Brain : a journal of neurology
September 14, 2022
James M Shine, Claire O'Callaghan, Ishan C Walpola et al.
63 citations
Serotonin in the brain can be understood as an extension of the gut's serotonergic system, which controls digestion. Central serotonin activity mimics a digestion/satiety circuit, where low serotonergic tone facilitates cognitive automaticity and higher tone helps identify flexible solutions when initial responses fail. This perspective explains serotonin's roles in reward processing, exploration, and psychedelic experiences, and clarifies links between serotonergic dysfunction and psychiatric symptoms.
Brain : a journal of neurology
July 1, 2019
Célia Lacaux, Charlotte Izabelle, Giulio Santantonio et al.
47 citations
People with narcolepsy, who enter REM sleep abnormally quickly and often experience lucid dreaming, show higher creativity than healthy controls. In a study of 185 narcolepsy patients and 126 controls, those with narcolepsy scored higher on the Test of Creative Profile (58.9 vs. 55.1) and the Creativity Achievement Questionnaire (10.4 vs. 6.4). Objective tests of creative performance in 30 patients and 30 controls also favored the narcolepsy group (4.3 vs. 3.7). Most narcolepsy symptoms—sleepiness, hypnagogic hallucinations, sleep paralysis, lucid dreaming, and REM sleep behavior disorder—were linked to higher creativity scores, suggesting that lifelong heightened REM sleep access may enhance creative potential.
Brain : a journal of neurology
May 13, 2025
Veith Weilnhammer, Marcus Rothkirch, Deniz Yilmaz et al.
11 citations
Perception normally balances external sensory signals with internal predictions based on prior knowledge. In a double-blind, placebo-controlled, cross-over experiment with healthy participants, the N-methyl-D-aspartate receptor (NMDAR) antagonist S-ketamine shifted perception toward the external mode, favoring sensory input over prior knowledge. A case-control study found that people with paranoid schizophrenia, a condition linked to NMDAR hypofunction, also spend more time in the external mode. This NMDAR-dependent shift suggests that schizophrenia symptoms may arise from recurring disconnections between perception and prior knowledge about the world.
Brain : a journal of neurology
June 3, 2025
Abhilasha Vishwanath, Mitchell J Bartlett, Torsten Falk et al.
8 citations
In a rat model of Parkinson's disease and levodopa-induced dyskinesia (LID), correlations between movement, gamma-band activity, and single-unit firing in primary motor cortex were high under control conditions but decreased considerably after levodopa administration, suggesting the motor cortex becomes functionally decoupled from ongoing movements during LID. This decoupling occurred in both dopamine-depleted and non-depleted hemispheres. Ketamine (20 mg/kg) disrupted finely tuned gamma oscillations, reduced LID, and moderately increased single-unit correlations with movement, but did not enhance gamma-band correlations with movement. Ketamine also reorganized cell-pair firing-rate correlations, inducing a distinct neural ensemble state in LID animals. The findings suggest the motor cortex does not directly trigger specific dyskinetic movements but may permit aberrant movements to emerge in downstream circuits.
Brain : a journal of neurology
June 12, 2025
Marwan H Othman, Attila Géry Toury-Puel, Karen Irgens Tanderup Hansen et al.
7 citations
In a double-blind, placebo-controlled trial, 50 intensive care unit patients with acute disorders of consciousness after brain injury received apomorphine, methylphenidate, or placebo. Automated pupillometry measured pupillary responses to verbal commands; neither drug significantly increased these responses overall. However, 20% of patients showed improved clinical arousal at least once after drug administration, with methylphenidate linked to more arousal events than placebo. Patients with greater baseline pupillary responsiveness were more likely to show arousal, suggesting this may predict stimulant effects. No adverse events occurred. The findings need replication but may guide future trials on consciousness recovery.
Brain : a journal of neurology
June 30, 2025
Sara Costi, Chloe Wigg, Erdem Pulcu et al.
3 citations
Ketamine, long used as an anesthetic, was first identified in 2000 as a fast-acting antidepressant. A single dose alleviates depressive symptoms, including anhedonia, within hours, and effects last for days. Research in animals indicates ketamine rapidly influences brain regions involved in punishment and reward processing, reverses negative affective biases in memories, and promotes stress resilience. Translating these findings to humans is ongoing, with emerging evidence suggesting similar mechanisms in healthy volunteers and patients. Clinical use is limited by acute side effects and unknown long-term safety. Understanding ketamine's mechanisms may guide development of safer rapid-acting antidepressants.
Brain : a journal of neurology
April 25, 2025
Mor Yam, Jolan Nassir, Danielle Galber et al.
3 citations
A recurrent gain-of-function mutation in GRIN2D, which encodes an NMDA receptor subunit, causes developmental and epileptic encephalopathies. Mice carrying the orthologous mutation show premature death, spontaneous seizures, early motor deficits, and later cognitive impairment, closely mirroring the human disease. Electrophysiological recordings in cerebellar Purkinje neurons revealed developmental changes: reduced spontaneous firing in immature mice and augmented synaptic response to NMDA in older mice. Electrocorticography showed continuous abnormal brain activity with narrowband oscillations in theta, alpha, and beta bands, similar to a patient with the same variant. Low-dose ketamine had limited effect; higher doses caused seizures. Memantine and phenytoin produced small corrective effects on brain activity. These abnormal oscillations may serve as a biomarker for drug response.