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Growing evidence highlights the potential of innovative rehabilitative interventions such as cognitive remediation and neuromodulation, aimed at reducing relapses in Alcohol Use Disorder (AUD). Enhancing their effectiveness requires a thorough description of the neural correlates of cognitive alterations in AUD. Past related attempts, however, were limited by the focus on selected neuro-cognitive variables. We aimed to fill this gap by combining, in 22 AUD patients and 18 controls, an extensive neuro-cognitive evaluation and metrics of intrinsic connectivity as highlighted by resting-state brain activity. We addressed an inherent property of intrinsic activity such as intra-network coherence, the temporal correlation of the slow synchronous fluctuations within resting-state networks, representing an early biomarker of alterations in the functional brain architecture underlying cognitive functioning. AUD patients displayed executive impairments involving working-memory, attention and visuomotor speed, reflecting abnormal coherence of activity and grey matter atrophy within default mode, in addition to the attentional and the executive networks. The stronger relationship between fronto-lateral coherent activity and executive performance in patients than controls highlighted possible compensatory mechanisms counterbalancing the decreased functionality of networks driving the switch from automatic to controlled behavior. These results provide novel insights into AUD patients’ cognitive impairments, their neural bases, and possible targets of rehabilitative interventions.

Introduction: Several functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks. Methods: Before and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features. Results: Before visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura. Conclusions: In individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

The salience network (SN), ventral attention network (VAN), dorsal attention network (DAN) and default mode network (DMN) have shown significant interactions and overlapping functions in bottom-up and top-down mechanisms of attention. In the present study, we tested if the SN, VAN, DAN and DMN connectivity can infer the gestational age (GA) at birth in a study group of 88 healthy neonates, scanned at 40 weeks of post-menstrual age, and with GA at birth ranging from 28 to 40 weeks. We also ascertained whether the connectivity within each of the SN, VAN, DAN and DMN was able to infer the average functional connectivity of the others. The ability to infer GA at birth or another network's connectivity was evaluated using a multivariate data-driven framework. The VAN, DAN and the DMN inferred the GA at birth (p < 0.05). The SN, DMN and VAN were able to infer the average connectivity of the other networks (p < 0.05). Mediation analysis between VAN's and DAN's inference on GA at birth found reciprocal transmittance of change with GA at birth of VAN's and DAN's connectivity (p < 0.05). Our findings suggest that the VAN has a prominent role in bottom-up salience detection in early infancy and that the role of the VAN and the SN may overlap in the bottom-up control of attention.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

The intrinsic connectivity of the salience network (SN) plays an important role in social behavior, however the directional influence that individual nodes have on each other has not yet been fully determined. In this study, we used spectral dynamic causal modeling to characterize the effective connectivity patterns in the SN for 44 healthy older adults and for 44 patients with behavioral variant frontotemporal dementia (bvFTD) who have focal SN dysfunction. We examined the relationship of SN effective connections with individuals' socioemotional sensitivity, using the revised self-monitoring scale, an informant-facing questionnaire that assesses sensitivity to expressive behavior. Overall, average SN effective connectivity for bvFTD patients differs from healthy older adults in cortical, hypothalamic, and thalamic nodes. For the majority of healthy individuals, strong periaqueductal gray (PAG) output to right cortical (p < .01) and thalamic nodes (p < .05), but not PAG output to other central pattern generators contributed to sensitivity to socioemotional cues. This effect did not exist for the majority of bvFTD patients; PAG output toward other SN nodes was weak, and this lack of output negatively influenced socioemotional sensitivity. Instead, input to the left vAI from other SN nodes supported patients' sensitivity to others' socioemotional behavior (p < .05), though less effectively. The key role of PAG output to cortical and thalamic nodes for socioemotional sensitivity suggests that its core functions, that is, generating autonomic changes in the body, and moreover representing the internal state of the body, is necessary for optimal social responsiveness, and its breakdown is central to bvFTD patients' social behavior deficits.

The default mode (DMN) and the salience (SN) networks show functional hypo-connectivity in Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD), respectively, along with patterns of hyper-connectivity. We tested the clinical and neurobiological effects of noninvasive stimulation over these networks in 45 patients (AD and bvFTD) who received either anodal (target network: DMN in AD, SN in bvFTD) or cathodal stimulation (target network: SN in AD, DMN in bvFTD). We evaluated changes in clinical, cognitive, functional and structural connectivity, and perfusion measures. In both patient groups, cathodal stimulation was followed by behavioral improvement, whereas anodal stimulation led to cognitive improvement. Neither functional connectivity nor perfusion showed significant effects. A significant interaction between DMN and SN functional connectivity changes and stimulation protocol was reported in AD. These results suggest a protocol-dependent response, whereby the protocols studied show divergent effects on cognitive and clinical measures, along with a divergent modulatory pattern of connectivity in AD.

The intrinsic connectivity of the salience network (SN) plays an important role in social behavior, however the directional influence that individual nodes have on each other has not yet been fully determined. In this study, we used spectral dynamic causal modeling to characterize the effective connectivity patterns in the SN for 44 healthy older adults and for 44 patients with behavioral variant frontotemporal dementia (bvFTD) who have focal SN dysfunction. We examined the relationship of SN effective connections with individuals' socioemotional sensitivity, using the revised self-monitoring scale, an informant-facing questionnaire that assesses sensitivity to expressive behavior. Overall, average SN effective connectivity for bvFTD patients differs from healthy older adults in cortical, hypothalamic, and thalamic nodes. For the majority of healthy individuals, strong periaqueductal gray (PAG) output to right cortical (p < .01) and thalamic nodes (p < .05), but not PAG output to other central pattern generators contributed to sensitivity to socioemotional cues. This effect did not exist for the majority of bvFTD patients; PAG output toward other SN nodes was weak, and this lack of output negatively influenced socioemotional sensitivity. Instead, input to the left vAI from other SN nodes supported patients' sensitivity to others' socioemotional behavior (p < .05), though less effectively. The key role of PAG output to cortical and thalamic nodes for socioemotional sensitivity suggests that its core functions, that is, generating autonomic changes in the body, and moreover representing the internal state of the body, is necessary for optimal social responsiveness, and its breakdown is central to bvFTD patients' social behavior deficits.

Interpreting others' beliefs, desires and intentions is known as "theory of mind" (ToM), and is often evaluated using simplified measurement tools, which may not correctly reflect the brain circuits that are required for real-life ToM functioning. We aimed to identify the brain structures necessary to correctly infer intentions from realistic scenarios by administering The Awareness of Social Inference Test, Enriched subtest to 47 patients with behavioural variant frontotemporal dementia, 24 patients with progressive supranuclear palsy syndrome, 31 patients with Alzheimer's syndrome, and 77 older healthy controls. Neuroimaging data was analyzed using voxel based morphometry, and participants' understanding of intentions was correlated with voxel-wise and region-of interest data. We found that structural integrity of the cinguloinsular cortex in the salience network (SN) was more pivotal for accurate ToM than previously described, emphasizing the importance of the SN for selectively recognizing and attending to social cues during ToM inferences.

Alcohol use disorder (AUD) is associated with brain-wide gray matter (GM) reduction, but the frontocerebellar circuit seems specifically affected by chronic alcohol consumption. T1 weighted MRI data from 38 AUD patients at one month of sobriety and three months later and from 25 controls were analyzed using voxel-based morphometry (VBM) and a graph theory approach (GTA). We investigated the degree to which the frontocerebellar circuit's integration within the brain's GM network architecture was altered by AUD-related GM volume loss. The VBM analyses did not reveal significant GM volume differences between relapsers and abstainers at either timepoint, but future relapsers at both timepoints had significantly less GM than controls in the frontocerebellar circuit. Abstainers, who at baseline also showed the most pronounced GM loss in the thalamus, showed a significant circuit-wide GM increase with inter-scan abstinence. The post-hoc GTAs revealed a persistent diffuse global atrophy in both AUD groups at follow-up relative to controls and different recovery patterns in the two AUD groups. Our findings suggest that future relapsers do not just present with a more severe expression of the same AUD consequences than abstainers, but that AUD affects the frontocerebellar circuit differently in relapsers and abstainers.

Background - Placebos (inert substances or procedures) can positively influence a person’s psychological and physical well-being, which is accompanied by specific changes in brain activity. There are many different types of placebos with different effects on health-related variables. This study investigated placebo effects in the context of religious beliefs and practices. The participants received an inert substance (tap water) along with the verbal suggestion that the water would come from the sanctuary in Lourdes (a major Catholic pilgrimage site with reports of miracle cures). We investigated changes in resting-state functional connectivity (rsFC) in three brain networks (default-mode, salience, cognitive control) associated with the drinking of the placebo water. Methods - A total of 37 females with the belief that water from the sanctuary in Lourdes has positive effects on their spiritual, emotional, and physical well-being participated in this placebo study with two sessions. The participants drank tap water that was labeled “Lourdes water” (placebo) before a 15-min resting-state scan in one session. In the other (control) session, they received tap water labeled as tap water. The participants rated their affective state (valence, arousal) during the session and were interviewed concerning specific thoughts, feelings, and bodily sensations directly after each of the two sessions. Results - The placebo reduced rsFC in the frontoparietal cognitive control network and increased rsFC in the salience network (insular-cerebellar connectivity). During the session, the participants rated their affective state as very pleasant and calm. The ratings did not differ between the two conditions. Immediately after the session, the participants reported increased intensity of pleasant bodily sensations (e.g., feelings of warmth, tingling) and feelings (e.g., gratefulness) for the “Lourdes water” condition. Conclusions - The present findings provide the first evidence that pl, Version of record

Rationale: Substance use peaks during the developmental period known as emerging adulthood (ages 18–25), but not every individual who uses substances during this period engages in frequent or problematic use. Although individual differences in neurocognition appear to predict use severity, mechanistic neurocognitive risk factors with clear links to both behavior and neural circuitry have yet to be identified. Here, we aim to do so with an approach rooted in computational psychiatry, an emerging field in which formal models are used to identify candidate biobehavioral dimensions that confer risk for psychopathology. Objectives: We test whether lower efficiency of evidence accumulation (EEA), a computationally characterized individual difference variable that drives performance on the go/no-go and other neurocognitive tasks, is a risk factor for substance use in emerging adults. Methods and results: In an fMRI substudy within a sociobehavioral longitudinal study (n = 106), we find that lower EEA and reductions in a robust neural-level correlate of EEA (error-related activations in salience network structures) measured at ages 18–21 are both prospectively related to greater substance use during ages 22–26, even after adjusting for other well-known risk factors. Results from Bayesian model comparisons corroborated inferences from conventional hypothesis testing and provided evidence that both EEA and its neuroimaging correlates contain unique predictive information about substance use involvement. Conclusions: These findings highlight EEA as a computationally characterized neurocognitive risk factor for substance use during a critical developmental period, with clear links to both neuroimaging measures and well-established formal theories of brain function.

Background - Placebos (inert substances or procedures) can positively influence a person’s psychological and physical well-being, which is accompanied by specific changes in brain activity. There are many different types of placebos with different effects on health-related variables. This study investigated placebo effects in the context of religious beliefs and practices. The participants received an inert substance (tap water) along with the verbal suggestion that the water would come from the sanctuary in Lourdes (a major Catholic pilgrimage site with reports of miracle cures). We investigated changes in resting-state functional connectivity (rsFC) in three brain networks (default-mode, salience, cognitive control) associated with the drinking of the placebo water. Methods - A total of 37 females with the belief that water from the sanctuary in Lourdes has positive effects on their spiritual, emotional, and physical well-being participated in this placebo study with two sessions. The participants drank tap water that was labeled “Lourdes water” (placebo) before a 15-min resting-state scan in one session. In the other (control) session, they received tap water labeled as tap water. The participants rated their affective state (valence, arousal) during the session and were interviewed concerning specific thoughts, feelings, and bodily sensations directly after each of the two sessions. Results - The placebo reduced rsFC in the frontoparietal cognitive control network and increased rsFC in the salience network (insular-cerebellar connectivity). During the session, the participants rated their affective state as very pleasant and calm. The ratings did not differ between the two conditions. Immediately after the session, the participants reported increased intensity of pleasant bodily sensations (e.g., feelings of warmth, tingling) and feelings (e.g., gratefulness) for the “Lourdes water” condition. Conclusions - The present findings provide the first evidence that pl, Version of record

Rationale: Substance use peaks during the developmental period known as emerging adulthood (ages 18–25), but not every individual who uses substances during this period engages in frequent or problematic use. Although individual differences in neurocognition appear to predict use severity, mechanistic neurocognitive risk factors with clear links to both behavior and neural circuitry have yet to be identified. Here, we aim to do so with an approach rooted in computational psychiatry, an emerging field in which formal models are used to identify candidate biobehavioral dimensions that confer risk for psychopathology. Objectives: We test whether lower efficiency of evidence accumulation (EEA), a computationally characterized individual difference variable that drives performance on the go/no-go and other neurocognitive tasks, is a risk factor for substance use in emerging adults. Methods and results: In an fMRI substudy within a sociobehavioral longitudinal study (n = 106), we find that lower EEA and reductions in a robust neural-level correlate of EEA (error-related activations in salience network structures) measured at ages 18–21 are both prospectively related to greater substance use during ages 22–26, even after adjusting for other well-known risk factors. Results from Bayesian model comparisons corroborated inferences from conventional hypothesis testing and provided evidence that both EEA and its neuroimaging correlates contain unique predictive information about substance use involvement. Conclusions: These findings highlight EEA as a computationally characterized neurocognitive risk factor for substance use during a critical developmental period, with clear links to both neuroimaging measures and well-established formal theories of brain function.

Background: Transcranial direct current stimulation (tDCS) of the cerebellum dynamically modulates cerebello-thalamo-cortical excitability in a polarity-specific manner during motor, visuo- motor and cognitive tasks. It remains to be established whether tDCS of the cerebellum impact also on resting-state intrinsically connected networks (ICNs). Such impact would open novel research and therapeutical doors for the neuromodulation of ICNs in human. Method: We combined tDCS applied over the right cerebellum and fMRI to investigate tDCS- induced resting-state intrinsic functional reconfiguration, using a randomized, sham-controlled design. fMRI data were recorded both before and after real anodal stimulation (2 mA, 20 min) or sham tDCS in 12 right-handed healthy volunteers. We resorted to a region-of-interest static correlational analysis and to a sliding window analysis to assess temporal variations in resting state FC between the cerebellar lobule VII and nodes of the main ICNs. Results: After real tDCS and compared with sham tDCS, functional changes were observed between the cerebellum and ICNs. Static FC showed enhanced or decreased correlation between cerebellum and brain areas belonging to visual, default-mode (DMN), sensorimotor and salience networks (SN) (p-corrected < 0.05). The temporal variability (TV) of BOLD signal was significantly modified after tDCS displaying in particular a lesser TV between the whole lobule VII and DMN and central executive network and a greater TV between crus 2 and SN. Static and dynamic FC was also modified between cerebellar lobuli. Conclusion: These results demonstrate short- and long-range static and majorly dynamic effects of tDCS stimulation of the cerebellum affecting distinct resting-state ICNs, as well as intracerebellar functional connectivity, so that tDCS of the cerebellum appears as a non-invasive tool reconfigurating the dynamics of ICNs., SCOPUS: ar.j, info:eu-repo/semantics/published

Alcohol use disorder (AUD) is associated with brain-wide gray matter (GM) reduction, but the frontocerebellar circuit seems specifically affected by chronic alcohol consumption. T1 weighted MRI data from 38 AUD patients at one month of sobriety and three months later and from 25 controls were analyzed using voxel-based morphometry (VBM) and a graph theory approach (GTA). We investigated the degree to which the frontocerebellar circuit's integration within the brain's GM network architecture was altered by AUD-related GM volume loss. The VBM analyses did not reveal significant GM volume differences between relapsers and abstainers at either timepoint, but future relapsers at both timepoints had significantly less GM than controls in the frontocerebellar circuit. Abstainers, who at baseline also showed the most pronounced GM loss in the thalamus, showed a significant circuit-wide GM increase with inter-scan abstinence. The post-hoc GTAs revealed a persistent diffuse global atrophy in both AUD groups at follow-up relative to controls and different recovery patterns in the two AUD groups. Our findings suggest that future relapsers do not just present with a more severe expression of the same AUD consequences than abstainers, but that AUD affects the frontocerebellar circuit differently in relapsers and abstainers.

Alcohol use disorder (AUD) is associated with brain-wide gray matter (GM) reduction, but the frontocerebellar circuit seems specifically affected by chronic alcohol consumption. T1 weighted MRI data from 38 AUD patients at one month of sobriety and three months later and from 25 controls were analyzed using voxel-based morphometry (VBM) and a graph theory approach (GTA). We investigated the degree to which the frontocerebellar circuit's integration within the brain's GM network architecture was altered by AUD-related GM volume loss. The VBM analyses did not reveal significant GM volume differences between relapsers and abstainers at either timepoint, but future relapsers at both timepoints had significantly less GM than controls in the frontocerebellar circuit. Abstainers, who at baseline also showed the most pronounced GM loss in the thalamus, showed a significant circuit-wide GM increase with inter-scan abstinence. The post-hoc GTAs revealed a persistent diffuse global atrophy in both AUD groups at follow-up relative to controls and different recovery patterns in the two AUD groups. Our findings suggest that future relapsers do not just present with a more severe expression of the same AUD consequences than abstainers, but that AUD affects the frontocerebellar circuit differently in relapsers and abstainers.

Individuals with autism spectrum disorder (ASD) are significantly more likely to experience sensory over-responsivity (SOR) compared to neurotypical controls. SOR in autism has been shown to be related to atypical functional connectivity in the salience network (SN), a brain network thought to help direct attention to the most relevant stimuli in one's environment. However, all studies to date which have examined the neurobiological basis of sensory processing in ASD have used primarily male samples so little is known about sex differences in the neural processing of sensory information. This study examined the relationship between SOR and resting-state functional connectivity in the SN for 37 males and 16 females with autism, ages 8-17 years. While there were no sex differences in parent-rated SOR symptoms, there were significant sex differences in how SOR related to SN connectivity. Relative to females with ASD, males with ASD showed a stronger association between SOR and increased connectivity between the salience and primary sensory networks, suggesting increased allocation to sensory information. Conversely, for females with ASD, SOR was more strongly related to increased connectivity between the SN and prefrontal cortex. Results suggest that the underlying mechanisms of SOR in ASD are sex specific, providing insight into the differences seen in the diagnosis rate and symptom profiles of males and females with ASD. LAY SUMMARY: Sensory over-responsivity (SOR) is common in autism. Most research on the neural basis of SOR has focused on males, so little is known about SOR or its neurobiology in females with autism spectrum disorder. Here despite no sex differences in SOR symptoms, we found sex differences in how SOR related to intrinsic connectivity in a salience detection network. Results show sex differences in the neural mechanisms underlying SOR and inform sex differences seen in diagnosis rates and symptom profiles in autism. Autism Res 2020, 13: 1489-1500.

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

Available online 16 December2019, Background: Dynamic functional network analysis may add relevant information about the temporal nature of the neurocognitive alterations in PD patients with impulse control disorders (PD-ICD). Our aim was to investigate changes in dynamic functional network connectivity (dFNC) in PD-ICD patients, and topological properties of such networks. Methods: Resting state fMRI was performed on 16 PD PD-ICD patients, 20 PD patients without ICD and 17 healthy controls, whose demographic, clinical and behavioral scores were assessed. We conducted a group spatial independent component analysis, sliding window and graph-theory analyses. Results: PD-ICD patients, in contrast to PD-noICD and HC subjects, were engaged across time in a brain configuration pattern characterized by a lack of between-network connections at the expense of strong withinnetwork connections (State III) in temporal, frontoinsular and cingulate cortices, all key nodes of the salience network. Moreover, this increased maintenance of State III in PD-ICD patients was positively correlated with the severity of impulsivity and novelty seeking as measured by specific scales. While in State III, these patients also exhibited increased local efficiency in all the aforementioned areas. Conclusions: Our findings show for the first time that PD-ICD patients have a dynamic functional engagement of local connectivity involving the limbic circuit, leading to the inefficient modulation in emotional processing and reward-related decision-making. These results provide new insights into the pathophysiology of ICD in PD patients and indicate that the dFC study of fMRI could be a useful biomarker to identify patients at risk to develop ICD.

Available online 16 December2019, Background: Dynamic functional network analysis may add relevant information about the temporal nature of the neurocognitive alterations in PD patients with impulse control disorders (PD-ICD). Our aim was to investigate changes in dynamic functional network connectivity (dFNC) in PD-ICD patients, and topological properties of such networks. Methods: Resting state fMRI was performed on 16 PD PD-ICD patients, 20 PD patients without ICD and 17 healthy controls, whose demographic, clinical and behavioral scores were assessed. We conducted a group spatial independent component analysis, sliding window and graph-theory analyses. Results: PD-ICD patients, in contrast to PD-noICD and HC subjects, were engaged across time in a brain configuration pattern characterized by a lack of between-network connections at the expense of strong withinnetwork connections (State III) in temporal, frontoinsular and cingulate cortices, all key nodes of the salience network. Moreover, this increased maintenance of State III in PD-ICD patients was positively correlated with the severity of impulsivity and novelty seeking as measured by specific scales. While in State III, these patients also exhibited increased local efficiency in all the aforementioned areas. Conclusions: Our findings show for the first time that PD-ICD patients have a dynamic functional engagement of local connectivity involving the limbic circuit, leading to the inefficient modulation in emotional processing and reward-related decision-making. These results provide new insights into the pathophysiology of ICD in PD patients and indicate that the dFC study of fMRI could be a useful biomarker to identify patients at risk to develop ICD.

Available online 16 December2019, Background: Dynamic functional network analysis may add relevant information about the temporal nature of the neurocognitive alterations in PD patients with impulse control disorders (PD-ICD). Our aim was to investigate changes in dynamic functional network connectivity (dFNC) in PD-ICD patients, and topological properties of such networks. Methods: Resting state fMRI was performed on 16 PD PD-ICD patients, 20 PD patients without ICD and 17 healthy controls, whose demographic, clinical and behavioral scores were assessed. We conducted a group spatial independent component analysis, sliding window and graph-theory analyses. Results: PD-ICD patients, in contrast to PD-noICD and HC subjects, were engaged across time in a brain configuration pattern characterized by a lack of between-network connections at the expense of strong withinnetwork connections (State III) in temporal, frontoinsular and cingulate cortices, all key nodes of the salience network. Moreover, this increased maintenance of State III in PD-ICD patients was positively correlated with the severity of impulsivity and novelty seeking as measured by specific scales. While in State III, these patients also exhibited increased local efficiency in all the aforementioned areas. Conclusions: Our findings show for the first time that PD-ICD patients have a dynamic functional engagement of local connectivity involving the limbic circuit, leading to the inefficient modulation in emotional processing and reward-related decision-making. These results provide new insights into the pathophysiology of ICD in PD patients and indicate that the dFC study of fMRI could be a useful biomarker to identify patients at risk to develop ICD.

Schizophrenia is a complex, debilitating mental disorder characterized by wide-ranging symptoms including delusions, hallucinations (so-called positive symptoms), and impaired motor and speech/language production (so-called negative symptoms). Salience-monitoring theorists propose that abnormal functional communication between the salience network (SN) and default mode network (DMN) begets positive and negative symptoms of schizophrenia, yet prior studies have predominately reported links between disrupted SN/DMN functional communication and positive symptoms. It remains unclear whether disrupted SN/DMN functional communication explains (1) solely positive symptoms or (2) both positive and negative symptoms of schizophrenia. To address this question, we incorporate time-lag-shifted functional network connectivity (FNC) analyses that explored coherence of the resting-state functional magnetic resonance imaging signal of 3 networks (anterior DMN, posterior DMN, and SN) with fixed time lags introduced between network time series (1 TR = 2 s; 2 TR = 4 s). Multivariate linear regression analysis revealed that severity of disordered thought and attentional deficits were negatively associated with 2 TR-shifted FNC between anterior DMN and posterior DMN. Meanwhile, severity of flat affect and bizarre behavior were positively associated with 1 TR-shifted FNC between anterior DMN and SN. These results provide support favoring the hypothesis that lagged SN/DMN functional communication is associated with both positive and negative symptoms of schizophrenia.

Loss of warmth is well-documented in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) at a group level, and has been linked to salience (SN) and semantic-appraisal (SAN) network atrophy. However, clinical observations of individual patients show much greater heterogeneity, thus measuring this clinical variability and identifying the underlying neurologic mechanisms is a critical step for understanding the symptom profile of any one patient. We used reliable change indexes with premorbid and current informant-based evaluations to characterize patterns of change on the warmth subscale of the Interpersonal Adjective Scale (IAS) questionnaire in 132 patients (21 bvFTD, 19 svPPA, 22 nonfluent variant primary progressive aphasia [nfvPPA], 37 Alzheimer's disease [AD]) and 33 healthy older adults. We investigated whether individual differences in warmth change were reflected in SN or SAN functional connectivity, or structural volume of individual brain regions in these two networks. Though one subset of patients showed significant drop in warmth to abnormally low levels (bvFTD: 38%; svPPA: 21%; nfvPPA: 5%; AD: 11%), a second subset significantly dropped but remained within the clinically normal range (bvFTD: 33%; svPPA: 21%; nfvPPA: 9%; AD: 5%), and a third subset did not drop and stayed in the clinically normal range (bvFTD: 29%; svPPA: 58%; nfvPPA: 86%; AD: 84%). Furthermore, interpersonal warmth score was strongly predicted by SN functional connectivity (p < .01), but not by SAN functional connectivity or by structural volume in these networks. Our results extend earlier group-level findings by showing wide individual variability in degree of disease-related reduction of interpersonal warmth and SN functional connectivity in bvFTD and svPPA, and highlight new approaches to revealing how brain connectivity predicts behavior on an individual patient level. Our findings suggest that measures of interpersonal warm

BackgroundPosterior cortical atrophy (PCA) is a clinical variant of Alzheimer's disease (AD) that presents with progressive visuospatial symptoms. While amnestic AD is characterized by disrupted default mode network (DMN) connectivity with corresponding increases in salience network (SN) connectivity, a visuospatial network appears to be disrupted early in PCA. Based on PCA patients' clinical features, we hypothesized that, in addition to early decreased integrity within the visuospatial network, patients with PCA would show increases in SN connectivity despite relative preservation of DMN. As the lateral pulvinar nucleus of the thalamus has direct anatomical connections with striate and extrastriate cortex and DMN, and the medial pulvinar is anatomically interconnected with SN, we further hypothesized that lateral and medial pulvinar nuclei might be implicated in intrinsic connectivity changes in PCA.Methods26 patients with PCA and 64 matched controls were recruited through UCSF Memory and Aging Center research programs. Each completed a standardized neuropsychological battery, structural MRI, and task-free fMRI. Seed-based functional correlations were used to probe networks of interest, including those seeded by the medial and lateral pulvinar thalamic nuclei, across the whole brain, and functional data analyses were adjusted for brain atrophy.ResultsPatients with PCA showed disproportionate deficits in the visuospatial domain; they also showed preserved social sensitivity and endorsed more depressive symptoms than HCs. PCA patients had significant parietooccipital atrophy accompanied by widespread connectivity decreases within the visuospatial network, enhanced connectivity between some structures in SN, and enhanced connectivity between key nodes of the DMN compared to controls. Increased SN connectivity correlated with a measure of social sensitivity, and increased DMN connectivity correlated with short-term memory performance. Medial pulvinar connectivity incr

ObjectiveWe aimed to understand the impact of dopamine receptor D4 (DRD4) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD4dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD4 is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration.Methods337 subjects, including healthy controls, patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) underwent genotyping, structural MRI, and cognitive/behavioral testing. We conducted whole-brain voxel-based morphometry to examine the relationship between DRD4 genotypes and brain atrophy patterns within and across groups. General linear modeling was used to evaluate relationships between genotype and cognitive/behavioral measures.ResultsDRD4 dampened-variants predicted gray matter atrophy in disease-specific regions of FTD in anterior cingulate, ventromedial prefrontal, orbitofrontal and insular cortices on the right greater than the left. Genotype predicted greater apathy and repetitive motor disturbance in patients with FTD. These results covaried with frontoinsular cortical atrophy. Peak atrophy patterned along regions of neuroanatomic vulnerability in FTD-spectrum disorders. In AD subjects and controls, genotype did not impact gray matter intensity.ConclusionsWe conclude that DRD4 polymorphisms with reduced functional potency exacerbate neuronal injury in sites of higher receptor density, which intersect with syndrome-specific regions undergoing neurodegeneration in FTD.

Facial cues, such as a person's age, provide important information for social interactions. Processing such facial cues can be affected by observer bias. However, there is currently no consensus regarding how the brain is processing facial cues related to age, and if facial age processing changes as a function of the age of the observer (i.e., own-age bias). The primary study aim was to investigate functional networks involved in processing own-age vs. other-age faces among younger and older adults and determine how emotional expression of the face modulates own-age vs. other-age face processing. The secondary study aim was to examine the relation between higher social cognitive processes (i.e., empathy) and modulation of brain activity by facial age and emotional expression. During functional magnetic resonance imaging (fMRI) younger and older participants were asked to recognize happy, angry, and neutral expressions in own-age and other-age faces. Functional connectivity analyses with the amygdala as seed showed that for own-age faces both age groups recruited a network of regions including the anterior cingulate and anterior insula that was involved in empathy and detection of salient information. Brain-behavior analyses furthermore showed that empathic responses in younger, but not in older, participants were positively correlated with engagement of the medial prefrontal cortex during processing of angry own-age faces. These findings identify the neurobehavioral correlates of facial age processing, and its modulation by emotion expression, and directly link facial cue processing to higher-order social cognitive functioning.

The neural bases of cognitive impairment(s) in alcohol use disorders (AUDs) have been explained either with the specific involvement of frontal regions mostly affected by alcohol neurotoxic effects, or with a global brain damage underlying different neuro-cognitive alterations. Novel insights into this issue might come from the analysis of resting-state brain activity, representing a baseline level of intrinsic connectivity within and between the networks underlying cognitive performance. We thus addressed the neural bases of cognitive impairment(s) in 22 AUD patients, compared with 18 healthy controls, by coupling resting-state fMRI with an in-depth neuropsychological assessment of the main cognitive domains. We assessed a relationship between AUD patients' cognitive impairment and two complementary facets of intrinsic brain functioning, i.e., intensity of activation and functional network connectivity, related to the strength of connectivity within and between resting-state networks, respectively. Alcoholic patients' decreased cognitive performance involved specifically an executive domain associated with attentional and working-memory tasks. This impairment reflected an abnormal relationship, in patients versus controls, between cognitive performance and the intensity of intrinsic activity in the dorsolateral prefrontal and striatal nodes of the executive control network. Functional connectivity between the same structures was positively correlated with executive performance in the whole sample, but significantly reduced in patients. The present data suggest that AUD patients' executive impairment reflects dysfunctional connectivity between the cortical and subcortical nodes of the networks underlying cognitive control on goal-directed behavior. This evidence provides a baseline for future studies addressing the abnormal neural architecture underlying cognitive impairment in AUDs and the outcome of rehabilitative treatment.

Facial cues, such as a person's age, provide important information for social interactions. Processing such facial cues can be affected by observer bias. However, there is currently no consensus regarding how the brain is processing facial cues related to age, and if facial age processing changes as a function of the age of the observer (i.e., own-age bias). The primary study aim was to investigate functional networks involved in processing own-age vs. other-age faces among younger and older adults and determine how emotional expression of the face modulates own-age vs. other-age face processing. The secondary study aim was to examine the relation between higher social cognitive processes (i.e., empathy) and modulation of brain activity by facial age and emotional expression. During functional magnetic resonance imaging (fMRI) younger and older participants were asked to recognize happy, angry, and neutral expressions in own-age and other-age faces. Functional connectivity analyses with the amygdala as seed showed that for own-age faces both age groups recruited a network of regions including the anterior cingulate and anterior insula that was involved in empathy and detection of salient information. Brain-behavior analyses furthermore showed that empathic responses in younger, but not in older, participants were positively correlated with engagement of the medial prefrontal cortex during processing of angry own-age faces. These findings identify the neurobehavioral correlates of facial age processing, and its modulation by emotion expression, and directly link facial cue processing to higher-order social cognitive functioning.

BackgroundPosterior cortical atrophy (PCA) is a clinical variant of Alzheimer's disease (AD) that presents with progressive visuospatial symptoms. While amnestic AD is characterized by disrupted default mode network (DMN) connectivity with corresponding increases in salience network (SN) connectivity, a visuospatial network appears to be disrupted early in PCA. Based on PCA patients' clinical features, we hypothesized that, in addition to early decreased integrity within the visuospatial network, patients with PCA would show increases in SN connectivity despite relative preservation of DMN. As the lateral pulvinar nucleus of the thalamus has direct anatomical connections with striate and extrastriate cortex and DMN, and the medial pulvinar is anatomically interconnected with SN, we further hypothesized that lateral and medial pulvinar nuclei might be implicated in intrinsic connectivity changes in PCA.Methods26 patients with PCA and 64 matched controls were recruited through UCSF Memory and Aging Center research programs. Each completed a standardized neuropsychological battery, structural MRI, and task-free fMRI. Seed-based functional correlations were used to probe networks of interest, including those seeded by the medial and lateral pulvinar thalamic nuclei, across the whole brain, and functional data analyses were adjusted for brain atrophy.ResultsPatients with PCA showed disproportionate deficits in the visuospatial domain; they also showed preserved social sensitivity and endorsed more depressive symptoms than HCs. PCA patients had significant parietooccipital atrophy accompanied by widespread connectivity decreases within the visuospatial network, enhanced connectivity between some structures in SN, and enhanced connectivity between key nodes of the DMN compared to controls. Increased SN connectivity correlated with a measure of social sensitivity, and increased DMN connectivity correlated with short-term memory performance. Medial pulvinar connectivity incr

ObjectiveWe aimed to understand the impact of dopamine receptor D4 (DRD4) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD4dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD4 is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration.Methods337 subjects, including healthy controls, patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) underwent genotyping, structural MRI, and cognitive/behavioral testing. We conducted whole-brain voxel-based morphometry to examine the relationship between DRD4 genotypes and brain atrophy patterns within and across groups. General linear modeling was used to evaluate relationships between genotype and cognitive/behavioral measures.ResultsDRD4 dampened-variants predicted gray matter atrophy in disease-specific regions of FTD in anterior cingulate, ventromedial prefrontal, orbitofrontal and insular cortices on the right greater than the left. Genotype predicted greater apathy and repetitive motor disturbance in patients with FTD. These results covaried with frontoinsular cortical atrophy. Peak atrophy patterned along regions of neuroanatomic vulnerability in FTD-spectrum disorders. In AD subjects and controls, genotype did not impact gray matter intensity.ConclusionsWe conclude that DRD4 polymorphisms with reduced functional potency exacerbate neuronal injury in sites of higher receptor density, which intersect with syndrome-specific regions undergoing neurodegeneration in FTD.

Loss of warmth is well-documented in behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) at a group level, and has been linked to salience (SN) and semantic-appraisal (SAN) network atrophy. However, clinical observations of individual patients show much greater heterogeneity, thus measuring this clinical variability and identifying the underlying neurologic mechanisms is a critical step for understanding the symptom profile of any one patient. We used reliable change indexes with premorbid and current informant-based evaluations to characterize patterns of change on the warmth subscale of the Interpersonal Adjective Scale (IAS) questionnaire in 132 patients (21 bvFTD, 19 svPPA, 22 nonfluent variant primary progressive aphasia [nfvPPA], 37 Alzheimer's disease [AD]) and 33 healthy older adults. We investigated whether individual differences in warmth change were reflected in SN or SAN functional connectivity, or structural volume of individual brain regions in these two networks. Though one subset of patients showed significant drop in warmth to abnormally low levels (bvFTD: 38%; svPPA: 21%; nfvPPA: 5%; AD: 11%), a second subset significantly dropped but remained within the clinically normal range (bvFTD: 33%; svPPA: 21%; nfvPPA: 9%; AD: 5%), and a third subset did not drop and stayed in the clinically normal range (bvFTD: 29%; svPPA: 58%; nfvPPA: 86%; AD: 84%). Furthermore, interpersonal warmth score was strongly predicted by SN functional connectivity (p < .01), but not by SAN functional connectivity or by structural volume in these networks. Our results extend earlier group-level findings by showing wide individual variability in degree of disease-related reduction of interpersonal warmth and SN functional connectivity in bvFTD and svPPA, and highlight new approaches to revealing how brain connectivity predicts behavior on an individual patient level. Our findings suggest that measures of interpersonal warm

BackgroundInternalizing symptoms like anxiety and depression are common and impairing in autism spectrum disorder (ASD). Here, we test the hypothesis that aberrant functional connectivity among three brain networks (salience network [SN], default mode network [DMN], and frontoparietal network [FPN]) plays a role in the pathophysiology of internalizing in ASD.MethodsWe examined the association between resting-state functional connectivity and internalizing in 102 adolescents and young adults with ASD (n = 49) or typical development (n = 53). Seed-to-target functional connectivity was contrasted between adolescents and young adults with ASD and typically developing subjects using a recent parcellation of the human cerebral cortex, and connections that were aberrant in ASD were analyzed dimensionally as a function of parent-reported internalizing symptoms.ResultsThree connections demonstrated robust overconnectivity in ASD: 1) the anterior insula to the retrosplenial cortex (i.e., SN-DMN), 2) the anterior insula to the frontal pole (i.e., SN-FPN), and 3) the dorsolateral prefrontal cortex to the retrosplenial cortex (i.e., FPN-DMN). These differences remained significant after controlling for age, and no age-related effects survived correction. The SN-DMN connection was associated with greater internalizing in ASD, mediated by a bigger difference between self- and parent-reported internalizing. Control analyses found that the other two connections were not associated with internalizing, and SN-DMN connectivity was not associated with a well-matched control measure (externalizing symptoms).ConclusionsThe present findings provide novel evidence for a specific link between SN-DMN overconnectivity and internalizing in ASD. Further, the mediation results suggest that intact anterior insula-retrosplenial connectivity may play a role in an individual's generating insight into his or her own psychopathology.

BackgroundSupportive parenting during childhood has been associated with many positive developmental outcomes for offspring in adulthood, including fewer health-risk behaviors. Little is known about the neural mechanisms underlying these associations.MethodsThe present study followed rural African Americans (n = 91, 52% female) from late childhood (11-13 years of age) to emerging adulthood (25 years of age). Parent-child communication was assessed at 11, 12, and 13 years of age. Functional magnetic resonance imaging was used at 25 years of age to measure resting-state functional connectivity of the anterior salience network (ASN). Harmful alcohol use and emotional eating were also assessed at 25 years of age. Structural equation modeling was used to test pathways from parent-child communication at 11 to 13 years of age to harmful alcohol use and emotional eating at 25 years of age via resting-state functional connectivity of the ASN.ResultsGreater parent-child communication between 11 and 13 years of age forecast greater resting-state functional connectivity of the ASN at 25 years of age which, in turn, was associated with lower harmful alcohol use and emotional eating at 25 years of age. Significant indirect effects through the ASN were present for both outcomes.ConclusionsThese findings indicate the importance of parenting in late childhood for adaptive behaviors and suggest a pathway via higher ASN coherence. This network was implicated in both harmful alcohol use and emotional eating, corroborating evidence of overlap in brain regions for dysregulated substance use and eating behaviors and revealing divergent pathways. These findings support the value of prevention and intervention efforts targeting parenting skills in childhood toward fostering long-term, adaptive neurocognitive development.

Connectivity in intrinsically connected networks (ICNs) may predict individual differences in cognition and behavior. The drastic alterations in socioemotional awareness of patients with behavioral variant frontotemporal dementia (bvFTD) are presumed to arise from changes in one such ICN, the salience network (SN). We examined how individual differences in SN connectivity are reflected in overt social behavior in healthy individuals and patients, both to provide neuroscientific insight into this key brain-behavior relationship, and to provide a practical tool to diagnose patients with early bvFTD. We measured SN functional connectivity and socioemotional sensitivity in 65 healthy older adults and 103 patients in the earliest stage [Clinical Dementia Rating (CDR) Scale score ≤1] of five neurodegenerative diseases [14 bvFTD, 29 Alzheimer's disease (AD), 20 progressive supranuclear palsy (PSP), 21 semantic variant primary progressive aphasia (svPPA), and 19 non-fluent variant primary progressive aphasia (nfvPPA)]. All participants underwent resting-state functional imaging and an informant described their responsiveness to subtle emotional expressions using the Revised Self-Monitoring Scale (RSMS). Higher functional connectivity in the SN, predominantly between the right anterior insula (AI) and both "hub" cortical and "interoceptive" subcortical nodes, predicted socioemotional sensitivity among healthy individuals, showing that socioemotional sensitivity is a behavioral marker of SN function, and particularly of right AI functional connectivity. The continuity of this relationship in both healthy and neurologically affected individuals highlights the role of socioemotional sensitivity as an early diagnostic marker of SN connectivity. Clinically, this is particularly important for identification of patients in the earliest stage of bvFTD, where the SN is selectively vulnerable.

In the behavioral variant of frontotemporal dementia (bvFTD), left-lateralized salience network dysfunction reduces basal activity in the parasympathetic nervous system, a branch of the autonomic nervous system that reduces arousal and fosters empathy and prosociality. Here we examined whether resting parasympathetic deficits in bvFTD related to diminished prosocial behavior. Eighty participants [30 with bvFTD, 25 with Alzheimer's disease (AD), and 25 healthy controls] completed a "helping task" in which we quantified participants' spontaneous reactions to an experimenter who struggled to find a lost key. Participants also underwent an assessment of baseline autonomic nervous system activity and structural magnetic resonance imaging. An exploratory factor analysis of participants' behaviors during the helping task revealed four factors: empathic concern, consolation, disengagement, and impatience. Patients with bvFTD had lower empathic concern and greater disengagement and impatience than the AD and healthy control groups. Patients with bvFTD had lower resting respiratory sinus arrhythmia and faster respiration and heart rates than patients with AD and healthy controls, a pattern consistent with parasympathetic dysfunction. Skin conductance level was also lower in bvFTD than in the other groups. Lower baseline respiratory sinus arrhythmia and faster baseline respiration rates, but not skin conductance level, predicted lower prosocial helping behaviors. Voxel-based morphometry analyses revealed that atrophy in the bilateral medial pulvinar nucleus of the thalamus, midcingulate cortex, and caudate was associated with lower empathic concern and consolation, and atrophy in the bilateral medial pulvinar nucleus of the thalamus, left frontoinsula, and left ventral striatum was associated with greater disengagement and impatience. Left-lateralized frontoinsula atrophy was associated with not only lower respiratory sinus arrhythmia but also with lower consolation and greate

The salience network is a distributed neural system that maintains homeostasis by regulating autonomic nervous system activity and social-emotional function. Here we examined how within-network connectivity relates to individual differences in human (including males and females) baseline parasympathetic and sympathetic nervous activity. We measured resting autonomic nervous system physiology in 24 healthy controls and 23 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease characterized by baseline autonomic deficits. Participants also underwent structural and task-free fMRI. First, we used voxel-based morphometry to determine whether salience network atrophy was associated with lower baseline respiratory sinus arrhythmia (a parasympathetic measure) and skin conductance level (a sympathetic measure) in bvFTD. Next, we examined whether functional connectivity deficits in 21 autonomic-relevant, salience network node-pairs related to baseline autonomic dysfunction. Lower baseline respiratory sinus arrhythmia was associated with smaller volume in left ventral anterior insula (vAI), weaker connectivity between bilateral vAI and bilateral anterior cingulate cortex (ACC), and stronger connectivity between bilateral ACC and bilateral hypothalamus/amygdala. Lower baseline skin conductance level, in contrast, was associated with smaller volume in inferior temporal gyrus, dorsal mid-insula, and hypothalamus; weaker connectivity between bilateral ACC and right hypothalamus/amygdala; and stronger connectivity between bilateral dorsal anterior insula and periaqueductal gray. Our results suggest that baseline parasympathetic and sympathetic tone depends on the integrity of lateralized salience network hubs (left vAI for parasympathetic and right hypothalamus/amygdala for sympathetic) and highly calibrated ipsilateral and contralateral network connections. In bvFTD, deficits in this system may underlie resting parasympathetic and sympathetic

Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) have been difficult to differentiate in clinical settings, as these two disorders are phenotypically similar and both exhibit atypical attention and executive functioning. Mischaracterizations between these two disorders can lead to inappropriate medication regimes, significant delays in special services, and personal distress to families and caregivers. There is evidence that ASD and ADHD are biologically different for attentional and executive functioning mechanisms, as only half of individuals with co-occurring ASD and ADHD respond to stimulant medication. Further, neurobehavioral work has supported these biological differences for ASD and ADHD, with both shared and distinct functional connectivity. In specific, two brain networks have been implicated in these disorders: the salience network (SN) and frontoparietal network (FPN). The SN is a network anchored by bilateral anterior insula and the dorsal anterior cingulate cortex and has been implicated in “bottom-up” attentional processes for both internal and external events. The FPN is anchored by lateral prefrontal cortex areas and the parietal lobe and plays a roll in “top-down” executive processes. Functional connectivity subgroups differentiated ASD from ADHD with between SN-FPN connectivity patterns, but not by within-SN or within-FPN connectivity patterns. Further, subgroup differences in ASD+ADHD comorbidity vs. ASD only were found for within-FPN connectivity.

The salience network is a distributed neural system that maintains homeostasis by regulating autonomic nervous system activity and social-emotional function. Here we examined how within-network connectivity relates to individual differences in human (including males and females) baseline parasympathetic and sympathetic nervous activity. We measured resting autonomic nervous system physiology in 24 healthy controls and 23 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease characterized by baseline autonomic deficits. Participants also underwent structural and task-free fMRI. First, we used voxel-based morphometry to determine whether salience network atrophy was associated with lower baseline respiratory sinus arrhythmia (a parasympathetic measure) and skin conductance level (a sympathetic measure) in bvFTD. Next, we examined whether functional connectivity deficits in 21 autonomic-relevant, salience network node-pairs related to baseline autonomic dysfunction. Lower baseline respiratory sinus arrhythmia was associated with smaller volume in left ventral anterior insula (vAI), weaker connectivity between bilateral vAI and bilateral anterior cingulate cortex (ACC), and stronger connectivity between bilateral ACC and bilateral hypothalamus/amygdala. Lower baseline skin conductance level, in contrast, was associated with smaller volume in inferior temporal gyrus, dorsal mid-insula, and hypothalamus; weaker connectivity between bilateral ACC and right hypothalamus/amygdala; and stronger connectivity between bilateral dorsal anterior insula and periaqueductal gray. Our results suggest that baseline parasympathetic and sympathetic tone depends on the integrity of lateralized salience network hubs (left vAI for parasympathetic and right hypothalamus/amygdala for sympathetic) and highly calibrated ipsilateral and contralateral network connections. In bvFTD, deficits in this system may underlie resting parasympathetic and sympathetic

Mindfulness has been described as an orientation of attention to the present moment, with openness and compassion. Individuals displaying high trait mindfulness exhibit this tendency as a more permanent personality attribute. The goal of this study was to gain insight on the neural substrates of trait mindfulness. Twenty-eight undergraduate students completed a measure of trait mindfulness, the Five-Facet Mindfulness Questionnaire (FFMQ), before undergoing a structural and a seven-minute resting state functional MRI scan. Resting-state data were analyzed using independent-component analyses. Individual differences on FFMQ scores were related to individual differences in functional connectivity of eight resting state networks. We found that, 1) cognitive and sensory networks provide valuable information on the neural substrates of trait mindfulness; and 2) trait mindfulness associated with greater integration of neural regions related to bodily sensation. This study supports the notion that trait mindfulness is associated with functional areas related to cognition and sensation.

The salience network is a distributed neural system that maintains homeostasis by regulating autonomic nervous system activity and social-emotional function. Here we examined how within-network connectivity relates to individual differences in human (including males and females) baseline parasympathetic and sympathetic nervous activity. We measured resting autonomic nervous system physiology in 24 healthy controls and 23 patients with behavioral variant frontotemporal dementia (bvFTD), a neurodegenerative disease characterized by baseline autonomic deficits. Participants also underwent structural and task-free fMRI. First, we used voxel-based morphometry to determine whether salience network atrophy was associated with lower baseline respiratory sinus arrhythmia (a parasympathetic measure) and skin conductance level (a sympathetic measure) in bvFTD. Next, we examined whether functional connectivity deficits in 21 autonomic-relevant, salience network node-pairs related to baseline autonomic dysfunction. Lower baseline respiratory sinus arrhythmia was associated with smaller volume in left ventral anterior insula (vAI), weaker connectivity between bilateral vAI and bilateral anterior cingulate cortex (ACC), and stronger connectivity between bilateral ACC and bilateral hypothalamus/amygdala. Lower baseline skin conductance level, in contrast, was associated with smaller volume in inferior temporal gyrus, dorsal mid-insula, and hypothalamus; weaker connectivity between bilateral ACC and right hypothalamus/amygdala; and stronger connectivity between bilateral dorsal anterior insula and periaqueductal gray. Our results suggest that baseline parasympathetic and sympathetic tone depends on the integrity of lateralized salience network hubs (left vAI for parasympathetic and right hypothalamus/amygdala for sympathetic) and highly calibrated ipsilateral and contralateral network connections. In bvFTD, deficits in this system may underlie resting parasympathetic and sympathetic

Background: The accurate choice of the site of non-invasive brain stimulation (NIBS) is an important factor in trial design. Objective: Based on the observation that Alzheimer's disease (AD) and behavioral frontotemporal dementia (bvFTD) affect specific large-scale networks, i.e., the default mode network (DMN) and the salience network (SN), respectively, we aimed to identify population-average coordinates of these networks that could be used as potential targets in NIBS trials aiming to modulate these circuits. Methods: A systematic literature search of resting-state functional MRI studies reporting DMN and SN stereotactic coordinates was performed according to PRISMA guidelines. Coordinate-based meta-analyses were conducted to identify consistent nodes of the DMN and SN using GingerALE BrainMap software and the activation likelihood estimation method. Results: DMN coordinates mapped primarily to mesial areas (posterior cingulate cortex/precuneus [Brodmann Area-BA 23/31] and medial prefrontal cortex [BA 9/10/32]). More superficial areas mapped to the bilateral parietal (angular gyrus [BA 39]), temporal (middle gyrus [BA 21]) and dorsolateral prefrontal (superior gyrus [BA 8]) cortex. SN coordinates mapped primarily to mesial and deep frontal areas (anterior insula, anterior cingulate cortex [BA 24/32]), but more superficial areas mapped to the bilateral parietal (supramarginal gyrus [BA 40]) and the right dorsolateral prefrontal (middle gyrus [BA 9/10]) cortex. Conclusions: NIBS should target the bilateral angular, the middle temporal cortex, or superior frontal gyri in AD for DMN modulation, and the right middle frontal or supramarginal gyri in bvFTD for SN modulation.

Objective The purpose of this systematic review is to systematically review the evidence relating to findings generated by multivariate pattern analysis (MVPA) following structural or functional magnetic resonance imaging (fMRI) to determine if this analysis is able to: a) Discriminate between individuals with musculoskeletal pain and healthy controls, b) Predict pain perception in healthy individuals stimulated with a noxious stimulus compared to those stimulated with a non-noxious stimulus. MethodsMEDLINE, CINAHL, Embase, PEDro, Google Scholar, Cochrane library and Web of Science were systematically screened for relevant literature using different combinations of keywords regarding structural and functional MRI analysed with MVPA, both in individuals with musculoskeletal pain and healthy controls. Reference lists of included articles were hand-searched for additional literature. Eligible articles were assessed on risk of bias and reviewed by two independent researchers. Results The search query returned 18 articles meeting the inclusion criteria. Methodological quality varied from poor to good. Seven studies investigated the ability of machine-learning algorithms to differentiate patient groups from healthy control participants. Overall, the review demonstrated that MVPA can discriminate between individuals with MSK pain and healthy controls with an overall accuracy ranging from 53% to 94%. Twelve studies utilized healthy control participants (using them as their own controls), during experimental pain paradigms aimed to investigate the ability of machine-learning to differentiate individuals stimulated with noxious stimuli from those stimulated with non-noxious stimuli, with ‘pain’ detection rates ranging from 60% to 94%. However, significant heterogeneity in patient conditions, study methodology and brain imaging techniques resulted in various findings that make study comparisons and formal conclusions challenging. Conclusion There is

Background: Changes in structural and functional central nervous system have been reported in narcolepsy, with large discrepancies between studies. No study has investigated yet spontaneous brain activity at wake in idiopathic hypersomnia (IH). We compared relative changes in regional brain metabolism in two central hypersomnia conditions with different clinical features, namely narcolepsy type 1 (NT1) and IH, and in healthy controls. Methods: Sixteen patients [12 males, median age 30 years (17-78)] with NT1, nine patients [2 males, median age 27 years (20-60)] with IH and 19 healthy controls [16 males, median age 36 years (17-78)] were included. 18F-fludeoxyglucose positron emission tomography (PET) was performed in all drug-free subjects under similar conditions and instructions to stay in a wake resting state. Results: We found increased metabolism in the anterior and middle cingulate and the insula in the two pathological conditions as compared to healthy controls. The reverse contrast failed to evidence hypometabolism in patients vs. controls. Comparisons between patient groups were non-significant. At sub-statistical threshold, we found higher right superior occipital gyrus glucose metabolism in narcolepsy and higher middle orbital cortex and supplementary motor area metabolism in IH, findings that require further confirmation. Conclusion: There is significant hypermetabolism in narcolepsy and IH in the wake resting state in a set of brain regions constitutive of the salience cortical network that may reflect a compensatory neurocircuitry activity secondary to sleepiness. Metabolic differences between the two disorders within the executive-control network may be a signature of abnormally functioning neural system leading to persistent drowsiness typical of IH., SCOPUS: ar.j, info:eu-repo/semantics/published

The brain continuously influences and perceives the physiological condition of the body. Related cortical representations have been proposed to shape emotional experience and guide behavior. Although previous studies have identified brain regions recruited during autonomic processing, neurological lesion studies have yet to delineate the regions critical for maintaining autonomic outflow. Even greater controversy surrounds hemispheric lateralization along the parasympathetic-sympathetic axis. The behavioral variant of frontotemporal dementia (bvFTD), featuring progressive and often asymmetric degeneration that includes the frontoinsular and cingulate cortices, provides a unique lesion model for elucidating brain structures that control autonomic tone. Here, we show that bvFTD is associated with reduced baseline cardiac vagal tone and that this reduction correlates with left-lateralized functional and structural frontoinsular and cingulate cortex deficits and with reduced agreeableness. Our results suggest that networked brain regions in the dominant hemisphere are critical for maintaining an adaptive level of baseline parasympathetic outflow.

ObjectiveThe salience network, an intrinsic brain network thought to modulate attention to internal versus external stimuli, has been consistently found to be atypical in autism spectrum disorders (ASD). However, little is known about how this altered resting-state connectivity relates to brain activity during information processing, which has important implications for understanding sensory overresponsivity (SOR), a common and impairing condition in ASD related to difficulty downregulating brain responses to sensory stimuli. This study examined how SOR in youth with ASD relates to atypical salience network connectivity and whether these atypicalities are associated with abnormal brain response to basic sensory information.MethodFunctional magnetic resonance imaging was used to examine how parent-rated SOR symptoms related to salience network connectivity in 61 youth (aged 8-17 years; 28 with ASD and 33 IQ-matched typically developing youth). Correlations between resting-state salience network connectivity and brain response to mildly aversive tactile and auditory stimuli were examined.ResultsSOR in youth with ASD was related to increased resting-state functional connectivity between salience network nodes and brain regions implicated in primary sensory processing and attention. Furthermore, the strength of this connectivity at rest was related to the extent of brain activity in response to auditory and tactile stimuli.ConclusionResults support an association between intrinsic brain connectivity and specific atypical brain responses during information processing. In addition, findings suggest that basic sensory information is overly salient to individuals with SOR, leading to overattribution of attention to this information. Implications for intervention include incorporating sensory coping strategies into social interventions for individuals with SOR.

Successful navigation of the environment requires attending and responding efficiently to objects and conspecifics with the potential to benefit or harm (i.e., that have value). In humans, this function is subserved by a distributed large-scale neural network called the "salience network". We have recently demonstrated that there are two anatomically and functionally dissociable salience networks anchored in the dorsal and ventral portions of the human anterior insula (Touroutoglou et al., 2012). In this paper, we test the hypothesis that these two subnetworks exist in rhesus macaques (Macaca mulatta). We provide evidence that a homologous ventral salience network exists in macaques, but that the connectivity of the dorsal anterior insula in macaques is not sufficiently developed as a dorsal salience network. The evolutionary implications of these finding are considered.