This paper proposes a radically new theory of phenomenal qualities (qualia): they are not intrinsic properties of sensory states but individualized signatures created by neural reinforcement learning history. The phenomenal character of experiencing red, sweet, or pain emerges from integrating current sensory input with an organism's unique history of reward associations, punishment...
Background/Objectives: Sensory deprivation, defined as a reduction or absence of external sensory input across one or more modalities, has long been investigated in extreme and experimental settings. More recently, its relevance has expanded to clinical contexts and environmental conditions. The present narrative review aims to synthesize current evidence on the neurobiological mechanisms,...
Opioid use disorder remains a major health challenge worldwide. Neuronal activity in the ventral pallidum (VP) regulates opioid reward and relapse to opioid seeking but the underlying cellular mechanisms remain largely unknown. A sizable population of VP neurons previously linked to drug relapse expresses the calcium binding protein parvalbumin (VP PV ). Across the brain parvalbumin neurons are...
Chronic stress disrupts glutamatergic and GABAergic plasticity in the medial prefrontal cortex (mPFC), impairing circuit integration and contributing to the pathophysiology of stress-related disorders, such as Major Depressive Disorder (MDD). Rapid-acting antidepressants like ketamine can rapidly reverse these deficits, but its clinical use is limited by psychotomimetic side effects. Notably,...
Background: Major depressive disorder (MDD) is increasingly framed as a failure of neuroplasticity. Excessive synaptic pruning in adolescence can leave circuits fragile; later stress then unmasks the weakness, whereas ketamine and related compounds can quickly rebuild critical synapses. Clinical data show that a single treatment often gives short relief, while repeated courses reduce relapse....
ElifeJanuary 13, 2026Colin Bredenberg, Fabrice Normandin, Blake Richards et al.
Classical psychedelics induce complex visual hallucinations in humans, generating percepts that are coherent at a low level, but which have surreal, dream-like qualities at a high level. While there are many hypotheses as to how classical psychedelics could induce these effects, there are no concrete mechanistic models that capture the variety of observed effects in humans, while remaining...
Abstract The emergence of non-hallucinogenic psychoplastogens signals a profound philosophical and therapeutic chasm in the discourse surrounding psychedelic medicine. Unlike psychedelic-assisted therapy, which emphasizes subjective experience as central to healing, psychoplastogens are framed as purely neuroplasticity-driven treatments, aiming to repair brain circuits without inducing altered...
Psychedelics are a diverse class of psychoactive compounds that profoundly alter perception, cognition, and emotional states. Recently, classical serotonergic agents, such as psilocybin and lysergic acid diethylamide (LSD), along with atypical agents such as methylenedioxymethamphetamine (MDMA, ecstasy) and ibogaine, have attracted renewed attention due to their rapid and sustained clinical...
Psychedelics lead to profound changes in subjective experience and behaviour, which are typically conceptualised in psychological terms rather than corresponding to an altered brain state or a distinct state of vigilance. Here, we performed chronic electrophysiological recordings from the neocortex concomitant with pupillometry in freely moving adult male mice following an injection of a...
The serotonin 2A receptor (5-HT2A) is a Gq/11-coupled receptor implicated in reward processing, neuropsychiatric disorders, and the actions of serotonergic psychedelics. Although 5-HT2A activation has been shown to engage endocannabinoid (eCB) signaling in several brain regions, its role in inhibitory synaptic plasticity within the nucleus accumbens (NAc) remains poorly understood. Here, we...