Prenatal exposure to air pollution and maternal depression: Combined effects on brain aging and mental health in young adulthood.

INTRODUCTION: Both maternal depression problems during pregnancy and prenatal exposure to air pollution have been associated with changes in the brain as well as worse mood and anxiety in the offspring in adulthood. However, it is not clear whether these effects are independent or whether and how they might interact and impact the brain age and mental health of the young adult offspring. METHODS: A total of 202 mother-child dyads from a prenatal birth cohort were assessed for maternal depression during pregnancy through self-report questionnaires administered in the early 90s, exposure to air pollutants (Sulfur dioxide [SO2], nitrogen oxides [NOx], and suspended particle matter [SPM]) during each trimester based on maternal address and air quality data, mental health of the young adult offspring (28-30 years of age; 52% men, all of European ancestry) using self-report questionnaires for depression (Beck Depression Inventory), mood dysregulation (Profile of Mood States), anxiety (State-Trait Anxiety Inventory), and psychotic symptoms (Schizotypal Personality Questionnaire), and brain age, estimated from structural magnetic resonance imaging (MRI) and previously published neuroanatomical age prediction model using cortical thickness maps. The brain age gap estimate (BrainAGE) was computed by subtracting structural brain age from chronological age. Trajectories of exposure to air pollution during pregnancy were assessed using Growth Mixture Modeling. The interactions of prenatal depression and prenatal exposure to air pollutants on adult mental health and BrainAGE were assessed using hierarchical linear regression. RESULTS: We revealed two distinct trajectories of exposure to air pollution during pregnancy: "early exposure," characterized by high exposure during the first trimester, followed by a steady decrease, and "late exposure," characterized by low exposure during the first trimester, followed by a steady increase in the exposure during the subsequent trimesters. Maternal depression during the first half of pregnancy interacted with NOX exposure trajectory, predicting mood dysregulation and schizotypal symptoms in young adults. In addition, maternal depression during the second half of pregnancy interacted with both NOx and SO2 exposure trajectories, respectively, and predicted BrainAGE in young adults. In those with early exposure to NOx, maternal depression during pregnancy was associated with worse mental health and accelerated brain aging in young adulthood. In contrast, in those with early exposure to SO2, maternal depression during pregnancy was associated with slower brain aging in young adulthood. CONCLUSIONS: Our findings provide the first evidence of the combined effects of prenatal exposure to air pollution and maternal depression on mental health outcomes and brain age in young adult offspring. Moreover, they point out the importance of the timing and trajectory of the exposure during prenatal development.

Prenatal exposure to alcohol and its impact on reward processing and substance use in adulthood.

Heavy maternal alcohol drinking during pregnancy has been associated with altered neurodevelopment in the child but the effects of low-dose alcohol drinking are less clear and any potential safe level of alcohol use during pregnancy is not known. We evaluated the effects of prenatal alcohol on reward-related behavior and substance use in young adulthood and the potential sex differences therein. Participants were members of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort who participated in its neuroimaging follow-up in young adulthood. A total of 191 participants (28-30 years; 51% men) had complete data on prenatal exposure to alcohol, current substance use, and fMRI data from young adulthood. Maternal alcohol drinking was assessed during mid-pregnancy and pre-conception. Brain response to reward anticipation and reward feedback was measured using the Monetary Incentive Delay task and substance use in young adulthood was assessed using a self-report questionnaire. We showed that even a moderate exposure to alcohol in mid-pregnancy but not pre-conception was associated with robust effects on brain response to reward feedback (six frontal, one parietal, one temporal, and one occipital cluster) and with greater cannabis use in both men and women 30 years later. Moreover, mid-pregnancy but not pre-conception exposure to alcohol was associated with greater cannabis use in young adulthood and these effects were independent of maternal education and maternal depression during pregnancy. Further, the extent of cannabis use in the late 20 s was predicted by the brain response to reward feedback in three out of the nine prenatal alcohol-related clusters and these effects were independent of current alcohol use. Sex differences in the brain response to reward outcome emerged only during the no loss vs. loss contrast. Young adult men exposed to alcohol prenatally had significantly larger brain response to no loss vs. loss in the putamen and occipital region than women exposed to prenatal alcohol. Therefore, we conclude that even moderate exposure to alcohol prenatally has long-lasting effects on brain function during reward processing and risk of cannabis use in young adulthood.

Levodopa may modulate specific speech impairment in Parkinson's disease: an fMRI study.

Hypokinetic dysarthria (HD) is a difficult-to-treat symptom affecting quality of life in patients with Parkinson's disease (PD). Levodopa may partially alleviate some symptoms of HD in PD, but the neural correlates of these effects are not fully understood. The aim of our study was to identify neural mechanisms by which levodopa affects articulation and prosody in patients with PD. Altogether 20 PD patients participated in a task fMRI study (overt sentence reading). Using a single dose of levodopa after an overnight withdrawal of dopaminergic medication, levodopa-induced BOLD signal changes within the articulatory pathway (in regions of interest; ROIs) were studied. We also correlated levodopa-induced BOLD signal changes with the changes in acoustic parameters of speech. We observed no significant changes in acoustic parameters due to acute levodopa administration. After levodopa administration as compared to the OFF dopaminergic condition, patients showed task-induced BOLD signal decreases in the left ventral thalamus (p = 0.0033). The changes in thalamic activation were associated with changes in pitch variation (R = 0.67, p = 0.006), while the changes in caudate nucleus activation were related to changes in the second formant variability which evaluates precise articulation (R = 0.70, p = 0.003). The results are in line with the notion that levodopa does not have a major impact on HD in PD, but it may induce neural changes within the basal ganglia circuitries that are related to changes in speech prosody and articulation.

Longitudinal study of epigenetic aging and its relationship with brain aging and cognitive skills in young adulthood.

Introduction: The proportion of older adults within society is sharply increasing and a better understanding of how we age starts to be critical. However, given the paucity of longitudinal studies with both neuroimaging and epigenetic data, it remains largely unknown whether the speed of the epigenetic clock changes over the life course and whether any such changes are proportional to changes in brain aging and cognitive skills. To fill these knowledge gaps, we conducted a longitudinal study of a prenatal birth cohort, studied epigenetic aging across adolescence and young adulthood, and evaluated its relationship with brain aging and cognitive outcomes. Methods: DNA methylation was assessed using the Illumina EPIC Platform in adolescence, early and late 20 s, DNA methylation age was estimated using Horvath's epigenetic clock, and epigenetic age gap (EpiAGE) was calculated as DNA methylation age residualized for batch, chronological age and the proportion of epithelial cells. Structural magnetic resonance imaging (MRI) was acquired in both the early 20 s and late 20 s using the same 3T Prisma MRI scanner and brain age was calculated using the Neuroanatomical Age Prediction using R (NAPR) platform. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale (WAIS) in the late 20 s. Results: The EpiAGE in adolescence, the early 20 s, and the late 20 s were positively correlated (r = 0.34-0.47), suggesting that EpiAGE is a relatively stable characteristic of an individual. Further, a faster pace of aging between the measurements was positively correlated with EpiAGE at the end of the period (r = 0.48-0.77) but negatively correlated with EpiAGE at the earlier time point (r = -0.42 to -0.55), suggesting a compensatory mechanism where late matures might be catching up with the early matures. Finally, higher positive EpiAGE showed small (Adj R2 = 0.03) but significant relationships with a higher positive brain age gap in all participants and lower full-scale IQ in young adult women in the late 20 s. Discussion: We conclude that the EpiAGE is a relatively stable characteristic of an individual across adolescence and early adulthood, but that it shows only a small relationship with accelerated brain aging and a women-specific relationship with worse performance IQ.

Bariatric surgery and its impact on depressive symptoms, cognition, brain and inflammation.

Background: Obesity has been associated with depressive symptoms and impaired cognition, but the mechanisms underlying these relationships are not well understood. It is also not clear whether reducing adiposity reverses these behavioral outcomes. The current study tested the impact of bariatric surgery on depressive symptoms, cognition, and the brain; using a mediation model, we also examined whether the relationship between changes in adiposity after the surgery and those in regional thickness of the cerebral cortex are mediated by changes in low-grade inflammation (as indexed by C-reactive protein; CRP). Methods: A total of 18 bariatric patients completed 3 visits, including one baseline before the surgery and two post-surgery measurements acquired at 6- and 12-months post-surgery. Each visit consisted of a collection of fasting blood sample, magnetic resonance imaging of the brain and abdomen, and assessment of depressive symptoms and cognition. Results: After surgery, we observed reductions of both visceral fat (p< 0.001) and subcutaneous fat (p< 0.001), less depressive symptoms (p< 0.001), improved verbal reasoning (p< 0.001), and reduced CRP (p< 0.001). Mediation analyses revealed that the relationships between the surgery-related changes in visceral fat and cortical thickness in depression-related regions are mediated by changes in CRP (ab=-.027, SE=.012, 95% CI [-.054, -,006]). Conclusion: These findings suggest that some of the beneficial effects of bariatric surgery on brain function and structure are due to a reduction of adiposity-related low-grade systemic inflammation.

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis.

This study focuses on white matter alterations in pharmacoresistant epilepsy patients with no visible lesions in the temporal and frontal lobes on clinical MRI (i.e. MR-negative) with lesions confirmed by resective surgery. The aim of the study was to extend the knowledge about group-specific neuropathology in MR-negative epilepsy. We used the fixel-based analysis (FBA) that overcomes the limitations of traditional diffusion tensor image analysis, mainly within-voxel averaging of multiple crossing fibres. Group-wise comparisons of fixel parameters between healthy controls (N = 100) and: (1) frontal lobe epilepsy (FLE) patients (N = 9); (2) temporal lobe epilepsy (TLE) patients (N = 13) were performed. A significant decrease of the cross-section area of the fixels in the superior longitudinal fasciculus was observed in the FLE. Results in TLE reflected widespread atrophy of limbic, thalamic, and cortico-striatal connections and tracts directly connected to the temporal lobe (such as the anterior commissure, inferior fronto-occipital fasciculus, uncinate fasciculus, splenium of corpus callosum, and cingulum bundle). Alterations were also observed in extratemporal connections (brainstem connection, commissural fibres, and parts of the superior longitudinal fasciculus). To our knowledge, this is the first study to use an advanced FBA method not only on the datasets of MR-negative TLE patients, but also MR-negative FLE patients, uncovering new common tract-specific alterations on the group level.

Association of Maternal Depression During Pregnancy and Recent Stress With Brain Age Among Adult Offspring.

Importance: Maternal mental health problems during pregnancy are associated with altered neurodevelopment in offspring, but the long-term relationship between these prenatal risk factors and offspring brain structure in adulthood remains incompletely understood due to a paucity of longitudinal studies. Objective: To evaluate the association between exposure to maternal depression in utero and offspring brain age in the third decade of life, and to evaluate recent stressful life events as potential moderators of this association. Design, Setting, and Participants: This cohort study examined the 30-year follow-up of a Czech prenatal birth cohort with a within-participant design neuroimaging component in young adulthood conducted from 1991 to 2022. Participants from the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort were recruited for 2 magnetic resonance imaging (MRI) follow-ups, one between ages 23 and 24 years (early 20s) and another between ages 28 and 30 years (late 20s). Exposures: Maternal depression during pregnancy; stressful life events in the past year experienced by the young adult offspring. Main Outcomes and Measures: Gap between estimated neuroanatomical vs chronological age at MRI scan (brain age gap estimation [BrainAGE]) calculated once in participants' early 20s and once in their late 20s, and pace of aging calculated as the differences between BrainAGE at the 2 MRI sessions in young adulthood. Results: A total of 260 individuals participated in the second neuroimaging follow-up (mean [SD] age, 29.5 [0.6] years; 135 [52%] male); MRI data for both time points and a history of maternal depression were available for 110 participants (mean [SD] age, 29.3 [0.6] years; 56 [51%] male). BrainAGE in participants' early 20s was correlated with BrainAGE in their late 20s (r = 0.7, P < .001), and a previously observed association between maternal depression during pregnancy and BrainAGE in their early 20s persisted in their late 20s (adjusted R2 = 0.04; P = .04). However, no association emerged between maternal depression during pregnancy and the pace of aging between the 2 MRI sessions. The stability of the associations between maternal depression during pregnancy and BrainAGE was also supported by the lack of interactions with recent stress. In contrast, more recent stress was associated with greater pace of aging between the 2 MRI sessions, independent of maternal depression (adjusted R2 = 0.09; P = .01). Conclusions and Relevance: The findings of this cohort study suggest that maternal depression and recent stress may have independent associations with brain age and the pace of aging, respectively, in young adulthood. Prevention and treatment of depression in pregnant mothers may have long-term implications for offspring brain development.

Multimodal combination of neuroimaging methods for localizing the epileptogenic zone in MR-negative epilepsy.

The objective was to determine the optimal combination of multimodal imaging methods (IMs) for localizing the epileptogenic zone (EZ) in patients with MR-negative drug-resistant epilepsy. Data from 25 patients with MR-negative focal epilepsy (age 30 ± 10 years, 16M/9F) who underwent surgical resection of the EZ and from 110 healthy controls (age 31 ± 9 years; 56M/54F) were used to evaluate IMs based on 3T MRI, FDG-PET, HD-EEG, and SPECT. Patients with successful outcomes and/or positive histological findings were evaluated. From 38 IMs calculated per patient, 13 methods were selected by evaluating the mutual similarity of the methods and the accuracy of the EZ localization. The best results in postsurgical patients for EZ localization were found for ictal/ interictal SPECT (SISCOM), FDG-PET, arterial spin labeling (ASL), functional regional homogeneity (ReHo), gray matter volume (GMV), cortical thickness, HD electrical source imaging (ESI-HD), amplitude of low-frequency fluctuation (ALFF), diffusion tensor imaging, and kurtosis imaging. Combining IMs provides the method with the most accurate EZ identification in MR-negative epilepsy. The PET, SISCOM, and selected MRI-post-processing techniques are useful for EZ localization for surgical tailoring.

Actions of a shaken heart: Interoception interacts with action processing.

In the present study, we investigated the modulatory influence of the unconscious, bodily arousal on motor-related embodied information. Specifically, we examined how the interoceptive prediction error interacts with the event-related potentials linked to action-effect processing. Participants were asked to perform a task with self-initiated or externally-triggered sounds while receiving synchronous or false auditory cardiac feedback. The results found that interaction of interoceptive manipulation and action-effect processing modulates the frontal subcomponent of the P3 response. During the synchronous cardiac feedback, the P3 response to self-initiated tones was enhanced. During the false cardiac feedback, the frontal cortical response was reversed. N1 and P2 components were affected by the interoceptive manipulation, but not by the interaction of interoception and action processing. These findings provide experimental support for the theoretical accounts of the interaction between interoception and action processing within a framework of predictive coding, manifested particularly in the higher stages of action processing.

The reduction of hippocampal volume in Parkinson's disease.

The volume of the hippocampus decreases more slowly than the volume of the cortex during normal aging. We explored changes in the hippocampus-to-cortex volume (HV:CTV) ratio with increasing age in non-demented Parkinson's disease (PD) patients as compared to healthy controls (HC). We also evaluated the association between the HV:CTV ratio and cognitive outcomes. Altogether 130 participants without dementia aged 51-88 years were consecutively enrolled, including 54 PD patients (mean age 67, standard deviation (SD) 8 years) and 76 HC (mean age 69, SD 7 years). All participants underwent structural magnetic resonance examination and psychological evaluation. Hippocampal and cortex volumes were determined from T1 and FLAIR scans using FreeSurfer software, and the HV:CTV ratio was calculated. Regression lines for age-dependence of the HV:CTV ratio for PD and HC groups were calculated. We further assessed the association between the HV:CTV ratio and cognitive tests examining hippocampus-related cognitive functions. PD patients and age-matched HC showed a significant difference in age-dependence of HV:CTV ratio (p value = 0.012), with a decreasing slope in PD and increasing slope in HC. In the PD group, a significant correlation (R = 0.561, p = 0.024) was observed between the HV:CTV ratio and the Digit Symbol-Coding test. The reduction of HV:CTV ratio is accelerated in pathological aging due to PD pathology. The HV:CTV ratio was associated with impaired processing speed, i.e., the cognitive function that is linked to subcortical alterations of both associated basal ganglia circuitry and the hippocampus.

Impact of Prenatal Stress on Amygdala Anatomy in Young Adulthood: Timing and Location Matter.

BACKGROUND: Exposure to maternal stress in utero has long-term implications for the developing brain and has been linked with a higher risk of depression. The amygdala, which develops during the early embryonic stage and is critical for emotion processing, might be particularly sensitive. METHODS: Using data from a neuroimaging follow-up of the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort (n = 129, 47% men, 23-24 years old), we studied the impact of prenatal stress during the first and second halves of pregnancy on the volume of the amygdala and its nuclei in young adult offspring. We further evaluated the relationship between amygdala anatomy and offspring depressive symptomatology. Amygdala nuclei were parcellated using FreeSurfer's automated segmentation pipeline. Depressive symptoms were measured via self-report using the Beck Depression Inventory. RESULTS: Exposure to stress during the first half of pregnancy was associated with smaller accessory basal (Cohen's f2 = 0.27, false discovery rate [FDR]-corrected p [pFDR] = .03) and cortical (Cohen's f2 = 0.29, pFDR = .03) nuclei volumes. This effect remained significant after correcting for sex, stress during the second half of pregnancy, maternal age at birth, birth weight, maternal education, and offspring's age at magnetic resonance imaging. These two nuclei showed a quadratic relationship with Beck Depression Inventory scores in young adulthood, where both smaller and larger volumes were associated with more depressive symptoms (accessory basal nucleus: adj. R2 = 0.05, pFDR = .015; cortical nucleus: adj. R2 = 0.04, pFDR = .015). CONCLUSIONS: We conclude that exposure to stress during the first half of pregnancy might have long-term implications for amygdala anatomy, which may in turn predict the experience of depressive symptoms in young adulthood.

Insights into déjà vu: Associations between the frequency of experience and amplitudes of low-frequency oscillations in resting-state functional magnetic resonance imaging.

The phenomenon of déjà vu (DV) has intrigued scientists for decades, yet its neurophysiological underpinnings remain elusive. Brain regions have been identified in which morphometry differs between healthy individuals according to the frequency of their DV experiences. This study built upon these findings by assessing if and how neural activity in these and other brain regions also differ with respect to DV experience. Resting-state fMRI was performed on 68 healthy volunteers, 44 of whom reported DV experiences (DV group) and 24 who did not (NDV group). Using multivariate analyses, we then assessed the (fractional) amplitude of low-frequency fluctuations (fALFF/ALFF), a metric that is believed to index brain tissue excitability, for five discrete frequency bands within sets of brain regions implicated in DV and those comprising the default mode network (DMN). Analyses revealed significantly lower values of fALFF/ALFF for specific frequency bands in the DV relative to the NDV group, particularly within mesiotemporal structures, bilateral putamina, right caudatum, bilateral superior frontal cortices, left lateral parietal cortex, dorsal and ventral medial prefrontal cortex, and the posterior cingulate cortex. The pattern of differences in fALFF/ALFF measures between the brains of individuals who have experienced DV and those who have not provides new neurophysiological insights into this phenomenon, including the potential role of the DMN. We suggest that the erroneous feeling of familiarity arises from a temporary disruption of cortico-subcortical circuitry together with the upregulation of cortical excitability.

Functional neuroanatomy of reading in Czech: Evidence of a dual-route processing architecture in a shallow orthography.

Introduction: According to the strong version of the orthographic depth hypothesis, in languages with transparent letter-sound mappings (shallow orthographies) the reading of both familiar words and unfamiliar nonwords may be accomplished by a sublexical pathway that relies on serial grapheme-to-phoneme conversion. However, in languages such as English characterized by inconsistent letter-sound relationships (deep orthographies), word reading is mediated by a lexical-semantic pathway that relies on mappings between word-specific orthographic, semantic, and phonological representations, whereas the sublexical pathway is used primarily to read nonwords. Methods: In this study, we used functional magnetic resonance imaging to elucidate neural substrates of reading in Czech, a language characterized by a shallo worthography. Specifically, we contrasted patterns of brain activation and connectivity during word and nonword reading to determine whether similar or different neural mechanisms are involved. Neural correlates were measured as differences in simple whole-brain voxel-wise activation, and differences in visual word form area (VWFA) task-related connectivity were computed on the group level from data of 24 young subject. Trial-to-trial reading reaction times were used as a measure of task difficulty, and these effects were subtracted from the activation and connectivity effects in order to eliminate difference in cognitive effort which is naturally higher for nonwords and may mask the true lexicality effects. Results: We observed pattern of activity well described in the literature mostly derived from data of English speakers - nonword reading (as compared to word reading) activated the sublexical pathway to a greater extent whereas word reading was associated with greater activation of semantic networks. VWFA connectivity analysis also revealed stronger connectivity to a component of the sublexical pathway - left inferior frontal gyrus (IFG), for nonword compared to word reading. Discussion: These converging results suggest that the brain mechanism of skilled reading in shallow orthography languages are similar to those engaged when reading in languages with a deep orthography and are supported by a universal dual-pathway neural architecture.

Dance Intervention Impact on Brain Plasticity: A Randomized 6-Month fMRI Study in Non-expert Older Adults.

Background: Dance is a complex activity combining physical exercise with cognitive, social, and artistic stimulation. Objectives: We aimed to assess the effects of dance intervention (DI) on intra and inter-network resting-state functional connectivity (rs-FC) and its association to cognitive changes in a group of non-demented elderly participants. Methods: Participants were randomly assigned into two groups: DI and life as usual (LAU). Six-month-long DI consisted of supervised 60 min lessons three times per week. Resting-state fMRI data were processed using independent component analysis to evaluate the intra and inter-network connectivity of large-scale brain networks. Interaction between group (DI, LAU) and visit (baseline, follow-up) was assessed using ANOVA, and DI-induced changes in rs-FC were correlated with cognitive outcomes. Results: Data were analyzed in 68 participants (DI; n = 36 and LAU; n = 32). A significant behavioral effect was found in the attention domain, with Z scores increasing in the DI group and decreasing in the LAU group (p = 0.017). The DI as compared to LAU led to a significant rs-FC increase of the default mode network (DMN) and specific inter-network pairings, including insulo-opercular and right frontoparietal/frontoparietal control networks (p = 0.019 and p = 0.023), visual and language/DMN networks (p = 0.012 and p = 0.015), and cerebellar and visual/language networks (p = 0.015 and p = 0.003). The crosstalk of the insulo-opercular and right frontoparietal networks were associated with attention/executive domain Z-scores (R = 0.401, p = 0.015, and R = 0.412, p = 0.012). Conclusion: The DI led to intervention-specific complex brain plasticity changes that were of cognitive relevance.

Dynamic Functional Connectivity Signifies the Joint Impact of Dance Intervention and Cognitive Reserve.

Research on dance interventions (DIs) in the elderly has shown promising benefits to physical and cognitive outcomes. The effect of DIs on resting-state functional connectivity (rs-FC) varies, which is possibly due to individual variability. In this study, we assessed the moderation effects of residual cognitive reserve (CR) on DI-induced changes in dynamic rs-FC and their association on cognitive outcomes. Dynamic rs-FC (rs-dFC) and cognitive functions were evaluated in non-demented elderly subjects before and after a 6-month DI (n = 36) and a control group, referred to as the life-as-usual (LAU) group (n = 32). Using linear mixed models and moderation, we examined the interaction effect of DIs and CR on changes in the dwell time and coverage of rs-dFC. Cognitive reserve was calculated as the residual difference between the observed memory performance and the performance predicted by brain state. Partial correlations accounting for CR evaluated the unique association between changes in rs-dFC and cognition in the DI group. In subjects with lower residual CR, we observed DI-induced increases in dwell time [t(58) = -2.14, p = 0.036] and coverage [t(58) = -2.22, p = 0.030] of a rs-dFC state, which was implicated in bottom-up information processing. Increased dwell time was also correlated with a DI-induced improvement in Symbol Search (r = 0.42, p = 0.02). In subjects with higher residual CR, we observed a DI-induced increase in coverage [t(58) = 2.11, p = 0.039] of another rs-dFC state, which was implicated in top-down information processing. The study showed that DIs have a differential and behaviorally relevant effect on dynamic rs-dFC, but these benefits depend on the current CR level.

Inferior parietal lobule involved in representation of "what" in a delayed-action Libet task.

Intentional motor action is typically characterized by the decision about the timing, and the selection of the action variant, known as the "what" component. We compared free action selection with instructed action, where the movement type was externally cued, in order to investigate the action selection and action representation in a Libet's task. Temporal and spatial locus of these processes was examined using the combination of high-density electroencephalography, topographic analysis of variance, and source reconstruction. Instructed action, engaging representation of the response movement, was associated with distinct negativity at the parietal and centro-parietal channels starting around 750 ms before the movement, which has a source particularly in the bilateral inferior parietal lobule. This suggests that in delayed-action tasks, the process of action representation in the inferior parietal lobule may play an important part in the larger parieto-frontal activity responsible for movement selection.

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion-weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR-negative epilepsy patients.

Cerebrocerebellar structural covariance in temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: The purpose of the study was to evaluate cerebral morphological changes in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and their relationship to the cerebellum. METHODS: The study cohort included 21 patients with intractable TLE-HS (14 left-sided, 7 right-sided) and 38 healthy controls (HC). All patients later underwent anteromedial temporal lobe resection. All subjects were examined using a 1.5-T magnetic resonance imaging (MRI). Volumes of distinct cerebral and cerebellar structures were measured using voxel-based morphometry. The structural covariance of temporal lobe structures, insula, and thalamus with cerebellar substructures was examined using partial least squares regression. RESULTS: Morphological changes were more significant in the group with left TLE-HS when comparing left-sided with right-sided structures as well as when comparing patients with controls. The gray matter volume (GMV) of the temporal lobe structures was smaller ipsilaterally to the seizure onset side in most cases. There was a significant amygdala enlargement contralateral to the side of hippocampal sclerosis in both patients with right and left TLE-HS as compared with controls. Selected vermian structures in patients with left but not right TLE-HS had significantly larger GMV than the identical substructures in controls. The structural covariance differed significantly between patients with left and right TLE-HS as compared with HC. The analysis revealed significant negative covariance between anterior vermis and mesial temporal structures in the group with left TLE-HS. No significance was observed for the group with right TLE-HS. CONCLUSION: There is significant asymmetry in the GMV of cerebral and cerebellar structures in patients with TLE-HS. Morphological changes are distinctly more pronounced in patients with left TLE-HS. The observed structural covariance between the cerebellum and supratentorial structures in TLE-HS suggests associations beyond the mesial temporal lobe structures and thalamus.

Maternal Depressive Symptoms During Pregnancy and Brain Age in Young Adult Offspring: Findings from a Prenatal Birth Cohort.

Maternal depression during pregnancy is associated with elevated risk of anxiety and depression in offspring, but the mechanisms are incompletely understood. Here we conducted a neuroimaging follow-up of a prenatal birth cohort from the European Longitudinal Study of Pregnancy and Childhood (n = 131; 53% women, age 23-24) to test whether deviations from age-normative structural brain development in young adulthood may partially underlie this link. Structural brain age was calculated based on previously published neuroanatomical age prediction models using cortical thickness maps from healthy controls aged 6-89. Brain age gap was computed as the difference between chronological and structural brain age. Participants also completed self-report measures of anxiety and mood dysregulation. Further, mothers of a subset of participants (n = 103, 54% women) answered a self-report questionnaire in 1990-1992 about depressive symptoms during pregnancy. Higher exposure to maternal depressive symptoms in utero showed a linear relationship with elevated brain age gap, which showed a quadratic relationship with anxiety and mood dysregulation in the young adult offspring. Our findings suggest that exposure to maternal depressive symptoms in utero may be associated with accelerated brain maturation and that deviations from age-normative structural brain development in either direction predict more anxiety and dysregulated mood in young adulthood.

The role of the striatum in visuomotor integration during handwriting: an fMRI study.

This study investigates the role of the dorsal/sensorimotor striatum in visuomotor integration (i.e., the transformation of internal visual information about letter shapes into motor output) during handwriting. Twenty healthy participants underwent fMRI scanning with tasks consisting of self-paced handwriting of alphabetically ordered single letters and simple dots, with both tasks performed without visual feedback. Functional connectivity (FC) from these two tasks was compared to demonstrate the difference between coordinated activity arising during handwriting and the activity during a simpler motor condition. Our study focused upon the writing-specific cortico-striatal network of preselected regions of interest consisting of the visual word form area (VWFA), anterior intraparietal sulcus/superior parietal lobule, striatum, premotor cortex/Exner's area, and primary and supplementary motor regions. We observed systematically increased task-induced cortico-striatal and cortico-cortical FC. This increased synchronization of neural activity between the VWFA, i.e., the visual cortical area containing information about letter shapes, and the frontoparietal motor regions is mediated by the striatum. These findings suggest the involvement of the striatum in integrating stored letter-shape information with motor planning and execution during handwriting.