Cortex

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.

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).

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.

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?

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.

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.

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.

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.

IntroductionUnderstanding the spatiotemporal distribution of cortical activation during language production is a central question in cognitive neuroscience with broad clinical applications. High spatial/temporal resolution recording over multiple brain regions and specific psycholinguistic manipulations with testable behavioral predictions are necessary to separate neural variance attributable to processing stages. ObjectiveWe combine a delayed naming paradigm with intracranial electrophysiology to identify spatiotemporally dissociated cortical networks supporting stages of speech production. MethodsSubjects (20 healthy, 15 intracranial electrophysiology) are presented visual stimuli to name but are instructed to delay response until a go cue at 0/400/1000ms. Exploiting the temporal variance induced by delay, we calculate stimulus/response-locked correlation of high gamma (70-200Hz) activity at each contact. We compare shifts in stimulus-response correlation space to response time (RT) to validate separation of networks. ResultsBehaviorally, the factor delay modulated the effect of lexical selection on RT (p=0.021) but did not modulate the effect of phonological planning (p=0.4), confirming the paradigm separates processing stages. Stimulus-response correlation analyses revealed globally-invariant structure across subjects. Certain regions showed strong stimulus-locking (occipital lobe) or response-locking (motor cortex), but most regions were intermediate. Shifts in correlation space identified dissociated networks that predicted substantial variance in RT from lexical selection (R2=0.64) and phonological density (R2=0.75). Using a leave-one-subject-out cross validation approach, these shifts explained 31.4% of variance in RT at the trial level. ConclusionStimulus-response correlation space reveals stable spatiotemporal signatures of psycholinguistic processing that generalize across individuals. This approach permits hyperalignment of neurophysiological data and functional separation of cortical networks in speech production across subjects.

Flow, as defined by Mihalyi Csikszentmihalyi (1975), is a holistic sensation experienced when individuals are fully immersed in an activity, resulting in a mental state characterized by a diminished sense of self and altered perception of time. To investigate the global neural dynamics underlying flow, we employed EEG microstate analysis to capture the spatial and temporal properties of dominant transient global brain states (Lehmann et al., 1998). In a study involving 43 participants playing the video game Thumper for 25 minutes, we extracted three four-minute EEG segments from each session corresponding to reported experiences of flow, boredom, and frustration, as determined by self-reports and performance metrics. Across conditions, six distinct microstate topographies (A-F) accounted for most of the global variance. Given that reduced self-referential processing is a key feature of flow, we hypothesized that flow would modulate the properties of microstates C and E, which have been associated with brain regions resembling the default mode network (DMN). Compared to boredom and frustration, the flow condition showed significantly decreased global explained variance, mean duration, time coverage, and occurrence frequency of microstate E, as well as reduced mean duration and time coverage of microstate C. These findings suggest that microstates associated with self-referential processing are shorter and less frequent during flow than during boredom and frustration. This supports the notion that the flow experience modulates global brain dynamics, particularly within the DMN. Furthermore, our results align with previous research reporting reduced DMN activity during meditative and psychedelic states, reinforcing the idea of diminished self-awareness in such conditions.

High intra-individual reaction time variability (RTV) is traditionally viewed through a deficit perspective and interpreted as a maladaptive signature of attentional lapses, cognitive inefficiency, and systemic noise. However, theories from motor learning and the competitive neurocognitive networks framework suggest that behavioral variability and reduced top-down control might actually facilitate certain forms of implicit skill acquisition. The present study addresses the apparent conflict between these perspectives by investigating whether elevated RTV serves as an adaptive, functional precursor to implicit statistical learning. Across two independent studies, participants completed the Alternating Serial Reaction Time (ASRT) task. We quantified early RTV during the initial task phase using multiple metrics -- coefficient of variation, inter-trial RTV, and ex-Gaussian parameters Sigma and Tau-- to predict subsequent statistical learning. Analyses controlled for baseline response speed and early learning artifacts, and test-retest reliability measures were also evaluated. Our results show that early RTV predicted later statistical learning measured via reaction times. This predictive relationship was most consistent for metrics capturing dynamic, moment-to-moment fluctuations (inter-trial RTV and Sigma) rather than extreme attentional lapses (Tau). While the effect size was relatively small, the association remained significant after controlling for potential statistical confounds. Furthermore, early RTV demonstrated strong test-retest stability. These findings challenge the exclusively deficit-oriented perspective on behavioral noise. Instead, we propose that elevated RTV may reflect an adaptive, exploratory processing tendency, analogous to kinematic exploration in motor learning, that could support the brains ability to implicitly extract and model probabilistic environmental regularities.

BackgroundTheta-frequency transcranial alternating current stimulation (tACS) over prefrontal cortex has been proposed to modulate working memory (WM), yet behavioral effects are often inconsistent. One potential source of variability is the tACS phase during stimulus presentation. ObjectiveWe tested whether behavioral performance during WM depends on the phase of prefrontal theta-tACS. MethodsTwenty participants completed two sessions of prefrontal 4 Hz tACS in a within-subject design, receiving active and sham stimulation in separate sessions. Participants performed a visuospatial change detection task (CDT) and a verbal N-back task. Stimulation effects on overall accuracy and reaction time were analyzed. Subsequently, phase-specific analyses related stimulation phase at task-relevant stimulus presentation to behavioral performance using circular regression models. Preferred phases across participants were tested using Rayleigh tests. ResultsNo significant overall effects of active compared with sham tACS on accuracy or reaction time were observed in either task. However, phase-specific analyses revealed stronger phase-dependent modulation of reaction time during active tACS compared with sham. In the CDT, this effect was present across difficulty levels, whereas in the N-back task it was observed only in the 3-back condition. No reliable phase-dependent effects were observed for accuracy. Preferred phases varied across participants and did not cluster around a common phase. ConclusionsPrefrontal theta-tACS can modulate WM performance in a phase-dependent manner even in the absence of average behavioral effects. The observation of phase-dependent reaction-time modulation across visuospatial and verbal WM tasks suggests that stimulation phase may be a relevant source of variability across cognitive domains.

Incomplete letter recognition tasks are frequently used to detect visual deficits arising from neurodegenerative syndromes, including Posterior Cortical Atrophy (PCA; visual-variant Alzheimers disease). A recent development of this approach is the Graded Incomplete Letters Test (GILT), which measures recognition thresholds for letters degraded by removing pixelated sections (decreasing completeness). Although GILT thresholds are strongly elevated in PCA relative to typical adults, the precise cortical visual impairments underlying these deficits are unclear, as is the potential contribution from age-related optical limitations. We compared candidate cortical factors (crowding and global integration) with optical limitations (blur and low contrast) by simulating these factors in typical adults (n=6) viewing incomplete letter stimuli. Participants identified foveally presented letters (12 alternatives), with completeness varied using QUEST. At baseline, thresholds averaged [~]5% completeness. Optical factors were simulated by separately applying blur and lowered contrast. These factors had minimal effect on thresholds, except where blur/contrast levels approached visibility limits, where thresholds rose modestly but remained far below clinical levels in PCA. Cortical factors were simulated by increasing crowding (disruptions from clutter) through peripheral presentation, with global-integration impairments simulated by varying pixel size to alter the distribution of degradation (limiting spatial integration) or degrading letters dynamically with limited-lifetime pixels (limiting temporal integration). These manipulations substantially elevated thresholds, with combined crowding and global-integration impairments increasing thresholds to levels comparable with PCA. We conclude that impaired incomplete letter recognition is driven primarily by cortical rather than optical factors, and that neurodegenerative deficits may reflect the combined impact of multiple cortical limitations.

Background: Anomia is common in frontotemporal dementia (FTD), although its clinical prominence varies by subtype, with the most marked impairment typically observed in primary progressive aphasia (PPA). It remains unclear whether naming impairment reflects language-specific impairment or broader cognitive severity, and how it relates to other cognitive domains across FTD syndromes. Methods: Fifteen healthy controls and twenty-two individuals across the FTD spectrum, including variant-specified and unclassifiable (NOS) presentations, completed two confrontation naming tasks (Boston Naming Test and Multilingual Naming Test) and a global cognitive screening measure (Montreal Cognitive Assessment, MoCA). Patient participants additionally completed a standardized language battery (Western Aphasia Battery Revised) and a comprehensive neuropsychological assessment (Uniform Data Set). Naming performance was compared between groups and associations with language severity, global cognition, and domain-specific cognitive functions were examined using regression analyses. Results: Naming was impaired in patients relative to healthy controls but did not differ between patient groups. Naming was strongly associated with language severity, but not global cognition. A significant group-by-MoCA interaction indicated that MoCA was positively associated with naming only in the unclassifiable group. In addition, naming was associated with episodic memory across both verbal and non-verbal domains. Conclusions: Naming in FTD primarily reflects language severity rather than global cognitive impairment. A robust association between naming and episodic memory suggests potential contributions from semantic cognition, shared frontally mediated retrieval processes, or parallel cognitive decline. These findings support the use of naming as a marker of language dysfunction while highlighting its relevance to broader cognitive systems in FTD.

I ntroduction: Prospective memory (PM) deficits in children with attention-deficit/hyperactivity disorder (ADHD) significantly impact academic and daily functioning. Through two experiments, this study investigated how cognitive load and encoding strategies modulate PM performance. Methods: Experiment 1 included 43 children (21 ADHD, 22 typically developing) who completed an n-back task under high and low cognitive load. Experiment 2 included 44 children with ADHD who were randomly assigned to either a standard encoding group or an implementation intention encoding group, also completing the n-back task under both load conditions. Results: Experiment 1 showed that children with ADHD had significantly lower PM accuracy than typically developing peers. Signal detection analysis revealed that this deficit stemmed from a more conservative response bias rather than impaired perceptual sensitivity. Unexpectedly, PM accuracy and perceptual sensitivity were higher under high cognitive load than low load for both groups. Experiment 2 demonstrated that implementation intention encoding significantly enhanced PM accuracy and perceptual sensitivity in children with ADHD, with stable effects across load conditions and no interference with ongoing task performance. Discussion: These findings indicate that PM deficits in children with ADHD reflect a conservative response strategy rather than an inability to detect target cues. Implementation intention encoding provides an effective, load-independent cognitive strategy for enhancing PM performance. These results offer novel insights into the cognitive mechanisms underlying PM deficits in ADHD and provide evidence-based guidance for targeted interventions.

It has been proposed that bilinguals have better executive function (EF) arising from the constant selection of one language while inhibiting the other, and gray matter has been found to differ in bilinguals in regions linked to EF (frontal-parietal and subcortical structures). Attention Deficit Hyperactivity Disorder (ADHD) is associated with poorer EF and neuroanatomical differences underlying EF. Given the EF advantage in bilinguals, we investigated whether a bilingual experience affects EF performance and brain structure differentially in those with ADHD. Using the Adolescent Brain and Cognitive Development Study, we compared early Spanish-English bilinguals and English-speaking monolinguals with and without ADHD. ANOVAs for the Flanker, Working Memory, and Card Sort Tasks revealed no main effects of Language Experience (Bilingual versus Monolingual), a main effect of Diagnostic Group for Card Sort (ADHD worse than Controls), and no interaction effects on performance for any task. ANOVAs for gray matter volume (GMV) revealed a main effect of Language Experience in many regions, a main effect of Diagnostic Group in some regions, but no interactions. GMV in left thalamus was affected by both ADHD and bilingualism, but the effect of ADHD was not significantly diminished or enhanced by the dual-language experience. For cortical thickness, there was a main effect of Language Experience in several regions, no main effect of Diagnostic Group, and no interactions. Taken together, bilingualism has some impact on EF performance, a strong impact on neuroanatomy, but there was no disproportionate impact by bilingualism on the differences caused by ADHD for any measure. Research HighlightsExecutive function and brain structure differ in ADHD and in bilinguals, prompting the need to investigate interactive effects. Bilingualism did not disproportionately affect performance differences in ADHD for executive function, nor for gray matter volume or for cortical thickness differences in ADHD. Gray matter volume was less in ADHD than non-ADHD, as well as greater in bilinguals than monolinguals in the left thalamus, but without interaction effect. These independent effects indicate that the brain basis of ADHD is not impacted by a dual-language experience.

Prior studies in bilinguals have reported relationships between brain structure and the dimensions of (i) language proficiency or (ii) language balance (the discrepancy between a bilinguals two proficiencies), but rarely both, even though they are highly related. These studies were often conducted in late bilinguals and the analyses limited to regions of interest. Here, we tested for relationships between brain structure and these two dimensions in 46 early cultural Spanish-English bilinguals (mean age = 16.7 years) at the level of the whole brain for gray matter volume (GMV) and cortical thickness (CT). Results revealed a positive association between GMV and proficiency in the weaker language in the right angular gyrus (AG; BA 39) extending into the superior temporal gyrus (BA 22). More balanced bilingualism was also associated with more GMV in the AG (BA 39), in addition to less GMV in left postcentral gyrus (BA 1), right cerebellum lobule IX and right superior occipital gyrus (BA 18). However, these relationships between GMV and balance disappeared after controlling for language proficiency. No significant associations were observed for CT and these two dimensions of language. Our findings suggest that relationships between GMV and balance are driven by language proficiency, and that the relationship between GMV and language proficiency likely does not involve language-specific mechanisms, given the location of the association is in the right inferior parietal cortex. Together, this study separates the neuroanatomical bases of these two language dimensions and places them in brain regions outside those usually targeted in prior studies. HighlightsO_LINeuroanatomy was correlated with proficiencies in early Spanish-English bilinguals C_LIO_LIRight angular gyrus gray matter volume (GMV) was positively related to proficiency C_LIO_LIGMV was positively related to balance, but not after controlling for proficiency C_LIO_LIRelations with these language dimensions are located outside of language cortex C_LIO_LINo significant associations were observed for cortical thickness C_LI

Background: Obsessive-compulsive disorder (OCD) is characterized by disturbing thoughts (obsessions) that initiate anxiety-reducing thoughts or behaviors (compulsions). For patients with treatment-resistant OCD (tr-OCD), neuromodulation techniques, like capsulotomy (a lesion in the anterior limb of the internal capsule) and deep brain stimulation (DBS), have emerged as interventions that likely regulate connectivity between the prefrontal cortex (PFC) and subcortical targets. Three patients (Cap-DBS1-3) underwent a failed capsulotomy followed by successful DBS. Here, we aimed to understand the brain connections disrupted by failed capsulotomy vs modulated by successful DBS. Methods: We used diffusion-weighted magnetic resonance imaging (dMRI) tractography in a control cohort with tr-OCD (n=12) and in two of the Cap-DBS patients themselves to determine connectivity profiles of the capsulotomy, volume of tissue activated (VTA), and potentially necessary tracts (VTA minus capsulotomy tracts). We used whole-brain, PFC-focused, and subcortically-focused tractography algorithms to fully explore the space of possible connections. Results: Capsulotomy regions-of-interest (ROIs) connected with a variety of PFC and subcortical regions. VTA ROIs and potentially necessary tracts had limited and inconsistent PFC connectivity but substantial subcortical connectivity. While correlated to the average OCD connectome (r = 0.214, 95% CI [0.177, 0.251]; r = 0.756, 95% CI [0.739, 0.772]), the Cap-DBS connectomes had many edges that were stronger (z-score > 3). Conclusions: The connectivity profile of potentially necessary tracts for successful DBS treatment after failed capsulotomy revealed a surprising proportion of subcortical regions and inconsistent PFC involvement, highlighting an often-ignored set of connections that may be critical to effective DBS.

The Disconnection Symptom Discoverer (DSD) model proposes to predict long-term performance on neuropsychological tests from stroke lesion disconnection profiles. The model requires external validation to determine reproducibility and generalizability to new and different patients. Here, we investigated whether the DSD supports accurate multi-domain cognitive outcome predictions at three different timepoints post stroke, in a clinically representative independent cohort. In this study, the DSD was used to predict visuospatial attention, verbal memory, and language scores in an independent cohort of 74 stroke survivors (mean age = 69.2, 39% female) with 3 repeated cognitive assessments. DSD-predicted scores were compared to observed neuropsychological scores collected at <2 weeks, six months, and > 2 years post-stroke. DSD-predicted language outcomes were significantly correlated with observed behaviour at the <2 weeks timepoint, but no other significant correlations between DSD-predicted scores were identified. Importantly, DSD-predicted verbal memory and visuospatial domain scores were not significantly correlated with observed behaviour at any of the considered timepoints (minimum p-value = 0.33). Across all tests and timepoints, DSD-predicted scores had an average Mean Absolute Error (MAE) of 0.21 (SD = 0.13, range = 0.04-0.43), with the highest errors occurring between predicted and observed memory scores. Larger stroke lesions were associated with higher MAE, indicating that the DSD performance was modulated by stroke severity. Overall, these results indicate that the DSD did not yield informative predictions of long-term cognitive outcomes in this external dataset. This finding provides an important illustration of potential overfitting issues within cognitive outcome prediction models, highlighting the need for caution when aiming to predict long-term post-stroke cognitive outcomes and further external validation of proposed models.

Background: The clinical applicability of large language models (LLMs) in Parkinson's disease (PD) management remains insufficiently characterized, particularly in generative responses to clinical vignette scenarios. Objective: To evaluate the quality of clinical assessments and management plans generated by a general-purpose LLM (Gemini 1.5 Pro) and a medically specialized LLM (OpenEvidence), and to compare their performance. Methods: Models generated free-text responses to 45 open clinical queries, focused on assessment of the situation, and recommended management plan. Two movement disorders fellows rated outputs using 5-point Likert scales, dichotomized into clinically appropriate ([&ge;]4) versus inappropriate ([&le;]3). Discrepancies were adjudicated by a senior movement disorders specialist. Paired comparisons used McNemar's test; qualitative analysis examined severe errors. Results: Gemini 1.5 Pro and OpenEvidence showed high rates of clinically appropriate assessments (80.0% vs. 86.7%) but lower performance in management plans (48.9% vs. 57.8%). Cases in which both assessment and plan were clinically appropriate occurred in 46.7% and 55.6% of cases, respectively. None of these differences reached statistical significance. Severe errors were uncommon in assessments (6.7% vs. 8.9%) but more frequent in plans (26.7% in both), predominantly reflecting treatment strategy errors. Conclusions: In generative clinical reasoning tasks involving Parkinson's disease management vignettes, LLMs demonstrated reasonable performance in assessment, but consistent limitations in plan generation. The medically specialized LLM demonstrated several qualitative advantages but no statistically significant performance benefit over the general-purpose model. Therefore, these tools should be used with appropriate caution in Parkinson's disease management, particularly regarding treatment recommendations.