Cortex

There is a predicted increase in older adults presenting with mild to severe cognitive impairment. Screening tools with high sensitivity are the first frontier in identifying a cognitive pathology; however, to ensure that they are measuring the intended concept or criterion, thorough psychometric procedures should be followed. In this study, convergent criterion validity of Riga Cognitive Screening Task was measured, using cortical thickness of regions of interest as the criterion. 106 older adults (Mage = 70.49, SD =8.08, 35.8% male) with varying levels of cognitive functioning were involved in the study. All participants underwent cognitive assessment with the screening task and a 3T MRI. Cortical thickness of selected temporal and parietal regions was used as a brain measure. Behavioural Partial Least Squares Correlation was conducted and one latent variable was extracted. The results confirmed that Riga Cognitive Screening Task shows good criterion validity, suggesting successful use for screening.

ObjectiveDemographic corrections (e.g., sex, education, race, ethnicity) are often applied when assessing cognition in adults; however, these corrections have significant limitations (e.g., using years of education does not capture the quality of, or access to, education). It is therefore critical to develop novel assessment options that are less susceptible to demographic factors. This study compared demographic effects on a verbal memory test and a performance-based test of cognition and daily functioning in older adults. Based on prior work, we hypothesized the performance-based tests would be less susceptible to demographic factors than paired associates learning. MethodData from 1326 participants (mean{+/-}SD age=61.9{+/-}10.9 yrs; Female = 1066, 80%) were collected through the MindCrowd electronic cohort, with 79 (6%) non-White, 109 (8.2%) identifying as Hispanic/Latino ethnicity, and 327 (25%) reporting education as less than a college degree. Paired associates learning is a well-established measure of medial temporal lobe-dependent learning and memory through recall of word-pairs, scored as the number of correct word pairs entered out of 36 possible. The performance-based test involved functional upper-extremity movement, specifically transporting beans to target cups in a repeating sequence (a task also shown to be dependent on the medial temporal lobe), scored as the intraindividual variability (standard deviation) in trial time across four consecutive trials. ResultsAs hypothesized, linear regression analysis showed that PAL was significantly affected by sex, education, race (particularly Black/African American), and ethnicity, whereas the performance-based test was affected only by sex and with a much smaller effect size than that of PAL. ConclusionsPerformance-based assessments may be an equitable approach to evaluating cognition without requiring score corrections, particularly for diverse populations.

BackgroundArtificial Intelligence (AI) based approaches to speech analysis have the potential to assist with objective speech error analysis in aphasia but off-the shelf tools often fail to detect speech errors due to prioritizing "fluent transcription." Speech production errors (dysfluencies) are hallmark diagnostic features of the nonfluent (nfvPPA) and logopenic (lvPPA) variants of primary progressive aphasia, yet they can be challenging to detect and characterize even by expert clinicians. This study aimed to evaluate whether the novel automated lightweight Scalable Speech Dysfluency Modeling system (SSDM-L), specifically designed to detect dysfluencies, could accurately distinguish PPA variants using voice recordings of individuals reading a brief passage. MethodParticipants included a total of 104 individuals, 40 with nfvPPA, 40 with lvPPA (matched on disease severity), and 24 healthy controls who read aloud the Grandfather Passage as part of a widely used motor speech evaluation (MSE). We automatically extracted ten speech error (dysfluency) variables using SSDM-L, including insertions, replacements, and deletions at both phoneme- and word-levels, and phoneme-level prolongations and repetitions. Group differences were assessed via ANCOVAs controlling for age, education, and disease severity (MMSE, CDR sum-of-boxes). To test clinical relevance, we performed correlation analyses with MSE ratings provided by experienced speech-language pathologists (i.e., gold standard) within the nfvPPA group. Classification performance was assessed by training random forest and XGBoost machine-learning models including 5-fold cross-validation. ResultsAll individuals read the entire passage in less than five minutes. SSDM-L detected eight of the ten predefined dysfluency features at sufficient frequency to include them in subsequent analyses. All eight features distinguished PPA from controls (p<.006). Individuals with nfvPPA made more errors than the lvPPA group on every feature (all p<.023). Each feature showed a moderate positive correlation with a global MSE apraxia/dysarthria score (r=.31-.56; p<.001-.053). Together, the eight features were able to classify nfvPPA versus lvPPA at AUC=.806 (random forest) and AUC=.776 (XGBoost). DiscussionAI-based automated speech error analysis accurately distinguished nfvPPA and lvPPA variants using a brief reading task. This quick error-sensitive scalable AI system has the potential of providing a practical tool to aid diagnosis in aphasia and motor speech disorders.

The neural signature of rhythm and tempo remains difficult to study in both humans and non-human primates. Here we recorded from the motor cortex of human participants implanted with intracortical microelectrode arrays while they performed a series of rhythmic tapping tasks. We found that rhythmic tapping elicited low-dimensional rotational neural dynamics whose radii varied in a tempo-dependent manner and axes related to kinematic properties. Moreover, we observed a spectrum of kinematic and neural behavior as participants shifted from low tempo punctuated taps to high tempo smoother, continuous taps. Surprisingly, we observed that tactile feedback strengthened the rotational dynamics despite reduced kinematic range. Moreover, while tempo preparation did not produce dynamics of their own, motor cortex encoded it in an orthogonal dimension. Finally, we found that switching tempos was achieved with smooth neural transitions that could only be separated in higher dimensions. These results show that motor cortex directly encodes a multitude of rhythm related features.

IntroductionSleep spindles are electroencephalographic elements characteristic of non-rapid eye movement sleep generated by thalamo-cortical interactions. Spindles have been linked to some of the cognitive benefits afforded by sleep and high spindle activity is associated with increased arousal threshold (deeper sleep). Here, we demonstrate that targeting the thalamus with Transcranial Electrical Stimulation with Temporal Interference (TES-TI) can enhance spindle activity. Methods24 participants (25.5 {+/-} 9.5 years; 69.6% F) underwent thalamic TES-TI stimulation during daytime naps. Three stimulation protocols were tested during stage 2 of non-rapid eye movement sleep (N2): fixed difference frequency of 10 Hz (TES15kHz-TI10Hz), difference frequency matched to individual spindle peak (TES15kHz-TIPeak), and carrier frequency only (TES15kHz). Spectral power in the spindle (sigma) band and integrated spindle activity (ISA) were compared before and during the stimulation, and across stimulation protocols. ResultsTES15kHz-TI10Hz stimulation was associated with a significant increase in sigma band power ({Delta}[x]STIM-PRE = 0.49 log10{micro}V2, p = 0.021) and ISA ({Delta}[x]STIM-PRE = 7.48 {micro}V/s, p = 0.042). Cluster-based analysis localized the increase in sigma power over the frontal and centro-parietal areas (p = 0.022). Linear mixed effects models showed that both sigma band power and ISA during stimulation increased significantly in TES15kHz-TI10Hz compared to the TES15kHz protocol ({beta} = 0.67 log10{micro}V2, p = 0.018; {beta} = 14.70 {micro}V/s, p = 0.0077), while the TES15kHz-TIPeak did not show the same effect. ConclusionsThis study provides evidence supporting the successful use of TES-TI targeting the thalamus to enhance sleep spindle activity. Stimulation at a fixed difference frequency of 10 Hz increased sigma band power and ISA, whereas neither stimulation matched to individual sigma band peak nor TES alone produced comparable effects. These promising results warrant further investigations into the cognitive and clinical impact of TES-TI, a non-invasive neuromodulation tool that can reach deep brain regions. Statement of significanceThis study provides evidence that thalamo-cortical networks, which are central to many physiological and pathological brain activities, can be modulated non-invasively in humans. More specifically, the findings show that transcranial electrical stimulation with temporal interference targeting the thalamus can selectively enhance sleep spindle activity. This work introduces a new strategy for precisely targeting sleep-generating mechanisms regulated by deep brain circuits without surgery or medication. Key next steps include determining how this increase in spindle activity can positively impact cognition and assessing the translational potential of this approach for clinical populations.

Repetitive head impacts (RHI) from contact and collision sports have been associated with later-life cognitive and neurobehavioral impairments, as well as neurodegenerative conditions such as chronic traumatic encephalopathy (CTE). RHI-associated clinical sequelae among female former soccer players, specifically, are not well understood. This cross-sectional study aimed to examine the relationship of RHI exposure proxies (e.g., total years of soccer play, highest level of play, and estimated cumulative heading frequency) with clinical measures (e.g., subjective cognitive complaints, objective cognitive performance, behavioral dysregulations, and depressive symptoms) among 3,174 women, aged 40 years or above, enrolled in the Head Impact and Trauma Surveillance Study (HITSS), all of whom played organized soccer. HITSS participants completed an online battery that elicited self-reported cognitive and behavioral complaints and depressive symptoms, and that assessed cognitive performing via computerized tests. Multivariable linear and logistic regression models estimated associations between soccer-related RHI proxies and outcome measures, adjusting for age and education. Among the former soccer players, longer duration of soccer play, higher level of play, and greater estimated cumulative heading frequency were significantly associated with worse self-reported cognitive functioning, greater behavioral dysregulation, and elevated depressive symptom severity (range of significant unstandardized B coefficients: 0.02 to 0.52). Higher estimated cumulative heading exposure was associated with higher odds of clinically meaningful elevations on subjective measures (OR range: 1.05 to 1.13) There were no associations between any of the RHI proxies and performance on the objective computerized cognitive assessments. Among middle-aged women who played organized soccer, cumulative RHI exposure was associated with small but statistically significant effects for measures of subjective cognitive complaints, behavioral functioning, and depressive symptoms. We found no associations for objective outcomes of cognitive function. Continued monitoring of this large cohort of female former soccer players will improve understanding of long-term consequences of soccer play.

Oscillatory coupling between respiration, heart rate, and cortical function is fundamental to physiological regulation yet remains poorly characterized in humans. Diminished respiratory heart rate variability (RespHRV)--the rhythmic heart rate modulation accompanying respiration--has emerged as a transdiagnostic biomarker of mental and physical health, reduced in anxiety, depression, cardiovascular disease, and aging (Beauchaine & Thayer, 2015; Menuet & Gourine et al., 2025). However, the cortical substrates that coordinate rhythmic cardiovascular-respiratory coupling are not well understood. Our current findings highlight the involvement of the left orbitofrontal cortex (OFC) in oscillatory cardiorespiratory dynamics. In adults aged 50-70 (N = 55; mean age = 60.1 {+/-} 6.0 years; 29 female), across both a slow-paced breathing condition and a random-paced breathing condition, greater heart rate oscillatory power during 9-week breathing training sessions predicted OFC volume increases. OFC changes were most strongly linked with upper low-frequency range power during practice (0.09-0.13 Hz; p < 0.005, cluster-corrected) but were not tightly constrained by precise breathing frequency. These effects covaried with improved attentional and executive performance, including reduced pupil responses to distractors and enhanced working-memory and associative-memory scores. Our findings identify the orbitofrontal cortex as a key site of cortical plasticity linked to rhythmic cardiovascular-respiratory engagement. By delineating how oscillatory body-brain coupling supports cognitive control-related processes, including attentional filtering and memory updating, this work bridges mechanistic neuroscience and translational intervention science, suggesting a frequency-general pathway through which simple breathing practices may enhance neurovisceral integration and cognitive resilience in aging. SummaryO_LIGreater oscillatory heart rate power during breathing training, particularly within the upper low-frequency range (0.09-0.13 Hz), predicted increases in left orbitofrontal cortex (OFC) volume. C_LIO_LIOFC volume increases were associated with improved attentional and executive performance, including reduced pupil reactivity to distractors and enhanced working-memory and associative-memory scores. C_LIO_LIThese findings suggest that rhythmic cardiovascular-respiratory coupling supports cortical plasticity and cognitive resilience, providing a frequency-general mechanism through which breathing practices enhance neurovisceral integration in aging. C_LI

Executive dysfunction affects nearly 50% of individuals with traumatic brain injuries (TBI), yet interventions targeting the underlying neural mechanisms remain limited. This study examined whether aerobic exercise modulates functional connectivity to improve executive function in individuals with mild TBI and identified the neural pathways mediating these improvements. In this secondary analysis of a 12-week pilot randomized controlled trial, participants with mild TBI (n=24) were randomized to aerobic exercise (n=12) or active balance control (n=12). Resting-state fMRI with multivariate pattern analysis revealed that aerobic exercise selectively altered functional connectivity patterns of the anterior cingulate cortex (ACC) compared to balance control. Post-hoc seed-to-voxel analyses identified widespread ACC connectivity differences between groups post-intervention while controlling for baseline, across 19 cortical regions spanning default mode, frontoparietal control, and salience networks. Critically, greater anticorrelation between the ACC and insula following aerobic exercise was associated with improved Trail Making Test B-A performance in the aerobic group ({beta}=46.92, p=0.04) but not the balance group, indicating that participants who developed stronger ACC-insula functional segregation showed greater reductions in executive function completion times. These findings establish the ACC-insula circuit as a critical neural substrate mediating exercise-induced executive function recovery after TBI and identify this pathway as a promising therapeutic target for exercise-based rehabilitation interventions.

INTRODUCTIONConnected speech analyses can help characterize linguistic impairments in primary progressive aphasia (PPA) and classify variants, however, manual transcription of speech samples is time-consuming and expensive. Automated speech recognition (ASR) may be efficacious for transcribing PPA speech. METHODSTranscripts of picture descriptions (109 PPA, 32 healthy controls (HC)) were generated using a manual, automated (Whisper) or semi-automated approach including a quality control (QC) step. We evaluated transcript accuracy, the reliability of ASR-derived linguistic features, and classification performance. RESULTSWhisper demonstrated lowest error rates for HC, followed by semantic, logopenic and non-fluent PPA variants. Errors correlated with overall disease severity for semantic and logopenic variants. QC of Whisper outputs reduced errors and improved the reliability of linguistic features. Overall, ASR-derived features achieved better classification performance than manual transcription features. DISCUSSIONResults support the use of off-the-shelf ASR for scalable, cost-efficient transcription of PPA speech and classification.

Restoring communication for people with dysarthria secondary to pontine stroke remains a critical challenge. Intracortical brain-computer interfaces (iBCIs) have demonstrated great potential for speech restoration in people with amyotrophic lateral sclerosis (ALS), with 1-24% word error rates (WERs) on a 125,000-word vocabulary. In pontine stroke, electrocorticography (ECoG) BCIs achieved 25.5% WERs with a smaller 1,024-word vocabulary. Whether intracortical BCI performance improvements extend to people with pontine stroke-induced dysarthria remains unclear. Here, we show that neural activity from a single 64-channel microelectrode array in orofacial motor cortex can predict attempted speech in a person with pontine stroke more accurately than prior ECoG BCI work and comparably to prior iBCI work. We trained a neural network decoder to predict phoneme probabilities from spiking rates and spike-band power as BrainGate2 participant T16 mimed (mouthed without vocalization) sentences from a large vocabulary. A series of language models converted these probabilities into word sequences. This decoding architecture has remained stable more than two years post-implantation, achieving a median 19.6% WER with a 125,000-word vocabulary and a median 10.0% WER with a 1,024-word vocabulary (a 60.8% reduction over prior ECoG studies). This framework also generalized beyond cue repetition, enabling T16 to communicate spontaneously via the iBCI in a question-and-answer setting with a 35.2% WER. These results demonstrate that brain-to-text decoding from a small patch of cortex can outperform ECoG-based systems in individuals with pontine stroke and is comparable to early speech iBCIs in individuals with ALS.

Sleep arousals trigger rapid autonomic shifts, yet their specific sympathetic signatures remain poorly characterized due to the mixed sympathetic-parasympathetic nature of traditional cardiovascular markers. Electrodermal activity (EDA), driven exclusively by sympathetic sudomotor pathways, offers a more direct opportunity to characterize arousal-related autonomic responses during sleep. This study quantifies the evolution of EDA-based features associated with arousal events in 100 adults using polysomnography and high-resolution EDA recordings. We implemented a time-varying frequency decomposition framework to isolate sleep-specific sympathetic components, extracting statistical and peak-based features from arousal segments and matched stable-sleep controls. Compared to controls, arousal segments exhibited robust sympathetic modulation in EDA persisting 40 seconds post-arousal. While long arousals produced robust responses, short arousals showed negligible sudomotor responses. REM and NREM sleep showed consistent feature trajectories, with greater variability during REM. The observed activation is primarily driven by clustered sympathetic bursts and amplitude enhancement rather than shifts in peak frequency. These findings establish EDA as a highly sensitive marker of sleep-related autonomic activation and provide a quantitative baseline for characterizing sympathetic responses to sleep arousals.

Structured AbstractO_ST_ABSObjectiveC_ST_ABSThis mixed-methods study investigated the lived-experience perspectives of receiving a novel, brief digital mental health intervention after psychological trauma. The online gamified imagery-competing task intervention (ICTI) involves one researcher-guided session followed by self-use. Tested in two randomised controlled trials (GAINS-01; GAINS-02), ICTI led to fewer intrusive memories at week-4, with the reduction sustained over 24 weeks, alongside reductions in post-traumatic stress. Here, we contrasted user experiences of ICTI with an Active Control (AC; music-listening task), and explored longer-term impact in qualitative interviews to contextualise GAINS-02 findings. Methods and AnalysisThe GAINS-02 trial randomised healthcare staff experiencing intrusive memories after work-related trauma to ICTI (N=40), AC (N=39), or treatment-as-usual (TAU; N=20). Expectancy was assessed before the researcher-guided session (Day 0), acceptability at week-4, and usage tracked for 24-weeks. Semi-structured interviews (N=27) were conducted in ICTI and AC arms only (15 at week-4; 12 during 12-24-weeks). Interviews were analysed using reflexive thematic analysis. ResultsPrior to use, many trial participants did not think the intervention would work, favouring AC over ICTI. However, after completing the tasks, participants found ICTI more acceptable and relevant to intrusive memories than AC. After the one guided session, median ICTI usage the next four weeks was 4.00 times with little additional use (once more) over the next 20 weeks because of lack of need. Potential implementation facilitators included ease of use, and advantages over existing interventions due to not needing to talk about the trauma, brevity, and lesser resource commitment. Perceived barriers included a lack of staff and manager education about the nature and consequences of intrusive memories, with a need for workplace buy-in and demonstration of organisational benefits. ConclusionHealthcare staff experiencing workplace-related trauma found ICTI to be acceptable and effective for reducing intrusive memories with low effort and emotional burden, even among participants who initially expressed scepticism. Participants highlighted implementation considerations including offering ICTI both within and outside the workplace, and providing a self-guided version of ICTI with optional support. Future work should assess cost-effectiveness, impacts on presenteeism and retention, and real-world implementation including the feasibility and effectiveness of a self-guided ICTI. Summary BoxO_ST_ABSWhat is already known on this topicC_ST_ABSIn a previous randomised controlled trial (GAINS-01) with Intensive Care Unit (ICU) staff exposed to work-related trauma, a brief online gamified imagery-competing task intervention (ICTI) reduced intrusive memories compared to usual care at four-weeks. What this study addsThe GAINS-02 randomised controlled trial replicated GAINS-01 and extended results by comparing ICTI to an active control (AC; music listening) task, enrolling hospital staff from outside ICU, and a follow-up period of 24-weeks. Qualitative interviews found that, despite initial scepticism from healthcare staff prior to using the intervention, ICTI was more acceptable than an AC due to specific effects on swiftly reducing intrusive memories and requiring minimal support or usage after an initial researcher-guided session. After one guided session, ICTI was used 4 more times in the first four weeks, with little additional usage (once) thereafter because of lack of need (i.e., no longer experiencing intrusive memories). How this study might affect research, practice or policyICTI is an efficacious scalable intervention to relieve staff of intrusive memories with effects sustained for at least 6-months. It was found to be more acceptable to participants than alternatives, requiring less time commitment than standard psychological treatments.

Deficits in inhibitory control are common across a wide range of psychiatric disorders and are closely linked to symptom severity, including emotional dysregulation, anxiety, substance misuse, and self-harm, making them an appealing target for intervention. Cognitive training offers a low-cost, scalable, and non-invasive strategy to strengthen inhibitory control; however, most existing paradigms target only a single facet of inhibition and rarely account for environmental influences, such as affective context. To address these gaps, we developed a computerized inhibitory control training paradigm to simultaneously engage three components of inhibition: preemptive, proactive, and reactive, while embedding trials within positive and negative affective contexts to assess the impact of emotional stimuli. Across two online experiments, participants completed the GAMBIT task in one session (Experiment 1, N = 300) or repeated over three sessions (Experiment 2, N = 65). The task included No-Go trials to train preemptive inhibition, stop-signal trials for reactive inhibition, and stop-signal anticipation trials to train proactive inhibition. Affective images of differing valence were presented as background stimuli to evaluate their impact on inhibitory performance. In Experiment 1, participants showed higher accuracy on No-Go versus reference Go trials ({beta}=1.45, SE=0.09, p<.001), confirming successful manipulation of preemptive inhibition. Reaction times were slower during anticipation trials across two different conditions ({beta}=0.16, SE=0.04, p<.001; {beta} = 0.07, SE = 0.04, p = 0.047), consistent with proactive slowing when anticipating a potential stop signal. Additionally, positive affective images ({beta} = 0.10, SE= 0.009, p < 0.001) further slowed RTs, indicating emotional interference with proactive control. In Experiment 2, the pattern of higher No-Go accuracy was replicated ({beta} = 0.91, SE = 0.11, p < .001) and accuracy generally improved over sessions ({beta} = 0.38, SE = 0.06, p < .001). In anticipation trials, RTs become shorter across sessions (session 2: {beta} = -0.25, SE = 0.06, p < .001; session 3: {beta} = -0.45, SE = 0.06, p < .001), reflecting practice-related gains, and SSRTs decreased over time (F(2,56) = 6.26, p = .004), consistent with enhanced reactive inhibition. Proactive inhibition was modulated by affective images, with both negative ({beta} = 0.04, SE = 0.02, p = .039) and positive ({beta} = 0.16, SE = 0.02, p < .001) affective images associated with slower RTs. Participants also reported reductions in self-assessed temper control by the last session (W = 25.5, p = .007, q = .037, d = -0.51) and usability ratings were high (all means [&ge;] 3.87/5). Together, these findings show that this paradigm recruits multiple forms of inhibitory control and yields training-related improvements in both performance and affective outcomes. This provides preliminary validation of a scalable, fully online inhibitory control training tool targeting multiple dissociable inhibitory processes within affective contexts. The approach holds promise as an accessible transdiagnostic intervention to support symptom improvement across psychiatric disorders, with future work needed to evaluate clinical efficacy in patient populations.

IntroductionNeurocognitive impairment (NCI) remains common among people living with HIV (PWH), particularly in low- and middle-income countries where accurate diagnostic tools are limited. In Peru, the lack of locally validated neuropsychological (NP) normative data in Spanish poses a major barrier to diagnosing HIV-associated NCI, especially among PWH who develop NCI at younger ages. This study aimed to develop regression-based NP norms for young and middle-aged Spanish-speaking adults in Lima, Peru and validate the norms in demographically similar PWH to improve diagnostic precision of HIV-associated NCI. MethodsA total of 164 healthy adults without HIV from Lima completed a comprehensive NP battery assessing memory, attention, executive function, and language, which are commonly affected in HIV-associated NCI. Multiple regression models were used to consider the influence of age, years of education, and sex on raw scores, yielding standardized demographically-adjusted norms for the population. The resulting norms were then applied to 310 PWH from Lima and then compared with previously published norms for Spanish speaking adults to evaluate performance differences. ResultsAge and education were the strongest predictors of performance across tests, while sex had minimal influence. Compared to people without HIV, PWH had significantly lower educational attainment (mean 12.6 vs. 13.7 years) and exhibited significantly worse performance on normed scores of Benson Figure Copy, Benson Figure Delayed Recall, Color Trails 1 and 2, Hopkins Verbal Learning Test - Revised, and WAIS-III Digit Symbol Coding, Digit Span, and Symbol Search. There were statistically significant differences between T-scores on nearly all tests between our population-specific norms and previously published norms in both directions, indicating potential over- and under-detection errors when applying norms from non-local samples. DiscussionOur findings highlight the utility of locally derived norms in detecting subtle cognitive changes among young and middle-aged PWH compared with previously published norms for Spanish-speakers. Application of these norms reveals significant between-group differences that may go undetected using non-local normative data or raw scores. Future efforts should focus on rural norm development and inclusion of individuals with lower educational backgrounds in Peru and other Latin American countries.

Lesion network mapping (LNM) links focal brain lesions to distributed neural circuits by projecting lesion locations through a normative functional connectome. van den Heuvel and colleagues recently showed how commonly used LNM procedures generate maps that converge on nonspecific, low-dimensional properties of the connectome, introducing a bias. Consequently, many published maps of different conditions appear strikingly similar. Here, we offer an alternative approach that does highlight distinct symptom-specific signals in LNM. In a multicenter dataset of 2,950 stroke patients, we replicate the expected convergence under the standard procedures, but also demonstrate how permuting symptom labels provides an appropriate null model that delivers distinct, biologically plausible networks for specific cognitive functions.

Sensory organization at the spinal segment level is commonly inferred from dermatomal maps that assume a fixed correspondence between cutaneous regions and spinal segments. However, based on the complexities of spinal neuroanatomy and neurophysiology, the distribution of sensory signals within the cord may be broader and less segment-specific than dermatomal maps suggest, leaving the segment-level localization of sensory-evoked activity in humans uncertain. Spinal cord functional magnetic resonance imaging (fMRI) is currently the only technique capable of noninvasively mapping sensory activity with high spatial resolution in the human spinal cord. However, its application remains technically challenging and is limited by the uncertainty in segmental localization. In this study, we leveraged recent advancements in spinal cord fMRI, including spinal nerve rootlet-based spatial normalization, to investigate how sensory information is represented and distributed within the human spinal cord during electrocutaneous stimulation of the third digit of the right hand (i.e., C7 dermatome). Forty healthy adults were scanned with electrocutaneous stimulation at four individualized intensities across multiple runs to quantify (i) the rostrocaudal distribution of sensory-evoked activity, (ii) intensity-dependent changes in detectability and localization, and (iii) the effect of normalization strategy on segmental localization. Across participants, stimulation produced activation localized in the lower cervical cord (e.g., C6-C8), with the most consistent segmental localization near C7. Stronger stimulation increased detectability and produced more consistent segmental localization across participants. Importantly, normalization that incorporated nerve rootlet landmarks sharpened localization and improved sensitivity relative to conventional intervertebral disc-based alignment. This highlights the value of functionally relevant anatomical landmarks for group inference in the spinal cord. Responses were strongest in the initial run and attenuated with repetition, suggesting habituation or adaptation that can bias multi-run paradigms if unmodeled. Together, our results define practical acquisition and analysis conditions (e.g., stimulation strength, anatomical alignment strategy, and run structure) under which segment-level spinal sensory responses can be detected, thereby supporting more reliable studies of human spinal cord future basic and translational studies, including pain mechanisms, sensory function, and spinal injury.

ObjectiveTo delineate the phenotype of juvenile myoclonic epilepsy (JME) with a focus on obsessive-compulsive personality disorder (OCPD) using multimodal psychiatric, neuropsychological, quantitative EEG (qEEG), and structural MRI markers within a predictive-processing/free-energy framework. MethodsWe prospectively studied 65 patients with JME and 68 matched healthy controls (HC). Participants completed DSM-IV SCID I/II interviews and a neuropsychological battery assessing working memory, psychomotor speed, mental flexibility, divided attention, inhibition, and phasic/tonic alertness; standard EEG and high-resolution structural MRI were acquired. Groups comprised HC and JME subgroups without psychiatric comorbidity, with non-OCPD Axis I/II diagnoses, and with OCPD. Welchs t-tests (FDR-corrected) and Hedges g quantified neuropsychological and alpha-band coherence differences. Surface-based analyses assessed cortical thickness/surface area. Exploratory regressions tested associations of OCPD, seizure freedom, and antiseizure medication (ASM) load with cognition; Kendalls tau tested coherence-cognition associations. ResultsCompared with HC, JME showed broad executive-attentional impairment, most pronounced in patients with psychiatric comorbidity. The OCPD subgroup exhibited particularly large slowing in psychomotor speed, inhibition (reaction time), and tonic alertness versus HC, while OCPD versus non-OCPD JME differences did not survive multiple-comparison correction. qEEG showed increased interhemispheric frontal and decreased temporal alpha coherence in JME, with temporal hypo-coherence strongest in those with psychiatric comorbidity; within JME, OCPD was linked to increased left fronto-temporal alpha coherence. In the MRI subsample, JME-OCPD demonstrated increased cortical thickness in left medial orbitofrontal and anterior cingulate regions (vs HC and vs JME without OCPD) and additional posterior occipito-temporal clusters versus HC. Regression and coherence-cognition associations were weak and non-significant after FDR correction. SignificanceJME features syndrome-level executive-attentional dysfunction and altered fronto-temporal network organization. Comorbid OCPD marks a subgroup with accentuated cognitive slowing and distinct medial prefrontal/cingulate structural and left fronto-temporal connectivity signatures, aligning with predictive-processing accounts of rigid, over-precise high-level priors. Key pointsJME is linked to broad executive-attentional impairment versus healthy controls. Psychiatric comorbidity amplifies cognitive deficits in JME. JME with OCPD shows particularly large slowing/inhibitory-control deficits versus controls, while OCPD vs non-OCPD differences within JME are modest. Alpha-band EEG coherence indicates altered network organization in JME and an OCPD-related increase in left fronto-temporal coherence within JME Surface-based MRI suggests an OCPD-related structural phenotype in JME, involving medial orbitofrontal/anterior cingulate cortical thickening

ObjectivesFunctional neurological symptoms which do not meet clinical definitions of functional neurological disorder (FND) are common in clinical practice. Understanding the distinction between these benign functional symptoms and FND is crucial in defining FND as an entity for study, and as a clinical syndrome. We aimed to measure the frequency of functional symptoms in people who do not have FND. MethodsA survey was administered to 95 clinicians who attended an international conference on FND. Participants were asked to report the occurrence and characteristics of experiences with features of functional sensory or motor symptoms, or dissociation. ResultsOf the 95 people who responded to the survey, 57.4% reported having experienced any functional symptoms, and 47.9% reported having experienced functional motor or sensory symptoms. The symptoms reported were generally short-lived and caused only mild distress and disruption. Most respondents who reported having experienced a functional symptom reported having had multiple events through their lives. InterpretationThe results suggest that the lifetime occurrence of functional neurological symptoms is at least two orders of magnitude higher than the prevalence of FND. The high prevalence of functional symptoms in people who have never had FND challenges the common assumption that the occurrence of functional neurological symptoms is synonymous with FND. We propose that FND is better conceived of as a failure of the mechanisms by which functional neurological symptoms resolve, rather than the occurrence of functional symptoms per se. This reconceptualization implies new research directions for the underlying aetiology of FND.

Lifestyle and environmental factors such as diet, physical activity, residential greenspace exposure, alcohol consumption, and sleep are increasingly promoted as modifiable targets for maintaining cognitive health and mitigating age-related decline. Yet, it remains unclear how well they predict cognitive functioning and, importantly, to what extent their associations with cognition are reflected in brain and bodily health. Here, we applied machine learning to multimodal data from over 10,000 UK Biobank participants to evaluate the predictive value of twelve lifestyle and environment domains, spanning physical activity, diet, smoking and alcohol consumption, sleep, sexual behavior, electronic device use, and environmental exposures, for cognitive functioning - both individually and in combination - and performed commonality analysis to quantify the extent to which these associations are captured by body and brain markers. A model integrating all lifestyle and environment domains explained 23% of the variance in cognition at an out-of-sample r=0.48, comparable to models based on body and brain measures. Physical activity, together with diet, alcohol consumption, sun exposure, and local environmental characteristics, emerged as the strongest predictors of cognitive functioning. A composite brain marker integrating three neuroimaging modalities accounted for 57.7% of the lifestyle-cognition association, while a composite body marker spanning nine physiological systems accounted for 47.8%. Jointly, lifestyle, environment, body, and brain captured nearly all age-related variation in cognition (92.6%). Collectively, these results indicate that integrating lifestyle and environmental factors enables robust prediction of cognitive functioning and that a substantial portion of this association is reflected in brain and body health.

BackgroundMotor threshold (MT) estimation is fundamental to transcranial magnetic stimulation (TMS), guiding individualized stimulation intensity in research and therapy. Conventional methods such as the 5-out-of-10 rule require many stimuli, while adaptive approaches like Parameter Estimation by Sequential Testing (PEST) improve efficiency but can exhibit poor convergence under certain conditions. ObjectiveThis study introduces the Bayesian Uncertainty Dynamic Algorithm for Parameter Estimation by Sequential Testing (BUDAPEST), a Bayesian adaptive method for fast, accurate MT estimation with user-controlled uncertainty. The aims were to validate its accuracy in simulations and human data, promote usability through a MATLAB-based graphical interface, and evaluate experimental utility through resting and active MT comparisons and session-to-session reliability. MethodsBUDAPEST infers MT from binary MEP responses using sequential Bayesian updating and terminates when a user-defined uncertainty threshold is reached. Performance was evaluated in 10,000 virtual simulations and in human rMT and aMT measurements across two sessions per subject, including 3x5 cortical motor mapping to assess physiological spatial patterns. ResultsIn simulations, BUDAPEST achieved a mean absolute error of 1.9% MSO within ~10 pulses using a 2% uncertainty criterion while avoiding PEST misestimations. In human data, MT estimates were accurate within {+/-}4% MSO and robust to initialization; rMT showed strong session-to-session reliability (r = 0.78), whereas aMT exhibited greater variability. Motor mapping revealed coherent excitability gradients centered on the hotspot. ConclusionBUDAPEST enables rapid, reliable, and uncertainty-controlled MT estimation while reducing procedure time and participant burden. The accompanying GUI facilitates immediate adoption in research and clinical TMS environments. HighlightsO_LIIntroduces BUDAPEST, a Bayesian uncertainty-aware algorithm for rapid and reliable TMS motor threshold estimation. C_LIO_LIAchieves accurate MT estimates ({approx}2% MSO error) in ~10 pulses with user-controlled trade-offs between precision and procedure duration. C_LIO_LIDemonstrates robust performance in simulations and human data, with strong resting MT reliability and an open-source GUI enabling immediate adoption. C_LI