Didier Pinault

Transition to psychotic disorders: From pathophysiology to innovative therapy

My goal is to develop, using preclinical models, innovative therapy to treat and prevent neuropsychiatric disorders. It is a conceptually- and data-driven long-term investigation based on the pathophysiological properties of neural networks. EEG combined with multisite cell-to-network exploration are implemented to measure the functional state of Cortico-Thalamo-Cortical systems under physiological, pathological, and therapeutic conditions. CTC systems are the fundamental, oscillating neural substrates of consciousness and attention-related sensorimotor and cognitive processes, and they are suitably electro-responsive to non-invasive, transcranial electrical stimulation. DP, June 28, 2021.

Frontoparietal anodal tDCS reduces ketamine-induced oscillopathies

(Top) Dorsal view of the rat skull showing the location of the EEG recording electrodes positioned on the parietal somatosensory cortex, and the stimulation electrodes, the cathode at the frontal cortex and the anode at the parietal cortex. The references of the EEG electrodes are positioned on the occipital ridges. (Bottom) The tDCS +0.25 or +0.50 mA was applied during the pathological state (keta or ketamine condition). Each column represents the percentage of the normalized power of the gamma- (30-80 Hz) or sigma-frequency (10-17 Hz) oscillations. T-test comparison, relative to the ketamine-tDCS 0 mA condition, of the ketamine-tDCS effect +0.25 or +0.50 mA (ns, not significant; * p <0.05). Adapted from Lahogue and Pinault, Translational Neuroscience, 2021.

Theoretical prediction of the cell-to-network effects of a frontoparietal anodal tDCS in the corticothalamic system.

(A) Simplified drawing of the hodology of the 3-neuron CT system. The layer 6 corticothalamic (CT) and thalamocortical (TC) neurons are glutamatergic while the thalamic reticular nucleus (TRN) neuron is GABAergic. Both TC and CT axons innervate the TRN. This system receives sensory (S), motor (M) and cognitive/associative (C) inputs. The layer VI CT neurons outnumber by a factor of about 10 the TC neurons. (B, left) Physiological UP and DOWN states: During the non-REM sleep, the TC system displays principally a synchronized state, characterized by the occurrence of delta oscillations and spindles; the TRN cell exhibits mainly rhythmic (at the delta-, theta- and spindle-frequency bands) high-frequency bursts of action potentials. The synchronized state includes two sub-states, UP and DOWN, which are usually associated with active and quiescent cellular firings, respectively. (B, right) Pathological persistent UP state: This ketamine-induced persistent UP state is believed to be an abnormal REM sleep. After a single systemic administration of a subanesthetizing low-dose of ketamine, the TC system displays a more desynchronized state (peak effect at about +15-20 minutes) characterized by the prominent occurrence of lower voltage and faster activities (>16 Hz), which include gamma- and higher-frequency oscillations. Under the ketamine condition, both the TC and the TRN neurons exhibit a persistent irregular and tonic firing containing more single APs than high-frequency bursts of APs. The bipolar anodal tDCS is expected to reduce, even to normalize, the ketamine-induced oscillopathies. Adapted from Mahdavi et al., Schizophrenia Research, 2020.