Biology subjects

Martinez-Canada, P.

Publications and source records attributed to Martinez-Canada, P..

4 recordsLinked to original sources

bioRxiv2026

Neurophysiological excitation/inhibition imbalance in young adults burdened with childhood interpersonal trauma

Adverse childhood experiences, such as violence, abuse, and neglect, are increasingly recognized as significant modifiers of brain development. Here, we tested whether adults with histories of childhood trauma, but without psychiatric comorbidities exhibit altered excitation/inhibition (E/I) balance, as indicated by electroencephalography (EEG) signatures. Participants, divided into low- trauma and high-trauma groups, underwent two experimental conditions: eyes-closed resting-state recording and a reaction-time task with visual stimuli. From these data, we computed 1/f spectral slopes, a widely used electrophysiological marker of E/I balance; we complemented these analyses with a leaky integrate-and-fire (LIF) microcircuit model combined with a biophysically grounded forward-modeling approach to simulate realistic brain signals and derive E/I balance estimates. Group comparisons for both slopes and E/I estimates revealed significant resting-state differences, characterized by a shift toward increased neuronal excitation in the high-trauma group. The high- trauma group exhibited altered stimulus-related 1/f slope dynamics relative to the pre-stimulus baseline, reflecting attenuated neuronal inhibition. E/I ratio measures were not significantly correlated with participants transient affective states. Together, these findings suggest that childhood trauma is associated with enduring, trait-like alterations in cortical E/I balance that extend beyond affective state and manifest across both resting and task-related brain dynamics. Significance StatementChildhood trauma is a major risk factor for mental illness, yet its lasting effects on basic brain physiology remain poorly understood. Using electroencephalography combined with biophysically grounded neural circuit modeling, we show that young adults with a history of childhood interpersonal trauma exhibit a persistent shift toward cortical hyperexcitation at rest and a reduced ability to engage inhibitory control during cognitive processing. These effects occur even in individuals without psychiatric diagnoses and are independent of current anxiety or depression, indicating a trait-like neurophysiological footprint of early adversity. This excitation-inhibition imbalance may represent a transdiagnostic vulnerability linking childhood trauma to later psychopathology.

neuroscience↗

bioRxiv2022

Combining Aperiodic 1/f Slopes and Brain Simulation: An EEG/MEG Proxy Marker of Excitation/Inhibition Imbalance in Alzheimer's Disease

Accumulation and interaction of amyloid-beta (A{beta}) and tau proteins during progression of Alzheimers disease (AD) are shown to tilt neuronal circuits away from balanced excitation/inhibition (E/I). Current available techniques for noninvasive interrogation of E/I in the intact human brain, e.g., magnetic resonance spectroscopy (MRS), are highly restrictive (i.e., limited spatial extent), have low temporal and spatial resolution and suffer from the limited ability to distinguish accurately between different neurotransmitters complicating its interpretation. As such, these methods alone offer an incomplete explanation of E/I. Recently, the aperiodic component of neural power spectrum, often referred to in the literature as the 1/f slope, has been described as a promising and scalable biomarker that can track disruptions in E/I potentially underlying a spectrum of clinical conditions, such as autism, schizophrenia, or epilepsy, as well as developmental E/I changes as seen in aging. Using 1/f slopes from resting-state spectral data and computational modelling we developed a new method for inferring E/I alterations in AD. We tested our method on recent freely and publicly available electroencephalography (EEG) and magnetoencephalography (MEG) datasets of patients with AD or prodromal disease and demonstrated the methods potential for uncovering regional patterns of abnormal excitatory and inhibitory parameters. Our results provide a general framework for investigating circuit-level disorders in AD and developing therapeutic interventions that aim to restore the balance between excitation and inhibition.

neuroscience↗

bioRxiv2020

Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that E:I imbalance may affect autism differently in males versus females. With a combination of in-silico modeling and in-vivo chemogenetic manipulations in mice, we first show that a time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), can be an index for underlying change in the synaptic E:I ratio. In autism we find that H is reduced, indicating increased excitation, in the medial prefrontal cortex (MPFC) of autistic males but not females. Increasingly intact MPFC H is also associated with heightened ability to behaviorally camouflage social-communicative difficulties, but only in autistic females. This work suggests that H in BOLD can index synaptic E:I ratio and that E:I imbalance affects autistic males and females differently.

neuroscience↗

bioRxiv2018

Firing-Rate Based Network Modeling of the dLGN Circuit: Effects of Cortical Feedback on Spatiotemporal Response Properties of Relay Cells

Visual signals originating in the retina pass through the dorsal geniculate nucleus (dLGN), the visual part of thalamus, on the way to the visual cortex. This is however not a simple feedforward flow of information: there is a significant feedback from cortical cells back to both relay cells and interneurons in the dLGN. Despite four decades of experimental and theoretical studies, the functional role of this feedback is still debated. Here we use a firing-rate model, the extended difference-of-gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells. For this model the responses are found by direct evaluation of two- or three-dimensional integrals allowing for fast and comprehensive studies of putative effects of different candidate organizations of the cortical feedback. Our analysis identifies a special mixed configuration of excitatory and inhibitory cortical feedback which seems to best account for available experimental data. This configuration consists of a slow (long-delay) and spatially widespread inhibitory feedback, combined with a fast (short-delayed) and spatially narrow excitatory feedback, where (iii) the excitatory/inhibitory ON-ON connections are accompanied respectively by inhibitory/excitatory OFF-ON connections, i.e. following a phase-reversed arrangement. The recent development of optogenetic and pharmacogenetic methods has provided new tools for more precise manipulation and investigation of the thalamocortical circuit, in particular for mice. Such data will expectedly allow the eDOG model to be better constrained by data from specific animal model systems than has been possible until now for cat. We have therefore made the Python tool pyLGN which allows for easy adaptation of the eDOG model to new situations.\n\nAuthor SummaryOn route from the retina to primary visual cortex, visually evoked signals have to pass through the dorsal lateral geniculate nucleus (dLGN). However, this is not an exclusive feed forward flow of information as feedback exists from neurons in the cortex back to both relay cells and interneurons in the dLGN. The functional role of this feedback remains mostly unresolved. Here, we use a firing-rate model, the extended difference-of-gaussians (eDOG) model, to explore cortical feedback effects on visual responses of dLGN relay cells. Our analysis indicates that a particular mix of excitatory and inhibitory cortical feedback agrees best with available experimental observations. In this configuration ON-center relay cells receive both excitatory and (indirect) inhibitory feedback from ON-center cortical cells (ON-ON feedback) where the excitatory feedback is fast and spatially narrow while the inhibitory feedback is slow and spatially widespread. In addition to the ON-ON feedback, the connections are accompanied by OFF-ON connections following a so-called phase-reversed (push-pull) arrangement. To facilitate further applications of the model, we have made the Python tool pyLGN which allows for easy modification and evaluation of the a priori quite general eDOG model to new situations.

neuroscience↗