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Although alterations of the default mode network (DMN) in schizophrenia (SZ) have been largely investigated, less research has been carried out on DMN alterations in different sub-phenotypes of this disorder. The aim of this pilot study was to compare DMN features among SZ patients with and without auditory verbal hallucinations (AVH). Three groups of 17 participants each were considered: patients with hallucinations (AVH-SZ), patients without hallucinations (nAVH-SZ) and age-matched healthy controls (HC). The DMN spatial pattern was similar between the nAVH-SZ and HC, but the comparison between these two groups and the AVH-SZ group revealed alterations in the left Angular Gyrus (lAG) node of the DMN. Using a novel approach based on normalized fractional Amplitude of Low-Frequency Fluctuations (fALFF), the AVH-SZ subgroup showed altered spectral activity in the DMN compared with the other two groups, especially in the lower-frequency bands (0.017-0.04 Hz). Significant positive correlations were found for both SZ groups collapsed, and for the nAVH-SZ group alone between delusional scores (PANSS-P1) and slow fALFF bands of the DMN. Narrowing the analysis to the ROI centered on the lAG, significant correlations were found in the AVH-SZ group for hallucination scores (PANSS-P3) and Slow-5 and Slow-4 (both positive), and Slow-3 (negative) fALFF bands. Our results reveal the central role of the lAG in relation to hallucinations, an important cortical area connecting auditory cortex with several hubs (including frontal linguistic centers) and involved in auditory process monitoring.

The visual cortex has been extensively studied to investigate its role in object recognition but to a lesser degree to determine how action planning influences the representation of objects' features. We used functional MRI and pattern classification methods to determine if during action planning, object features (orientation and location) could be decoded in an action-dependent way. Sixteen human participants used their right dominant hand to perform movements (Align or Open reach) towards one of two 3D-real oriented objects that were simultaneously presented and placed on either side of a fixation cross. While both movements required aiming towards target location, Align but not Open reach movements required participants to precisely adjust hand orientation. Therefore, we hypothesized that if the representation of object features is modulated by the upcoming action, pre-movement activity pattern would allow more accurate dissociation between object features in Align than Open reach tasks. We found such dissociation in the anterior and posterior parietal cortex, as well as in the dorsal premotor cortex, suggesting that visuomotor processing is modulated by the upcoming task. The early visual cortex showed significant decoding accuracy for the dissociation between object features in the Align but not Open reach task. However, there was no significant difference between the decoding accuracy in the two tasks. These results demonstrate that movement-specific preparatory signals modulate object representation in the frontal and parietal cortex, and to a lesser extent in the early visual cortex, likely through feedback functional connections.

Background: Functional movement disorders include a wide spectrum of clinically documented movement disorders without an apparent organic substrate. Objective: To explore the functional connectivity (FC) of the primary motor (M1) cortex in functional dystonia (FD) patients relative to healthy controls, with a focus on different clinical phenotypes. Methods: Forty FD patients (12 fixed [FixFD]; 28 mobile [MobFD]) and 43 healthy controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]) underwent resting state fMRI. A seed-based FC analysis was performed using bilateral M1 as regions of interest. Results: Compared to controls, FD patients showed reduced FC between left M1 and left dorsal anterior cingulate cortex, and between right M1 and left M1, premotor/supplementary motor area (SMA), dorsal posterior cingulate cortex (PCC), and bilateral precuneus. Relative to yHC, FixFD patients showed reduced FC between M1 and precuneus bilaterally. Compared to oHC, MobFD patients revealed reduced FC between right M1 and left M1, premotor/SMA, dorsal-PCC, bilateral primary sensory cortices and parieto-occipital areas, and increased FC of right M1 with right associative visual cortex and bilateral ventral-PCC. FixFD patients, relative to MobFD, showed lower FC between the right M1 and right associative visual area, and bilateral precuneus and ventral-PCC. Conclusions: This study suggests an altered brain FC of the motor circuit with areas involved in emotional processes and sense of agency in FD. FixFD patients showed FC abnormalities mainly in areas related to sense of agency, while MobFD in regions involved in sensorimotor functions (reduced FC) and emotional processing (increased FC).

Graphical abstract, Highlights • Associations between caregiver-infant behaviours during social interactions and brain development outcomes were investigated. • Caregivers' and infants' behaviours in interactions related to children’s structural, functional and connectivity measures. • Concurrent associations between behavioural and brain measures were apparent as early as three months postnatally. • Long-term associations between behaviours in early interactions and brain development outcomes were observed decades later. • Individual differences in early interactions and associated brain development is an important avenue for further research., From birth, interactions with others are an integral part of a person’s daily life. In infancy, social exchanges are thought to be critical for optimal brain development. This systematic review explores this association by drawing together infant studies that relate adult-infant behaviours – coded from their social interactions - to children’s brain measures collected during a neuroimaging session in infancy, childhood, adolescence or adulthood. In total, we identified 55 studies that explored associations between infants’ social interactions and neural measures. These studies show that several aspects of caregiver-infant behaviours are associated with, or predict, a variety of neural responses in infants, children and adolescents. The presence of both concurrent and long-term associations - some of which are first observed just a few months postnatally and extend into adulthood - open an important research avenue and motivate further longitudinal studies.

Background: Brain interdependencies can be studied from either a structural/anatomical perspective ("structural connectivity") or by considering statistical interdependencies ("functional connectivity" [FC]). Interestingly, while structural connectivity is by definition pairwise (white-matter fibers project from one region to another), FC is not. However, most FC analyses only focus on pairwise statistics and they neglect higher order interactions. A promising tool to study high-order interdependencies is the recently proposed O-Information, which can quantify the intrinsic statistical synergy and the redundancy in groups of three or more interacting variables. Methods: We analyzed functional magnetic resonance imaging (fMRI) data obtained at rest from 164 healthy subjects with ages ranging in 10 to 80 years and used O-Information to investigate how high-order statistical interdependencies are affected by age. Results: Older participants (from 60 to 80 years old) exhibited a higher predominance of redundant dependencies compared with younger participants, an effect that seems to be pervasive as it is evident for all orders of interaction. In addition, while there is strong heterogeneity across brain regions, we found a "redundancy core" constituted by the prefrontal and motor cortices in which redundancy was evident at all the interaction orders studied. Discussion: High-order interdependencies in fMRI data reveal a dominant redundancy in functions such as working memory, executive, and motor functions. Our methodology can be used for a broad range of applications, and the corresponding code is freely available. Impact statement Past research has showcased multiple changes to the brain's structural and functional properties caused by aging. Here we expand prior work through recent advancements in multivariate information theory, which provide richer and more theoretically principled analyses than existing alternatives. We show that the brains of older participants contain more redundant information at multiple spatial scales-that is, activation in different brain regions is less diverse, compared with younger participants-and identify a "redundancy core" constituted by prefrontal and motor cortices, which might explained impaired performance in the old population in functions such as working memory and executive control. ispartof: BRAIN CONNECTIVITY vol:11 issue:9 pages:734-744 ispartof: location:United States status: published

© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Introduction: We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods: For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights: We investigated brain network predictors of dementia symptom onset Frontotemporal dementia results in characteristic dynamic network patterns Alterations in network dynamics are associated with neuropsychological impairment Network dynamic changes predict symptomatic conversion in presymptomatic carriers Network dynamic changes are associated with longitudinal cognitive decline., GENFI was funded by the Medical Research Council UK (MR/M023664/1), the Bluefield Project, the JPND GENFI-PROX grant (by DLR/BMBF 2019-02248) and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198). The study was co-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge (BRC-1215-20014), the Cambridge Centre for Parkinson-plus (RG95450); the Wellcome Trust (220258); the Evelyn Trust (17/09) and Medical Research Council (SUAG/092 116768).

Brain decoding is a process of decoding human cognitive contents from brain activities. However, improving the accuracy of brain decoding remains difficult due to the unique characteristics of the brain, such as the small sample size and high dimensionality of brain activities. Therefore, this paper proposes a method that effectively uses multi-subject brain activities to improve brain decoding accuracy. Specifically, we distinguish between the shared information common to multi-subject brain activities and the individual information based on each subject’s brain activities, and both types of information are used to decode human visual cognition. Both types of information are extracted as features belonging to a latent space using a probabilistic generative model. In the experiment, an publicly available dataset and five subjects were used, and the estimation accuracy was validated on the basis of a confidence score ranging from 0 to 1, and a large value indicates superiority. The proposed method achieved a confidence score of 0.867 for the best subject and an average of 0.813 for the five subjects, which was the best compared to other methods. The experimental results show that the proposed method can accurately decode visual cognition compared with other existing methods in which the shared information is not distinguished from the individual information.

The ability to keep track of time is one of the fundamental human behaviours that enhance survival in the wild. It is still an essential skill that enables an individual to function well in modern society. In the present study, we tested the attentional gate model, one of the most common conceptual frameworks in studies of subjective time perception. Its utility has been well established, but it has been criticised for its lack of neurophysiological support; few studies attempted to systematically identify its components and their neural correlates. Previous studies established that the dorsolateral prefrontal cortex (DLPFC) was associated with working memory tasks and a correlation between activity in the cerebellum and the timing of tasks. An fMRI study was conducted to confirm that these two cortical regions were activated during the execution of a new time discrimination task that considers individual variations in subjective time perception. Simulations were conducted to optimize the electrode placement in order to maximize the electric fields of tDCS perturbation to these two areas. According to the attentional gate model, hypotheses about tDCS perturbation to subjective time perception, attention and working memory were formulated and tested. Attention and working memory were measured by the attention network and N-back tasks. There are weak effects to the perceived subjective equivalent and the reaction time in the attention network task, but both are not statistically significant after correction for multiple comparisons. Exploration analyses show a link between attention and subjective time perception after tDCS perturbation. To conclude, the results do not support the attentional gate model, but show a linkage between attention and subjective time perception in terms of similar neural circuits and their relationships under certain circumstances.

Postnatal depression (PND) has an estimated prevalence of 6.5 to 12.9%. In addition to the direct consequences for women, PND also interferes with the maternal-infant interaction, contributing to long-term cognitive and emotional impairments in exposed offspring. It is unclear how PND differs from major depressive disorder (MDD) more generally, and if PND represents a distinct subtype of depression. We explored whether women with a history of PND have specific differences in brain activation associated with sex hormone changes during the late luteal phase of the menstrual cycle, compared to parous women with either a past history of MDD outside of the postnatal period, or an absent history of MDD (‘never depressed’). Thirty mothers (history of PND (n = 10), history of MDD (n = 10), and ‘never depressed’ (n = 10)) underwent blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) acquisition during an emotional faces task. Amygdala activity was analysed using a region of interest (small volume correction) approach. There was a significant reduction in BOLD response to positive emotional faces in the right amygdala in women with a history of PND compared to women with a history of MDD. A similar but non-significant trend was found in the left amygdala in women with a history of PND compared to ‘never depressed’ women. Our findings support the hypothesis that women with vulnerability to PND represent a distinct subgroup of women with a differential sensitivity to changes in sex hormones. Further, albeit highly tentative, they provide a putative biomarker that could assist in detection of women at-risk to PND. Electronic supplementary material The online version of this article (10.1007/s00737-020-01051-x) contains supplementary material, which is available to authorized users.

Background and Objectives: Family-based behavioral treatment (FBT) is the recommended treatment for children with common obesity. However, there is a large variability in short- and long-term treatment response and mechanisms for unsuccessful treatment outcomes are not fully understood. In this study, we tested if brain response to visual food cues among children with obesity before treatment predicted weight or behavioral outcomes during a 6-mo. behavioral weight management program and/or long-term relative weight maintenance over a 1-year follow-up period. Subjects and Methods: Thirty-seven children with obesity (age 9–11y, 62% male) who entered active FBT (attended 2 or more sessions) and had outcome data. Brain activation was assessed at pre-treatment by functional magnetic resonance imaging across an a priori set of appetite-processing brain regions that included the ventral and dorsal striatum, medial orbitofrontal cortex, amygdala, substantia nigra/ventral tegmental area and insula in response to viewing food images before and after a standardized meal. Results: Children with more robust reductions in brain activation to high-calorie food cue images following a meal had greater declines in BMI z-score during FBT (r= 0.42; 95% CI: 0.09, 0.66; P=0.02) and greater improvements in Healthy Eating Index scores (r= −0.41; 95% CI: −0.67, −0.06; P=0.02). In whole-brain analyses, greater activation in the ventromedial prefrontal cortex, specifically by high-calorie food cues, was predictive of better treatment outcomes (whole-brain cluster corrected P=0.02). There were no significant predictors of relative weight maintenance and initial behavioral or hormonal measures did not predict FBT outcomes. Conclusions: Children’s brain responses to a meal prior to obesity treatment were related to treatment-based weight outcomes, suggesting that neurophysiologic factors and appetitive drive, more so than initial hormone status or behavioral characteristics, limit intervention success.

Background: Motor impairments in those with isolated REM sleep behaviour disorder (iRBD) significantly increases the likelihood of developing Lewy body disease (e.g. Parkinson’s disease and Dementia with Lewy Bodies). Objective: This study sought to explore the prodromal process of neurodegeneration by examining the neural signature underlying motor deficits in iRBD patients. Methods: A virtual reality (VR) gait paradigm (which has previously been shown to elicit adaptive changes in gait performance whilst navigating doorways in Parkinson’s Disease - PD) was paired with fMRI to investigate whether iRBD patients demonstrated worsened motor performance and altered connectivity across frontoparietal, motor and basal ganglia networks compared to healthy controls. Forty participants (23 iRBD and 17 healthy controls) completed the virtual reality gait task whilst in the MRI scanner, and an additional cohort of 19 Early PD patients completed the behavioural virtual reality gait task. Results: As predicted, iRBD patients demonstrated slower and more variable stepping compared to healthy control participants and demonstrated an exaggerated response when navigating narrow compared to wide doorways, a phenomenon characteristically seen in PD. The iRBD patients also demonstrated less BOLD signal change in the left posterior putamen and right mesencephalic locomotor region, as well as reduced functional connectivity between the frontoparietal network and the motor network, when navigating narrow versus wide doorways compared to healthy control participants. Conclusions: Taken together, this study demonstrates that iRBD patients have altered task-related brain connectivity, which may represent the neural underpinnings of early motor impairments that are evident in iRBD.

Background With increasing obese populations worldwide, developing interventions to modulate food-related brain processes and functions is particularly important. Evidence suggests that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may modulate the reward–control balance towards facilitation of cognitive control and possible suppression of reward-related mechanisms that drive food cue-induced craving. This protocol describes a clinical trial that investigates the neurocognitive mechanisms of action for tDCS to modulate food cue-reactivity and cravings in people with obesity. Method The NeuroStim-Obesity trial is a prospective, randomized, sham-controlled, double-blind single-session tDCS trial targeting food craving in those with obesity or overweighed. Once randomized, 64 adults with obesity or overweighed complete one session in which they receive either active or sham tDCS over the DLPFC (anode F4 and cathode F3, 2 mA intensity for 20 min). The primary outcome is change in neural response to the food cue-reactivity task in the ventral striatum after a single-session bilateral tDCS compared to sham stimulation. Secondary outcomes include changes in food craving evaluated by the Food Craving Questionnaire-State (FCQ-S). We will also explore the predictive role of brain structure and functional networks assessed by structural and functional magnetic resonance imaging (MRI) during both task performance and the resting-state that are acquired pre- and post-intervention to predict response to tDCS. Discussion The results will provide novel insight into neuroscience for the efficacy of tDCS and will advance the field towards precision medicine for obesity. Exploratory results will examine the potential predictive biomarkers for tDCS response and eventually provide personalized intervention for the treatment of obesity. Trial registration Iranian Registry of Clinical Trials (IRCT) IRCT20121020011172N4. Retrospectively registered on 4 June 2020

The preservation of cognitive function into old age is a public health priority. Cerebral hypoperfusion is a hallmark of dementia but its impact on maintaining cognitive ability across the lifespan is less clear. We investigated the relationship between baseline cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) response during a fluid reasoning task in a population-based adult lifespan cohort. As age differences in CBF could lead to non-neuronal contributions to the BOLD signal, we introduced commonality analysis to neuroimaging to dissociate performance-related CBF effects from the physiological confounding effects of CBF on the BOLD response. Accounting for CBF, we confirmed that performance- and age-related differences in BOLD responses in the multiple-demand network were implicated in fluid reasoning. Age differences in CBF explained not only performance-related BOLD responses, but also performance-independent BOLD responses. Our results suggest that CBF is important for maintaining cognitive function, while its non-neuronal contributions to BOLD signals reflect an age-related confound. Maintaining perfusion into old age may serve to support brain function and preserve cognitive performance.

This review focuses on the evidence for neurotherapeutics for attention deficit/hyperactivity disorder (ADHD). EEG-neurofeedback has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safety and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatment.

Pain perception and the ability to modulate arising pain vary tremendously between individuals. It has been shown that endurance athletes possess higher pain tolerance thresholds and a greater effect of conditioned pain modulation than nonathletes, both indicating a more efficient system of endogenous pain inhibition. The aim of the present study was to focus on the neural mechanisms of pain processing in endurance athletes that have not been investigated yet. Therefore, we analyzed the pain processing of 18 male athletes and 19 healthy male nonathletes using functional magnetic resonance imaging. We found lower pain ratings in endurance athletes compared to nonathletes to physically identical painful stimulation. Furthermore, brain activations of athletes versus nonathletes during painful heat stimulation revealed reduced activation in several brain regions that are typically activated by nociceptive stimulation. This included the thalamus, primary and secondary somatosensory cortex, insula, anterior cingulate cortex, midcingulate cortex, dorsolateral prefrontal cortex, and brain stem (BS). Functional connectivity analyses revealed stronger network during painful heat stimulation in athletes between the analyzed brain regions except for connections with the BS that showed reduced functional connectivity in athletes. Post hoc correlation analyses revealed associations of the subject's fitness level and the brain activation strengths, subject's fitness level and functional connectivity, and brain activation strengths and functional connectivity. Together, our results demonstrate for the first time that endurance athletes do not only differ in behavioral variables compared to nonathletes, but also in the neural processing of pain elicited by noxious heat., The aim of the present study was to focus on the neural mechanisms of pain processing in endurance athletes that have not been investigated yet. Therefore, we analyzed the pain processing of 18 male athletes and 19 healthy male nonathletes using functional magnetic resonance imaging. Together, our results demonstrate for the first time that endurance athletes do not only differ in behavioral variables compared to nonathletes, but also in the neural processing of pain elicited by noxious heat.

Bipolar disorder (BD) is a psychiatric condition causing acute dysfunctional mood states and emotion regulation. Specific neuropsychological features are often present also among patients in euthymic phase, who do not show clear psychotic symptoms, and for whom the characterization from functional magnetic resonance imaging (fMRI) is very limited. This study aims at identifying the neural and behavioral correlates of the default mode network (DMN) using the fractional amplitude of low frequency fluctuations (fALFF). Eighteen euthymic BD patients (10 females; age = 54.50 ± 11.38 years) and sixteen healthy controls (HC) (8 females; age = 51.16 ± 11.44 years) underwent a 1.5T fMRI scan at rest. The DMN was extracted through independent component analysis. Then, DMN time series was used to compute the fALFF, which was correlated with clinical scales. From the between-group comparison, no significant differences emerged in correspondence to regions belonging to the DMN. For fALFF analysis, we reported significant increase of low-frequency fluctuations for lower frequencies, and decreases for higher frequencies compared to HC. Correlations with clinical scales showed that an increase in higher frequency spectral content was associated with lower levels of mania and higher levels of anxious symptoms, while an increase in lower frequencies was linked to lower depressive symptoms. Starting from our findings on the DMN in euthymic BD patients, we suggest that the fALFF derived from network time series represents a viable approach to investigate the behavioral correlates of resting state networks, and the pathophysiological mechanisms of different psychiatric conditions.

Background Comprehensive hemodynamic impairment mapping using blood oxygenation‐level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age‐matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO 2 stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion‐weighted imaging. Sixty‐seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole‐brain and ipsilateral hemisphere mean BOLD‐CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, P =0.004 and 0.09±0.09 versus 0.18±0.04, P P =0.01 and 0.09±0.09 versus 0.15±0.05, P =0.01); however, only 40 (58%) patients of the cohort showed significant BOLD‐CVR impairment. Conversely, there was no difference in mean BOLD‐CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD‐CVR impairment. No significant BOLD‐CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06, P =0.12). Conclusions Comprehensive BOLD‐CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.

Dynamic facial expressions of emotions constitute natural and powerful means of social communication in daily life. A number of previous neuroimaging studies have explored the neural mechanisms underlying the processing of dynamic facial expressions, and indicated the activation of certain social brain regions (e.g., the amygdala) during such tasks. However, the activated brain regions were inconsistent across studies, and their laterality was rarely evaluated. To investigate these issues, we measured brain activity using functional magnetic resonance imaging in a relatively large sample (n = 51) during the observation of dynamic facial expressions of anger and happiness and their corresponding dynamic mosaic images. The observation of dynamic facial expressions, compared with dynamic mosaics, elicited stronger activity in the bilateral posterior cortices, including the inferior occipital gyri, fusiform gyri, and superior temporal sulci. The dynamic facial expressions also activated bilateral limbic regions, including the amygdalae and ventromedial prefrontal cortices, more strongly versus mosaics. In the same manner, activation was found in the right inferior frontal gyrus (IFG) and left cerebellum. Laterality analyses comparing original and flipped images revealed right hemispheric dominance in the superior temporal sulcus and IFG and left hemispheric dominance in the cerebellum. These results indicated that the neural mechanisms underlying processing of dynamic facial expressions include widespread social brain regions associated with perceptual, emotional, and motor functions, and include a clearly lateralized (right cortical and left cerebellar) network like that involved in language processing.

Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer's disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown. In this paper, we propose an extended HOFC method, termed inter-network high-order FC (IN-HOFC), as a useful complement to the traditional inter-network FC methods, for characterizing more complex organizations among the large-scale brain networks. In the IN-HOFC, both network definition and inter-network FC are defined in a high-order manner. To test whether IN-HOFC is more sensitive to cognition decline due to brain diseases than traditional inter-network FC, 77 mild cognitive impairments (MCIs) and 89 controls are compared among the conventional methods and our IN-HOFC. The result shows that IN-HOFCs among three temporal lobe-related high-order networks are dampened in MCIs. The impairment of IN-HOFC is especially found between the anterior and posterior medial temporal lobe and could be a potential MCI biomarker at the network level. The competing network-level low-order FC methods, however, either revealing less or failing to detect any group difference. This work demonstrates the biological meaning and potential diagnostic value of the IN-HOFC in clinical neuroscience studies.

BackgroundAutism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD) are neurodevelopmental disorders with considerable overlap in terms of their defining symptoms of compulsivity/repetitive behaviour. Little is known about the extent to which ASD and OCD have common versus distinct neural correlates of compulsivity. Previous research points to potentially common dysfunction in frontostriatal connectivity, but direct comparisons in one study are lacking. Here, we assessed frontostriatal resting-state functional connectivity in youth with ASD or OCD, and healthy controls. In addition, we applied a cross-disorder approach to examine whether repetitive behaviour across ASD and OCD has common neural substrates.MethodsA sample of 78 children and adolescents aged 8–16 years was used (ASD n = 24; OCD n = 25; healthy controls n = 29), originating from the multicentre study COMPULS. We tested whether diagnostic group, repetitive behaviour (measured with the Repetitive Behavior Scale-Revised) or their interaction was associated with resting-state functional connectivity of striatal seed regions.ResultsNo diagnosis-specific differences were detected. The cross-disorder analysis, on the other hand, showed that increased functional connectivity between the left nucleus accumbens (NAcc) and a cluster in the right premotor cortex/middle frontal gyrus was related to more severe symptoms of repetitive behaviour.ConclusionsWe demonstrate the fruitfulness of applying a cross-disorder approach to investigate the neural underpinnings of compulsivity/repetitive behaviour, by revealing a shared alteration in functional connectivity in ASD and OCD. We argue that this alteration might reflect aberrant reward or motivational processing of the NAcc with excessive connectivity to the premotor cortex implementing learned action patterns.

The link between spatial (where) and temporal (when) aspects of the neural correlates of most psychological phenomena is not clear. Elucidation of this relation, which is crucial to fully understand human brain function, requires integration across multiple brain imaging modalities and cognitive tasks that reliably modulate the engagement of the brain systems of interest. By overcoming the methodological challenges posed by simultaneous recordings, the present report provides proof‐of‐concept evidence for a novel approach using three complementary imaging modalities: functional magnetic resonance imaging (fMRI), event‐related potentials (ERPs), and event‐related optical signals (EROS). Using the emotional oddball task, a paradigm that taps into both cognitive and affective aspects of processing, we show the feasibility of capturing converging and complementary measures of brain function that are not currently attainable using traditional unimodal or other multimodal approaches. This opens up unprecedented possibilities to clarify spatiotemporal integration of brain function., By overcoming the methodological challenges posed by simultaneous recordings, the present report provides proof‐of‐concept evidence for a novel approach using three complementary imaging modalities: functional magnetic resonance imaging, event‐related potentials, and event‐related optical signals. Using the emotional oddball task, a paradigm that taps into both cognitive and affective aspects of processing, we show the feasibility of capturing converging and complementary measures of brain function that are not currently attainable using traditional unimodal or other multimodal approaches. This opens up unprecedented possibilities to clarify spatiotemporal integration of brain function.

The aim of this study is to identify robust resting state-functional connectivity (rs-FC) alterations and their correlations with the neuropsychological characteristics of Ultra-High Risk (UHR) for psychosis subjects compared to healthy controls (HCs). Twenty individuals with UHR and sixteen HCs underwent resting-state functional magnetic resonance imaging (rs-fMRI) and a cognitive battery evaluating attention, episodic memory and executive functions. Compared to HCs, UHR individuals showed working memory and set-shifting impairments. In functional connectivity (FC) analyses, the Default Mode Network (DMN) of the UHR subjects displayed increased FC with the visual areas and decreased FC with the Dorsal Attention Network (DAN). Additionally, the salience network (SN) of the UHR subjects displayed increased connectivity with wide posterior cortical areas in the temporal, parietal and occipital lobes, corresponding to posterior nodes of the SN itself, the Somato-Motor Network (SMN) and the DAN. The SN connectivity with the left SMN and DAN was positively correlated with the Trail Making Test - B scores of the UHR subjects. These findings show that the SN and DMN, which mostly show abnormal connectivity patterns in psychosis, are also affected in UHR subjects, while the SN plays a more central role with its hyperconnectivity to the DAN and SMN. WOS:000754753700003 35093807 Q3

Background Escalation of commitment is a common bias in human decision making. The present study examined (1) differences in neural recruitment for escalation and de-escalation decisions of prior investments, and (2) how the activations of these brain networks are affected by two factors that can arguably modulate escalation decisions: (i) self-responsibility, and (ii) framing of the success probabilities. Results Imaging data were obtained from functional magnetic resonance imaging (fMRI) applied to 29 participants. A whole-brain analysis was conducted to compare brain activations between conditions. ROI analysis, then, was used to examine if these significant activations were modulated by two contextual factors. Finally, mediation analysis was applied to explore how the contextual factors affect escalation decisions through brain activations. The findings showed that (1) escalation decisions are faster than de-escalation decisions, (2) the corresponding network of brain regions recruited for escalation (anterior cingulate cortex, insula and precuneus) decisions differs from this recruited for de-escalation decisions (inferior and superior frontal gyri), (3) the switch from escalation to de-escalation is primarily frontal gyri dependent, and (4) activation in the anterior cingulate cortex, insula and precuneus were further increased in escalation decisions, when the outcome probabilities of the follow-up investment were positively framed; and activation in the inferior and superior frontal gyri in de-escalation decisions were increased when the outcome probabilities were negatively framed. Conclusions Escalation and de-escalation decisions recruit different brain regions. Framing of possible outcomes as negative leads to escalation decisions through recruitment of the inferior frontal gyrus. Responsibility for decisions affects escalation decisions through recruitment of the superior (inferior) gyrus, when the decision is framed positively (negatively).

Misinformation has triggered government inquiries and threatens the perceived legitimacy of campaign processes and electoral outcomes. A new identity polarization has arisen between Remain and Leave sympathizers in the UK Brexit debate, with associated accusations of misinformation use. Competing psychological accounts of how people come to accept and defend misinformation pit self-reinforcing motivated cognition against lack of systematic reasoning as possible explanations. We harness insights from political science, cognitive neuroscience and psychology to examine the impact of trust and identity on information processing regarding Brexit in a group of Remain identifiers. Behaviourally, participants' affective responses to Brexit-related information are affected by whether the emotional valence of the message is compatible with their beliefs on Brexit (positive/negative) but not by their trust in the source of information. However, belief in the information is significantly affected by both (dis)trust in information source and by belief compatibility with the valence of the information. Neuroimaging results confirm this pattern, identifying areas involved in judgements of the self, others and automatic processing of affectively threatening stimuli, ultimately supporting motivated cognition accounts of misinformation endorsement. This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.

Functional magnetic resonance imaging (fMRI) can be seriously impaired by patient motion. The purpose of this study was to characterize the typical motion in a clinical population of patients in disorders of consciousness and compare the performance of retrospective correction with rigid-body realignment as implemented in widely used software packages. 63 subjects were scanned with an fMRI visual checkerboard paradigm using a 3 T scanner. Time series were corrected for motion, and the resulting transformations were used to calculate a motion score. SPM, FSL, AFNI and AIR were evaluated by comparing the motion obtained by re-running the tool on the corrected data. A publicly available sample fMRI dataset was modified with the motion detected in each patient with each tool. The performance of each tool was measured by comparing the number of supra-threshold voxels after standard fMRI analysis, both in the sample dataset and in simulated fMRI data. We assessed the effect of user-changeable parameters on motion correction in SPM. We found the equivalent motion in the patient population to be 1.4 mm on average. There was no significant difference in performance between SPM, FSL and AFNI. AIR was considerably worse, and took more time to run. We found that in SPM the quality factor and interpolation method have no effect on the cluster size, while higher separation and smoothing reduce it. We showed that the main packages SPM, FSL and AFNI are equally suitable for retrospective motion correction of fMRI time series. We show that typically only 80% of activated voxels are recovered by retrospective motion correction.

Functional magnetic resonance imaging (fMRI) has become the leading method for measuring the human brain response to sensory stimuli. However, olfaction fMRI lags behind vision and audition fMRI for 2 primary reasons: First, the olfactory brain areas are particularly susceptible to imaging artifacts, and second, the olfactory stimulus is particularly difficult to control in the fMRI environment. A component of the latter is related to the odorant delivery human–machine interface, namely the point where odorants exit the dispensing apparatus to reach at the nose. Previous approaches relied on either nasal cannulas or nasal masks, each associated with particular drawbacks and discomforts. Here, we provide detailed descriptions and instructions for transforming the MRI head-coil into an olfactory microenvironment, or odor canopy, where odorants can be switched on and off in less than 150 ms without cannula or mask. In a proof-of-concept experiment, we demonstrate that odor canopy provides for clearly dissociable odorant presence and absence, with no nonolfactory cues. Moreover, we find that odor canopy is rated more comfortable than nasal mask, and we demonstrate that using odor canopy in the fMRI generates a typical olfactory brain response. We conclude in recommending this approach for minimized discomfort in fMRI of olfaction.

The experimental manipulation of neural activity by neurostimulation techniques overcomes the inherent limitations of correlative recordings, enabling the researcher to investigate causal brain-behavior relationships. But only when stimulation and recordings are combined, the direct impact of the stimulation on neural activity can be evaluated. In humans, this can be achieved non-invasively through the concurrent combination of transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). Concurrent TMS-fMRI allows the assessment of the neurovascular responses evoked by TMS with excellent spatial resolution and full-brain coverage. This enables the functional mapping of both local and remote network effects of TMS in cortical as well as deep subcortical structures, offering unique opportunities for basic research and clinical applications. The purpose of this review is to introduce the reader to this powerful tool. We will introduce the technical challenges and state-of-the art solutions and provide a comprehensive overview of the existing literature and the available experimental approaches. We will highlight the unique insights that can be gained from concurrent TMS-fMRI, including the state-dependent assessment of neural responsiveness and inter-regional effective connectivity, the demonstration of functional target engagement, and the systematic evaluation of stimulation parameters. We will also discuss how concurrent TMS-fMRI during a behavioral task can help to link behavioral TMS effects to changes in neural network activity and to identify peripheral co-stimulation confounds. Finally, we will review the use of concurrent TMS-fMRI for developing TMS treatments of psychiatric and neurological disorders and suggest future improvements for further advancing the application of concurrent TMS-fMRI.

Transcranial direct current stimulation (tDCS) over prefrontal cortex (PFC) regions is currently proposed as therapeutic intervention for major depression and other psychiatric disorders. The in-depth mechanistic understanding of this bipolar and non-focal stimulation technique is still incomplete. In a pilot study, we investigated the effects of bifrontal stimulation on brain metabolite levels and resting state connectivity under the cathode using multiparametric MRI techniques and computational tDCS modeling. Within a double-blind cross-over design, 20 subjects (12 women, 23.7 ± 2 years) were randomized to active tDCS with standard bifrontal montage with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the right DLPFC. Magnetic resonance spectroscopy (MRS) was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma aminobutyric acid (GABA) concentration in these areas. Resting-state functional connectivity MRI (rsfcMRI) was acquired before and after the stimulation. The individual distribution of tDCS induced electric fields (efields) within the MRS voxel was computationally modelled using SimNIBS 2.0. There were no significant changes of Glu, Glx and GABA levels across conditions but marked differences in the course of Glu levels between female and male participants were observed. Further investigation yielded a significantly stronger Glu reduction after active compared to sham stimulation in female participants, but not in male participants. For rsfcMRI neither significant changes nor correlations with MRS data were observed. Exploratory analyses of the effect of efield intensity distribution on Glu changes showed distinct effects in different efield groups. Our findings are limited by the small sample size, but correspond to previously published results of cathodal tDCS. Future studies should address gender and efield intensity as moderators of tDCS induced effects. Electronic supplementary material The online version of this article (10.1007/s00406-020-01177-0) contains supplementary material, which is available to authorized users.

Topics: Functional Magnetic Resonance Imaging (fMRI) evaluation of HyberBaric Oxygen Therapy (HBOT) effects on chronic cerebral stroke Patients (Pts). Introduction: Our aim was to evaluate with fMRI, in a 3 Tesla system, the functional effects of HBOT on the Central Nervous System (CNS) in four Pts with established ischaemic and haemorrhagic cerebral strokes (2 Pts each). To our knowledge, no author used this Magnetic Resonance (MR) technique for this purpose, till now. Methods: All four Pts underwent a fMRI study before and after 40 HBOT sessions, with a time window of a few days. They carried out two language (text listening, silent word-verb generation) and two motor (hand and foot movements) tasks (30 s On-Off block paradigms). Results: After HBOT, all Pts reported a clinical improvement, mostly concerning language fluency and motor paresis. fMRI analysis demonstrated an increase in both the extent and the statistical significance of most of the examined eloquent areas. Conclusions: These changes were consistent with the clinical improvement in all Pts, suggesting a possible role of fMRI in revealing neuronal functional correlates of neuronal plasticity and HBOT-related neoangiogenesis. Although only four Pts were examined, fMRI proved to be a sensitive, non-invasive and reliable modality for monitoring neuronal functional changes before and after HBOT.

[Abstract] Repetitive, monotonic, and effortful voluntary muscle contractions performed for just a few weeks, i.e., resistance training, can substantially increase maximal voluntary force in the practiced task and can also increase gross motor performance. The increase in motor performance is often accompanied by neuroplastic adaptations in the central nervous system. While historical data assigned functional relevance to such adaptations induced by resistance training, this claim has not yet been systematically and critically examined in the context of motor performance across the lifespan in health and disease. A review of muscle activation, brain and peripheral nerve stimulation, and imaging data revealed that increases in motor performance and neuroplasticity tend to be uncoupled, making a mechanistic link between neuroplasticity and motor performance inconclusive. We recommend new approaches, including causal mediation analytical and hypothesis-driven models to substantiate the functional relevance of resistance training-induced neuroplasticity in the improvements of gross motor function across the lifespan in health and disease.

Family dogs are exposed to a continuous flow of human speech throughout their lives. However, the extent of their abilities in speech perception is unknown. Here, we used functional magnetic resonance imaging (fMRI) to test speech detection and language representation in the dog brain. Dogs (n = 18) listened to natural speech and scrambled speech in a familiar and an unfamiliar language. Speech scrambling distorts auditory regularities specific to speech and to a given language, but keeps spectral voice cues intact. We hypothesized that if dogs can extract auditory regularities of speech, and of a familiar language, then there will be distinct patterns of brain activity for natural speech vs. scrambled speech, and also for familiar vs. unfamiliar language. Using multivoxel pattern analysis (MVPA) we found that bilateral auditory cortical regions represented natural speech and scrambled speech differently; with a better classifier performance in longer-headed dogs in a right auditory region. This neural capacity for speech detection was not based on preferential processing for speech but rather on sensitivity to sound naturalness. Furthermore, in case of natural speech, distinct activity patterns were found for the two languages in the secondary auditory cortex and in the precruciate gyrus; with a greater difference in responses to the familiar and unfamiliar languages in older dogs, indicating a role for the amount of language exposure. No regions represented differently the scrambled versions of the two languages, suggesting that the activity difference between languages in natural speech reflected sensitivity to language-specific regularities rather than to spectral voice cues. These findings suggest that separate cortical regions support speech naturalness detection and language representation in the dog brain.

Funder: Amsterdam Neuroscience, Accurate identification of brain function is necessary to understand neurocognitive aging, and thereby promote health and well‐being. Many studies of neurocognitive aging have investigated brain function with the blood‐oxygen level‐dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is, therefore, essential to distinguish the age effects on vascular versus neural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable, and robust means to calibrate vascular responsivity, as an alternative to breath‐holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age‐related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health (CVH) and cerebrovascular function, are insufficient when used alone to fully explain age‐related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and cerebrovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population‐based, lifespan Cam‐CAN cohort. After controlling for cardiovascular and cerebrovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and cerebrovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age differences in RSFA, after controlling for CVH. The results were consistent between voxel‐level analysis and independent component analysis. Our findings indicate that cardiovascular and cerebrovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterize neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.

Background Growing literature continues to identify brain regions that are functionally altered in bipolar disorder. However, precise functional network correlates of bipolar disorder have yet to be determined due to inconsistent results. The overview of neurological alterations from a large‐scale network perspective may provide more comprehensive results and elucidate the neuropathology of bipolar disorder. Here, we critically review recent neuroimaging research on bipolar disorder using a network‐based approach. Methods A systematic search was conducted on studies published from 2009 through 2019 in PubMed and Google Scholar. Articles that utilized functional magnetic resonance imaging technique to examine altered functional activity of major regions belonging to a large‐scale brain network in bipolar disorder were selected. Results A total of 49 studies were reviewed. Within‐network hypoconnectivity was reported in bipolar disorder at rest among the default mode, salience, and central executive networks. In contrast, when performing a cognitive task, hyperconnectivity among the central executive network was found. Internetwork functional connectivity in the brain of bipolar disorder was greater between the salience and default mode networks, while reduced between the salience and central executive networks at rest, compared to control. Conclusion This systematic review suggests disruption in the functional activity of large‐scale brain networks at rest as well as during a task stimuli in bipolar disorder. Disrupted intra‐ and internetwork functional connectivity that are also associated with clinical symptoms suggest altered functional connectivity of and between large‐scale networks plays an important role in the pathophysiology of bipolar disorder., The investigation of the brain alterations with a large‐scale network perspective may provide a more comprehensive way in elucidating the neuropathology of a disorder. This systematic review evaluates recent literature and suggests alteration in the functional activity of large‐scale brain networks including the default mode, salience, and central executive networks in bipolar disorder. Furthermore, disrupted intra‐ and internetwork functional connectivity are also associated with clinical symptoms of bipolar disorder, which highlight the importance of large‐scale networks in the pathophysiology of bipolar disorder.

Social feedback, such as praise or critique, profoundly impacts our mood and social interactions. It is unknown, however, how parents experience praise and critique about their child and whether their mood and neural responses to such ‘vicarious’ social feedback are modulated by parents’ perceptions of their child. Parents (n = 60) received positive, intermediate and negative feedback words (i.e. personality characteristics) about their adolescent child during a magnetic resonance imaging scan. After each word, parents indicated their mood. After positive feedback their mood improved and activity in ventromedial prefrontal cortex and posterior cingulate cortex/precuneus increased. Negative feedback worsened parents’ mood, especially when perceived as inapplicable to their child, and increased activity in anterior cingulate cortex, anterior insula, dorsomedial prefrontal cortex and precuneus. Parents who generally viewed their child more positively showed amplified mood responses to both positive and negative feedback and increased activity in dorsal striatum, inferior frontal gyrus and insula in response to negative feedback. These findings suggest that vicarious feedback has similar effects and engages similar brain regions as observed during feedback about the self and illustrates this is dependent on parents’ beliefs of their child’s qualities and flaws. Potential implications for parent–child dynamics and children’s own self-views are discussed.

Background Although repetitive transcranial magnetic stimulation (‘TMS’) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran’s Health Administration. Methods Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at ‘baseline’ pre-TMS commencement, ‘first week’ after initiation of TMS (targeting five sessions) and ‘post-treatment’ at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. Discussion To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. Trial registration ClinicalTrials.gov NCT04663481, December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of the same disease spectrum of adult-onset neurodegenerative diseases that affect the motor and cognitive functions, respectively. Multiple common genetic loci such as fused in sarcoma (FUS) have been identified to play a role in ALS and FTD etiology. Current studies indicate that FUS mutations incur gain-of-toxic functions to drive ALS pathogenesis. However, how the disease-linked mutations of FUS affect cognition remains elusive. Using a mouse model expressing an ALS-linked human FUS mutation (R514G-FUS) that mimics endogenous expression patterns, we found that FUS proteins showed an age-dependent accumulation of FUS proteins despite the downregulation of mouse FUS mRNA by the R514G-FUS protein during aging. Furthermore, these mice developed cognitive deficits accompanied by a reduction in spine density and long-term potentiation (LTP) within the hippocampus. At the physiological expression level, mutant FUS is distributed in the nucleus and cytosol without apparent FUS aggregates or nuclear envelope defects. Unbiased transcriptomic analysis revealed a deregulation of genes that cluster in pathways involved in nonsense-mediated decay, protein homeostasis, and mitochondrial functions. Furthermore, the use of in vivo functional imaging demonstrated widespread reduction in cortical volumes but enhanced functional connectivity between hippocampus, basal ganglia and neocortex in R514G-FUS mice. Hence, our findings suggest that disease-linked mutation in FUS may lead to changes in proteostasis and mitochondrial dysfunction that in turn affect brain structure and connectivity resulting in cognitive deficits.

Accumulating research shows that prenatal exposure to maternal stress increases the risk for behavioral and mental health problems later in life. This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome. Effects of maternal stress on offspring neurodevelopment, cognitive development, negative affectivity, difficult temperament and psychiatric disorders are shown in numerous epidemiological and case-control studies. Offspring of both sexes are susceptible to prenatal stress but effects differ. There is not any specific vulnerable period of gestation; prenatal stress effects vary for different gestational ages possibly depending on the developmental stage of specific brain areas and circuits, stress system and immune system. Biological correlates in the prenatally stressed offspring are: aberrations in neurodevelopment, neurocognitive function, cerebral processing, functional and structural brain connectivity involving amygdalae and (pre)frontal cortex, changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous system.

Objectives To explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS). Methods Seventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed. Results Compared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG. Conclusions MRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms. Trial registration NCT01152632. Registered 27 June 2010.

Background Chronic migraine (CM) can be associated with aberrant long-range connectivity of MRI-derived resting-state networks (RSNs). Here, we investigated how the fractal dimension (FD) of blood oxygenation level dependent (BOLD) activity may be used to estimate the complexity of RSNs, reflecting flexibility and/or efficiency in information processing in CM patients respect to healthy controls (HC). Methods Resting-state MRI data were collected from 20 untreated CM without history of medication overuse and 20 HC. On both groups, we estimated the Higuchi’s FD. On the same subjects, fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from diffusion tensor imaging and correlated with the FD values. Results CM showed higher FD values within dorsal attention system (DAS) and the anterior part of default-mode network (DMN), and lower FD values within the posterior DMN compared to HC. Although FA and MD were within the range of normality, both correlated with the FD values of DAS. Conclusions FD of DAS and DMN may reflect disruption of cognitive control of pain in CM. Since the normal microstructure of the thalamus and its positive connectivity with the cortical networking found in our CM patients reminds similar results obtained assessing the same structures but with the methods of neurophysiology, in episodic migraine during an attack, this may be yet another evidence in supporting CM as a never-ending migraine attack.

Recent evidence points to a role of the primary visual cortex that goes beyond visual processing into high-level cognitive and motor-related functions, including action planning, even in absence of feedforward visual information. It has been proposed that, at the neural level, motor imagery is a simulation based on motor representations, and neuroimaging studies have shown overlapping and shared activity patterns for motor imagery and action execution in frontal and parietal cortices. Yet, the role of the early visual cortex in motor imagery remains unclear. Here we used multivoxel pattern analyses on functional magnetic resonance imaging (fMRI) data to examine whether the content of motor imagery and action intention can be reliably decoded from the activity patterns in the retinotopic location of the target object in the early visual cortex. Further, we investigated whether the discrimination between specific actions generalizes across imagined and intended movements. Eighteen right-handed human participants (11 females) imagined or performed delayed hand actions towards a centrally located object composed of a small shape attached on a large shape. Actions consisted of grasping the large or small shape, and reaching to the center of the object. We found that despite comparable fMRI signal amplitude for different planned and imagined movements, activity patterns in the early visual cortex, as well as dorsal premotor and anterior intraparietal cortex, accurately represented action plans and action imagery. However, movement content is similar irrespective of whether actions are actively planned or covertly imagined in parietal but not early visual or premotor cortex, suggesting a generalized motor representation only in regions that are highly specialized in object directed grasping actions and movement goals. In sum, action planning and imagery have overlapping but non identical neural mechanisms in the cortical action network.

Reading comprehension is a complex task that depends on multiple cognitive and linguistic processes. According to the updated Simple View of Reading framework, in adults, individual variation in reading comprehension can be largely explained by combined variance in three component abilities: (1) decoding accuracy, (2) fluency, and (3) language comprehension. Here we asked whether the neural correlates of the three components are different in adults with dyslexia as compared to typically-reading adults and whether the relative contribution of these correlates to reading comprehension is similar in the two groups. We employed a novel naturalistic fMRI reading task to identify the neural correlates of individual differences in the three components using whole-brain and literature-driven regions-of-interest approaches. Across all participants, as predicted by the Simple View framework, we found distinct patterns of associations with linguistic and domain-general regions for the three components, and that the left-hemispheric neural correlates of language comprehension in the angular and posterior temporal gyri made the largest contributions to explaining out-of-scanner reading comprehension performance. These patterns differed between the two groups. In typical adult readers, better fluency was associated with greater activation of left occipitotemporal regions, better comprehension with lesser activation in prefrontal and posterior parietal regions, and there were no significant associations with decoding. In adults with dyslexia, better fluency was associated with greater activation of bilateral inferior parietal regions, better comprehension was associated with greater activation in some prefrontal clusters and lower in others, and better decoding skills were associated with lesser activation of bilateral prefrontal and posterior parietal regions. Extending the behavioral findings of skill-level differences in the relative contribution of the three components to reading comprehension, the relative contributions of the neural correlates to reading comprehension differed based on dyslexia status. These findings reveal some of the neural correlates of individual differences in the three components and the underlying mechanisms of reading comprehension deficits in adults with dyslexia., National Institutes of Health (Grants F32- HD100064, S10OD021569)