Biology subjects

Chowdhury, F. A.

Publications and source records attributed to Chowdhury, F. A..

5 recordsLinked to original sources

bioRxiv2026

Impaired Associative Memory, Inference, and Theta Dynamics in Postictal Psychosis of Epilepsy

Postictal psychosis (PIP) is a severe complication occurring in 2% of people with epilepsy (PWE) whose underlying pathophysiology remains poorly understood. Although historically considered separate from other forms of psychosis, newer evidence demonstrates a shared genetic susceptibility. People with schizophrenia are typically impaired at both associative learning and inferring connections between overlapping associations. Successful associative encoding, retrieval, and inference can each be predicted by changes in frontotemporal theta band activity, which is impaired in rodent models and people with schizophrenia. Here, we recorded high-density scalp EEG from PWE with history of PIP and well-matched control participants while they undertook a memory inference task. We found that associative memory and inference were both impaired in the PIP group, despite no difference in item recognition. Moreover, we found disrupted theta activity during memory encoding and the retrieval of inferred associations in PWE with PIP that likely originated from the medial temporal and frontal lobes. These results suggest a pattern of behavioural deficits and altered neural dynamics common to both PIP and schizophrenia. Interpreted in conjunction with previous genetic studies, they may reflect shared neural mechanisms contributing to psychopathology in both conditions and argue that PIP is a model of more general psychoses.

neuroscience↗

bioRxiv2025

CYB5R3 Controls Sex-Specific Stress Erythropoiesis via Heme-Biosynthesis

Cytochrome b5 reductase 3 (CYB5R3) or met-hemoglobin reductase is an oxidoreductase that maintains hemoprotein and cellular redox balance, yet its contribution to erythropoiesis under stress conditions remains unclear. Motivated by prior observations that the hypomorphic CYB5R3 T117S blunts hydroxyurea-induced fetal hemoglobin responses in patients with sickle cell disease, we tested whether CYB5R3 contributes to the regulation of erythropoiesis. Hematopoietic lineage-specific CYB5R3 knockout mice exhibited markedly impaired erythropoietic induction in response to chronic hypoxia compared to controls, with males showing a more pronounced deficit, and splenectomy further exacerbating this impairment. Genetic deletion of CYB5R3 in human CD34 progenitors reduced globin expression and disrupted terminal erythroid differentiation. Meanwhile, CYB5R3 knockdown in K562 cells produced a heme-deficient state whereby only exogenous heme but not hydroxyurea, iron, or upstream precursors restored globin synthesis. Transcriptomic profiling revealed coordinated downregulation of erythroid transcription factors and multiple enzymes in the heme biosynthetic pathway, which was reversed with heme treatment. Together, these results reveal an unexpected function for CYB5R3 beyond met-hemoglobin reduction, positioning it as a central metabolic regulator of sex-specific stress erythropoiesis and unveiling a heme-restricted vulnerability that may augment disease severity in anemia, hemoglobinopathies, and individuals carrying CYB5R3 loss-of-function variants. Key pointsO_LICYB5R3 is required for effective stress erythropoietic induction, with a more pronounced impact in males. C_LIO_LIErythroid-specific CYB5R3 deficiency creates a heme-limited state, impairing erythroblast differentiation and maturation. C_LI

molecular biology↗

bioRxiv2019

Theta power and theta-gamma coupling support spatial memory retrieval

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations during spatial memory function, and how this relates to subsequent behaviour. Here we asked ten human epilepsy patients undergoing intracranial EEG recording to perform a desk-top virtual reality spatial memory task, and found that increased theta power in two discrete bands ( low 2-5Hz and high 6-9Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between low theta phase and gamma amplitude during the same period was associated with improved task performance. These results support a role of theta oscillations and theta-gamma phase-amplitude coupling in human spatial memory function.

neuroscience↗

bioRxiv2019

Slow changes in seizure pathways in individual patients with focal epilepsy

Personalised medicine requires that treatments adapt to not only the patient, but changing factors within each individual. Although epilepsy is a dynamic disorder that is characterised by pathological fluctuations in brain state, surprisingly little is known about whether and how seizures vary in the same patient. We quantitatively compared within-patient seizure network dynamics using intracranial recordings of over 500 seizures from 31 patients with focal epilepsy (mean 16.5 seizures/patient). In all patients, we found variability in seizure paths through the space of possible network dynamics, producing either a spectrum or clusters of different dynamics. Seizures with similar pathways tended to occur closer together in time, and a simple model suggested that seizure pathways change on circadian and/or slower timescales in the majority of patients. These temporal relationships occurred independent of whether the patient underwent antiepileptic medication reduction. Our results suggest that various modulatory processes, operating at different timescales, shape within-patient seizure dynamics, leading to variable seizure pathways that may require tailored treatment approaches.

neuroscience↗

bioRxiv2019

Dynamic network properties of the interictal brain determine whether seizures appear focal or generalised

ObjectiveCurrent explanatory concepts suggest seizures emerge from ongoing dynamics of brain networks. It is unclear how brain network properties determine focal or generalised seizure onset, or how network properties can be described in a clinically-useful manner. Understanding network properties would cast light on seizure-generating mechanisms and allow to quantify in the clinic the extent to which a seizure is focal or generalised.\n\nMethods68 people with epilepsy and 38 healthy controls underwent 19 channel scalp EEG recording. Functional brain networks were estimated in each subject using phase-locking between EEG channels in the 6-9Hz band from segments of 20s without interictal discharges. Simplified brain dynamics were simulated using a computer model. We introduce three concepts: Critical Coupling (Cc), the ability of a network to generate seizures; Onset Index (OI), the tendency of a region to generate seizures; and Participation Index (PI), the tendency of a region to become involved in seizures.\n\nResultsCc was lower in both patient groups compared with controls. OI and PI were more variable in focal-onset than generalised-onset cases. No regions showed higher OI and PI in generalised-onset cases than in healthy controls; in focal cases, the regions with highest OI and PI corresponded to the side of seizure onset.\n\nConclusionsProperties of interictal functional networks from scalp EEG can be estimated using a computer model and used to predict seizure likelihood and onset patterns. Our framework, consisting of three clinically-meaningful measures, could be implemented in the clinic to quantify the diagnosis and seizure onset pattern.

neuroscience↗