Intrinsic Connectivity Distribution Research Articles

Low-calorie diet-induced weight loss is associated with altered brain connectivity and food desire in obesity.

The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity. A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis. After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger. A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.

Intrinsic connectivity demonstrates a shared role of the posterior cingulate for cue reactivity in both gambling and cocaine use disorders

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development.

Diagnostic group differences and exploratory sex differences in intrinsic connectivity during fMRI Stroop in individuals with and without cocaine use disorder

BackgroundSex-/gender-related differences in cognitive control and how they relate to addictions may inform novel treatment options. Cognitive control, including Stroop performance, has been linked to addictions and treatment outcomes. The extent to which women and men with cocaine use disorder (CUD) show brain and behavioral differences relating to Stroop performance has not been previously studied. We examined sex-related differences in Stroop-related brain connectivity in female and male CUD and healthy-comparison (HC) subjects. Methods40 individuals with CUD (20 female) and 40 HC (20 female) subjects matched on age, race, and ethnicity completed an fMRI Stroop task. Intrinsic connectivity distribution (ICD) and mean-adjusted ICD analyses were conducted to identify differences related to sex and diagnostic group. Stroop task performance was also considered. ResultsBehavioral results confirmed a Stroop effect. A main effect of diagnostic group indicated that the CUD versus HC group showed lower connectivity in the prefrontal cortex, frontal gyrus, cingulate gyrus, precuneus, cerebellum, and somatosensory, visual, and auditory areas. An exploratory main effect of sex suggested that males may show relatively lower connectivity than females in the cerebellum and brainstem, although connectivity was largely similar across sexes. ConclusionsIntrinsic connectivity during cognitive control varied by diagnostic group and possibly by sex. The findings suggest that interventions targeting cognitive control in CUD should consider sex.

Sex differences in default mode network connectivity in healthy aging adults.

Women show an increased lifetime risk of Alzheimer's disease (AD) compared with men. Characteristic brain connectivity changes, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function throughout aging is poorly understood. We investigated sex differences in DMN connectivity over the lifespan in 595 cognitively healthy participants from the Human Connectome Project-Aging cohort. We used the intrinsic connectivity distribution (a robust voxel-based metric of functional connectivity) and a seed connectivity approach to determine sex differences within the DMN and between the DMN and whole brain. Compared with men, women demonstrated higher connectivity with age in posterior DMN nodes and lower connectivity in the medial prefrontal cortex. Differences were most prominent in the decades surrounding menopause. Seed-based analysis revealed higher connectivity in women from the posterior cingulate to angular gyrus, which correlated with neuropsychological measures of declarative memory, and hippocampus. Taken together, we show significant sex differences in DMN subnetworks over the lifespan, including patterns in aging women that resemble changes previously seen in preclinical AD. These findings highlight the importance of considering sex in neuroimaging studies of aging and neurodegeneration.

A graph theory neuroimaging approach to distinguish the depression of bipolar disorder from major depressive disorder in adolescents and young adults

BackgroundMarkers to differentiate depressions of bipolar disorder (BD-Dep) from depressions of major depressive disorder (MDD-Dep), and for more targeted treatments, are critically needed to decrease current high rates of misdiagnosis that can lead to ineffective or potentially deleterious treatments. Distinguishing, and specifically treating the depressions, during the adolescent/young adult epoch is especially important to decrease illness progression and improve prognosis, and suicide, as it is the epoch when suicide thoughts and behaviors often emerge. With differences in functional connectivity patterns reported when BD-Dep and MDD-Dep have been studied separately, this study used a graph theory approach aimed to identify functional connectivity differences in their direct comparison. MethodsFunctional magnetic resonance imaging whole-brain functional connectivity (Intrinsic Connectivity Distribution, ICD) measures were compared across adolescents/young adults with BD-Dep (n = 28), MDD-Dep (n = 20) and HC (n = 111). Follow-up seed-based connectivity was conducted on regions of significant ICD differences. Relationships with demographic and clinical measures were assessed. ResultsCompared to the HC group, both the BD-Dep and MDD-Dep groups exhibited left-sided frontal, insular, and medial temporal ICD increases. The BD-Dep group had additional right-sided ICD increases in frontal, basal ganglia, and fusiform areas. In seed-based analyses, the BD-Dep group exhibited increased interhemispheric functional connectivity between frontal areas not seen in the MDD-Dep group. LimitationsModest sample size; medications not studied systematically. ConclusionsThis study supports bilateral and interhemispheric functional dysconnectivity as features of BD-Dep that may differentiate it from MDD-Dep in adolescents/young adults and serve as a target for early diagnosis and treatment strategies.

Graph theory analysis of whole brain functional connectivity to assess disturbances associated with suicide attempts in bipolar disorder

Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph‐theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD.

Sex differences in connectivity in the default mode network in healthy aging adults

AbstractBackgroundTwo‐thirds of individuals diagnosed with Alzheimer’s disease (AD) are women, but the reasons for women’s elevated risk are unknown, and sex differences in brain aging trajectories are poorly understood. Both symptomatic AD and aging are associated with decreased connectivity within the default mode network (DMN), which supports short‐term memory processing, while individuals with preclinical AD show increased connectivity in some DMN regions. We sought to identify sex‐based differences in DMN connectivity over the lifespan in a large cross‐sectional study of healthy adults.MethodWe examined functional MRI data from a cross‐sectional cohort of n=595 cognitively normal individuals (aged 36‐100 years; 249 females) drawn from the Human Connectome Project‐Aging (HCP‐A) dataset (Harms et al., 2018; Bookheimer et al., 2019). Preprocessing followed our previously described pipeline, with stringent motion thresholds applied. The four resting‐state scans for each individual were averaged and masked to a standard DMN parcellation (Yeo et al., 2011). We calculated within‐network connectivity of each DMN voxel using the intrinsic connectivity distribution (ICD) (Scheinost et al., 2012), a robust voxel‐based metric of functional connectivity, and used a general linear model to assess the main effect of sex on within‐network ICD with increasing age.ResultFemales showed relative hyperconnectivity in posterior DMN with age compared to males, but lower connectivity in anterior nodes (Fig 1). Specifically, z‐scores for female minus male contrasts for posterior clusters were 3.9 (posterior cingulate), 4.5 (R angular gyrus), and 4.7 (L), and for anterior clusters were ‐4.1 (R frontal pole) and ‐4.3 (L).ConclusionIn a large sample of healthy aging adults, women showed increased connectivity in posterior, and decreased connectivity in anterior, nodes of the DMN compared with their aging male counterparts. Interestingly, individuals with preclinical AD show a similar pattern of posterior hyperconnectivity, often interpreted as the compensatory response of a network under stress. These findings provide early clues to a potential role for network‐level sex differences in explaining women’s increased vulnerability to AD as they age.

Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior.

Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8–16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.

Sex-specific associations between traumatic experiences and resting-state functional connectivity in the Philadelphia Neurodevelopmental Cohort.

Traumatic experiences during childhood or adolescence are a significant risk factor for multiple psychiatric disorders and adversely affect multiple cognitive functions. Resting-state functional magnetic resonance imaging has been used to investigate the effects of traumatic experiences on functional connectivity, but the impact of sex differences has not been well documented. This study investigated sex-specific associations between resting-state functional connectivity (rsFC) and traumatic experiences in typically developing youth. The sample comprised 1395 participants, aged 8-21 years, from the Philadelphia Neurodevelopmental Cohort. Traumatic experiences were assessed based on the structured psychiatric evaluation. Sex, the number of traumatic events, and their interaction were regressed onto voxel-wise intrinsic connectivity distribution parameter values derived from resting-state functional magnetic resonance imaging. Brain regions that passed cluster correction were used as seeds to define resting-state networks. After quality control, the final sample had 914 participants with mean (SD) age 14.6 (3.3) years; 529 (57.8%) females; 437 (47.8%) experienced at least one kind of traumatic event. Four discrete anatomical clusters showed decreased functional connectivity as the number of traumatic events increased. The resting-state networks defined by using these four clusters as seeds corresponded with the somatomotor network. Sex-specific associations were identified in another three clusters for which males showed increased connectivity, and females showed decreased connectivity as the number of traumatic events increased. The resting-state networks defined by the three sex-specific clusters corresponded with the default mode network (DMN). In youth without psychiatric diagnoses, traumatic experiences are associated with an alteration of rsFC in brain regions corresponding with the somatomotor network. Associations differ in direction between males and females in brain regions corresponding with the DMN, suggesting sex-specific responses to early exposure to trauma.

A graph theory-based whole brain approach to assess mood state differences in adolescents and young adults with bipolar disorder.

Identifying hubs of brain dysfunction in adolescents and young adults with Bipolar I Disorder (BDAYA ) could provide targets for early detection, prevention, and treatment. Previous neuroimaging studies across mood states of BDAYA are scarce and often examined limited brain regions potentially prohibiting detection of other important regions. We used a data-driven whole-brain Intrinsic Connectivity Distribution (ICD) approach to investigate dysconnectivity hubs across mood states in BDAYA . Functional magnetic resonance imaging whole-brain ICD data were investigated for differences across four groups: BDAYA -depressed (n=22), BDAYA -euthymic (n=45), BDAYA -elevated (n=24), and healthy controls (HC, n=111). Clusters of ICD differences were assessed for regional dysconnectivity and mood symptom relationships. Analyses were also performed for BDAYA overall (vs. HC) ICD differences persisting across mood states. ICD was higher in the BDAYA- depressed group than other groups in bilateral ventral/rostral/dorsal prefrontal cortex (PFC) and right lenticular nucleus (LN) (pcorrected <0.05). In BDAYA -depressed, functional connectivity (FC) was increased between these regions with their contralateral homologues and PFC-medial temporal FC was more negative (p<0.005). PFC-related findings correlated with depression scores (p<0.05). The overall BDAYA group showed ICD increases in more ventral left PFC and right cerebellum, present across euthymia and acute mood states. This ICD approach supports a PFC hub of inter- and intra-hemispheric frontotemporal dysconnectivity in BDAYA with potential trait features and disturbances of higher magnitude during depression. Hubs were also revealed in LN and cerebellum, less common foci of BD research. The hubs are potential targets for early interventions to detect, prevent, and treat BD.

A Graph Theoretical Connectome Measure to Assess Whole Brain Functional Connectivity Disturbances Associated With Suicide Attempts in Bipolar Disorder

Bipolar Disorder (BD) confers a high risk for suicidal behavior. Most studies have used a priori regions or seed-based measures to elucidate the neurobiological substrates of suicide behaviors in BD, which may miss important hubs of dysfunction relevant to suicide behaviors and their prevention. Here, a voxel-wise graph-theoretical connectome measure, the intrinsic connectivity distribution (ICD) was used to map whole-brain functional disturbances associated with suicide attempts in BD.

Effects of Smoking Status and State on Intrinsic Connectivity

BackgroundSmoking behavior during the first 24 hours of a quit attempt is a significant predictor of longer-term abstinence, yet little is known about the neurobiology of early tobacco abstinence. Specifically, the effects of acute tobacco deprivation and reinstatement on brain function—particularly at the level of large-scale network dynamics and assessed across the entire brain—remain incompletely understood. To address this gap, this study used a mixed within- and between-subjects design to assess the effects of smoking status (yes/no smoker) and state (deprived vs. satiated) on whole-brain patterns of intrinsic connectivity. MethodsParticipants included 42 tobacco smokers who underwent resting-state functional magnetic resonance imaging following overnight abstinence (deprived state) and following smoking reinstatement (satiated state, randomized order across participants). Sixty healthy control nonsmokers underwent a single resting-state scan using the same acquisition parameters. Functional connectivity data were analyzed using both a canonical network-of-interest approach and a whole-brain, data-driven approach, i.e., intrinsic connectivity distribution. ResultsNetwork-of-interest–based analyses indicated decreased functional connectivity within frontoparietal and salience networks among smokers relative to nonsmokers as well as effects of smoking state on default mode connectivity. In addition, intrinsic connectivity distribution analyses identified novel between-group differences in subcortical-cerebellar and corticocerebellar networks that were largely smoking state dependent. ConclusionsThese data demonstrate the importance of considering smoking state and the utility of using both theory- and data-driven analysis approaches. These data provide much-needed insight into the functional neurobiology of early abstinence, which may be used in the development of novel treatments.

Neurological Functional Connectivity in Unilateral Coronal Synostosis: A Side-Based Comparison.

Unicoronal synostosis (UCS) has been associated with reading, language, and social dysfunction. Limited brain function connectivity studies exist for UCS with none devoted to comparing outcomes by side of synostosis (left versus right-sided UCS). Twelve patients with surgically treated UCS, 7 right-sided and 5 left-sided, were age matched to healthy controls. Resting state functional MRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany). Data was collected with intrinsic connectivity distribution and seed-connectivity analysis using BioImage Suite (Yale School of Medicine). Region of interest analysis was performed based on Brodmann areas related to emotional, executive, language, motor, and visuo-spatial function. Significance was set at P < 0.05. Compared to controls, all UCS patients demonstrated decreased connectivity in areas of the parietal and temporal cortices responsible for visuo-motor coordination and language function. Right UCS patients demonstrated decreased intrinsic connectivity in regions related to complex motor movement and proprioception relative to control subjects. Left UCS patients demonstrated decreased seed connectivity between regions of the parietal lobe and occipital lobe related to motor coordination, visual function, and language compared to right UCS patients. Unicoronal synostosis had decreased functional connectivity in regions associated with memory, visual information processing, and motor function. Moreover, left-sided UCS had decreased connectivity in circuits for motor coordination and language when compared to right-sided UCS. This study provides data suggestive of long-term sequelae of UCS that varies by sidedness, which may be responsible for neurocognitive impairments found in previous cognitive analyses.

1994-P: Task-Oriented Connectivity Analysis of Disease-Dependent Effects of Diet

Previous results have demonstrated that short-term dieting attenuates neuronal inhibitory control on appetite measured with blood-oxygen-level-dependent (BOLD) responses to a food cue task. Because recent studies have suggested that functional connectivity measured during the task is strongly predictive of disease states, we sought to investigate the effect of weight loss on brain functional connectivity during the picture viewing task. Sixteen healthy obese (10F/6M, age 44.4±8 years, BMI 32.7±2) and 9 type 2 diabetes (T2DM) obese subjects (5F/4M, age 48±9, BMI 33.9±2) underwent functional MRI (fMRI) before and after an 8-week low-calorie diet. Brain connectivity (BOLD) was recorded while subjects viewed preselected images (high-calorie food, low-calorie food, and non-food). Participants lost 2.9±2.8 kg (p&amp;lt;0.05) weight after the diet. Using intrinsic connectivity distribution (ICD) analysis, there was a significant diet effect (p&amp;lt; 0.01) in the inferior pons, hypothalamus, and inferior medial hippocampus across all subjects. Diet by group interaction in ICD (p &amp;lt;0.001) was observed in the inferior anterior amygdala, inferior medial hippocampus, and hypothalamus, brain regions involved in the modulation of emotion and glucose metabolism. These results highlight the adaptive nature of neuronal control on diet and provide novel evidence for a variable nature of inhibitory neuronal adaptions in metabolic diseases. Disclosure C. Watt: None. T.K. Stanley: None. C. Lacadie: None. K.W.Y. Lam: None. M. Savoye: None. R. Sinha: None. T. Constable: None. D. Seo: None. J.J. Hwang: Research Support; Self; General Electric. R. Belfort-DeAguiar: Research Support; Self; Silver Palate Kitches. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK045735, K23 DK098286-02, R01DK020495); National Institutes of Health (UL1TR001863)

Altered intrinsic connectivity distribution in internet gaming disorder and its associations with psychotherapy treatment outcomes.

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.

Mood State Differences in Intrinsic Connectivity Distribution of Adolescents and Young Adults With Bipolar Disorder

Mood State Differences in Intrinsic Connectivity Distribution of Adolescents and Young Adults With Bipolar Disorder

Controlling for the effect of arterial-CO2 fluctuations in resting-state fMRI: Comparing end-tidal CO2 clamping and retroactive CO2 correction

The BOLD signal, as the basis of functional MRI, arises from both neuronal and vascular factors, with their respective contributions to resting state-fMRI still unknown. Among the factors contributing to “physiological noise”, dynamic arterial CO2 fluctuations constitutes the strongest and the most widespread modulator of the grey-matter rs-fMRI signal. Some important questions are: (1) if we were able to clamp arterial CO2 such that fluctuations are removed, what would happen to rs-fMRI measures? (2) falling short of that, is it possible to retroactively correct for CO2 effects with equivalent outcome? In this study 13 healthy subjects underwent two rs-fMRI acquisitions. During the “clamped” run, end-tidal CO2 (PETCO2) is clamped to the average PETCO2 level of each participant, while during the “free-breathing” run, the PETCO2 level is passively monitored but not controlled. PETCO2 correction was applied to the free-breathing data by convolving PETCO2 with its BOLD response function, and then regressing out the result. We computed the BOLD resting-state fluctuation amplitude (RSFA), as well as seed-independent mean functional connectivity (FC) as the weighted global brain connectivity (wGBC). Furthermore, connectivity between conditions were compared using coupled intrinsic-connectivity distribution (ICD) method. We ensured that PETCO2 clamping did not significantly alter heart-beat and respiratory variation. We found that neither PETCO2 clamping nor correction produced significant change in RSFA and wGBC. In terms of the ICD, PETCO2 clamping and correction both reduced FC strength in the majority of grey matter regions, although the effect of PETCO2 correction is considerably smaller than the effect of PETCO2 clamping. Interestingly, we found the effect of the commonly employed white-mater/cerebrospinal-fluid regression to be similar to that of PETCO2 clamping than global-signal regression. Nonetheless, both methods reduce functional connectivity significantly more than does PETCO2 clamping.Furthermore, while PETCO2 clamping reduced inter-subject variability in FC, PETCO2 correction increased the variability. Overall PETCO2 correction is not the equivalent of PETCO2 clamping, although it shifts FC values towards the same direction as clamping does.

Abstract 26: Neurologic Functional Connectivity In Unicoronal Craniosynostosis: A Side-based Comparison

Purpose: Unicoronal synostosis has been associated with impaired reading, language, and social function. Functional MRI (fMRI) can evaluate brain connectivity in targeted brain regions to compare imaging analysis to previously published clinical performance. fMRI was used in this study to compare brain function connectivity in unicoronal synostosis (UCS) and compare outcomes by cerebral dominance (left versus right-sided UCS). Methods: Twelve adolescents with surgically treated UCS, 7 right-sided and 5 left-sided, were individually matched to age, gender and handedness controls. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany). Data was collected with intrinsic connectivity distribution and seed-connectivity analysis with BioImage Suite (Yale School of Medicine). Region of interest (ROI) analysis was performed based on Brodmann’s areas (BA) related to emotional, executive, language, motor and visuo-spatial function, left BA5, 6, 7, 18, 19, 37, 39, and 44. BA5, 6, 7 are areas of the frontal and parietal cortex important for visuomotor coordination and complex movement. BA18, 19 are areas of the occipital lobe related to visual information processing. BA 37, 39, and 44 are areas of the fusiform, angular gyri and temporal lobe important for language function. P<0.05 was significant. Results: Compared to controls, all UCS patients demonstrated decreased connectivity in left BA7, bilateral BA39, and right BA41 (p<0.01)), which are areas of the parietal and temporal cortices responsible for vision, language function, and motor coordination. Right UCS patients demonstrated increased connectivity in right BA17, BA18, BA19, BA20, BA36 when compared to controls (p<0.05). In the ROI analysis, right UCS exhibited decreased connectivity between the anterior cingulate cortex and right BA18, 19, and 37 compared to controls (p<0.05). The increased connectivity in BA17-20 (visual processing regions) supports our previous neurocognitive study results of increased visual perception abilities in right UCS patients. The subsequent decreased connectivity between BA18-19 and the anterior cingulate cortex (a section of which is implicated in complex motor coordination) is supported by neurocognitive data that shows decreased visual-motor integration ability in right UCS. This decreased connectivity between the aforementioned areas and the anterior cingulate gyrus despite increased intrinsic connectivity may also imply discordance in connecting emotion and executive function to language and visual information in right UCS patients. Connectivity between the left parahippocampus and right BA36, 37, and 54 was increased (p<0.05). Compared to controls and right UCS, left UCS demonstrated decreased connectivity between left BA6 and left BA17 and 18 (p<0.05). Left UCS patients did not demonstrate significantly different intrinsic or seed-based connectivity to right UCS or controls otherwise. Conclusion: Unilateral coronal synostosis had decreased connectivity and greater potential for neurocognitive dysfunction in regions associated with memory, visual information processing, and motor function. Moreover, left-sided UCS had decreased connectivity in circuits crucial in complex motor movement when compared to right-sided UCS. This study provides data suggestive of long-term sequelae of UCS that varies by sidedness, which may underlie the different phenotypes of neurocognitive impairment found in previous cognitive analyses.

Dynamic-flip-angle ECG-gating with nuisance signal regression improves resting-state BOLD functional connectivity mapping by reducing cardiogenic noise.

To investigate an ECG-gated dynamic-flip-angle BOLD sequence with improved robustness against cardiogenic noise in resting-state fMRI. ECG-gating minimizes the cardiogenic noise but introduces T1 -dependent signal variation, which is minimized by combination of a dynamic-flip-angle technique and retrospective nuisance signal regression (NSR) using signals of white matter, CSF, and global average. The technique was studied with simulations in a wide range of T1 and B1 fields and phantom imaging with pre-programmed TR variations. Resting-state fMRI of 20 healthy subjects was acquired with non-gated BOLD (NG), ECG-gated constant-flip-angle BOLD (GCFA), ECG-gated BOLD with retrospective T1 -correction (GRC), and ECG-gated dynamic-flip-angle BOLD (GDFA), all processed by the same NSR method. GDFA was compared to alternative methods over temporal SNR (tSNR), seed-based connectivity, and whole-brain voxelwise connectivity based on intrinsic connectivity distribution (ICD). A previous large-cohort data set (N = 100) was used as a connectivity gold standard. Simulations and phantom imaging show substantial reduction of the T1 -dependent signal variation with GDFA alone, and further reduction with NSR. The resting-state study shows improved tSNR in the basal brain, comparing GDFA to NG, after both processed with NSR. Furthermore, GDFA significantly improved subcortical-subcortical and cortical-subcortical connectivity for several representative seeds and significantly improved ICD in the brainstem, thalamus, striatum, and prefrontal cortex, compared to the other 3 approaches. GDFA with NSR improves mapping of the resting-state functional connectivity of the basal-brain regions by reducing cardiogenic noise.

Data-Driven Analysis of Functional Connectivity Reveals a Potential Auditory Verbal Hallucination Network.

Schizophrenia is a severe global health problem, with over half of such patients experiencing auditory verbal hallucinations (AVHs). A better understanding of the neural correlates differentiating patients experiencing AVHs from patients not experiencing AVHs and healthy controls may identify targets that lead to better treatment strategies for AVHs. Employing 2 data-driven, voxel-based measure of functional connectivity, we studied 46 patients with schizophrenia or schizoaffective disorder (28 experiencing AVHs and 18 not experiencing AVHs). Twenty healthy controls matched for age, gender, ethnicity, education level, handedness, and estimated verbal intelligence were included for comparison. The intrinsic connectivity distribution (ICD) was used to model each voxel’s connectivity to the rest of the brain using a Weibull distribution. To investigate lateralization of connectivity, we used cross-hemisphere ICD, a method that separates the contribution of each hemisphere to interrogate connectivity laterality. Patients with AVHs compared with patients without AVHs exhibited significantly decreased whole-brain connectivity in the medial prefrontal cortex and posterior cingulate cortex, less lateralized connectivity in left putamen, and more lateralized connectivity in left interior frontal gyrus. Correlations with Auditory Hallucination Rating Scale (AHRS) and post hoc seed connectivity analyses revealed significantly altered network connectivity. Using the results from all analyses comparing the patient groups and correlations with AHRS, we identified a potential AVH network, consisting of 25 nodes, showing substantial overlap with the default mode network and language processing networks. This network as a whole, instead of individual nodes, may represent actionable targets for interventions.