Adaptation shapes local cortical reactivity: from bifurcation diagram and simulations to human physiological and pathological responses

Abstract

Human studies employing intracerebral and transcranial perturbations suggest that the input-output properties of cortical circuits are dramatically affected during sleep in healthy subjects as well as in awake patients with multifocal and focal brain injury. In all these conditions, cortical circuits react to direct stimulation with an initial activation followed by suppression of activity (Off-period) that disrupts the build-up of sustained causal interactions typically observed in healthy wakefulness. The transition to this stereotypical response is of clinical relevance, being associated with loss of consciousness or loss of function. Here, we provide a mechanistic explanation of these findings by means of mean-field theory and simulations of a cortical-like module endowed with activity-dependent adaptation. First, we show that fundamental aspects of the local responses elicited in humans by direct cortical stimulation can be replicated by systematically varying the relationships between adaptation strength and excitation level in the network. Then, we reveal a region in the adaptation-excitation parameter space of key relevance for both physiological and pathological conditions, where spontaneous activity and responses to perturbation diverge in their ability to reveal Off-periods. Finally, we substantiate through simulations of connected cortical-like modules the role of adaptation mechanisms in preventing cortical neurons from engaging in reciprocal causal interactions, as suggested by empirical studies. These modeling results provide a general theoretical framework and a mechanistic interpretation for a body of neurophysiological measurements that bears key relevance for physiological states as well as for the assessment and rehabilitation of brain-injured patients.

Local Neuronal Sleep after Stroke: The role of cortical bistability in brain reorganization

“…The phenomenon of cortical bistability entails a profound membrane hyperpolarization after a transient activity increase [10]. More precisely, after an initial activation, e.g., triggered by the external TMS-perturbation, neurons rapidly plunge into a silent down-state that disrupts the emergence of complex long-range responses and sustained interactions usually observed during wakefulness [9,10,41]. It has been suggested that this phenomenon is influenced by enhanced adaptation mechanisms such as activity-dependent potassium currents, decreased modulation from activating systems, and increased GABAergic inhibition [11][12][13]42].…”

An integrative, multiscale view on consciousness theories_Eary version of paper in press in NEURON

“…Both dendritic decoupling and the breakdown of recurrent interactions are expected to result in dramatic decreases in the brain's capacity for integrated information. Along these lines, the collapse of complexity observed experimentally during sleep and in vegetative state patients is associated with a breakdown of feedback interactions [143][144][145][146] .…”