In people with major depressive disorder, the balance between excitation and inhibition across the brain's cortex is disrupted, particularly in the parietal and prefrontal-cingulate regions. Using resting-state functional magnetic resonance imaging data from 254 patients and 451 healthy controls, the Hurst exponent—a proxy for excitation-inhibition balance—was found to be significantly reduced in patients. This imbalance was linked to specific gene expression related to neuronal structure, metabolism, and mitochondrial function, as well as to neurotransmitter systems including GABA, opioid, serotonin, and synaptic density. In a separate trial of 32 patients with treatment-resistant depression, ketamine increased the Hurst exponent in the anterior cingulate and medial prefrontal cortices, suggesting that restoring excitation-inhibition balance may underlie ketamine's antidepressant effects.
Consciousness is linked to how neural activity shifts along a unimodal-transmodal cortical axis, a simple signature that is abnormally elevated under psychedelics and in psychosis. This hierarchical dynamic reflects changes in global brain integration and connectome diversity. Quasi-periodic patterns show hierarchical heterogeneity as spatiotemporally propagating waves tied to arousal, a pattern also seen in macaques. The spatial distribution of the principal cortical gradient aligns with genetic transcription of the histaminergic system and functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, the authors propose that global consciousness is supported by efficient hierarchical processing along a low-dimensional macroscale gradient.