Biology subjects

Kambi, N. A.

Publications and source records attributed to Kambi, N. A..

5 recordsLinked to original sources

bioRxiv2024

Primate thalamic nuclei select abstract rules and shape prefrontal dynamics

Flexible behavior depends on abstract rules to generalize beyond specific instances, and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BG), enable thalamus to select rules. We measured activity across PFC and connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in ventroanterior thalamus (VA) - the main thalamic hub between BG and PFC. Mediodorsal thalamus (MD) also represented rule information before PFC, persisting to help maintain activation of relevant PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was first to represent information about behavioral outcomes. A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. This suggests that thalamus selects high-level cognitive information from PFC and monitors behavioral outcomes of these selections.

neuroscience↗

bioRxiv2021

Thalamic deep brain stimulation as a paradigm to reduce consciousness: implications for cortico-striatal dynamics, absence epilepsy and consciousness studies

Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes reminiscent of absence epilepsy, here termed absence-like activity (ALA), with decreased behavior and vacant staring coinciding with low-frequency oscillations. DBS modulated ALA likelihood in a frequency-specific manner. ALA events corresponded to decreases in measures of neural complexity (entropy) and integration ({Phi}*), an index of consciousness, and substantial changes to communication in CST circuits. During ALA, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of ALA and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method - but at different stimulation frequencies - can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of absence epilepsy and other consciousness disorders. SIGNIFICANCEWe use tailored, multi-microelectrode thalamic deep brain stimulation to reversibly decrease consciousness for otherwise healthy, wakeful animals in a stimulation frequency-dependent manner. This represents a bidirectional mechanism for controlling consciousness, as the same method can increase consciousness under certain conditions. Theories of consciousness debate the relative contribution of parietal and frontal lobes, and largely ignore subcortical contributions. In this study, changes in consciousness predominantly involve changes in subcortical and parietal regions, implying that they contribute more to consciousness than frontal regions. Further, decreases in consciousness (indexed by {Phi}*) coincide with decreased movement, staring, and low-frequency activity in the EEG, similar to absence epilepsy. Thus, the systems-level mechanisms for decreased consciousness in this study have broader clinical implications for absence epilepsy.

neuroscience↗

bioRxiv2020

More than just front or back: Parietal-striatal-thalamic circuits predict consciousness level

Major theories of consciousness disagree on the key neural substrates. In Global Neuronal Workspace Theory and Higher-order Theories, consciousness depends on frontal cortex, whereas Integrated Information Theory and Recurrent Processing Theory highlight posterior contributions. Most theories omit subcortical influences. To test these theories, we performed simultaneous frontal, parietal, striatal and thalamic recordings from awake, sleeping and anesthetized macaques, further manipulating consciousness with deep-brain thalamic stimulation. Information theoretic measures and machine learning approaches suggested parietal cortex, striatum and thalamus contribute more to consciousness level than frontal cortex. While these findings provide greater support for Integrated Information Theory than the others, the theory does not incorporate subcortical structures such as the striatum. We therefore propose that thalamo-striatal circuits have a cause-effect structure to generate integrated information. One Sentence SummaryParietal, but not frontal, circuits incorporating striatum and thalamus predict consciousness.

neuroscience↗

bioRxiv2020

Receptors, circuits and neural dynamics for prediction

Learned associations between stimuli allow us to model the world and make predictions, crucial for efficient behavior; e.g., hearing a siren, we expect to see an ambulance and quickly make way. While there are theoretical and computational frameworks for prediction, the circuit and receptor-level mechanisms are unclear. Using high-density EEG, Bayesian modeling and machine learning, we show that inferred "causal" relationships between stimuli and frontal alpha activity account for reaction times (a proxy for predictions) on a trial-by-trial basis in an audio-visual delayed match-to-sample task which elicited predictions. Predictive beta feedback activated sensory representations in advance of predicted stimuli. Low-dose ketamine, a NMDA receptor blocker - but not the control drug dexmedetomidine - perturbed behavioral indices of predictions, their representation in higher-order cortex, feedback to posterior cortex and pre-activation of sensory templates in higher-order sensory cortex. This study suggests predictions depend on alpha activity in higher-order cortex, beta feedback and NMDA receptors, and ketamine blocks access to learned predictive information.

neuroscience↗

bioRxiv2019

Central thalamus modulates consciousness by controlling layer-specific cortical interactions

Consciousness is the capacity to experience ones environment and internal states. The minimal mechanisms sufficient to produce this experience, the neural correlates of consciousness (NCC), are thought to involve thalamocortical and intracortical interactions, but the key operations and circuit paths are unclear. We simultaneously recorded neural activity in central thalamus and across layers of fronto-parietal cortex in awake, sleeping and anesthetized macaques. Spiking activity was selectively reduced in deep cortical layers and thalamus during unconsciousness, as were intracolumnar and interareal interactions at alpha and gamma frequencies. Gamma-frequency stimulation, when focused on the central lateral thalamus of anesthetized macaques, counteracted these neural changes and restored consciousness. These findings suggest that the NCC involve both corticocortical feedforward and feedback pathways coordinated with intracolumnar and thalamocortical loops.\n\nSummaryStimulation of central lateral thalamus counters anesthesia to restore wake cortical dynamics and consciousness.

neuroscience↗