity. DISCUSSION: This mechanistic framework links E/I balance and connectivity to altered visual motion illusion representations in AD and suggests that E/I and connectivity measures may provide probes of early AD neurobiology. The framework may also generalize beyond vision.
Recurrent cortical circuits are hypothesized to perform Bayesian posterior sampling through their stochastic dynamics. Yet identifying which sampling algorithm a circuit intrinsically implements, as opposed to mapping manually designing algorithms onto circuits, requires rigorous theoretical analysis of the biological circuit dynamics, and remains a fundamental open challenge because of the analytical intractability of nonlinear recurrent dynamics. Here, we tackle this challenge through comprehensive theoretical analysis of analytically tractable nonlinear recurrent circuit dynamics used in neuroscience research-- the continuous attractor network (CAN). Surprisingly, we find that the circuit, without any non-Gaussian components in its connectivity or internal variability, intrinsically emerges heavy-tailed subspaces dynamics described as scale-mixture Langevin posterior sampling. The mechanism emerges from the circuits own nonlinear dynamics: divisive normalization renders the overall population activation Gamma-distributed which multiplicatively modulates the time constant of the Langevin sampling in the stimulus feature subspace. Eventually, this scale-mixture structure produces a heavy-tailed (Student-t) sampling step size distribution, significantly accelerating the sampling speed. Moreover, the scale-mixture Langevin sampling approaches a Levy-like regime in the weak input limit. Our results analytically identify an intrinsic circuit algorithm embedded in subspaces of nonlinear recurrent dynamics, and establish a minimal circuit mechanism for endogenous heavy-tail statistics without any explicit non-Gaussian components.
Ananth Vedururu Srinivas, Carmen C. Canavier · q-bio.NC
Computational models 94%Methods 30%
Abstract
In order to study oscillators coupled by pulses emitted at discrete times, it is generally assumed that the effect of each pulse is an instantaneous phase shift, with a possible conduction delay between emission and receipt. However, we are interested in neural oscillators in which each pulse (action potential) activates a biexponential synapse, and at high frequencies, the duration of the synaptic conductance may be greater than the network period. Therefore, the effect of received pulses can summate over the course of several cycles. To overcome this limitation, we previously defined a mean field approach for a single synchronous population. Here, we extend it to two alternating synchronous populations by assuming a perturbation of a single oscillator from one of the synchronous populations which is represented by a single self-connected neural oscillator. The train of delayed biexponential synapses emitted by each oscillator is divided into a tonic and a phasic component. Because of the continuous rather than pulsatile nature of the input, we had to drop the concept of oscillator phase and derive self-consistent criteria for the existence and stability of an alternating firing pattern between two synchronous populations based solely on the perturbation of time intervals from their steady state values. Simulations showed that for high frequency oscillations as defined above, the mean field approach predicts the existence and stability of phase-locking between two synchronous populations better than the instantaneous phase shift approach. This approach may generalize to other forms of coupling amongst non-neural oscillators.
Bhattacharya, N., Nair, S. S., Chakravarthy, V. S. et al. · neuroscience
Computational models 93%
Abstract
Parkinson's disease (PD) gait is characterized by reduced walking speed, short shuffling steps, increased double stance time, and increased step time variability. The most debilitating symptom in PD is freezing of gait (FOG), a context-dependent locomotion arrest, mostly occurring while encountering turns, obstacles, and narrow pathways. FOG is more pronounced during turning, a complex task that challenges motor planning and execution. Here, we simulate this phenomenon using a computational model inspired by the cortico-basal ganglia circuitry, based on reinforcement learning (RL) principles. In the model, the agent was trained to learn a value profile while navigating a path that involved turning. To simulate PD conditions, we clamped the temporal difference (TD) error, typically associated with dopaminergic signaling. Our model results show that compared to healthy controls (HC), PD non-freezers and PD freezers exhibit a reduction in turning velocity and step length, alongside an attenuated compensatory step-width widening at the sharpest turn, more pronounced in PD freezers, who additionally show increased step time variability. These kinematic impairments worsen during tighter turns. Ultimately, this model implicates FOG as a problem of impaired estimation of value over space and could potentially represent a generalized deficit in gait impairments in PD.
Beiran, M., Marschall, O., Zemlianova, K. et al. · neuroscience
Computational models 91%Neural coding 68%
Abstract
Neural activity during performance of a cognitive or motor task is often described as lying on a low-dimensional manifold in the space of all possible activity patterns. When multiple tasks are performed, an individual brain region's activity may generate multiple such manifolds. Several models have been introduced to explain this capability, each with different assumptions concerning architecture and inputs. Here, we develop a theory of multi-tasking according to which models and experimental paradigms can be organized. We introduce a distinction between sequential and simultaneous multi-tasking, the performance of one task at a time or multiple in parallel. We show that interference between tasks often prevents multi-tasking and introduce a model of ``task barcodes" that circumvents this problem and parameterizes a neuronal population's task selectivity. Our theory reveals categorical distinctions between neural circuit mechanisms supporting multi-tasking that can be probed using physiological recordings.
Broor, M., Ogunniyi, K., Williamson, L. et al. · neuroscience
Methods 90%
Abstract
Black participants remain underrepresented in electroencephalography (EEG) research, partly because current EEG devices work poorly with dense, coily Type 4 Afro-textured hair. Research-grade EEG typically wires electrodes on a cap, and therefore the electrodes often fail to reach the scalp through dense, Afro-textured hair. Protocols that ask Black participants to unbraid or restyle protective hairstyles add burdens that discourage enrollment in research studies. To address this, we designed and tested 3D-printed attachments that fit onto an EEG electrode and anchored it directly in the hair, using the hairstyle itself as the mounting structure. We fabricated three design configurations for natural Afro-textured hair, cornrows/braids, and twists/microlocs. Seventeen healthy adults with Type 4a-4c hair used electrode attachments that matched their hairstyle. During a single visit, EEG was recorded with 16 conventional cap electrodes defined by the international 10-20 system and with 16 electrodes using novel electrode attachments anchored directly to their hair. Participants completed resting and walking trials with each system. Electrode-to-scalp distance and gel volume were measured during setup. Electrode disconnection, impedance, signal quality (i.e. peak alpha power and aperiodic (1/f) component), and comfort level were measured throughout the data collection. Compared with the conventional cap, the novel attachments reduced electrode-to-scalp distance, gel use, and impedance. Twenty percent of the conventional cap electrodes failed to connect to the scalp compared with 0.1% of novel electrodes. Impedance rose across trials for the conventional cap, whereas the novel attachments showed a smaller increase and maintained lower impedance throughout. Signal quality was significantly better using the novel attachments, while comfort level did not differ between systems. In conclusion, hair-anchored electrode attachment may present a feasible alternative to conventional cap-based EEG for people with Type 4 hair, yielding more usable channels and better signal quality, and supporting more inclusive EEG acquisition.