Biology subjects

Haggerty, E. B.

Publications and source records attributed to Haggerty, E. B..

6 recordsLinked to original sources

bioRxiv2023

Network structure influences the strength of learned neural representations

Human experience is built upon sequences of discrete events. From those sequences, humans build impressively accurate models of their world. This process has been referred to as graph learning, a form of structure learning in which the mental model encodes the graph of event-to-event transition probabilities [1], [2], typically in medial temporal cortex [3]-[6]. Recent evidence suggests that some network structures are easier to learn than others [7]-[9], but the neural properties of this effect remain unknown. Here we use fMRI to show that the network structure of a temporal sequence of stimuli influences the fidelity with which those stimuli are represented in the brain. Healthy adult human participants learned a set of stimulus-motor associations following one of two graph structures. The design of our experiment allowed us to separate regional sensitivity to the structural, stimulus, and motor response components of the task. As expected, whereas the motor response could be decoded from neural representations in postcentral gyrus, the shape of the stimulus could be decoded from lateral occipital cortex. The structure of the graph impacted the nature of neural representations: when the graph was modular as opposed to lattice-like, BOLD representations in visual areas better predicted trial identity in a held-out run and displayed higher intrinsic dimensionality. Our results demonstrate that even over relatively short timescales, graph structure determines the fidelity of event representations as well as the dimensionality of the space in which those representations are encoded. More broadly, our study shows that network context influences the strength of learned neural representations, motivating future work in the design, optimization, and adaptation of network contexts for distinct types of learning over different timescales.

neuroscience↗

bioRxiv2022

Parametric modulation of the blink reflex provides an individual difference measure of trigeminal sensitivity

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5 - 60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable decrease in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This decrease was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity. Impact statementO_LIThere has been limited study of how variation in stimulus intensity influences the cutaneous blink response. We describe how variation in the intensity of an air-puff stimulus relates to the amplitude of the blink response using a two-parameter model. The parameters of the model capture individual differences in response, which may be used in future studies to identify population differences in trigeminal sensitivity. C_LI

neuroscience↗

bioRxiv2022

Retinal ganglion cell endowment is correlated with optic tract fiber cross section, not density

There is substantial variation between healthy individuals in the number of retinal ganglion cells (RGC) in the eye, with commensurate variation in the number of axons in the optic tracts. Fixel-based analysis of diffusion MR produces estimates of fiber density (FD) and cross section (FC). Using these fixel measurements along with retinal imaging, we asked if individual differences in RGC tissue volume are correlated with individual differences in FD and FC measurements obtained from the optic tracts, and subsequent structures along the cortical visual pathway. We find that RGC endowment is correlated with optic tract FC, but not with FD. RGC volume had a decreasing relationship with measurements from subsequent regions of the visual system (LGN volume, optic radiation FC/FD, and V1 surface area). However, we also found that the variations in each visual area were correlated with the variations in its immediately adjacent visual structure. We only observed these serial correlations when FC is used as the measure of interest for the optic tract and radiations, but no significant relationship was found when FD represented these white matter structures. From these results, we conclude that the variations in RGC endowment, LGN volume, and V1 surface area are better predicted by the overall cross section of the optic tract and optic radiations as compare to the intra-axonal restricted signal component of these white matter pathways. Additionally, the presence of significant correlations between adjacent, but not distant, anatomical structures suggests that there are multiple, local sources of anatomical variation along the visual pathway.

neuroscience↗

bioRxiv2021

Melanopic stimulation does not affect psychophysical threshold sensitivity for luminance flicker

In addition to the cone photoreceptors the retina contains intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells express the photopigment melanopsin and are known to be involved in reflexive visual functions such as pupil response and photo-entrainment of the circadian rhythm. It is possible that the ipRGCs contribute to conscious visual perception, either by providing an independent signal to the geniculo-striate pathway, or by interacting with and thus modifying signals arising from "classical" retinal ganglion cells that combine and contrast cone input. Here, we tested for the existence of an interaction by asking if a 350% change in melanopsin stimulation alters psychophysical sensitivity for the detection of luminance flicker. In Experiment 1, we tested for a change in the threshold for detecting luminance flicker in three participants after they adapted to backgrounds with different degrees of tonic melanopsin stimulation. In Experiments 2 and 3, this test was repeated, but now for luminance flicker presented on a transient pedestal of melanopsin stimulation. Across the three experiments, no effect of melanopsin stimulation upon threshold flicker sensitivity was found. Our results suggest that even large changes in melanopsin stimulation do not affect near-threshold, cone-mediated visual perception.

neuroscience↗

bioRxiv2020

Enhanced reflexive eye closure is mediated by ipRGC signals and is specific to migraine with visual aura

ObjectiveTo assess the contribution of the melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs) and the cones to reflexive eye closure as an implicit measure of interictal photophobia in migraine. MethodsWe studied twenty participants in each of three groups: headache-free (HAf) controls, migraine without aura (MwoA), and migraine with visual aura (MwA). Participants viewed spectral pulses that selectively targeted melanopsin, the cones, or their combination while we recorded orbicularis oculi electromyography (OO-EMG) and blinking rate. ResultsTime course analysis of OO-EMG demonstrated that reflexive eye closure was tightly coupled to the spectral pulses. Compared to both the MwoA and HAf control groups, the MwA group had enhanced OO-EMG and blinking activity in response to melanopsin and cone stimulation in combination and in isolation. This response scaled with the contrast of the stimulus. ConclusionsOur findings suggest that ipRGC signals, whether elicited by melanopsin stimulation or from presumed extrinsic cone input, provide the afferent input for light-induced reflexive eye closure in a photophobic state. Participants with migraine and visual aura had a distinctly different response to visual stimulation as compared to the other two groups. This is in contrast to prior findings in this same cohort in whom higher explicit ratings of visual discomfort were found for both MwA and MwoA as compared to controls. Such a dissociation suggests distinct pathophysiology in forms of migraine, interacting with separate neural pathways by which ipRGC signals elicit implicit and explicit signs of visual discomfort.

neuroscience↗

bioRxiv2020

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

Second only to headache, photophobia is the most debilitating symptom reported by people with migraine. While the melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to play a role, how cone and melanopsin signals are integrated in this pathway to produce visual discomfort is poorly understood. We studied 60 people: 20 without headache and 20 each with interictal photophobia from migraine with or without aura. Participants viewed pulses of spectral change that selectively targeted melanopsin, the cones, or both, and rated the degree of visual discomfort produced by these stimuli while we also recorded pupil responses. We examined the data within a model that describes how cone and melanopsin signals are weighted and combined at the level of the retina, and how this combined signal is transformed into a rating of discomfort or pupil response. Our results indicate that people with migraine do not differ from headache-free controls in the manner in which melanopsin and cone signals are combined. Instead, people with migraine demonstrate an amplification of integrated ipRGC signals for discomfort. This effect of migraine is selective for ratings of visual discomfort, in that an amplification of pupil responses was not seen in the migraine group, nor were group differences found in surveys of other behaviors putatively linked to ipRGC function (chronotype, seasonal sensitivity, presence of a photic sneeze reflex). By revealing a dissociation in the amplification of discomfort versus pupil response, our findings suggest a post-retinal alteration in processing of ipRGC signals for photophobia in migraine. SignificanceThe melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs) may contribute to photophobia in migraine. We measured visual discomfort and pupil responses to cone and melanopsin stimulation--the photoreceptor inputs to the ipRGCs--in people with and without migraine. We find that people with migraine do not differ from those without headaches in how cone and melanopsin signals are weighted and combined to produce visual discomfort. Instead, migraine is associated with an amplification of ipRGC signals for discomfort. This effect of migraine upon ipRGC signals is limited to photophobia, as we did not find an enhancement of pupil responses or a change in other behaviors linked to ipRGC function. Our findings suggest a post-retinal amplification of ipRGC signals for photophobia in migraine.

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