The precise neuromodulatory mechanisms underlying consciousness and its disorders, despite growing evidence in both animals and humans, remain poorly understood at the subcortical level. The basal ganglia, a key component of the cortico-basal ganglia-thalamo-cortical loop, are known to play a crucial role in mediating consciousness and behavioural responsiveness to the environment. Here, we...
Boris B Quednow, Rebecca C Coray; Reply: The consequences of MDMA use are not easily disentangled from other drug use or lifestyle factors, Brain, , awag17
BrainMay 5, 2026Richard Somervail, Sofija Perovic, Rory John Bufacchi et al.
Sudden and isolated sensory stimuli (SISS) likely signal environmental events demanding immediate behavioural responses. These stimuli-which are widely and persistently used in both basic and clinical neuroscience to explore sensory processing and perception-also trigger some of the largest and most widespread electrocortical responses in the awake mammalian brain. These responses are often...
Introduced in 2014 and revised in 2018, the entropic brain hypothesis has accrued a wealth of supportive evidence. The hypothesis states that-along a dimension of the size of phenomenal consciousness-expansive states reliably exhibit increased brain entropy whereas the inverse applies for states of no or reduced consciousness. Examples of expansive states include expert meditation, flicker...
Regular recreational use of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") has been consistently linked to verbal memory dysfunctions, whose neurobiological origins remain unclear. Although neurochemical, structural, and functional alterations resulting from repeated MDMA intake have been identified in user populations, only limited knowledge exists regarding potential interrelationships...
Ketamine's potential as a rapid-acting antidepressant was first identified in 2000, despite its long-standing use as an anesthetic agent. Clinically, ketamine alleviates depressive symptoms, including the difficult to treat symptom of anhedonia, within hours, with the effects of a single dose lasting for days. Since then, research has focused on uncovering the mechanisms underlying its rapid...
BrainJune 12, 2025Marwan H Othman, Attila Géry Toury-Puel, Karen Irgens Tanderup Hansen et al.7 citations
In the intensive care unit (ICU), management of unresponsive patients with brain injury focuses on preventing secondary brain damage. Therapeutic strategies that directly promote the recovery of consciousness are urgently needed. In an investigator-initiated, randomized, placebo-controlled, double-blind, cross-over trial, we studied the effects of apomorphine and methylphenidate in ICU patients...
Gamma-band and single-unit neural activity in primary motor cortex are involved in the control of movement. This activity is disrupted in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), a debilitating consequence of dopamine replacement therapy for PD. Physiological features of LID include pathological narrowband gamma oscillations, finely tuned gamma and altered primary motor...
Perception integrates external sensory signals with internal predictions that reflect prior knowledge about the world. Previous research suggests that this integration is governed by slow alternations between an external mode, driven by sensory signals, and an internal mode, shaped by prior knowledge. Using a double-blind, placebo-controlled, cross-over experiment in healthy human participants,...
Pathogenic variants in GRIN2D, encoding one of the subunits of the NMDA receptor (NMDAR), are associated with developmental and epileptic encephalopathies (DEEs). Unusual for de novo mutations, the recurrent, de-novo, gain of function, missense mutation c.1999G>A (p.Val667Ile) was discovered in multiple patients. We characterized a mouse model carrying the orthologous Grin2d mutation, using...
What happens in the brain when a person spends three hours viewing a single painting? Geoffrey Schott examines the account of an art history professor who did just that, and considers what their observations reveal about the differences between seeing and looking, and between looking and perceiving.
BrainJune 18, 2024E. Bartoli, E. Devara, H. Q. Dang et al.
Abstract The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent...
Abstract The use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing...
Integrating independent but converging lines of research on brain function and neurodevelopment across scales, this article proposes that serotonin 2A receptor (5-HT2AR) signalling is an evolutionary and developmental driver and potent modulator of the macroscale functional organization of the human cerebral cortex. A wealth of evidence indicates that the anatomical and functional organization...
BrainOctober 17, 2023Laura Crucianelli, A. Reader, H. Ehrsson
Abstract The sense of body ownership (i.e. the feeling that our body or its parts belong to us) plays a key role in bodily self-consciousness and is believed to stem from multisensory integration. Experimental paradigms such as the rubber hand illusion have been developed to allow the controlled manipulation of body ownership in laboratory settings, providing effective tools for investigating...
The neuromodulatory arousal system imbues the nervous system with the flexibility and robustness required to facilitate adaptive behaviour. While there are well understood mechanisms linking dopamine, noradrenaline and acetylcholine to distinct behavioural states, similar conclusions have not been as readily available for serotonin. Fascinatingly, despite clear links between serotonergic...
Abstract Classic psychedelic drugs such as psilocybin and lysergic acid diethylamide (LSD) have recaptured the imagination of both science and popular culture, and may have efficacy in treating a wide range of psychiatric disorders. Human and animal studies of psychedelic drug action in the brain have demonstrated the involvement of the serotonin 2A (5-HT2A) receptor and the cerebral cortex in...
The word consciousness has different meanings to different people. Michael Graziano argues that the three major perspectives on consciousness – the spiritual, the hard problem, and the self-model – represent a progression in our understanding, with only the self-model framework able to account for subjective experience.
Abstract A common observation in EEG research is that consciousness vanishes with the appearance of delta (1–4 Hz) waves, particularly when those waves are high amplitude. High amplitude delta oscillations are frequently observed in states of diminished consciousness, including slow wave sleep, anaesthesia, generalized epileptic seizures, and disorders of consciousness, such as coma and the...
Cognitive dysfunction affects 40-80% of patients with multiple sclerosis. Smoking cannabis may add to these deficits. It is unclear whether coming off cannabis results in cognitive improvement. To address this question, 40 patients with multiple sclerosis who started using cannabis after the onset of multiple sclerosis and who used it for at least 4 days a week over many years were divided by...
Some studies suggest a link between creativity and rapid eye movement sleep. Narcolepsy is characterized by falling asleep directly into rapid eye movement sleep, states of dissociated wakefulness and rapid eye movement sleep (cataplexy, hypnagogic hallucinations, sleep paralysis, rapid eye movement sleep behaviour disorder and lucid dreaming) and a high dream recall frequency. Lucid dreaming...
BrainAugust 1, 2018Tineke Grent-'t-Jong, Davide Rivolta, Joachim Gross et al.
Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded...
What does an eminent neuroanatomist dream of at night? The panic of being an auxiliary professor and receiving last minute instructions from the Dean to lecture on osteology? ‘Anxiety, distress … upon reviewing the bones in my memory. I list those of the hand: scaphoids, capitate, and I did not know any more’; or perhaps of secretly cutting slices of medulla for staining in a boarding house at...
While chronic cocaine use is associated with abnormalities in both brain structure and function within and interactions between regions, previous studies have been limited to interrogating structure and function independently, and the detected neural differences have not been applied to independent samples to assess the clinical relevance of results. We investigated consequences of structural...
In extensive studies with two split-brain patients we replicate the standard finding that stimuli cannot be compared across visual half-fields, indicating that each hemisphere processes information independently of the other. Yet, crucially, we show that the canonical textbook findings that a split-brain patient can only respond to stimuli in the left visual half-field with the left hand, and...