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. Significance StatementSuppression of cortical activity following an initial activation is a defining feature of deep sleep in healthy subjects and wakefulness in patients affected by focal and multifocal brain injuries. Experimental findings suggest that these bimodal responses disrupt the emergence of complex interactions among cortical regions, leading to loss of consciousness or functional impairments. Given their practical implications, it is important to study the mechanisms involved within a general theoretical framework. Using a neuronal network model, we provide evidence for a key role of activity-dependent adaptation mechanisms in shaping the responses to perturbation and in affecting the build-up of complex cortical interactions. Overall, this work provides a mechanistic interpretation relevant for the stratification, follow-up, and rehabilitation of brain-injured patients.