1. Activity-dependent adaptation mechanisms shape local cortical reactivity in physiological and pathological conditions: an in-silico study

COEX 

Several human studies employing intracerebral and transcranial perturbations reported the cortical network as unable to engage in large-scale and complex interactions during non-rapid eye movement (NREM) sleep and anesthesia. In both conditions, cortical bistability, which is the tendency of cortical circuits to fall into an Off-period after an initial activation, is in a key position to hinder large-scale complex interactions. Accumulating evidence suggests that cortical bistability characterizes not only NREM sleep and anesthesia in healthy subjects; it also marks wakefulness in vegetative state patients and the perilesional area surrounding focal cortical lesions in awake stroke patients, leading to loss of consciousness and loss of functions, respectively. Given the important clinical implications, it is crucial to understand the nature of cortical bistability and its impact on cortical responsiveness. In this talk, we will suggest a mechanistic explanation of the experimental findings above by means of mean-field theory and simulations of a cortical-like module endowed with activity-dependent adaptation. First, we will show that fundamental aspects of the local responses elicited in humans by direct cortical stimulations can be replicated by systematically varying the relationships between adaptation strength and excitation level in the network. Then, we will 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 will 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.