ELECTROPHYSIOLOGICAL CAUSAL MEASURES IN THE HUMAN AND MOUSE BRAIN REVEAL CORTICO-CORTICAL AND CORTICO-THALAMO-CORTICAL INTERACTIONS UNDER PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS

The brain is a causal system in which interactions between neurons sustain our perceptive, behavioral, and cognitive functions. As such, understanding brain functioning requires experimental approaches that can capture causal interactions between its elements far beyond mere temporal correlations. In this thesis, I will survey experimental approaches to probe causality in the brain, with the final goal to, at least partially, unveil the neural circuits engaged by causal manipulations in humans. The work reported here has been primarily published in the peer-reviewed literature (11 papers). A twelfth manuscript is in press, a thirteenth one is under review, and a fourteenth one is in preparation. In this overview of my thesis work, I will start by briefly introducing the theoretical concepts of causality, necessity, and sufficiency, together with their translation into experimental conditions. Starting from these ideas, I will present causality-based approaches in animal and human neuroscience, outlining their major advantages and limitations. Then, I will illustrate new techniques that overcame some of the major limitations of causality-based approaches, allowing to obtain insights from non-invasive causality-based approaches in human neurophysiology. Leveraging these and additional techniques, I will illustrate how causality-based approaches can be exploited to gain valuable information for research purposes, revealing the functioning of brain circuits under physiological and pathological conditions. Capitalizing on this knowledge, I will showcase how causality-based approaches can be applied to neurological and neurosurgical patients to gain valuable information that can benefit diagnosis and prognosis in pathological conditions. Finally, I will summarize how our studies help disentangle cortical and thalamic contributions to the response to a cortical perturbation under physiological conditions, and how these contributions can be altered under pathological conditions, such as focal brain lesions.