Biology subjects

Cusack, R.

Publications and source records attributed to Cusack, R..

13 recordsLinked to original sources

bioRxiv2026

Brain representations of visual short-term memories during healthy human aging: occipital decline and frontoparietal compensation

Visual short-term memory declines steeply with age, but the link to neural representations of memory content remains unknown. We used fMRI decoding to relate remembered motion-direction representations in visual and frontoparietal cortex to age and performance, in 115 adults, aged 25-87, from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort. Decoding was strongest in visual cortex, but also significant in frontoparietal regions, with different profiles. Visual representations weakened with memory load and age, and statistically mediated age-related performance decline, especially during recall. This coupling, however, weakened with age: some older adults retained stronger visual representations than performance implied, suggesting impaired access to a partially preserved memory trace. Frontoparietal representations, instead, were largely insensitive to load and strengthened with age during maintenance, partially offsetting performance decline. Therefore, interventions to boost VSTM in older adults might target compensatory frontoparietal representations during memory maintenance, and readout of untapped visual representations at recall.

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bioRxiv2026

The development of coarse and fine feature tuning in infant visual cortex

Objects can be recognized from visual features at multiple spatial scales, from coarse global shape to fine local detail. How infant visual cortex encodes these features across the visual hierarchy, however, remains unknown. We combined awake infant fMRI with developmentally inspired deep neural networks (DNNs) trained and tested with different levels of image blur to probe cortical tuning to coarse and fine visual features. V1 showed mature tuning to coarse and fine features by 2 months. In contrast, infant extrastriate cortex (V2-V4) followed a protracted developmental trajectory and was biased toward coarse object features relative to adults. This relative bias persisted at 9 months and was not readily explained by developing acuity. The sustained coarse-feature bias contrasted with DNNs, in which low-spatial-frequency representations took longest to converge with visual cortex during training, revealing distinct developmental biases in object-feature tuning in biological and artificial visual systems.

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bioRxiv2023

Instructive and reorganizing effects of experience on development of human visual cortices

Comparisons of visual cortex function across blind and sighted adults reveals effects of experience on human brain function. Since almost all research has been done with adults, little is known about the developmental origins of plasticity. We compared resting state functional connectivity of visual cortices of blind adults (n = 30), blindfolded sighted adults (n = 50) to a large cohort of infants (Developing Human Connectome Project, n = 475). Visual cortices of sighted adults show stronger coupling with non-visual sensory-motor networks (auditory, somatosensory/motor), than with higher-cognitive prefrontal cortices (PFC). In contrast, visual cortices of blind adults show stronger coupling with higher-cognitive PFC than with nonvisual sensory-motor networks. Are infant visual cortices functionally like those of sighted adults, with blindness leading to functional change? We find that, on the contrary that secondary visual cortices of infants are functionally more like those of blind adults: stronger coupling with PFC than with nonvisual sensory-motor networks, suggesting that visual experience modifies elements of the sighted-adult long-range functional connectivity profile. Infant primary visual cortices are in-between blind and sighted adults i.e., more balanced PFC and sensory-motor connectivity than either adult group. The lateralization of occipital-to-frontal connectivity in infants resembles the sighted adults, consistent with the idea that blindness leads to functional change. These results suggest that both vision and blindness modify functional connectivity through experience-driven (i.e., activity-dependent) plasticity.

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bioRxiv2021

Naturalistic stimuli reveal a critical period in visual cortex development: Evidence from adult-onset blindness

How do life experiences impact cortical function? In people who are born blind, the "visual" cortices are recruited for nonvisual tasks such as Braille reading and sound localization (e.g., Collignon et al., 2011; Sadato et al., 1996). The mechanisms of this recruitment are not known. Do visual cortices have a latent capacity to respond to nonvisual information that is equal throughout the lifespan? Alternatively, is there a sensitive period of heightened plasticity that makes visual cortex repurposing possible during childhood? To gain insight into these questions, we leveraged naturalistic auditory stimuli to quantify and compare cross-modal responses congenitally blind (CB, n=22), adult-onset blind (vision loss >18 years-of-age, AB, n=14) and sighted (n=22) individuals. Participants listened to auditory excerpts from movies; a spoken narrative; and matched meaningless auditory stimuli (i.e., shuffled sentences, backwards speech) during fMRI scanning. These rich naturalistic stimuli made it possible to simultaneous engage a broad range of cognitive domains. We correlated the voxel-wise timecourses of different participants within each group. For all groups, all stimulus conditions induced synchrony in auditory cortex and for all groups only the narrative stimuli synchronized responses in higher-cognitive fronto-parietal and temporal regions. Inter-subject synchrony in visual cortices was high in the CB group for the movie and narrative stimuli but not for meaningless auditory controls. In contrast, visual cortex synchrony was equally low among AB and sighted blindfolded participants. Even many years of blindness in adulthood fail to enable responses to naturalistic auditory information in visual cortices of people who had sight as children. These findings suggest that cross-modal responses in visual cortex of people born blind reflect the plasticity of developing visual cortex during a sensitive period.

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bioRxiv2021

Typical and disrupted brain circuitry for conscious awareness in full-term and preterm infants

One of the great frontiers of consciousness science is understanding how early consciousness arises in the development of the human infant. The reciprocal relationship between the default mode network (DMN) and frontoparietal networks -- the dorsal attention network (DAN) and executive control network (ECN) -- is thought to facilitate integration of information across the brain and its availability for conscious access to a wide set of mental operations. It remains unknown whether the brain mechanism of conscious awareness is instated in infants from birth. To address this gap, we asked what the impact of prematurity and neonate age is on the development the default mode and fronto-parietal networks, and of their reciprocal relationship. To address these questions, we used the Developing Human Connectome Project (dHCP), a unique Open Science project which provides a large sample of neonatal functional Magnetic Resonance Imaging (fMRI) data with high temporal and spatial resolution. Resting state fMRI data for full-term neonates (N = 282, age 41.2 w {+/-} 12 d), and preterm neonates scanned at term-equivalent age (TEA) (N = 73, 40.9 w {+/-} 14.5 d), or before TEA (N = 73, 34.6 w {+/-} 13.4 d) were obtained from the dHCP, and for a reference adult group (N = 176, 22 - 36 years), from the Human Connectome Project. For the first time, we show that the reciprocal relationship between the DMN and DAN was present at full-term birth or TEA. Although different from the adult networks, the DMN, DAN and ECN were present as distinct networks at full-term birth or TEA, but premature birth disrupted network development. By contrast, neonates before TEA showed dramatic underdevelopment of high-order networks. Only the DAN was present as a distinct network and the reciprocal network relationship was not yet formed. Our results suggest that, at full-term birth or by term-equivalent age, infants possess key features of the neural circuitry that enables integration of information across diverse sensory and high-order functional modules, giving rise to conscious access. Conversely, they suggest that this brain infrastructure is not present before infants reach term-equivalent age. These findings improve understanding of the ontogeny of high-order network dynamics that support conscious awareness, and of their disruption by premature birth.

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bioRxiv2020

The brain-bases of responsiveness variability under moderate anaesthesia

Anaesthesia combined with functional neuroimaging provides a powerful approach for understanding the brain mechanisms of consciousness. Although propofol is used ubiquitously in clinical interventions that reversibly suppress consciousness, it shows large inter-individual variability, and the brain bases of this variability remain poorly understood. We asked whether three networks key to conscious cognition -- the dorsal attention (DAN), executive control (ECN), and default mode (DMN) -- underlie responsiveness variability under anaesthesia. Healthy participants (N=17) were moderately anaesthetized during narrative understanding and resting state conditions inside the Magnetic Resonance Imaging scanner. A target detection task measured behavioural responsiveness. An independent behavioural study (N=25) qualified the attention demands of narrative understanding. 30% of participants were unaffected in their response times, thus thwarting a key aim of anaesthesia -- the suppression of behavioural responsiveness. Individuals with stronger functional connectivity within the DAN and ECN, between them, and to the DMN, and with larger grey matter volume in frontal regions were more resilient to anaesthesia. For the first time, we show that responsiveness variability during propofol anaesthesia relates to inherent differences in brain structure and function of the fronto-parietal networks, which can be predicted prior to sedation. Results highlight novel markers for improving awareness monitoring during clinical anaesthesia. Key pointsO_LIModerate propofol anaesthesia showed highly variable effects across individuals C_LIO_LI30% of healthy participants response times were unaffected by anaesthesia and 70% had significantly delayed, fragmented, or fully omitted responses C_LIO_LIGrey matter volume in frontal cortex and functional connectivity of the fronto-parietal networks predicted resilience to anaesthesia C_LI

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bioRxiv2019

Representation of semantic information in ventral areas during encoding is associated with improved visual short-term memory

We rely upon visual short-term memory (VSTM) for continued access to perceptual information that is no longer available. Despite the complexity of our visual environments, the majority of research on VSTM has focused on memory for lower-level perceptual features. Using more naturalistic stimuli, it has been found that recognizable objects are remembered better than unrecognizable objects. What remains unclear, however, is how semantic information changes brain representations in order to facilitate this improvement in VSTM for real-world objects. To address this question, we used a continuous report paradigm to assess VSTM (precision and guessing rate) while participants underwent functional magnetic resonance imaging (fMRI) to measure the underlying neural representation of 96 objects from 4 animate and 4 inanimate categories. To isolate semantic content, we used a novel image generation method that parametrically warps images until they are no longer recognizable while preserving basic visual properties. We found that intact objects were remembered with greater precision and a lower guessing rate than unrecognizable objects (this also emerged when objects were grouped by category and animacy). Representational similarity analysis of the ventral visual stream found evidence of category and animacy information in anterior visual areas during encoding only, but not during maintenance. These results suggest that the effect of semantic information during encoding in ventral visual areas boosts visual short-term memory for real-world objects.

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bioRxiv2019

Category-Selective Visual Regions Have Distinctive Signatures of Connectivity in Early Infancy

The development of the ventral visual stream is shaped both by an innate proto-organization and by experience. The fusiform face area (FFA), for example, has stronger connectivity to early visual regions representing the fovea and lower spatial frequencies. In adults, category-selective regions in the ventral stream (e.g. the FFA) also have distinct signatures of connectivity to widely distributed brain regions, which are thought to encode rich cross-modal, motoric, and affective associations (e.g., tool regions to the motor cortex). It is unclear whether this long-range connectivity is also innate, or if it develops with experience. We used MRI diffusion-weighted imaging with tractography to characterize the connectivity of face, place, and tool category-selective regions in neonates (N=445), 1-9 month old infants (N=11), and adults (N=14). Using a set of linear-discriminant classifiers, category-selective connectivity was found to be both innate and shaped by experience. Connectivity for faces was the most developed, with no evidence of significant change in the time period studied. Place and tool networks were present at birth but also demonstrated evidence of development with experience, with tool connectivity developing over a more protracted period (9 months). Taken together, the results support an extended proto-organizon to include long-range connectivity that could provide additional constraints on experience dependent development.

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bioRxiv2018

Functional diversity of brain networks supports consciousness and verbal intelligence

How are the myriad stimuli arriving at our senses transformed into conscious thought? To address this question, in a series of studies, we asked whether a common mechanism underlies loss of information processing in unconscious states across different conditions, which could shed light on the brain mechanisms of conscious cognition. With a novel approach, we brought together for the first time, data from the same paradigm--a highly engaging auditory-only narrative--in three independent domains: anesthesia-induced unconsciousness, unconsciousness after brain injury, and individual differences in intellectual abilities during conscious cognition. During external stimulation in the unconscious state, the functional differentiation between the auditory and fronto-parietal systems decreased significantly relatively to the conscious state. Conversely, we found that stronger functional differentiation between these systems in response to external stimulation predicted higher intellectual abilities during conscious cognition, in particular higher verbal acuity scores in independent cognitive testing battery. These convergent findings suggest that the responsivity of sensory and higher-order brain systems to external stimulation, especially through the diversification of their functional responses is an essential feature of conscious cognition and verbal intelligence.

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bioRxiv2018

Animacy and real world size shape object representations in the human medial temporal lobes

Identifying what an object is, and whether an object has been encountered before, is a crucial aspect of human behavior. Despite this importance, we do not have a complete understanding of the neural basis of these abilities. Investigations into the neural organization of human object representations have revealed category specific organization in the ventral visual stream in perceptual tasks. Interestingly, these categories fall within broader domains of organization, with distinctions between animate, inanimate large, and inanimate small objects. While there is some evidence for category specific effects in the medial temporal lobe (MTL), it is currently unclear whether domain level organization is also present across these structures. To this end, we used fMRI with a continuous recognition memory task. Stimuli were images of objects from several different categories, which were either animate or inanimate, or large or small within the inanimate domain. We employed representational similarity analysis (RSA) to test the hypothesis that object-evoked responses in MTL structures during recognition-memory judgments also show evidence for domain-level organization along both dimensions. Our data support this hypothesis. Specifically, object representations were shaped by either animacy, real-world size, or both, in perirhinal and parahippocampal cortex, as well as the hippocampus. While sensitivity to these dimensions differed when structures when probed individually, hinting at interesting links to functional differentiation, similarities in organization across MTL structures were more prominent overall. These results argue for continuity in the organization of object representations in the ventral visual stream and the MTL.

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bioRxiv2017

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months

ObjectiveFunctional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. Methods: This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants (n=65, included in final analyses: n=53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 minutes of fcMRI acquired during natural sleep at term-equivalent age.\n\nResultsDisruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course.\n\nConclusionfcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

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bioRxiv2017

Differences in the spatial and temporal patterns of head motion during MRI of adults and infants

AimHead motion has a profound effect on MRI, and will contaminate comparisons of function or structure between groups that move differently. This work compares adults and infants. Infants might move differently for physical, physiological and cognitive reasons, but so far these differences have not been quantified.\n\nMethodsThe spatial modes and total magnitude of motion in the MRI scanner were measured (N=211). The effects of group (infant vs. adult) and stimulation paradigm (auditory vs. visual) were evaluated.\n\nResultsSpatial modes of motion were found to be distinct between infant and adult groups. Infants had less anterior-posterior translational motion, but greater motion in other dimensions, often with complex multi-axis patterns. In magnitude distribution, sleeping infants often remained more still than adults, but when movement did occur it was more extreme and abrupt. Two groups of adults presented with different stimulation showed similar shapes of motion.\n\nConclusionThe spatial modes and magnitude distribution of motion differed substantially between groups, and must be considered carefully as a confound in comparisons of structure or function. The abruptness and magnitude of movement suggests that for infants relative to adults post-processing strategies such as de-noising are likely to be more effective than prospective motion correction.\n\nKey notesO_LIQuantified the spatial and temporal distribution of motion during MRI in 211 adults and neonates\nC_LIO_LIThe different spatial modes in adults and infants were visualized and statistically contrasted\nC_LIO_LIThe magnitude of motion had \"heavier tails\" in infants, with more still periods, and more large movements, than adults.\nC_LI

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bioRxiv2016

The neural basis of precise visual short-term memory for complex recognisable objects

Recent evidence suggests that visual short-term memory (VSTM) capacity estimated using simple objects, such as colours and oriented bars, may not generalise well to more naturalistic stimuli. More visual detail can be stored in VSTM when complex, recognisable objects are maintained compared to simple objects. It is not yet known if it is recognisability that enhances memory precision, nor whether maintenance of recognisable objects is achieved with the same network of brain regions supporting maintenance of simple objects.\n\nWe used a novel stimulus generation method to parametrically warp photographic images along a continuum, allowing separate estimation of the precision of memory representations and the number of items retained. The stimulus generation method was also designed to create unrecognisable, though perceptually matched, stimuli, to investigate the impact of recognisability on VSTM. We adapted the widely-used change detection and continuous report paradigms for use with complex, photographic images.\n\nAcross three functional magnetic resonance imaging (fMRI) experiments, we demonstrated greater precision for recognisable objects in VSTM compared to unrecognisable objects. This clear behavioural advantage was not the result of recruitment of additional brain regions, or of stronger mean activity within the core network. Representational similarity analysis revealed greater variability across item repetitions in the representations of recognisable, compared to unrecognisable complex objects. We therefore propose that a richer range of neural representations support VSTM for complex recognisable objects.

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