Biology subjects

Fallah, M.

Publications and source records attributed to Fallah, M..

10 recordsLinked to original sources

bioRxiv2026

Brainstem cholinergic cell loss causes slowly-developing motor impairments

Pedunculopontine nucleus (PPN) cholinergic degeneration is a feature of Parkinson's disease (PD), but it is difficult to isolate the symptoms and circuit alterations caused by cholinergic cell loss in PD, where multiple nuclei are simultaneously degenerating. Here we develop a novel mouse model of brainstem cholinergic cell loss to define the timeline of symptom development and map physiological adaptations within the brainstem. Mild motor symptoms, including balance and motor learning deficits reminiscent of early-stage PD, developed after cholinergic lesion with an unexpected long delay. Ex vivo whole-cell recordings showed that cholinergic cell loss increased excitatory synaptic drive onto glutamatergic PPN neurons and increased their intrinsic ability to generate sustained action potential output. In parallel, fiber photometry experiments revealed a slight increase in glutamatergic sensory responsiveness that closely tracked the delayed onset of behavioral symptoms. Together, these results reveal that brainstem cholinergic cell loss triggers the reorganization of motor-related brainstem circuits, providing critical insight into the consequences of non-dopaminergic degeneration in PD.

neuroscience↗

bioRxiv2026

Comparison of Four Assays That Measure Antibodies to Ebola Virus Glycoprotein

The accurate measurement of Ebola virus (EBOV)-specific antibody responses is crucial to assessing immunity induced by EBOV infection or vaccination. For this purpose, the Filovirus Animal Nonclinical Group (FANG) anti-EBOV glycoprotein (GP1,2) ELISA is considered the "gold-standard". However, it has limitations such as high repeat-rates and variability, and low throughput. Here, we describe two new alternative assays: a Single-Molecule Assay Planar EBOV GP1,2 ELISA and a multiplexed EBOV GP1,2, EBOV nucleoprotein, and EBOV Viral Protein 40 Luminex assay, and compare these with two versions of the FANG ELISA. Samples were selected from participants receiving vaccine or placebo in a randomized, placebo-controlled, double-blinded study of two EBOV vaccines (PREVAIL 1), and a longitudinal cohort study of Ebola virus disease (EVD) survivors and their close contacts (PREVAIL 3). All four assays were concordant in their measurements of anti-EBOV GP1,2-specific immunoglobulin G responses, allowing for the determination of conversion equations for antibody measurements across assays. In addition, all four showed a similar ability to distinguish vaccine recipients from placebo recipients and EVD survivors from their close contacts. Compared to the FANG assays, the Quanterix and Luminex assays had lower variability, lower repeat rates, and higher throughput, making them good alternatives for future studies.

immunology↗

bioRxiv2025

Visual Attention in Peripersonal Space

Bringing the hand near a visual stimulus enhances visual processing. This effect is linked to peripersonal space (PPS), the body-centered region where visual and proprioceptive information interact. Despite extensive behavioral evidence, the neural basis of this interaction in early visual cortex remains unclear. In this study, we investigated how hand proximity modulates orientation selectivity in area V2 by recording single-neuron responses from two rhesus monkeys. The monkeys performed a fixation task while their hand was positioned near a visual stimulus while either being visible or occluded, and compared with when the hand was away from the stimulus. When the near hand was visible, neural firing rates in V2 were significantly higher, accompanied by sharper orientation tuning. In contrast, occluding the hand broadened orientation tuning compared to when the hand was away. These effects emerged rapidly after stimulus onset and were coherent across the population, demonstrating that PPS is actively prioritized during visual processing. Together, the findings reveal two complementary (feedback) signals in V2: a congruence-driven enhancement when visual and proprioceptive inputs align, and a mismatch-driven suppression when they conflict, indicating that V2 integrates multisensory cues to encode PPS and support action-relevant visual processing.

neuroscience↗

bioRxiv2025

Hemifield-Specific Motion Extrapolation Reveals Limits of Interhemispheric Integration

The accurate perception of moving objects is a fundamental challenge for the visual system, which must compensate for neural processing delays. Motion extrapolation is a proposed mechanism whereby the brain predicts an objects future position. We investigated how an objects motion history shapes its perceived position using the flash-jump illusion, in which a brief color change in a moving bar is mislocalized as further along the direction of motion. Across two experiments, we found that longer preceding motion sequences improved localization accuracy, consistent with motion adaptation. This effect occurred regardless of whether motion continued after the flash. Notably, mislocalization transiently reappeared as the object crossed the vertical midline, suggesting that motion adaptation and motion extrapolation operate independently between within each hemifield. Manipulating the length of the sequence in each hemifield in Experiment 2 confirmed that this adaptation is spatially confined to each hemifield, with limited interhemispheric transfer. The results align with a Bayesian framework in which the brain integrates signals from both hemispheres, with midline crossings triggering a shift from adapted to unadapted neural populations. We identify motion extrapolation, supported by hemifield-specific adaptation in area MT and integration in area MST, as the mechanism behind these midline discontinuities. This work reframes smooth pursuit not just as a tracking behaviour, but as a functional solution to overcome the inherent limits of interhemispheric motion processing.

neuroscience↗

bioRxiv2024

Inhibitory basal ganglia nuclei differentially innervate pedunculopontine nucleus subpopulations and evoke opposite motor and valence behaviors.

The canonical basal ganglia model predicts that the substantia nigra pars reticulata (SNr) and the globus pallidus externa (GPe) will have specific effects on locomotion: the SNr inhibiting locomotion and the GPe enhancing it. In this study, we use in vivo optogenetics to show that the GPe exerts non-canonical effects on locomotion while the SNr has no gross motor impact through inhibition of the PPN. We also show that these structures mediate opposing effects on reward. To understand how these structures differentially modulate the PPN, we use ex vivo whole-cell recording with optogenetics to comprehensively dissect the SNr and GPe synaptic connections to regionally- and molecularly-defined populations of PPN neurons. The SNr inhibits all PPN subtypes, but most strongly inhibits caudal glutamatergic neurons. The GPe selectively inhibits caudal glutamatergic and GABAergic neurons, avoiding both cholinergic and rostral cells. This circuit characterization reveals non-canonical basal ganglia pathways for locomotion and valence. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/606694v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@11e6a13org.highwire.dtl.DTLVardef@1c63735org.highwire.dtl.DTLVardef@5282b7org.highwire.dtl.DTLVardef@103da4a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Dynamics of Saccade Trajectory Modulation by Distractors: Neural Activity Patterns in the Frontal Eye Field

The sudden appearance of a visual distractor shortly before saccade initiation can capture spatial attention and modulate the saccade trajectory in spite of the ongoing execution of the initial plan to shift gaze straight to the saccade target. To elucidate the neural correlates underlying these curved saccades, we recorded from single neurons in the frontal eye field (FEF) of two rhesus monkeys shifting gaze to a target while an isoeccentric distractor appeared either left or right of the target at various delays after target presentation. We found that the population level of pre-saccadic activity encoded the direction of the saccade trajectory. Stronger activity occurred when saccades curved toward the distractor, and weaker when saccades curved away. This relationship held whether the distractor was ipsilateral or contralateral to the recorded neurons. Meanwhile, visually responsive neurons showed asymmetrical patterns of excitatory responses that varied with the location of the distractor and the duration of distractor processing relating to attentional capture and distractor inhibition. During earlier distractor processing, neurons encoded curvature towards the distractor. During later distractor processing, neurons encoded curvature away from the distractor. This was observed when saccades curved away from distractors contralateral to the recording site and when saccades curved towards distractors ipsilateral to the recording site. These findings indicate that saccadic motor planning involves dynamic push-pull hemispheric interactions producing attraction or repulsion for potential but unselected saccade targets. Significant StatementThis study not only advances our understanding of oculomotor function in dynamic environments but also has potential clinical relevance for diagnosing and understanding disorders characterized by abnormal saccade trajectories. Our research elucidates the neural mechanisms behind saccade trajectories that are not always linear due to the brains integration of multiple visual cues and/or motor plans. By analyzing the frontal eye field (FEF) activity in rhesus monkeys, we found that saccade directionality and timing are influenced by the interaction between FEF visual neurons representing target and distractor stimuli. The FEFs role extends beyond a winner-takes-all approach, incorporating saccade vector averaging computations that produce curved saccades. Furthermore, ipsilateral visual neurons encode distractor suppression that drives curvature away from the distractor.

neuroscience↗

bioRxiv2024

Identifying a Distractor Produces Object-Based Inhibition in an Allocentric Reference Frame for Saccade Planning

We investigated whether distractor inhibition occurs relative to the target or fixation in a perceptual decision-making task using a purely saccadic response. Previous research has shown that during the process of discriminating a target from distractor, saccades made to a target deviate towards the distractor. Once discriminated, the distractor is inhibited, and trajectories deviate away from the distractor. Saccade deviation magnitudes provide a sensitive measure of target-distractor competition dependent on the distance between them. While saccades are planned in an egocentric reference frame (locations represented relative to fixation), object-based inhibition has been shown to occur in an allocentric reference frame (objects represented relative to each other independent of fixation). By varying the egocentric and allocentric distances of the target and distractor, we found that only egocentric distances contributed to saccade trajectories shifts towards the distractor during active decision-making. When the perceptual decision-making process was complete, and the distractor was inhibited, both ego- and allocentric distances independently contributed to saccade trajectory shifts away from the distractor. This is consistent with independent spatial and object-based inhibitory mechanisms. Therefore, we suggest that distractor inhibition is maintained in cortical visual areas with allocentric maps which then feeds into oculomotor areas for saccade planning.

neuroscience↗

bioRxiv2022

Target-distractor competition modulates saccade trajectories in space and object-space

Saccade planning and execution can be affected by a multitude of factors present in a target selection task. Recent studies have shown that the similarity between a target and nearby distractors affects the curvature of saccade trajectories, due to target-distractor competition. To further understand the nature of this competition, we varied the distance between and the similarity of complex target and distractor objects in a delayed match-to-sample task to examine their effects on saccade trajectories and better understand the underlying neural circuitry. For trials with short saccadic reaction times (SRTs) when target-distractor competition is still active, we found a robust effect of distance consistent with saccade vector averaging, whereas the effect of similarity suggested the existence of an object-based suppressive surround. At longer SRTs there was sufficient time for competition between the objects to complete and the distractor to be inhibited, which resulted in saccade trajectory deviations exhibiting the effects of a spatial suppressive surround. In terms of similarity, as the target-distractor similarity decreased, the initial saccade angle shifted towards the target, reflecting stronger distractor inhibition. There were no interactions between distance and similarity at any point in the time-course of target-distractor competition. Taken together, saccade trajectories reflect target-distractor competition that is affected independently by both spatial and object-space suppressive surrounds. The differences in saccade trajectories at short and long SRTs distinguish between active and completed decision-making processes. Thus, saccade responses are more beneficial than manual responses in studies of decision-making models. Significance StatementThis is the first study to determine that the distance and similarity between visual objects independently affect saccade trajectories driven by the target-distractor competition process. Thus, spatiotemporal and object identity factors separately feed into saccade planning and execution, resulting in modulations of saccade trajectory metrics which are based on spatial and object-space suppressive surround mechanisms. Furthermore, this modulation of trajectory metrics distinguishes between active and complete decision-making processes. The findings are important for understanding the dynamic networks guiding target selection and are relevant for further development of decision-making models, as well as eye-tracking applications in health and disease.

neuroscience↗

bioRxiv2021

Feature-based attention induces surround suppression during the perception of visual motion

Feature-based attention prioritizes the processing of the attended feature while strongly suppressing the processing of nearby ones. This creates a non-linearity or attentional suppressive surround predicted by the Selective Tuning model of visual attention. However, previously reported effects of feature-based attention on neuronal responses are linear, e.g., feature-similarity gain. Here, we investigated this apparent contradiction by neurophysiological and psychophysical approaches. Responses of motion direction-selective neurons in area MT/MST of monkeys were recorded during a motion task. When attention was allocated to a stimulus moving in the neurons preferred direction response tuning curves showed its minimum for directions 60-90 degrees away from the preferred direction, an attentional suppressive surround. This effect was modeled via the interaction of two Gaussian fields representing excitatory narrowly-tuned and inhibitory widely-tuned inputs into a neuron, with feature-based attention predominantly increasing the gain of inhibitory inputs. We further showed using a motion repulsion paradigm in humans that feature-based attention produces a similar non-linearity on motion discrimination performance. Our results link the gain modulation of neuronal inputs and tuning curves examined through the feature-similarity gain lens to the attentional impact on neural population responses predicted by the Selective Tuning model, providing a unified framework for the documented effects of feature-based attention on neuronal responses and behavior.

neuroscience↗

bioRxiv2020

Oculomotor Target Selection is Cortically Mediated by Complex Objects

Successful oculomotor target selection often requires discriminating visual features but it remains contentious whether oculomotor substrates encoding saccade vectors functionally contribute to this process. One possibility is that visual features are discriminated cortically and oculomotor modules select the object with the highest activation in the set of all preprocessed cortical object representations, while an alternative possibility is that oculomotor modules actively discriminate potential targets based on visual features. If the latter view is correct, these modules should not require input from specialized visual cortices encoding the task relevant features. We therefore examined whether the latency of visual onset responses elicited by abrupt distractor onsets is consistent with input from specialized visual cortices by non-invasively measuring human saccade metrics (saccade curvature, endpoint deviations, saccade frequency, error proportion) as a function of distractor processing time for novel, visually complex distractors that had to be discriminated from a target to guide saccades. Visual onset response latencies were ~110 ms, consistent with projections from anterior cortical sites specialized for object processing. Surprisingly, oculomotor visual onset responses encoded features, as we manipulated the visual similarity between targets and distractors and observed an increased visual onset response magnitude and duration when the distractor was highly similar to the target, which was not attributable to an inhibitory processing delay. Visual onset responses were dynamically modulated by executive function, as these responses were anticipatorily extinguished over the time course of the experiment. As expected, the latency of distractor-related inhibition was modulated by the behavioral relevance of the distractor. Significance StatementWe provide novel insights into the role of the oculomotor system in saccadic target selection by challenging the convention that neural substrates that encode oculomotor vectors functionally contribute to target discrimination. Our data show that the oculomotor system selects a winner from amongst the preprocessed object representations output from specialized visual cortices as supposed to discriminating visual features locally. We also challenge the convention that oculomotor visual onset responses are feature-invariant, as they encoded task-relevance.

neuroscience↗