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

Summary

Deep brain stimulation (DBS) of the central lateral thalamus in macaques can produce episodes resembling absence epilepsy, termed absence-like activity (ALA), characterized by decreased behavior, vacant staring, and low-frequency oscillations. The likelihood of ALA depended on stimulation frequency. During ALA, neural complexity (entropy) and integration (Φ*), an index of consciousness, decreased, and communication within cortico-striato-thalamic circuits changed substantially. Power spectral density and coherence at low frequencies increased, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in network configurations that dissociated parietal and subcortical structures. The same DBS method, at different frequencies, can also increase consciousness in anesthetized macaques, offering a flexible tool for studying consciousness and informing clinical research on absence epilepsy and other disorders of consciousness.

Study at a glance

Abstract

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 (Φ*), 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.