Biology subjects

Montgomery, D. P.

Publications and source records attributed to Montgomery, D. P..

3 recordsLinked to original sources

bioRxiv2025

Periodic and aperiodic contributions to EEG delta power are translatable and complementary Angelman syndrome biomarkers

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of maternal UBE3A expression. With promising AS therapies now in clinical trials, there is a pressing need for reliable and translatable biomarkers. Elevated EEG delta power is a hallmark of AS and a promising biomarker, but traditional measures conflate delta oscillations with broadband spectral shifts, limiting interpretability and utility. We dissociated periodic and aperiodic contributions to delta power using spectral parameterization in children with AS and Ube3a mutant mice. In both species, elevated delta power reflected a combination of increased periodic delta oscillations and elevated aperiodic slope and offset. These features were linked to different behavioral domains and followed divergent developmental trajectories, suggesting distinct underlying mechanisms. Together, our findings establish aperiodic changes as a novel translatable EEG biomarker for AS and support the complementary use of periodic and aperiodic features in preclinical and clinical research.

neuroscience↗

bioRxiv2025

Cortical responses to conflicting binocular stimuli in mouse primary visual cortex

Binocular vision requires that the brain integrate input from both eyes to form a unified percept. Small interocular differences support depth perception (stereopsis), while larger disparities can cause diplopia or binocular rivalry. The neural mechanisms by which early visual circuits process concordant versus conflicting binocular signals remain incompletely understood, particularly in the case of large disparities. Here, we used visually evoked potential (VEP) recordings, unit recordings, and 2-photon calcium imaging in the binocular region of mouse primary visual cortex (bV1) to examine how distinct forms of binocular disparity engage local circuits. Using a dichoptic display, we found that interocular phase disparities reduced VEP magnitude through decreased neuronal firing early in the response (40-80 ms after stimulus onset). In contrast, orientation disparities also decreased VEP magnitude, but via increased firing later in the response (100-200 ms). This late activity was enhanced in both regular-spiking (putative excitatory) and fast-spiking (putative parvalbumin-positive inhibitory) units. In contrast, calcium imaging revealed that somatostatin-positive interneurons were suppressed during orientation conflict. These findings suggest that phase differences suppress bV1 responses via feedforward mechanisms, while orientation disparities prolong activity through disinhibition mediated by somatostatin-positive interneurons. Our results identify distinct circuit pathways recruited by different forms of binocular conflict, clarify how early visual cortex contributes to binocular integration, and provide a foundation for investigating perceptual suppression and rivalry. IMPACT STATEMENTDistinct forms of binocular conflict engage separate circuit mechanisms in mouse primary visual cortex, revealing how interocular disparities shape population activity through feedforward and disinhibitory processes.

neuroscience↗

bioRxiv2020

Visual recognition is heralded by shifts in local field potential oscillations and inhibitory networks in primary visual cortex

Learning to recognize and filter familiar, irrelevant sensory stimuli eases the computational burden on the cerebral cortex. Inhibition is a candidate mechanism in this filtration process, and oscillations in the cortical local field potential (LFP) serve as markers of the engagement of different inhibitory neurons. We show here that LFP oscillatory activity in visual cortex is profoundly altered as male and female mice learn to recognize an oriented grating stimulus--low frequency ([~]15 Hz peak) power sharply increases while high frequency ([~]65 Hz peak) power decreases. These changes report recognition of the familiar pattern, as they disappear when the stimulus is rotated to a novel orientation. Two-photon imaging of neuronal activity reveals that parvalbumin-expressing inhibitory neurons disengage with familiar stimuli and reactivate to novelty, whereas somatostatin-expressing inhibitory neurons show opposing activity patterns. We propose a model in which the balance of two interacting interneuron circuits shifts as novel stimuli become familiar. Significance StatementHabituation, familiarity and novelty detection are fundamental cognitive processes that enable organisms to adaptively filter meaningless stimuli and focus attention on potentially important elements of their environment. We have shown that this process can be studied fruitfully in the mouse primary visual cortex by using simple grating stimuli for which novelty and familiarity are defined by orientation, and by measuring stimulus-evoked and continuous local field potentials. Altered event-related and spontaneous potentials, and deficient habituation, are well-documented features of several neurodevelopmental psychiatric disorders. The paradigm described here will be valuable to interrogate the origins of these signals and the meaning of their disruption more deeply.

neuroscience↗