Biology subjects

Norcia, A. M.

Publications and source records attributed to Norcia, A. M..

At least 19 recordsLinked to original sources

bioRxiv2026

Dose-dependent ultrasound neuromodulation of the human brain

Transcranial ultrasound stimulation (TUS) can noninvasively modulate deep brain structures, but the relationship between delivered dose and neuromodulatory response remains poorly characterized in humans. Here, we show that ultrasound-induced tissue displacement measured in vivo predicts local and downstream functional neuromodulation. In 24 healthy adults, we combined magnetic resonance acoustic radiation force imaging (MR-ARFI) with concurrent TUS-fMRI in a double-blind, counterbalanced, within-subject design. Relative to active control stimulation, targeting the lateral geniculate nucleus (LGN) increased visually evoked BOLD responses in the LGN and ipsilateral primary visual cortex, localized to the retinotopic projection zone of the stimulated LGN site. Displacement predicted effect magnitude in both regions across participants and covaried with voxelwise responses within participants. Simulated in situ intensity showed no significant association with displacement or neuromodulatory response. These findings link in vivo mechanical displacement to functional modulation of a human thalamocortical circuit, providing an empirical basis for individualized dosing in causal neuroscience and clinical intervention.

neuroscience↗

bioRxiv2026

Psychophysical validation of calibrated white-noise and tuned-noise auditory masks for transcranial focused ultrasound

Auditory confounds have proven to be a major hurdle in the elucidation of veridical neuromodulation effects with transcranial ultrasound stimulation (TUS). Auditory noise masks are an essential method to reduce the audibility of TUS and have shown promise in several studies. Here we describe a novel approach for design, calibration, and psychometric validation of auditory noise masks to reduce the perceptibility of TUS. White noise masks and spectrum-tuned masks matched to a TUS protocol that generates highly salient auditory costimulation (487.5 Hz pulse repetition frequency, 10% duty cycle, 68 W/cm2 pulse-peak average intensity, 500 kHz acoustic frequency) were generated, and dB(A) levels were calibrated with an artificial ear. The masker levels needed to reduce TUS detection performance in a two-interval forced choice task were determined with an adaptive QUEST+ staircase in 20 neurotypical participants. Detection performance of this highly salient TUS protocol was driven to near chance performance (<55%) in 17/20 participants with white-noise and 18/20 participants with spectrum-tuned noise. However, high masker levels approaching safety limits were needed to render TUS inaudible for the majority of participants, indicating the need for formal masker calibration for these TUS settings. Additionally, against expectation the spectrum-tuned masker did not significantly outperform the white-noise masker, suggesting that perceptibility of TUS auditory costimulation does not lawfully follow the sound expected from its pulse envelope and the known spectrum of human hearing.

neuroscience↗

bioRxiv2026

Effects of transcranial focused ultrasound stimulation to human lateral geniculate nucleus on visual perception and steady-state visual evoked potentials

Transcranial ultrasound stimulation (TUS) is an emerging tool to non-invasively modulate neural activity in deep brain areas. A key need in accelerating TUS into cognitive neuroscience and neuropsychiatry is to better understand how different sonication parameters relate to neuromodulatory effects. Here we assess the role of pulse repetition frequency (PRF), a key TUS parameter thought to determine the relative contribution of molecular displacement and acoustic radiation force effects on neural tissue using the human subcortical visual pathway as a testbed. We combined frequency-tagged steady-state visual evoked potential (SSVEP) measures of contrast-response with contrast increment detection psychophysics as neural and behavioral readouts of visual pathway function. We used structural MRIs and acoustic simulations to target the lateral geniculate nucleus (LGN). Concurrent with visual stimulus presentation, the left LGN or a more superficial control site were stimulated with a neuronavigated depth-steerable 4-element TUS transducer at a range of PRFs with 68 W/cm2 free-water ISPPA, and a 10% duty cycle. An effective white-noise auditory mask blinded participants to stimulation conditions. Recordings from 25 neurotypical participants failed to detect any impact of TUS on SSVEP response amplitude, SSVEP response latency, or perceptual behavior. Analysis of simulations generated from the measured transducer positions grant reasonably high confidence that the LGN was within the TUS focus in most participants, with no correlation between targeting accuracy and changes in activity during TUS. Our results provide a cautionary note about the effect size of neuronavigated TUS for online causal manipulations in cognitive and clinical neuroscience.

neuroscience↗

bioRxiv2025

MatClassRSA v2 release: A MATLAB toolbox for M/EEG classification, proximity matrix construction, and visualization

MatClassRSA is a MATLAB toolbox that performs magnetoen-cephalography and electroencephalography (M/EEG) classification and other analyses related to Representational Similarity Analysis (RSA). The toolbox is designed for cognitive neuroscience researchers who wish to perform classification-based decoding analyses of their data--often repeated trials of evoked responses--or derive Representational Dissimilarity Matrices (RDMs) as input to RSA. Organized as a collection of usercalled functions, MatClassRSA v2 comprises five main modules: Preprocessing, Reliability, Classification, RDM Computation, and Visualization. The Classification module supports multiple classifiers (LDA, RF, SVM) and classification schemes (e.g., multiclass, pairwise, cross-validated, train-test, hyperparameter optimization) and offers basic statistical analyses via permutation testing. Functions in other modules include, for example, trial-averaging and noise normalization; reliability estimation; non-classification RDM construction; and hierarchical and non-hierarchical clustering visualizations. The toolbox is freely available on GitHub under an MIT license and includes the main codebase, a User Manual, example function calls, and illustrative analyses. This preprint provides a general background of M/EEG classification for RSA as well as a narrative overview of the v2 MatClassRSA release, its updated functionalities, and illustrative analyses performed using the toolbox.

neuroscience↗

bioRxiv2025

Spatial Attention and Session Day Independently Modulate Human Visual Cortical Plasticity

Stimulus-specific response potentiation (SSRP) is a noninvasive form of cortical neuroplasticity elicited by repeated presentation of high-contrast visual stimuli. Analogous to long-term potentiation, SSRP has been proposed to exhibit input specificity, with potentiation confined to neural populations driven by the induction stimulus. In rodent models, SSRP effects accumulate across days; however, it remains unclear whether selective attention influences the magnitude or specificity of potentiation in humans. Here, we examined whether covert spatial attention modulates SSRP strength using high-density electroencephalography (EEG) in neurotypical adults. An established SSRP paradigm was modified to include an attention task during induction. Pre- and post-induction amplitudes were measured using frequency-tagged (6 and 7.5 reversals/s) bilateral hemifield contrast-sweep checkerboard steady-state visual evoked potentials (SSVEPs). The 10-minute, high-contrast, 2 Hz sign-reversing induction stimulus was presented exclusively to the left hemifield, with the right serving as control. Across two experimental sessions, participants attended either toward or away from the potentiated hemifield during induction. SSRP produced increased post-induction amplitudes in both hemifields, challenging the notion of strict input specificity. Potentiation was significantly greater on the second session day, independent of attention condition. Notably, attention enhanced SSRP in naive but not experienced observers, reflecting a significant interaction between attention and session day. Together, these findings suggest that (1) human SSRP may not be strictly stimulus-specific, (2) attention modestly enhances SSRP during initial exposure, and (3) repeated induction produces a robust plasticity effect that occludes attentional modulation.

neuroscience↗

bioRxiv2025

Strong mnemonic prediction errors increase cognitive control, attention, and arousal

Ongoing experience is continuously processed in the context of past events. Divergence between current experience and memory-based predictions (i.e., a mnemonic prediction error; MPE) is theorized to be a signal that encoding, as opposed to retrieval, should be prioritized. We asked how MPEs place demands on control and attention-related processes, and whether these demands differ as a function of prediction strength. We investigated these questions across two experiments, wherein we recorded scalp electroencephalography and/or pupillometry as 101 young human adults performed an associative memory task. Strong MPEs, more so than weak MPEs, increased physiological indices of cognitive control (frontal theta), attention (posterior alpha and pupil size), and arousal (pupil size). Greater cognitive control (frontal theta) during strong MPEs promoted better learning of prediction violating (i.e., unexpected) stimuli. Collectively, these findings reveal multiple pathways through which the mind and brain respond adaptively to violations of strong mnemonic predictions.

neuroscience↗

bioRxiv2025

Reading fluency development is predicted by cortical latency

The development of fluent literacy skills from childhood to adolescence is strongly constrained by the temporal dynamics of word recognition. Capturing the neural basis of these subtle timing changes in word recognition has remained challenging with EEG measures that lack reliability at the individual subject level. Here, we leverage phase information from Steady-State Visual Evoked Potentials (SSVEPs) to derive precise and reliable temporal dynamics of neural signatures underlying visual word form recognition at the individual level and examine their relationship to reading fluency and comprehension. Typically developing readers (N = 68), aged 8-15 years, viewed a stream of four-character stimulus strings presented at 3 Hz. Significant SSVEP signals emerged for nearly all participants. Signals at 3, 6, and 9 Hz harmonics exhibited a phase pattern consistent with a delay model, indicating a mean latency of approximately 170 milliseconds. Individual variations in latencies demonstrated (a) high internal consistency (R = .94); (b) stability across variations in letter string forms (familiar words, nonwords with familiar letters, nonwords with unfamiliar pseudo-characters); (c) a linear relationship with age; and most remarkably, (d) a predictive relationship with individual variation in reading fluency and reading comprehension. These results establish SSVEP visual word form latency as a promising approach for investigating the neural basis of reading development, paving the way for future translational applications in education and offering potential solutions to broader societal challenges in promoting population-level reading fluency.

neuroscience↗

bioRxiv2024

Brain plasticity for visual words: Elementary school teachers can drive changes in weeks that rival those formed over years

This study aims to investigate the impact of vocabulary acquisition through short-term classroom learning and its relation to broader forms of vocabulary learning through long-term exposure in daily life. Through a two week of "learning sprint" in collaboration with a local elementary school and EEG-Steady State Visual Evoked Potentials (EEG-SSVEP) paradigm, we assessed new vocabulary learning in first and second graders within their pedagogical environment. We then compared the results with the word frequency effect, a well-established phenonmenon that reflects long-term vocabulary learning. After two weeks of classroom instruction, newly acquired words elicited neural responses similar to those of high-frequency words, with the effect significantly correlated with childrens phonological decoding skills. Additionally, we successfully replicated the word frequency effect using the SSVEP paradigm for the first time. These findings highlight the potential of the "learning sprint" model for conducting neuroscience research in authentic educational settings, thereby fostering a stronger connection between education and neuroscience.

neuroscience↗

bioRxiv2024

Visual field asymmetries in responses to ON and OFF pathway biasing stimuli

Recent reports suggest the ON and OFF pathways are differentially susceptible to selective vision loss in glaucoma. Thus, perimetric assessment of ON- and OFF-pathway function may serve as a useful diagnostic. However, this necessitates a developed understanding of normal ON/OFF pathway function around the visual field and as a function of input intensity. Here, using electroencephalography, we measured ON- and OFF-pathway biased contrast response functions in the upper and lower visual fields. Using the steady-state visually evoked potential paradigm, we flickered achromatic luminance probes according to a saw-tooth waveform, the fast-phase of which biased responses towards the ON or OFF pathways. Neural responses from the upper and lower visual fields were simultaneously measured using frequency tagging - probes in the upper visual field modulated at 3.75Hz, while those in the lower visual field modulated at 3Hz. We find that responses to OFF/decrements are larger than ON/increments, especially in the lower visual field. In the lower visual field, both ON and OFF responses were well described by a sigmoidal non-linearity. In the upper visual field, the ON pathway function was very similar to that of the lower, but the OFF pathway function showed reduced saturation and more cross-subject variability. Overall, this demonstrates that the relationship between the ON and OFF pathways depends on the visual field location and contrast level, potentially reflective of natural scene statistics.

neuroscience↗

bioRxiv2023

Two disparity channels in human visual cortex with different contrast and blur sensitivity

PurposeOur goal is to describe the contrast and blur sensitivity of multiple horizontal disparity sub-systems and to relate them to the contrast and spatial sensitivities of their monocular inputs. MethodsSteady-State Visual Evoked Potentials (SSVEPs) amplitudes were recorded in response to Dynamic Random Dot Stereograms (DRDS) alternating at 2 Hz between zero disparity and varying magnitudes of crossed disparity for disparity plane and disparity grating stimuli. Half-image contrasts ranged between 2.5 and 80% and over a range of Gaussian blurs from 1.4 to 12 arcmin. Separate experiments measured contrast and blur sensitivity for the monocular half-images. ResultsThe first and second harmonics disparity responses were maximal for disparity gratings and for the disparity plane condition, respectively. The first harmonic of the disparity grating response was more affected by both contrast and blur than was the second harmonic of the disparity plane response which had higher contrast sensitivity than the first harmonic. ConclusionThe corrugation frequency, contrast and blur tuning of the first harmonic suggest that it reflects activity of neurons tuned to higher luminance spatial frequencies that are selective for relative disparity, whereas the second harmonic reflects the activity of neurons sensitive to absolute disparity that are driven by low monocular spatial spatial frequencies. Translational RelevanceSSVEPs to DRDS provide two objective neural measures of disparity processing, the first harmonic - whose stimulus preferences are similar to those of behavioral stereoacuity - and the second harmonic that represents an independent disparity-specific, but not necessarily stereoscopic mechanism.

neuroscience↗

bioRxiv2023

When Do Visual Category Representations Emerge in Infants' Brains?

Organizing the continuous stream of visual input into categories like places or faces is important for everyday function and social interactions. However, it is unknown when neural representations of these and other visual categories emerge. Here we used steady state evoked potential electroencephalography to measure cortical responses in infants at 3-4 months, 4-6 months, 6-8 months, and 12-15 months, when they viewed controlled, gray-level images of faces, limbs, corridors, characters, and cars. We found that distinct responses to these categories emerge at different ages. Reliable brain responses to faces emerge first, at 4-6 months, followed by limbs and places around 6-8 months. Between 6-15 months response patterns become more distinct, such that a classifier can decode what an infant is looking at from their brain responses. These findings have important implications for assessing typical and atypical cortical development as they not only suggest that category representations are learned, but also that representations of categories that may have innate substrates emerge at different times during infancy.

neuroscience↗

bioRxiv2022

Starting to see a pattern: Longitudinal SSVEP signals reveal how growth in children's cortical sensitivity to visual word form structure is uniquely linked to two-year growth in reading fluency

Learning to read depends on the ability to extract precise details of letter combinations, which convey critical information that distinguishes tens of thousands of visual word forms. To support fluent reading skill, one crucial neural developmental process is ones brain sensitivity to statistical constraints inherent in combining letters into visual word forms. To test this idea in early readers, we tracked the impact of two years of schooling on within-subject longitudinal changes in cortical responses to different properties of words (coarse tuning for print, and fine tuning to visual word forms and whole word representations) and their growth in reading skill. Three stimulus contrasts--words versus pseudofonts, words versus pseudowords, pseudowords versus nonwords--were presented while high-density EEG Steady-State Visual Evoked Potentials (SSVEPs, n=31) were recorded. Internalization of abstract visual word form structures over two years of reading experience resulted in a near doubling of SSVEP amplitude, with increasing left lateralization. Longitudinal changes in brain responses to such word form structural information were linked to the growth in reading, especially in rapid automatic naming for letters. No such changes were observed for whole word representation processing and coarse tuning for print. Collectively, these findings indicate that sensitivity to visual word form structure develops rapidly through exposure to print and is linked to growth in reading skill. Research HighlightsO_LILongitudinal changes in cognitive responses to coarse print tuning, visual word from structure, and whole word representation were examined in early readers. C_LIO_LIVisual word form structure processing demonstrated striking patterns of growth with nearly doubled in EEG amplitude and increased left lateralization. C_LIO_LILongitudinal changes in brain responses to visual word form structural information were linked to the growth in rapid automatic naming for letters. C_LIO_LINo longitudinal changes were observed for whole word representation processing and coarse tuning for print. C_LI

scientific communication and education↗

bioRxiv2022

Stability of steady-state visual evoked potential contrast response functions

A repeated measure of neural activity that is stable over time when unperturbed is needed to be able to meaningfully measure neuroplastic changes in the brain. With sensory-evoked potentials in particular, repeated presentation of stimuli can generate neuroplasticity by itself under certain conditions. We assessed the repeated-measure within-day and across-day stability of the steady-state visual-evoked potential (ssVEP), a high signal-to-noise electrophysiological readout of neural activity in human visual cortex, in preparation for studies of visual cortical neuroplasticity. Steady-state VEP contrast-sweep responses were measured daily for 4 days (four 20-trial blocks per day, 22 participants). Response amplitudes were stable in individual participants, with measured across-block and across-day coefficients of variation (CV= SD / Mean) of 12{+/-}1% and 19{+/-}2%, respectively. No consistent changes in response amplitude were observed either across blocks or across days. We conclude that contrast-sweep steady-state VEPs provide a stable human neurophysiological measure well-suited for repeated-measures studies.

neuroscience↗

bioRxiv2022

Cognitive penetrability of scene representations based on horizontal image disparities

The structure of natural scenes is signaled by many visual cues. Principal amongst them are the binocular disparities created by the laterally separated viewpoints of the two eyes. Disparity cues are believed to be processed hierarchically, first in terms of local measurements of absolute disparity and second in terms of more global measurements of relative disparity that allow extraction of the depth structure of a scene. Psychophysical and oculomotor studies have suggested that relative disparities are particularly relevant to perception, whilst absolute disparities are not. Here, we compare neural responses to stimuli that isolate the absolute disparity cue with stimuli that contain additional relative disparity cues, using the high temporal resolution of EEG to determine the temporal order of absolute and relative disparity processing. By varying the observers task, we assess the extent to which each cue is cognitively penetrable. We find that absolute disparity is extracted before relative disparity, and that task effects arise only at or after the extraction of relative disparity. Our results indicate a hierarchy of disparity processing stages leading to the formation of a proto-object representation upon which higher cognitive processes can act.

neuroscience↗

bioRxiv2022

Rapid Selectivity to Natural Images Across Layers of Primate V1

Visual systems are thought to have adapted to the statistical properties of natural scenes. However, the extent to which visual neurons respond selectively to natural images, and the stage at which that selectivity emerges remains unclear. To address these questions, we recorded the visual activity of neurons in macaque V1 using high-density electrode arrays (Neuropixels), and compared neuronal responses to images presented at three levels of naturalness. We found that within 60 ms of stimulus onset, neurons in all cortical layers, including input layers 4C alpha and beta, responded more vigorously to natural images than to statistically matched naturalistic texture and noise images. The result remained when residual variations in the local image statistics were factored out. V1 neurons also showed high population and lifetime sparseness for natural images. Across the population of V1 neurons, sensitivity to natural images exceeded the sensitivity to other image categories. The results reveal a rapid and pervasive preference for natural images is present at the earliest stages of cortical processing.

neuroscience↗

bioRxiv2021

Early detection of sublexical and lexical processing in beginning readers: evidence from Steady-State Visual Evoked Potentials (SSVEPs)

There are multiple levels of processing relevant to reading that vary in their visual, sublexical and lexical orthographic processing demands. Segregating distinct cortical sources for each of these levels has been challenging in EEG studies of early readers. To address this challenge, we applied recent advances in analyzing high-density EEG using Steady-State Visual Evoked Potentials (SSVEPs) via data-driven Reliable Components Analysis (RCA) in a group of early readers spanning from kindergarten to second grade. Three controlled stimulus contrasts--familiar words versus unfamiliar pseudofonts, familiar words versus orthographically legal pseudowords, and orthographically legal pseudowords versus orthographically illegal nonwords--were used to isolate visual print/letter selectivity, sublexical processing, and lexical processing, respectively. We found robust responses specific to each of these processing levels, even in kindergarteners who have limited knowledge of print. Moreover, comparing amplitudes of these three stimulus contrasts across three reading fluency-based groups and three grade-based groups revealed fluency group and grade group main effects only for lexical contrast (i.e., words versus orthographically legal pseudowords). Furthermore, we found that sublexical orthography-related responses shifted their topographic distribution from the right to left hemisphere from kindergarten to first and second grades. Results suggest that, with more sensitive measures, the sublexical and lexical fine tuning for words--as a bio-marker of reading ability--can be detected at a much earlier stage than previously assumed. Declarations of interestNone

neuroscience↗

bioRxiv2021

Transcranial Focused Ultrasound Neuromodulation of the Thalamic Visual Pathway in a Large Animal Model

BackgroundNeuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. ObjectiveThe purpose of this study was to determine whether MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) and cortical brain oscillations in a large animal model. MethodsThe lateral geniculate nucleus (LGN) on one side was identified with T2-weighted MRI in sheep (all male, n=9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm a tight sonication focus. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time-frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics. ResultsThe VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input, but not when TUS is applied by itself. ConclusionTUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.

neuroscience↗

bioRxiv2021

Vergence accuracy in an autostereoscopic display

When fixating an object, observers typically under or over-converge by a small amount, a phenomenon known as "fixation disparity". Fixation disparity is typically measured with physical fixation targets and dichotically presented nonius lines. Here we made fixation disparity measurements with an autostereoscopic display, varying the retinal eccentricity and disparity of the fixation targets. Measurements were made in a group of four practiced observers and in a group of thirteen experimentally naive observers. Fixation disparities with a zero-disparity target were in the direction of fixation behind the plane of the screen and the magnitude of the fixation disparity grew with the eccentricity of the fixation targets (1-5 deg in the practiced observers and 1 - 10 deg in the naive observers). Fixation disparity also increased with increasing disparity of the targets, especially when they were presented at crossed disparities. Fixation disparities were larger overall for naive observers who additionally did not converge in front of the screen when vergence demand was created by crossed disparity fusion locks presented at 5 and 10 deg eccentricities.

neuroscience↗