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Cortex

Elsevier BV

Preprints posted in the last 90 days, ranked by how well they match Cortex's content profile, based on 102 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Novel tool use does not depend on mechanical reasoning: evidence from apraxia

Du, Y.; Thibault, S.; Yates, J.; Buxbaum, L. J.; Krakauer, J. W.; Wong, A.

2026-05-18 neuroscience 10.64898/2026.05.14.724638 medRxiv
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A hallmark of human intelligence is the ability to use tools. Yet the cognitive processes supporting this ability remain debated. One contemporary view holds that mechanical reasoning is central for tool use, especially in the case of tools with which we have no prior experience. However, previous support for the role of mechanical reasoning often relies on circular logic, wherein poor performance on novel tool-use tasks is taken as evidence that impaired mechanical reasoning causes tool-use deficits in limb apraxia. To address this limitation, we independently assessed mechanical reasoning and novel tool use in separate tasks in individuals with limb apraxia, and compared their performance to individuals without apraxia. We also examined whether these two abilities are similarly associated with other cognitive abilities including motor imagery, mental rotation of non-body objects, general reasoning, and spatial working memory. Finally, we explored brain-behavior relationships using support vector regression lesion-symptom mapping. Our behavioral and imaging data together showed that mechanical reasoning does not underlie novel tool-use deficits in apraxia. Graphical analysis further revealed that novel tool use and mechanical reasoning loaded onto distinct latent clusters: novel tool use was strongly associated with other praxis abilities yet separable from cognitive abilities that require reasoning and mental simulation, whereas mechanical reasoning was primarily linked to other high-level reasoning abilities but not tool use. These findings challenge the notion that mechanical reasoning is central to tool-use ability, and instead suggest that tool use is more likely to be an intuitive or automatic process.

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Computer Vision Scoring of Figure Copy and Recall

Woods, D. L.; Hall, K.; Jaramillo, I.; Blank, M.; Geraci, K.; Boghassian, A.; Pebler, P.

2026-06-11 neurology 10.64898/2026.06.10.26355298 medRxiv
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Objective. Figure copy and recall tests are sensitive measures of visuoconstruction and visual episodic memory, but their clinical is constrained by labor-intensive manual scoring. We developed and validated an automated, element-level scoring pipeline using Vertex AI object detection for the tablet-based figure copy and recall tasks in the California Cognitive Assessment Battery (CCAB). The automated scoring pipeline duplicated the scoring procedures used by expert manual raters. Methods. A normative sample of 2,011 community-dwelling adults aged 18-90 completed figure copy and delayed recall trials at baseline, with subsamples retested at 1 day and at 6, 18, and 30 months. Participants completed the drawings with their index finger on a tablet computer with finger position digitized to analyze the speed and timing of individual drawing strokes A convolutional object-detection model trained on the Vertex AI AutoML Vision platform identified each of twelve canonical figure elements in rendered drawings. Separate element presence and location scores were computed after homographically warping drawings onto a canonical template to produce trial-level Element, Location, and Total scores. To compare Vertex and human scores, Vertex AI and expert human raters independently scored 1500 randomly selected drawings to evaluate inter-rater agreement, including a common subset of 100 drawings scored by Vertex AI and all raters. Results. Total scores were virtually indistinguishable (r = 0.966) from human-human agreement (mean r = 0.971) as were Element presence scores (mean r = 0.959 vs. r = 0.963). Location-score agreement (r = 0.951) was slightly below the human-human mean (r = 0.972) due to pixel-level analysis by Vertex AI that was impossible for human raters. The Vertex pipeline showed no preferential advantage for the single expert rater who categorized Elements during training. Automated scores showed strong demographic gradients, age effects on Recall (r = -0.32) were approximately twice those in Copy conditions (r = -0.16). A Memory Cost score (Recall - Copy) showed a monotonic age-related decline from +0.40 z in the youngest subjects to -0.54 z in the oldest. Kinetic analysis revealed that drawing speed and efficiency showed significant age-related changes. Overnight test-retest reliability was high (Recall r = 0.72) and the Recall trial showed a large overnight learning effect ({Delta} = +1.18) that continued with repeated tests up to 30 months ({Delta} = +0.75).

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Causes and consequences of unawareness (anosognosia) of tool-action errors after left-hemisphere stroke

Thibault, S.; Williamson, R.; Wong, A. L.; Buxbaum, L. J.

2026-04-02 neuroscience 10.64898/2026.03.31.715610 medRxiv
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Many individuals with limb apraxia after left-hemisphere stroke exhibit a lack of awareness of their tool-related action errors, i.e., unawareness of apraxia (UA; also called anosognosia of apraxia). Little is known about the prevalence of UA, the relationship between UA and apraxia severity, or its underlying mechanisms. Here, we assessed both the causes and consequences of UA. Based on a mechanistic model, we hypothesized that UA may arise because of deficits in representations signaling how tool-related movements should look and feel--a component of action knowledge--and that degradation of this knowledge impedes the detection of mismatches between planned and actual tool-related actions. We further predicted that a consequence of UA is a reduction in error-correction attempts. Fifty-six individuals with chronic LCVA gestured to show how to use tools. Immediately after the gesture production task, participants were asked if they made any errors. All participants also completed an action knowledge task to measure the integrity of tool-related movement goals. Individuals were denoted as exhibiting UA if they performed below a normative cutoff for apraxia yet reported making no errors. Our sample included 21 individuals with apraxia; of these, nearly half (48%) exhibited UA. These two groups made a comparable number of gesture errors and were of equivalent stroke severity, yet individuals with UA had significantly more impaired action knowledge. Additionally, individuals with UA were less likely to attempt to correct their errors compared to individuals who were aware of their apraxia. These data support the hypothesis that action knowledge (how tool actions look and feel) serves a key role in error detection and awareness of apraxia and may contribute to the difficulties with everyday tasks experienced by many people with apraxia.

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Rotating Letters in the Mind's Eye: Behavioral and electro-cortical associations with 3D Mental-Rotation Ability

Khan, R.; Bekiari, S.; Hierck, B.; Salvatori, D.; Kenemans, L.

2026-05-14 neuroscience 10.64898/2026.05.11.724360 medRxiv
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Mental rotation in 3D is a key cognitive skill involving dynamic spatial transformations, for which pronounced individual differences have been documented. Here we ask whether individual differences in 3D abilities can be explained by analogous differences in 2D abilities. 3D mental-rotation was assessed by the Vandenberg & Kruse Mental Rotation Test (3D-MRT) and examined for association with performance and underlying electrocortical mechanisms during a 2D letter rotation task. Participants (N=40) first completed the MRT and then performed a computerized 2-D letter rotation task in which they had to identify whether letters were oriented in a standard or a mirrored direction (parity judgment) when rotated at 0{degrees}, 60{degrees}, 120{degrees}, and 180{degrees} while EEG was recorded. Reaction times (RTs) and error rates increased with angular disparity. The angular disparity effect on RT was smaller for mirrored letters. Low, relative to high, 3D-MRT scoring participants showed more pronounced accuracy declines at higher rotation angles. An EEG Event Related Potential (ERP) known as the Rotation-Related Negativity (RRN) became more pronounced with increasing angular disparity. High 3D-MRT scores were associated with a stronger RRN response at central-parietal sites. In addition, the ERP-P3b wave was more pronounced at central-parietal sites for low 3D-MRT scorers, independent of angular disparity. It is concluded that 3D rotational ability is positively associated with 2D mental rotation performance, and more strongly with enhanced recruitment of neural visual-spatial cortical representations than with enhanced recruitment of more general cognitive resources.

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High-Frequency Activity for Language Mapping during Stereo-EEG: Comparison with Direct Cortical Stimulation

Sagar, P.; Hudson, M.; wittayacharoenpong, T.; Cockle, E.; Mcilroy, A.; Bunyamin, J.; Laing, J.; Gutman, M.; Hunn, M.; Kwan, P.; O'Brien, T. J.; Rayner, G.; Neal, A.

2026-05-04 neurology 10.64898/2026.04.30.26352093 medRxiv
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ObjectiveDirect cortical stimulation (DCS) is the gold standard for language mapping during SEEG but is prone to false negatives and false positives that may contribute to post-operative dysphasia or else overly conservative resections. Task-induced high-frequency activity (HFA, 30-200Hz) is an emerging functional biomarker that may augment DCS, but its clinical utility remains uncertain. We aimed to quantify HFAs diagnostic concordance with DCS, assessing its potential as both a surrogate marker and a screening tool. MethodsIn this single-centre prospective study, 23 adults undergoing SEEG completed language mapping with DCS and HFA. HFA was mapped using auditory and visual naming tasks (ANT/VNT), quantified via Morlet wavelet transforms with baseline-normalised z-scores. DCS-positive channels were those where 50Hz stimulation elicited language disruption. HFA distribution was examined independently of DCS. HFA-DCS concordance was assessed for individual and combined (ANT+VNT; maximal HFA across tasks) conditions at channel and sublobar levels across two thresholds: a specificity-optimized stringent threshold (Z>0.8) to examine HFA as a surrogate for DCS, and a sensitivity-optimized permissive threshold (Z>0.3) to evaluate its potential as a screening tool. ResultsTwelve (52%) participants were female, and 17 (74%) were MRI-negative. HFA patterns differed by task: VNT produced greater HFA magnitude in the dominant frontal lobe (p=0.0498), while ANT produced greater magnitude and activation rate in the non-dominant temporal lobe (p=0.015; p=0.0189), highest in the non-dominant superior temporal gyrus. In the combined condition, concordance with DCS was low at the stringent threshold (channel-wise sensitivity/specificity=0.24/0.88; region-wise=0.43/0.77). Sensitivity improved at the permissive threshold (channel-wise 0.56, NPV=0.96), with region-wise sensitivity of 0.75, specificity=0.45, and NPV=0.94. SignificanceRegion-level HFA at a permissive threshold is useful for identifying language-negative regions and prioritising DCS testing. Poor concordance at a stringent threshold suggests HFA and DCS index distinct functional properties and are not interchangeable. Anatomically plausible HFA localisation supports the need for further multimodal validation to clarify its role in presurgical mapping. Key PointsO_LIHFA and DCS show threshold- and scale-dependent diagnostic concordance for language mapping during SEEG C_LIO_LISensitivity-optimized sublobar HFA shows high negative predictive value and moderate sensitivity for DCS-positive language sites C_LIO_LIThese metrics support sublobar HFA as a screening tool to exclude non-eloquent regions and streamline DCS language mapping C_LIO_LISpecificity-optimized HFA concords poorly with DCS, indicating these markers index distinct properties and are not interchangeable C_LIO_LICombined HFA/DCS profiles may help stratify surgical risk: HFA-/DCS-regions as low risk, while HFA+/DCS+ sites denote high risk C_LI

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Minimally verbal children with autism may see the point, but do not (always) point to what they see:A behavioral and eye-tracking study in visual perceptual processing

Sykes-Haas, H. S.; Bonneh, Y. S.

2026-06-01 neuroscience 10.1101/2025.06.26.661808 medRxiv
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During typical development, non-social visual object recognition emerges in the first year of life, engaging low-level visual cues and higher-level mechanisms involving inference and prior knowledge. How these processes function in minimally verbal autism (mvASD) remains poorly understood. We studied children with mvASD (n=22, 6-11 years) using touchscreen-based oddball and contour-detection tasks targeting low-level stimuli (e.g. shape and orientation), and mid-level stimuli (e.g. illusory Kanizsa contours and 3D shapes). Pointing and eye-gaze responses were measured. Typically developing children (n=22, 6-12 years) served as a reference group. Accuracy and reaction-time profiles among mvASD participants were heterogeneous across experimental visual tasks and standardized developmental measures. All mvASD participants detected targets in the easiest condition, and approximately half succeeded across low-level tasks. Overall performance declined with increasing visual complexity, consistent with attenuated inference-based processing; communication ability and nonverbal reasoning together accounted for approximately 69% of between-participant variance in visual task performance. Critically, exploratory analyses suggested systematic perception-action dissociations rather than random error. First, the majority of participants who failed to point correctly (n=9) reliably fixated the correct target. Second, in the Kanizsa oddball task, nearly half of successful mvASD participants pointed to local inducers rather than the illusory figure center, unlike TDs. Third, more participants showed within-age-range nonverbal reasoning performance on Ravens colorful progressive matrices when responding by puzzle placement than by pointing. These converging findings challenge interpretations of mvASD performance as reflecting perceptual or cognitive capacity alone, suggesting visual signals may guide action selection differently in mvASD. Lay SummaryMinimally verbal children with autism showed individual differences in visual processing tasks. While developmental measures like communication ability and reasoning skills predicted most of the variation in performance, exploratory observations revealed an intriguing pattern: the same children sometimes succeeded when using their eyes to indicate answers but failed when pointing or performing better when placing puzzle pieces than pointing in a booklet to identical visual display. Several children who correctly detected illusory triangular shapes consistently touched the corner pieces rather than the triangle centers. These patterns suggest that performance depends not only on developmental and visual perceptual abilities, but also on how children are asked to respond. Parents and educators should consider: might a child who fails a pointing-based test succeed with a different response method?

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Distinct cortical regions support the coding of order across visual and auditory working memory

Vivion, M.; Mathy, F.; Guida, A.; Mondot, L.; Ramanoel, S.

2026-03-26 neuroscience 10.64898/2026.03.26.714445 medRxiv
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Spatialization in working memory refers to the spatial coding of non-spatial information along a mental horizontal line when encoding verbal material. This phenomenon is thought to support working memory by facilitating order encoding. Although it has been observed for both visually and auditorily presented stimuli, no direct comparison has yet examined whether these modalities rely on similar neural mechanisms. In this study, we investigated whether spatialization in visual and auditory modalities involves shared or distinct patterns of activity within the working-memory network. Forty-nine participants performed both a visual and an auditory working memory SPoARC task of the same verbal material, allowing to study the cortical patterns associated with distinct serial positions at both encoding and recognition across sensory modalities. Whole-brain analyses revealed similar frontoparietal networks across conditions. In addition, a representational similarity analysis (RSA) was conducted to assess the similarity of neural patterns between early and late serial positions in a sequence and across sensory modalities. This multivoxel pattern analysis revealed modality-dependent patterns distinguishing early and late positions in the inferior frontal gyrus. Additional modality-specific effects were observed in the anterior intraparietal sulcus in the visual modality and in the posterior hippocampus in the auditory modality. Drawing on the framework proposed by Bottini & Doeller (2020), we propose that order decoding in the IPS might reflect a low-dimensional spatial coding of order (e.g., along a horizontal axis), whereas order decoding in the hippocampus might reflect higher-dimensional spatial representations or temporal representations.

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The Effects of Learnability and Reward Responsiveness on Reward Processing

Oloriz, A.; Hassall, C. D.

2026-04-14 neuroscience 10.64898/2026.04.13.718323 medRxiv
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For methodological reasons, reward processing is commonly studied using random feedback and unlearnable tasks. It remains unclear whether task learnability influences reward-related brain activity, and whether this effect depends on individual differences such as reward responsiveness. We addressed this question by administering a behavioural activation system (BAS) scale before recording electroencephalography (EEG) while participants completed learnable and unlearnable versions of the "doors" task, a standard two-choice paradigm. Despite matched outcome likelihoods across conditions, participants reported greater motivation, enjoyment, and perceived performance in the learnable task. Contrary to our predictions, the amplitude of the reward positivity (RewP) - a frontocentral ERP index of reward processing - did not depend on task learnability and reward responsiveness. However, learnability and reward responsiveness effects became apparent when the analysis was restricted to high performers. Within this subgroup, participants low in reward responsiveness showed an enhanced RewP when the task was learnable. These findings suggest that contextual factors such as task learnability can interact with individual differences, informing ongoing efforts to identify the RewP as a biomarker of disordered reward processing.

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A discovery and replication study of dyslexia does not reveal reproducible gray matter volume differences

Schug, A. K.; Gutierrez-Schieferl, I. S.; Eden, G. F.

2026-05-07 neuroscience 10.64898/2026.05.05.722925 medRxiv
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Two decades of research have provided evidence for gray matter volume (GMV) differences in developmental dyslexia (or reading disability, RD) in the left perisylvian cortex. However, there are concerns about result inconsistencies, likely attributable to small sample sizes, lenient statistical thresholds, and insufficient accounting for demographic variables and global GMV (Ramus et al., 2018). To address these concerns, we conducted a Discovery and Replication Study (N=262) using data from the Adolescent Brain Cognitive Development Study. We found GMV differences between the RD and Control Groups did not replicate across the Discovery and Replication Studies using voxel-based morphometry (VBM) in Statistical Parametric Mapping (SPM), and that a more conservative threshold yielded far fewer results. We then conducted Reproducibility Studies and first found that when using surface-based morphometry in FreeSurfer instead of VBM, the Discovery and the Replication Study results again failed to converge. Second, we combined all groups in a factorial VBM/SPM analysis and the interaction analysis provided quantitative confirmation for diverging between-group difference results across the two studies. Third, we tested for the role of covariates of no interest and found that when total GMV is not controlled for, this divergence dissipates and group differences in RD (main effect of Reading Ability) are amplified. In conclusion, replication of GMV differences in RD is low, even when using large, well-matched groups, and analyses approaches play a modulating role. As such, results from prior studies using lenient statistical thresholds and not accounting for total GMV should therefore be viewed with caution.

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Beyond Neural Noise: Critical Dynamics Predict Slower Reaction Times in Adults With and Without ADHD

DallaVecchia, A.; Zink, N.; O'Connell, S. R.; Betts, S. S.; Noah, S.; Hillberg, A.; Oliva, M. T.; Reid, R. C.; Cohen, M. S.; Simpson, G. V.; Karalunas, S. L.; Calhoun, V. D.; Lenartowicz, A.

2026-03-17 neuroscience 10.64898/2026.03.13.711705 medRxiv
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Historically, neural variability observed during task was interpreted as "noise," assumed to obscure meaningful signal and thus something to be minimized both analytically by researchers and functionally by the brain. Changes to this signal-to-noise ratio have been proposed as a possible neural mechanism behind the increased reaction-time variability (RTV) in attention deficit hyperactivity disorder (ADHD). However, not all variability is the same - in some cases, variability can have some underlying "statistical structure" that can be beneficial to information processing. The challenge lies in distinguishing meaningful variability from random noise. The edge-of-synchrony critical point, which describes a system poised between synchronous and asynchronous regimes, could be a good theoretical framework to study these different types of neural variability. In this study, we investigate whether changes in criticality and oscillatory dynamics preceded slower behavioral responses during a bimodal continuous performance task in ADHD. We find evidence that, prior to slower responses, neural dynamics shift toward criticality in both ADHD and control groups, suggesting that increase variability in ADHD and during attention lapses are related to structured variability and not necessarily random noise. Notably, these findings run counter predictions based on the proposed model and previous literature on neural noise in this population, challenging predictions of edge-of-synchrony criticality as a unifying account of neural variability and behavioral performance. Furthermore, this effect did not emerge at the between-subject level, underscoring the limitations of relying on between-subject correlations to infer neural mechanisms. Impact StatementOur findings add new perspective to the hypothesis that links neural variability to reaction time variability in adults with and without ADHD. We found that neural dynamics shift towards criticality prior to slow reaction times in adults with and without ADHD, but in ADHD, dynamics lie closer to criticality regardless of response type, suggesting a different "attractor" state.

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Theory of mind predicts conversational success in early right hemisphere stroke recovery

Suazo, A.; Blake, M. L.; Schnur, T.

2026-04-27 neuroscience 10.64898/2026.04.23.720418 medRxiv
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Those living with right hemisphere damage (RHD) often struggle with engaging in aspects of conversation that require understanding what a speaker means. There is growing evidence that conversation relies on deducing the speakers perspective, an ability known as theory of mind (ToM). However, whether conversation deficits after RHD relate to ToM deficits is unknown. Here, we related individual differences in conversational success to ToM in 33 speakers during the early stages of RHD (median 5 days post-stroke) in comparison to 16 age- and education-matched controls. We measured conversational success as the number of differences identified between two images while participants conversed with study coordinators. A non-verbal false belief task measured ToM abilities.1 Baseline cognitive tasks assessed visual inattention, inhibitory control/visual selective attention and working memory. Mixed-effects linear modeling revealed that the ToM ability to explicitly infer others perspectives while managing conflict with ones own was the most significant predictor of conversational success ({beta} = 0.51, p = .02). Results were independent of demographic factors, conversation partner and baseline cognitive abilities. These findings provide the first empirical evidence in unilateral RHD that the ability to reason about a partners knowledge and manage conflict with ones privileged perspective is critical for successful conversation. Results support theoretical models of ToM as a cognitive basis for everyday conversation. The clinical implications underscore the importance of socio-cognitive screening and ToM-based interventions to enhance communication outcomes in stroke rehabilitation.

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Neural mechanisms of handedness for precision drawing: hand-dependent engagement of cortical networks for bimanual control and tool use

Kapil, N.; Kim, T.; Gassass, S.; Zhou, R.; Carter, A. R.; Dobbins, I. G.; Liu, L.; McAvoy, M. P.; Wheelock, M. D.; Wang, Y.; Brogan, D. M.; Dy, C. J.; Susan, M. E.; Philip, B. A.

2026-03-16 neuroscience 10.1101/2025.11.18.689091 medRxiv
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Neural mechanisms underlying handedness remain poorly understood. We used functional magnetic resonance imaging (fMRI) to study performance of a visually guided drawing task with each hand. We hypothesized that the left superior parietal lobule supports drawing with either hand, and individuals with chroninc peripheral nerve injury (PNI) to the dominant hand use the same mechanism as healthy adults. Methods33 right-handed adults (23 healthy, 10 patients) underwent fMRI while performing a precision drawing task, alternating between the right hand (RH) and left hand (LH). 20 regions of interest (12 a priori and 8 post-hoc) were examined for LH>RH effects on BOLD magnitude and on functional connectivity (FC) modulation via generalized psychophysiological interaction. ResultsDuring LH drawing, contralateral primary motor cortex (M1) had lower magnitude, and greater FC with two networks of equal-or-greater magnitude: left M1-dorsal premotor, and intrahemispheric parieto-temporal network. Contralateral M1 also had reduced interhemispheric FC with inferior parietal lobule, which exhibited lower magnitude. Patient group did not interact with these effects. ConclusionsThree neural mechanisms differentiate LH from RH drawing. First, a left hemisphere bimanual control network engages intrahemispherically (directly) during RH drawing and interhemispherically (indirectly) during LH drawing. Second, LH drawing increases engagement of a contralateral network that may reflect increased task demands. Third, RH drawing increases engagement of an interhemispheric tool use network. The first and third networks may explain the dominant hands performance advantages. PNI patients use the same mechanisms, highlighting their potential as a neuromodulatory target to enhance LH performance after RH impairment.

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Perceived vs. actual navigation ability: Differences between autistic and typically developing children

McKeown, D. J.; Cruzado, O. S.; Colombo, G.; Angus, D. J.; Schinazi, V. R.

2026-04-13 psychiatry and clinical psychology 10.64898/2026.04.09.26350542 medRxiv
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PurposeNavigational ability develops throughout childhood alongside the maturation of brain regions supporting egocentric and allocentric processing. In Autism Spectrum Disorder (ASD), atypical hippocampal development may impact flexible spatial memory; however, findings on navigational ability in autistic children remain inconsistent. This study aimed to compare both objective and perceived navigation ability in children with ASD and typically developing (TD) peers. MethodTwenty-six children with high-functioning ASD and twenty-five age- and gender-matched TD children (M_age = 12.04 years, SD = 1.64) completed a battery of navigational tasks from the Spatial Performance Assessment for Cognitive Evaluation (SPACE), including Path Integration, Egocentric Pointing, Mapping, Associative Memory, and Perspective Taking. Perceived navigation ability was assessed using the Santa Barbara Sense of Direction (SBSOD) scale. ResultsNo significant group differences were observed across any objective navigation tasks. However, children with ASD reported significantly lower perceived navigation ability compared to TD peers. ConclusionThese findings suggest a dissociation between perceived and actual navigational ability in ASD. By early adolescence, objective navigation performance appears intact, potentially reflecting sufficient maturation of underlying neural systems or the presence of compensatory mechanisms. The results underscore the importance of incorporating objective, task-based measures when assessing cognitive abilities in autistic populations.

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Obsessive-compulsive disorder and abstract sequence task contributions shift prefrontal cortical connectivity

Hyde, H.; McLaughlin, N. C. R.; Garnaat, S. L.; Desrochers, T. M.

2026-05-23 neuroscience 10.64898/2026.05.22.727273 medRxiv
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Obsessive-compulsive disorder (OCD) is characterized, in part, by repetitive, sequential behaviors, such as cleaning rituals, yet underlying neural circuitry related to abstract sequencing in OCD remains poorly understood. Prior work has implicated a set of cortical regions activated during abstract sequences, which are defined by rules rather than specific stimulus features (Desrochers et al., 2022). These regions include the rostrolateral prefrontal cortex (RLPFC) that is necessary for performance on abstract sequence tasks (Desrochers et al., 2015), as well as the anterior cingulate cortex/dorsolateral prefrontal cortex (ACC/DLPFC), supplementary motor area (SMA), middle temporal gyrus (MTG), and temporo-occipital junction (TOJ) that are differentially activated in OCD compared to healthy participants during abstract sequencing (Doyle et al., 2026). It remains unclear, however, whether these regions form a coordinated circuit, and how their interactions may differ in OCD. In the present study, we examined task based functional and effective connectivity among these regions using a previously published dataset. We tested hypotheses that connectivity within this circuit would be altered in OCD relative to healthy controls (HCs), and that prefrontal regions (ACC/DLPFC and RLPFC) would direct information to downstream regions (SMA, MTG, and TOJ) during a sequential task. We found that connectivity within this circuit differed significantly between groups. HCs exhibited less negative connectivity from the ACC/DLPFC to the TOJ and stronger positive coupling between the MTG and TOJ, as well as stronger coordination between the RLPFC and DLPFC, suggesting coordinated prefrontal control. In contrast, individuals with OCD showed increased connectivity between the RLPFC and MTG, indicating a more direct influence of RLPFC on posterior regions. Effective connectivity analyses further indicated that, across participants, the ACC/DLPFC and MTG function as central hubs of information flow, with task-related inputs entering the circuit via the TOJ, propagating through the MTG to the RLPFC, and subsequently modulating ACC/DLPFC and downstream regions. These findings suggest a shared underlying circuit architecture in OCD and healthy participants despite differences in functional coupling, particularly involving prefrontal cortical regions. Overall, differences arise at the level of functional coordination within a preserved circuit for abstract sequential processing in OCD, adding to current neurobiological models of OCD and suggesting a novel circuit that supports abstract sequencing.

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Altered Saccades, Pupil, and Blink Responses in Functional Motor Disorder: Insight into Neurobiological Mechanisms

Sutorova, K.; Riek, H. C.; Pitigoi, I. C.; Brien, D. C.; Krupkova, B.; Novakova, L.; Sieger, T.; Munoz, D. P.; Serranova, T.

2026-03-26 neurology 10.64898/2026.03.24.26349168 medRxiv
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BackgroundFunctional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye-tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink and pupil responses in FMD and healthy controls performing an interleaved pro-/anti-saccade task, and to investigate the relationships between oculomotor measures and motor and non-motor symptom severity. MethodsWe conducted video-based eye-tracking in 104 patients with clinically definite FMD and 115 age- and sex-matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain-related, dissociative, non-motor somatic symptoms. Clinician-rated motor severity and centrally acting medication was recorded in FMD patients. ResultsCompared to controls, FMD patients showed increased anti-saccade error rates (p < 0.001), anticipatory saccades (p [&le;] 0.003), altered blink distribution (p < 0.001), and reduced pupil dilation velocity (p < 0.001). However, reduced pupil dilation velocity was not significant in subsample of unmedicated patients. Higher anti-saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non-motor somatic symptom burden, and motor severity (all p < 0.05). ConclusionsWe hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD. WHAT IS ALREADY KNOWN ON THIS TOPICFMD is increasingly interpreted through predictive coding models suggesting abnormalities in predictions about motor and sensory states driven by abnormally focused attention. Yet the underlying neurobiology remains poorly defined. Empirical studies directly probing basic predictive processes in FMD are scarce, and implicit cognitive-motor interactions, particularly those involving motor learning and adaptation, have been insufficiently explored. WHAT THIS STUDY ADDSOnly two previous studies have used eye-tracking in FMD, focusing mainly on diagnostic saccadic markers. Using time-series analyses of saccadic, blink, and pupillary data, we show abnormalities in inhibitory control, predictive processing, and implicit learning. Due to strong homology between human and primate neurophysiology and neuroimaging findings in oculomotor control, the findings can be linked to dysfunction within cortico-basal ganglia circuits. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYOculomotor abnormalities correlated with motor and non-motor symptom severity, indicating mechanistic relevance. The findings provide empirical support for predictive coding accounts and point to involvement of subcortical structures including projections from the frontal cortex to the basal ganglia. This highlights the value of studying cortico-basal ganglia circuits with implications for treatment and of developing oculomotor measures as potential biomarkers in FMD.

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Naming Performance in Bilinguals with Alzheimer's Disease and Mild Cognitive Impairment

Sainz-Pardo, M.; Hernandez, M.; Suades, A.; Juncadella, M.; Ortiz-Gil, J.; Ugas, L.; Sala, I.; Lleo, A.; Calabria, M.

2026-03-25 neurology 10.64898/2026.03.23.26349075 medRxiv
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Introduction. There is consistent evidence of a disadvantage in bilinguals' speech production compared to monolinguals in healthy individuals, but studies investigating this phenomenon in clinical populations such as Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) are scarce. Given that both clinical groups are characterized by wordfinding difficulties, understanding how bilingualism influences speech production in these populations is essential. Methods. Early and highly proficient Catalan-Spanish bilinguals (active bilinguals) were compared to Spanish-dominant speakers with low proficiency in Catalan (passive bilinguals) using a picture-naming task. The study included 58 older adults, 66 patients with AD, and 124 individuals with MCI. Reaction times, accuracy, and error types were collected in the naming task in each individual's dominant language. Results. First, active bilinguals demonstrated faster naming latencies than passive bilinguals, particularly for low-frequency words. Second, active bilinguals with MCI exhibited more naming errors than passive bilinguals with MCI, including a higher incidence of crosslanguage intrusions and anomia. Third, passive bilinguals with MCI and AD showed more semantic errors than active bilinguals. Discussion. These findings underscore the impact of second language use on naming performance in MCI and AD. Moreover, they provide insight into the potential mechanisms underlying lexical retrieval differences in bilinguals, including lexico-semantic processing and language control.

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Meaning for reading pseudowords: errors reveal semantic influences on pseudoword reading after stroke

Staples, R.; Anderson, E. J.; Dyslin, S. M.; Laks, A. B.; DeMarco, A. T.; Turkeltaub, P.

2026-05-15 neuroscience 10.64898/2026.05.13.724881 medRxiv
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Impaired reading, i.e., alexia, is common after left hemisphere stroke. The most common deficit in alexia is a difficulty reading aloud pronounceable novel words, also called pseudowords. While semantic and phonological processes both subserve reading real words, pseudoword reading deficits in alexia are typically ascribed to phonological deficits alone. Some theories, however, suggest that pseudoword reading relies in part on lexical-semantic knowledge, such that semantic deficits could also contribute to poor pseudoword reading in alexia. Leveraging a large sample of left-hemisphere stroke survivors, we examine the cognitive and neural substrates of pseudoword reading accuracy and two error types: lexicalization errors, where a pseudoword is incorrectly read as a real word, and nonword errors, where a pseudoword is read as an incorrect nonword. 76 left-hemisphere stroke survivors read 60 pseudowords aloud, and performed two pseudoword repetition tasks to assess phonological processing and two picture naming tasks to assess mappings between lexical semantics and phonology. Regression models assessed how pseudoword repetition and naming related to overall accuracy and rates of lexicalization and nonword errors in pseudoword reading. Voxel-based and connectome lesion-symptom mapping localized the neural territory responsible for these errors. Both pseudoword repetition and naming independently related to pseudoword reading accuracy. Pseudoword repetition but not naming deficits predicted higher rates of lexicalization errors, while naming but not pseudoword repetition deficits predicted higher rates of nonword errors. Greater nonword error rate also predicted smaller imageability effects in real word reading (t(71)=-3.2, p=0.002). Lexicalization errors were associated with lesions to and disconnections of the left putamen and basal ganglia. Nonword errors were associated with lesions to the superior and middle temporal gyri, as well as broad temporo-parietal disconnections, overlapping with previous lesion-mapping results implicating these regions in semantic contributions to word reading. These results suggest that lexicalization errors result from impaired planning and execution of novel motor plans, causing a reliance on the well-learned motor plans associated with lexical items. In contrast, greater rates of nonword errors, relative to lexicalization errors, occur when semantic contributions to reading are impaired. Overall, these findings demonstrate that semantic processes are involved in reading pseudowords, at least in stroke alexia. These findings support connectionist accounts of reading in which damage in the direct orthography to phonology route for reading leads to reliance on semantic representations, even for pseudowords, suggesting a reinterpretation of pseudoword reading as a pure measure of phonological reading deficits.

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Causal dependencies between frontal and temporal lobe regions underlying word search and retrieval

Winzer, B.; Burns, W.; Chikoti, R.; Strawderman, E.; Meyers, S. P.; Walter, K. A.; Pilcher, W. H.; Tivarus, M. E.; Mahon, B. Z.; Garcea, F. E.

2026-05-22 neuroscience 10.64898/2026.05.20.726706 medRxiv
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Verbal fluency is a behavioral task that requires the generation of words from a semantic category (category fluency) or words beginning with a specific letter (letter fluency). Although word production engages a frontal-temporal-parietal network, no studies have tested how lesions to temporal and parietal lobe areas that represent semantic and phonological knowledge dampen neural responses in the left pars triangularis and the left pars opercularis, two adjacent regions in the left inferior frontal gyrus implicated in word search and retrieval. Here, 52 patients with temporal lobe lesions underwent clinical functional MRI while performing the category and letter fluency tasks. We investigated where lesion presence was inversely related to the magnitude of task-specific neural responses in pars triangularis and pars opercularis using a technique referred to as voxel-based lesion activity mapping (VLAM). We found that lesions to the left anterior superior temporal gyrus, left temporal pole, left hippocampus, left insula, and underlying inferior fronto-occipital fasciculus were associated with reduced neural responses in the left pars triangularis during the category fluency task. Lesion damage to the right hippocampus was associated with reduced neural responses in the left pars opercularis during category fluency. By contrast, lesions to the left posterior superior temporal gyrus, left supramarginal gyrus, left parietal operculum, and the inferior fronto-occipital fasciculus and left arcuate fasciculus were associated with reduced neural responses in the left pars triangularis and the left pars opercularis during the letter fluency task. These results suggest that anatomically dissociable brain networks interact with the left inferior frontal gyrus when different search strategies constrain the retrieval of word representations.

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Iconic Sound-Shape Correspondences in Aphasia

Dorsi, J.; Sandberg, C.; Lacey, S.; Nygaard, L.; Sathian, K.

2026-05-19 neuroscience 10.64898/2026.05.18.725976 medRxiv
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PurposeTo examine speech iconicity for shape in aphasia, we compared iconicity ratings from people with aphasia to those from neurologically intact individuals and evaluated how iconicity relates to phonological and semantic processing profiles in aphasia. MethodEleven people with aphasia and 11 age- and gender-matched neurologically intact participants rated how rounded or pointed 50 auditory pseudowords sounded using a 5-point scale. Ratings from participants with aphasia were compared to predicted iconicity ratings derived from reference ratings from prior work and to ratings from neurologically intact participants. For each participant with aphasia, correlations between individual ratings and predicted ratings were related to measures of phonological and semantic processing. ResultsRatings from people with aphasia were significantly correlated with both the predicted ratings and the ratings from neurologically intact participants. The strength of the correlation between individual ratings and predicted ratings did not differ significantly between groups, although there was a trend toward weaker correlations in the aphasia group. There were indications that greater language impairment was associated with greater disruption of iconicity ratings; in particular, deficits in phonological segmentation and semantic processing were associated with reduced sensitivity to shape iconicity. ConclusionThese findings suggest that sensitivity to shape iconicity is preserved in individuals with aphasia to varying degrees. The specific nature of language impairment appears to play an important role in determining iconicity processing in aphasia.

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Inhibition in motion: Test-retest reliability of inhibitory kinematics in a go/no-go mouse tracking task

Mahesan, D.; Sharma, K.; Weinerth, M. K.; Dhaka, S.; Meinzer, M.; Fischer, R.

2026-05-09 neuroscience 10.64898/2026.05.06.722889 medRxiv
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Response inhibition, the ability to suppress contextually inappropriate actions, is a cornerstone of cognitive control and is commonly assessed using paradigms such as the go/no-go task. However, traditional go/no-go paradigms rely on binary outcomes such as commission errors, which offer limited insight into the dynamic, graded behavioral adjustments underlying successful stopping. The present study developed a novel mouse-tracking go/no-go paradigm with a dynamic start to capture inhibitory processes during ongoing execution. Twenty-three healthy young adults completed the task in two sessions separated by approximately one week to evaluate the test-retest reliability of standard behavioral measures (error rates and reaction times), and three kinematic features: path length, mean velocity, and mean acceleration. Results revealed robust differences between go and no-go trials across all measures. Successful inhibition was characterized by significantly shorter path lengths and reduced mean velocity and acceleration compared to go trials. Critically, all measures demonstrated moderate-to-good test-retest reliability across sessions, with intraclass correlation coefficients ranging from .75 to .85 for go trials and from .59 to .83 for no-go trials. These findings establish construct validity and psychometric reliability of the current mouse-tracking go/no-go paradigm. The demonstrated stability of these measures provides the methodological foundation for their use in cross-sectional, longitudinal, and intervention research targeting inhibitory control.