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Abstract 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.

IntroductionThe 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.MethodsDNA 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.ResultsThe 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.DiscussionWe 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.

BackgroundObesity 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).MethodsA 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.ResultsAfter 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]).ConclusionThese 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.

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.

Cortical changes associated with cognitive decline in Parkinson's disease (PD) are not fully explored and require investigations with established diagnostic classification criteria.We used MRI source-based morphometry to evaluate specific differences in grey matter volume patterns across 4 groups of subjects: healthy controls (HC), PD with normal cognition (PD-NC), PD with mild cognitive impairment (MCI-PD) and PD with dementia (PDD).We examined 151 consecutive subjects: 25 HC, 75 PD-NC, 29 MCI-PD, and 22 PDD at an Italian and Czech movement disorder centre. Operational diagnostic criteria were applied to classify MCI-PD and PDD. All structural MRI images were processed together in the Czech centre. The spatial independent component analysis was used to assess group differences of local grey matter volume.We identified two independent patterns of grey matter volume deviations: a) Reductions in the hippocampus and temporal lobes; b) Decreases in fronto-parietal regions and increases in the midbrain/cerebellum. Both patterns differentiated PDD from all other groups and correlated with visuospatial deficits and letter verbal fluency, respectively. Only the second pattern additionally differentiated PD-NC from HC.Grey matter changes in PDD involve areas associated with Alzheimer-like pathology while fronto-parietal abnormalities are possibly an early marker of PD cognitive decline. These findings are consistent with a non-linear cognitive progression in PD.

IntroductionAltered subjective visual sensitivity manifests as feelings of discomfort or overload elicited by intense and irritative visual stimuli. This can result in a host of visual aberrations including visual distortions, elementary visual hallucinations and visceral responses like dizziness and nausea, collectively referred to as “pattern glare.” Current knowledge of the underlying neural mechanisms has focused on overall excitability of the visual cortex, but the individual contribution of excitatory and inhibitory systems has not yet been quantified.MethodsIn this study, we focus on the role of glutamate and γ-aminobutyric acid (GABA) as potential mediators of individual differences in subjective visual sensitivity, measured by a computerized Pattern Glare Test—a series of monochromatic square-wave gratings with three different spatial frequencies, while controlling for psychological variables related to sensory sensitivity with multiple questionnaires. Resting neurotransmitter concentrations in primary visual cortex (V1) and right anterior insula were studied in 160 healthy participants using magnetic resonance spectroscopy.ResultsData showed significant differences in the perception of visual distortions (VD) and comfort scores between men and women, with women generally reporting more VD, and therefore the modulatory effect of sex was considered in a further examination. A general linear model analysis showed a negative effect of occipital glutamate on a number of reported visual distortions, but also a significant role of several background psychological traits. When assessing comfort scores in women, an important intervening variable was the menstrual cycle.DiscussionOur findings do not support that baseline neurotransmitter levels have a significant role in overreactivity to aversive stimuli in neurotypical population. However, we demonstrated that biological sex can have a significant impact on subjective responses. Based on this additional finding, we suggest that future studies investigate aversive visual stimuli while examining the role of biological sex.

Abstract 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.

Abstract 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.

IntroductionAccording 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.MethodsIn 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.ResultsWe 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.DiscussionThese 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.

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.

Interoception plays a key role in experiencing emotions, as it provides information about bodily arousal. Cardiac feedback manipulation proved to be a useful tool for exploring interoceptive processes. However, previous research showed inconclusive results on the influence of synchronous and false cardiac feedback on autonomic arousal. In the present study, we measured the influence of accelerated false cardiac feedback on participants’ heart rate, respiratory rate and heart rate variability. Furthermore, we were interested in the modulatory effect of interoceptive accuracy measured by the Schandry task. Participants’ ECG and respiratory rate were recorded during experimental task involving presentation of synchronous and false auditory cardiac feedback. Contrary to our assumption, false cardiac feedback elicited deceleration of heart rate and reduction of heart rate variability. Interoceptive accuracy had no effect on either variable. According to participant’s reports, cardiac and the respiratory deceleration may come from down-regulatory responses to the distorted feedback.

Purpose: Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by focal seizures with dominant auditory symptomatology. We present a case report of an 18-year-old patient with acute onset of seizures associated with epilepsy. Based on the clinical course of the disease and the results of the investigation, the diagnosis of ADLTE with a proven mutation in the RELN gene, which is considered causative, was subsequently confirmed. The aim of this study was to use 3 Tesla (3 T) magnetic resonance imaging (MRI) and advanced neuroimaging methods in a patient with a confirmed diagnosis of ADTLE. Methods: 3 T MRI brain scan and advanced neuroimaging methods were used in the standard protocols to analyzse voxel-based MRI, cortical thickness, and functional connectivity. Results: Morphometric MRI analysis (blurred grey-white matter junctions, voxel-based morphometry, and cortical thickness analysis) did not provide any informative results. The functional connectivity analysis revealed higher local synchrony in the patient in the left temporal (middle temporal gyrus), left frontal (supplementary motor area, superior frontal gyrus), and left parietal (gyrus angularis, gyrus supramarginalis) regions and the cingulate (middle cingulate gyrus) as compared to healthy controls. Conclusions: Evidence of multiple areas of functional connectivity supports the theory of epileptogenic networks in ADTLE. Further studies are needed to elucidate this theory. Keywords: Autosomal dominant temporal lobe epilepsy, RELN gene, 3 Tesla brain MRI, Functional connectivity, Epileptogenic networks

Objectives: The aim was to describe the contribution of basal ganglia (BG) thalamo-cortical circuitry to the whole-brain functional connectivity in focal epilepsies. Methods: Interictal resting-state fMRI recordings were acquired in 46 persons with focal epilepsies. Of these 46, 22 had temporal lobe epilepsy: 9 left temporal (LTLE), 13 right temporal (RTLE); 15 had frontal lobe epilepsy (FLE); and 9 had parietal/occipital lobe epilepsy (POLE). There were 20 healthy controls. The complete weighted network was analyzed based on correlation matrices of 90 and 194 regions. The network topology was quantified on a global and regional level by measures based on graph theory, and connection-level changes were analyzed by the partial least square method. Results: In all patient groups except RTLE, the shift of the functional network topology away from random was observed (normalized clustering coefficient and characteristic path length were higher in patient groups than in controls). Links contributing to this change were found in the cortico-subcortical connections. Weak connections (low correlations) consistently contributed to this modification of the network. The importance of regions changed: decreases in the subcortical areas and both decreases and increases in the cortical areas were observed in node strength, clustering coefficient and eigenvector centrality in patient groups when compared to controls. Node strength decreases of the basal ganglia, i.e. the putamen, caudate, and pallidum, were displayed in LTLE, FLE, and POLE. The connectivity within the basal ganglia–thalamus circuitry was not disturbed; the disturbance concerned the connectivity between the circuitry and the cortex. Significance: Focal epilepsies affect large-scale brain networks beyond the epileptogenic zones. Cortico-subcortical functional connectivity disturbance was displayed in LTLE, FLE, and POLE. Significant changes in the resting-state functional connectivity between cortical and subcortical structures suggest an important role of the BG and thalamus in focal epilepsies.

Introduction: Recent studies of patients with multiple sclerosis (MS) have revealed disturbances in distinct components of social cognition, such as impaired mentalizing and empathy. The present study investigated this socio-cognitive profile in MS patients in more detail, by examining their performance on tasks measuring more fundamental components of social cognition and any associated disruptions to gray-matter volume (GMV).Methods: We compared 43 patients with relapse-remitting MS with 43 age- and sex-matched healthy controls (HCs) on clinical characteristics (depression, fatigue), cognitive processing speed, and three aspects of low-level social cognition; specifically, imitative tendencies, visual perspective taking, and emotion recognition. Using voxel-based morphometry, we then explored relationships between GMV and these clinical and behavioral measures.Results: Patients exhibited significantly slower processing speed, poorer perspective taking, and less imitation compared with HCs. These impairments were related to reduced GMV throughout the putamen, thalami, and anterior insula, predominantly in the left hemisphere. Surprisingly, differences between the groups in emotion recognition were not significant.Conclusion: Less imitation and poorer perspective taking indicate a cognitive self-bias when faced with conflicting self- and other-representations. This suggests that impaired self-other distinction, and an associated subcortical pattern of GM atrophy, might underlie the socio-cognitive disturbances observed in MS.

Moving in a co-ordinated fashion with another individual changes our behaviour towards them; we tend to like them more, find them more attractive, and are more willing to co-operate with them. It is generally assumed that this effect on behaviour results from alterations in representations of self and others. Specifically, through neurophysiological perception-action matching mechanisms, interpersonal motor co-ordination (IMC) is believed to forge a neural coupling between actor and observer, which serves to blur boundaries in conceptual self-other representations and causes positive views of the self to be projected onto others. An investigation into this potential neural mechanism is lacking, however. Moreover, the specific components of IMC that might influence this mechanism have not yet been specified. In the present study we exploited a robust behavioural phenomenon--automatic imitation--to assess the degree to which IMC influences neural action observation-execution matching mechanisms. This revealed that automatic imitation is reduced when the actions of another individual are perceived to be synchronised in time, but are spatially incongruent, with our own. We interpret our findings as evidence that IMC does indeed exert an effect on neural perception-action matching mechanisms, but this serves to promote better self-other distinction. Our findings demonstrate that further investigation is required to understand the complex relationship between neural perception-action coupling, conceptual self-other representations, and social behaviour.

Using intracerebral EEG recordings in a large cohort of human subjects, we investigate the time course of neural cross-talk during a simple cognitive task. Our results show that human brain dynamics undergo a characteristic sequence of synchronization patterns across different frequency bands following a visual oddball stimulus. In particular, an initial global reorganization in the delta and theta bands (2-8 Hz) is followed by gamma (20-95 Hz) and then beta band (12-20 Hz) synchrony.