Biology subjects

Shaikhouni, A.

Publications and source records attributed to Shaikhouni, A..

5 recordsLinked to original sources

bioRxiv2026

Opposing effects of slow and fast theta synchrony on working memory in the human hippocampal-orbitofrontal network

Working memory (WM) enables us to maintain and manipulate information over time, but how the brain organizes sequential information locally and across networks remains unclear. Recent work suggests that slow and fast theta oscillations serve different roles in memory, yet their distinct contributions to sequential WM are unknown. Based on evidence that the hippocampus (HC) and orbitofrontal cortex (OFC) support sequential WM and that slower theta cycles provide optimal temporal windows for organizing items in WM, we predicted that these regions would coordinate via slow theta dynamics. We analyzed intracranial EEG from the HC, OFC, and amygdala (AMY) in 21 neurosurgical patients (7 female, 13-54 years of age; M {+/-} SD, 30 {+/-} 11.2 years) performing a delayed match-to-sample WM task. We assessed phase locking between regions, phase-amplitude coupling within regions, and neuronal phase coding for slow (~1-4.5 Hz) and fast (~4.5-8 Hz) theta oscillations. We found significant slow and fast theta synchrony between all regions, but identical anatomical pathways produced opposing behavioral effects depending on oscillatory frequency, particularly during higher cognitive demand. Slow theta synchrony was associated with faster response times (RTs), while fast theta synchrony between HC and OFC hindered both accuracy and RTs. Unexpectedly, AMY modulated RT through demand-dependent slow theta synchrony, where AMY-OFC synchrony predicted faster RTs during maintenance and HC-AMY synchrony predicted faster RTs during higher cognitive demand. Sustained coupling between slow theta oscillations and high-frequency broadband activity within each region suggests that local organization coincides with beneficial network behavioral effects. These results establish a frequency-opponent mechanism in which theta oscillation frequencies determine whether HC-OFC circuits facilitate or impair sequential WM.

neuroscience↗

bioRxiv2026

Somatic variants activating the RAS-MAPK pathway confer susceptibility to hippocampal sclerosis in drug-resistant epilepsy

Hippocampal sclerosis is a frequent finding in pediatric epilepsy surgery and has traditionally been regarded as an acquired lesion. It commonly co-occurs with focal cortical dysplasia (FCD IIIa), yet whether hippocampal injury is secondary to seizures or reflects a shared underlying etiology remains unresolved. Here we identified somatic variants activating the RAS-MAPK pathway in 40% of patients with hippocampal sclerosis, but in none with non-sclerotic hippocampus. Gain-of-function variants in PTPN11 were the most common finding, with mutations present in both cortex and hippocampus and enriched in hippocampal neurons, consistent with a shared developmental origin. In mice, Ptpn11D61Y mutants developed profound hippocampal degeneration and gliosis following subthreshold kainic acid exposure, whereas wild-type controls were unaffected. p38-dependent stress pathways were upregulated in patients and mice, suggesting a mechanism through which ERK-p38 crosstalk lowers the threshold for seizure-induced injury. These results provide a genetic explanation for FCD IIIa, elucidate the role of somatic mutations within the RAS-MAPK pathway in driving hippocampal sclerosis, and provide a target for pathway-specific interventions for intractable seizures.

neuroscience↗

bioRxiv2025

Distributed theta networks support the control of working memory: Evidence from scalp and intracranial EEG

We combined scalp EEG and intracranial EEG (iEEG) to identify spectral and network-level signatures of executive control during a delayed match-to-sample task working memory task. To isolate executive processes, we contrasted test and sample phases, matched in perceptual input but differing in cognitive demand. Scalp EEG revealed increased frontal midline theta event-related spectral perturbations (ERSPs), dynamic increases and decreases in posterior theta-alpha ERSPs, and decreased central alpha-beta ERSPs during the test phase. These local spectral changes were accompanied by enhanced frontoposterior theta phase synchrony and network hub strength, predicting higher behavioral accuracy. Using a novel cross-modal scalp EEG-iEEG ERSP similarity approach, we localized the sources of scalp-derived frontal midline, posterior, and central control effects to medial frontal, parietal, temporal, and occipital regions. Our results integrate power and connectivity measures across scalp and iEEG, linking local spectral fluctuations to broader network organization. Together, they support a model in which executive control emerges from flexible, temporally precise coordination between medial frontal control hubs and posterior representational systems.

neuroscience↗

bioRxiv2025

Declarative Memory Through the Lens of Single-Trial Peaks in High-Frequency Power

Declarative memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global network organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated throughout the network. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across the medial temporal lobe (MTL) and prefrontal cortex (PFC). HFB peak activity was earlier in the MTL than PFC. Anchoring analyses of theta phase clustering and connectivity to HFB peaks revealed strong phase clustering locked to HFB peaks in the PFC, as well as connectivity between the PFC and MTL that predicted individual memory performance. Graph analysis revealed specific connections amidst sparse network connectivity during memory success. This study demonstrates that transient brain states linked to internal physiological events support memory and refines our understanding of local and network-level process interactions. HighlightsO_LIMemory-linked theta activity is time-locked to internal brain events C_LIO_LINetwork connectivity changes dynamically during memory processing C_LIO_LISparse network connectivity supports successful memory C_LIO_LISpecific sequences of transient states may be critical for declarative memory C_LI

neuroscience↗

bioRxiv2024

The development of aperiodic neural activity in the human brain

The neurophysiological mechanisms supporting brain maturation are fundamental to attention and memory capacity across the lifespan. Human brain regions develop at different rates, with many regions developing into the third and fourth decades of life. Here, in this preregistered study (https://osf.io/gsru7), we analyzed intracranial EEG (iEEG) recordings from widespread brain regions in a large developmental cohort. Using task-based (i.e., attention to-be-remembered visual stimuli) and task-free (resting-state) data from 101 children and adults (5.93 - 54.00 years, 63 males; n electrodes = 5691), we mapped aperiodic (1/[f]-like) activity, a proxy of neural noise, with steeper slopes indexing less noise and flatter slopes indexing more noise. We reveal that aperiodic slopes flatten with age into young adulthood in both association and sensorimotor cortices, challenging models of early sensorimotor development based on brain structure. In prefrontal cortex (PFC), attentional state modulated age effects, revealing steeper task-based than task-free slopes in adults and the opposite in children, consistent with the development of cognitive control. Age-related differences in task-based slopes also explained age-related gains in memory performance, linking the development of PFC cognitive control to the development of memory. Last, with additional structural imaging measures, we reveal that age-related differences in gray matter volume are similarly associated with aperiodic slopes in association and sensorimotor cortices. Our findings establish developmental trajectories of aperiodic activity in localized brain regions and illuminate the development of PFC control during adolescence in the development of attention and memory.

neuroscience↗