M165. CEREBELLAR VOLUMES REDUCED IN PATIENTS WITH SCHIZOPHRENIA BASED ON ANATOMICAL, TASK-FREE AND TASK-BASED FUNCTIONAL PARCELLATIONS

Abstract Background Cerebellum is not only responsible for motor functions but is also involving in cognitive and emotional processes (Strick et al. 2009). Recent advances in imaging technologies allow us to examine the cerebellum in a much more systematic way including functional parcellations of cerebellum (e.g. 7-Network parcellation based on the resting state functional connectivity, Buckner et al., 2011; and task-based functional parcellation, King et al., 2019). These functional parcellations further uncover the important roles of cerebellum in non-motor functions. In the past two decades, altered cerebellar structure and function have been observed in schizophrenia patients, with the anterior (lobules III-V) and the posterior cerebellum (lobules VI, VIIa, Crus I, and Crus II, VIII) as regions commonly reported (Bernard & Mittal 2015). Using the 7-Network task-free parcellation, a recent multisite mega-analysis reported that patients with schizophrenia exhibited robust grey matter reduction in cerebellum (Moberget et al., 2018). The present study aimed to examine the cerebellar grey matter volumes in schizophrenia patients using anatomical, task-free connectivity-based and task-based functional parcellations. We also explored how the cerebellar volumes changes along with age in schizophrenia patients and healthy controls. Methods Twenty-nine patients with schizophrenia (SCZ, mean age = 22.0±2.5 years) and 55 healthy controls (HC, mean age = 23.5±3.6 years) were recruited to undertake structural magnetic resonance imaging (MRI) brain scan on a GE 750 scanner. Cerebellar volumes were measured by a high-resolution Spatially Unbiased Infratentorial (SUIT) toolbox (Diedrichsen, 2006). Regional cerebellar grey matter volumes were calculated for each participant based on anatomical (SUIT atlas) and functional atlases (7 regions of task-free parcellation; 10 regions of task-based parcellation) of the cerebellum. The group comparisons on regional cerebellar volumes were conducted in SPSS v19.0, taking total ICV as a covariate. The correlations between age and cerebellar volumes of those regions showing significant group differences were conducted. The significance threshold was set at p < 0.05. Results Regarding the anatomical atlas, SCZ patients exhibited reduced grey matter volumes of the superior posterior cerebellum, mainly in lobules Crus II, VIIb and VIIIa. Regarding the task-free parcellation, SCZ patients exhibited smaller volumes in cerebellar regions showing functional connectivity with frontoparietal network and default mode network. Regarding the task-based parcellation, smaller volumes of cerebellar regions that activated during verbal fluency task (ROI9) was observed in SCZ patients. Correlation analyses between age and cerebellar volumes of those regions with significant group differences further reported negative correlations between age and lobule Crus II in both SCZ patients and HC (SCZ: r = -0.44, p < 0.05; HC: r = -0.43, p = 0.001). Moreover, negative correlations between age and cerebellar regions showing functional connectivity with frontoparietal network was observed in HC only (r = -0.30, p < 0.05), whereas negative correlations between age and lobules VIIb (r = -0.48, p < 0.01), VIIIa (r = -0.39, p < 0.05) and ROI9 of task-based atlas (r = -0.43, p < 0.05) were observed in SCZ patients. Discussion Our findings showed reduced cerebellar grey matter volumes and the abnormal age-related changes of cerebellum in SCZ patients, especially in the regions related to frontoparietal network and cognitive function. These findings may highlight an important role of cerebellum underlying the mechanisms of cognitive dysfunction in mental disorders.

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Cognitive Profiles of Amyotrophic Lateral Sclerosis Differ in Resting-State Functional Connectivity: An fMRI Study

Frontiers in Neuroscience ◽

10.3389/fnins.2021.682100 ◽

2021 ◽

Vol 15 ◽

Author(s):

Anna G. M. Temp ◽

Martin Dyrba ◽

Charlotte Büttner ◽

Elisabeth Kasper ◽

Judith Machts ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Functional Connectivity ◽

Resting State ◽

Group Differences ◽

Cognitively Impaired ◽

Healthy Controls ◽

Cognitive Profiles ◽

Resting State Functional Connectivity ◽

Als Patients ◽

Lateral Sclerosis

BackgroundHalf of all amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) patients are classified as cognitively impaired, of which 10% have frontotemporal dementia (FTD), and an additional 40% suffer from a frontotemporal syndrome not severe enough to be described as dementia (cognitively impaired/ALSci). As changes in cerebral function measured by resting-state magnet resonance imaging (rs-fMRI) are known in ALS, we investigated whether group differences in resting-state functional connectivity (RSFC) networks could be observed between ALS patients with different cognitive profiles against healthy controls (HC). Furthermore, we correlated cognition and motor functioning with network connectivity.MethodsHealthy controls, 69, and 97 ALS patients underwent functional MRI scanning and cognitive assessment. The ALS patients were categorized as non-impaired (ALSni; n = 68), cognitively impaired (ALSci; n = 21), and ALS-FTD (n = 8). Group differences in connectivity of the default mode network (DMN), motor network (MN), and ventral attention network (VAN) were investigated using a full-factorial model; correlations between global cognitive performance, shifting, and motor symptom severity were established using Pearson’s correlation.ResultsAt a liberal alpha level of uncorrected p < 0.005 and a cluster size exceeding 20 voxels, we found widespread decreases in functional connectivity in all three networks when comparing ALS patients to HC. Similar patterns of hypoconnectivity in the bilateral motor cortices and frontotemporal emerged when comparing the ALSci and ALS-FTD patients to those not cognitively impaired. Hyperconnectivity in the DMN temporal gyrus correlated with worse global cognition; moreover, hyperconnectivity in the VAN thalamus, insula, and putamen correlated with worse shifting ability. Better-preserved motor function correlated with higher MN connectivity. Only the motor-related effects prevailed at a more conservative significance level of pFDR< 0.001.ConclusionResting-state functional connectivity differs between cognitive profiles of ALS and is directly associated with clinical presentation, specifically with motor function, and cognitive shifting.

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Age-related differences in resting state functional connectivity in pediatric migraine

The Journal of Headache and Pain ◽

10.1186/s10194-021-01274-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Tiffany Bell ◽

Akashroop Khaira ◽

Mehak Stokoe ◽

Megan Webb ◽

Melanie Noel ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Power Spectra ◽

Interaction Effects ◽

Resting State Functional Connectivity ◽

Default Mode ◽

Pediatric Migraine ◽

Age Related ◽

Status Interaction ◽

Underlying Mechanisms

Abstract Background Migraine affects roughly 10% of youth aged 5–15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes. Methods Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7–15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis. Results We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks. Conclusions We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.

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Effects of aging on emotion recognition from dynamic multimodal expressions and vocalizations

Scientific Reports ◽

10.1038/s41598-021-82135-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Diana S. Cortes ◽

Christina Tornberg ◽

Tanja Bänziger ◽

Hillary Anger Elfenbein ◽

Håkan Fischer ◽

...

Keyword(s):

Older Adults ◽

Emotion Recognition ◽

Positive Emotions ◽

Negative Emotions ◽

Group Differences ◽

Significant Group ◽

Positivity Effect ◽

Video Recordings ◽

Age Related ◽

Effects Of Aging

AbstractAge-related differences in emotion recognition have predominantly been investigated using static pictures of facial expressions, and positive emotions beyond happiness have rarely been included. The current study instead used dynamic facial and vocal stimuli, and included a wider than usual range of positive emotions. In Task 1, younger and older adults were tested for their abilities to recognize 12 emotions from brief video recordings presented in visual, auditory, and multimodal blocks. Task 2 assessed recognition of 18 emotions conveyed by non-linguistic vocalizations (e.g., laughter, sobs, and sighs). Results from both tasks showed that younger adults had significantly higher overall recognition rates than older adults. In Task 1, significant group differences (younger > older) were only observed for the auditory block (across all emotions), and for expressions of anger, irritation, and relief (across all presentation blocks). In Task 2, significant group differences were observed for 6 out of 9 positive, and 8 out of 9 negative emotions. Overall, results indicate that recognition of both positive and negative emotions show age-related differences. This suggests that the age-related positivity effect in emotion recognition may become less evident when dynamic emotional stimuli are used and happiness is not the only positive emotion under study.

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Reduced resting state functional connectivity with increasing age-related hearing loss and McGurk susceptibility

Scientific Reports ◽

10.1038/s41598-020-74012-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Alina Schulte ◽

Christiane M. Thiel ◽

Anja Gieseler ◽

Maike Tahden ◽

Hans Colonius ◽

...

Keyword(s):

Hearing Loss ◽

Functional Connectivity ◽

Resting State ◽

Mcgurk Effect ◽

Functional Coupling ◽

Resting State Functional Connectivity ◽

Visual Integration ◽

Age Related ◽

Hearing Thresholds ◽

Age Related Hearing Loss

Abstract Age-related hearing loss has been related to a compensatory increase in audio-visual integration and neural reorganization including alterations in functional resting state connectivity. How these two changes are linked in elderly listeners is unclear. The current study explored modulatory effects of hearing thresholds and audio-visual integration on resting state functional connectivity. We analysed a large set of resting state data of 65 elderly participants with a widely varying degree of untreated hearing loss. Audio-visual integration, as gauged with the McGurk effect, increased with progressing hearing thresholds. On the neural level, McGurk illusions were negatively related to functional coupling between motor and auditory regions. Similarly, connectivity of the dorsal attention network to sensorimotor and primary motor cortices was reduced with increasing hearing loss. The same effect was obtained for connectivity between the salience network and visual cortex. Our findings suggest that with progressing untreated age-related hearing loss, functional coupling at rest declines, affecting connectivity of brain networks and areas associated with attentional, visual, sensorimotor and motor processes. Especially connectivity reductions between auditory and motor areas were related to stronger audio-visual integration found with increasing hearing loss.

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Altered Functional Connectivity Patterns of Parietal Subregions Contribute to Cognitive Dysfunction in Patients with White Matter Hyperintensities

Journal of Alzheimer s Disease ◽

10.3233/jad-210315 ◽

2021 ◽

pp. 1-11

Author(s):

Qiang Wei ◽

Shanshan Cao ◽

Yang Ji ◽

Jun Zhang ◽

Chen Chen ◽

...

Keyword(s):

White Matter ◽

Functional Connectivity ◽

White Matter Hyperintensities ◽

Parietal Lobe ◽

Small Vessel Disease ◽

Anterior Cingulate ◽

Healthy Controls ◽

Cingulate Gyrus ◽

Anterior Cingulate Gyrus ◽

Resting State Functional Connectivity

Background: The white matter hyperintensities (WMHs) are considered as one of the core neuroimaging findings of cerebral small vessel disease and independently associated with cognitive deficit. The parietal lobe is a heterogeneous area containing many subregions and play an important role in the processes of neurocognition. Objective: To explore the relationship between parietal subregions alterations and cognitive impairments in WHMs. Methods: Resting-state functional connectivity (rs-FC) analyses of parietal subregions were performed in 104 right-handed WMHs patients divided into mild (n = 39), moderate (n = 37), and severe WMHs (n = 28) groups according to the Fazekas scale and 36 healthy controls. Parietal subregions were defined using tractographic Human Brainnetome Atlas and included five subregions for superior parietal lobe, six subregions for inferior parietal lobe (IPL), and three subregions for precuneus. All participants underwent a neuropsychological test battery to evaluate emotional and general cognitive functions. Results: Differences existed between the rs-FC strength of IPL_R_6_2 with the left anterior cingulate gyrus, IPL_R_6_3 with the right dorsolateral superior frontal gyrus, and the IPL_R_6_5 with the left anterior cingulate gyrus. The connectivity strength between IPL_R_6_3 and the left anterior cingulate gyrus were correlated with AVLT-immediate and AVLT-recognition test in WMHs. Conclusion: We explored the roles of parietal subregions in WMHs using rs-FC. The functional connectivity of parietal subregions with the cortex regions showed significant differences between the patients with WMHs and healthy controls which may be associated with cognitive deficits in WMHs.

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Parental Education, Ethnicity, and Functional Connectivity between Nucleus Accumbens and Frontoparietal Network

10.5772/intechopen.101335 ◽

2021 ◽

Author(s):

Shervin Assari

Keyword(s):

Nucleus Accumbens ◽

Functional Connectivity ◽

Resting State ◽

Parental Education ◽

Black People ◽

Right Hemisphere ◽

Latino Youth ◽

Resting State Functional Connectivity ◽

Cross Sectional ◽

Frontoparietal Network

While studies have indicated an association between socioeconomic status (SES) and neuroimaging measures, weaker SES effects are shown for Blacks than Whites. This is, in part, due to processes such as stratification, racism, minoritization, and othering of Black people in the United States. However, less is known about Latino youth. This study had two aims: First, to test the association between parental education and the right and left nucleus accumbens (NAcc) resting-state functional connectivity with the frontoparietal network (FPN) in children; and second, to investigate ethnic heterogeneity in this association. This cross-sectional study used data from the Adolescent Brain Cognitive Development (ABCD) study. We analyzed the resting-state functional connectivity data (rsFC) of 10,840 US preadolescents who were between 9 and 10 years old. The main outcomes were the NAcc resting-state functional connectivity with FPN separately calculated for right and left hemispheres. Parental education was our independent variable. Family structure, sex, and age were covariates. Furthermore, ethnicity (Latino vs. non-Latino) was regarded as the moderator. We used mixed-effects regression for data analysis with and without interaction terms between parental education and ethnicity. Most participants (n = 8690; 80.2%) were non-Latino and 2150 (19.8%) were Latino. Parental education was associated with higher right and left NAcc resting-state functional connectivity with FPN. Ethnicity showed statistically significant interactions with parental education, suggesting that the positive associations between parental education and right and left NAcc resting-state functional connectivity with FPN were different in non-Latino and Latino children. For right hemisphere, we found significantly stronger and for left hemisphere, we found significantly weaker association for Latino compared with non-Latino preadolescents. Preadolescents’ NAcc resting-state functional connectivity with FPN depends on the intersections of ethnicity, parental education, and laterality.

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Predicting dysfunctional age-related task activations from resting-state network alterations

10.1101/678086 ◽

2019 ◽

Cited By ~ 1

Author(s):

Ravi D. Mill ◽

Brian A. Gordon ◽

David A. Balota ◽

Jeffrey M. Zacks ◽

Michael W. Cole

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Functional Connectivity ◽

Resting State ◽

Cognitive Task ◽

Low Risk ◽

Flow Modeling ◽

Resting State Functional Connectivity ◽

Age Related

AbstractAlzheimer’s disease (AD) is linked to changes in fMRI task activations and fMRI resting-state functional connectivity (restFC), which can emerge early in the timecourse of illness. Study of these fMRI correlates of unhealthy aging has been conducted in largely separate subfields. Taking inspiration from neural network simulations, we propose a unifying mechanism wherein restFC network alterations associated with Alzheimer’s disease disrupt the ability for activations to flow between brain regions, leading to aberrant task activations. We apply this activity flow modeling framework in a large sample of clinically unimpaired older adults, which was segregated into healthy (low-risk) and at-risk subgroups based on established imaging (positron emission tomography amyloid) and genetic (apolipoprotein) risk factors for AD. We identified healthy task activations in individuals at low risk for AD, and then by estimating activity flow using at-risk AD restFC data we were able to predict the altered at-risk AD task activations. Thus, modeling the flow of healthy activations over at-risk AD connectivity effectively transformed the healthy aged activations into unhealthy aged activations. These results provide evidence that activity flow over altered intrinsic functional connections may act as a mechanism underlying Alzheimer’s-related dysfunction, even in very early stages of the illness. Beyond these mechanistic insights linking restFC with cognitive task activations, this approach has potential clinical utility as it enables prediction of task activations and associated cognitive dysfunction in individuals without requiring them to perform in-scanner cognitive tasks.Significance StatementDeveloping analytic approaches that can reliably predict features of Alzheimer’s disease is a major goal for cognitive and clinical neuroscience, with particular emphasis on identifying such diagnostic features early in the timeline of disease. We demonstrate the utility of an activity flow modeling approach, which predicts fMRI cognitive task activations in subjects identified as at-risk for Alzheimer’s disease. The approach makes activation predictions by transforming a healthy aged activation template via the at-risk subjects’ individual pattern of fMRI resting-state functional connectivity (restFC). The observed prediction accuracy supports activity flow as a mechanism linking age-related alterations in restFC and task activations, thereby providing a theoretical basis for incorporating restFC into imaging biomarker and personalized medicine interventions.

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Dynamic Interhemispheric Desynchronization in Marmosets and Humans With Disorders of the Corpus Callosum

Frontiers in Neural Circuits ◽

10.3389/fncir.2020.612595 ◽

2020 ◽

Vol 14 ◽

Author(s):

Diego Szczupak ◽

Cecil C. Yen ◽

Cirong Liu ◽

Xiaoguang Tian ◽

Roberto Lent ◽

...

Keyword(s):

Functional Connectivity ◽

Corpus Callosum ◽

Resting State ◽

Human Subjects ◽

Healthy Controls ◽

Resting State Functional Connectivity ◽

Periodic Patterns ◽

Lower Strength ◽

Neuronal Communication ◽

Clear Explanation

The corpus callosum, the principal structural avenue for interhemispheric neuronal communication, controls the brain’s lateralization. Developmental malformations of the corpus callosum (CCD) can lead to learning and intellectual disabilities. Currently, there is no clear explanation for these symptoms. Here, we used resting-state functional MRI (rsfMRI) to evaluate the dynamic resting-state functional connectivity (rsFC) in both the cingulate cortex (CG) and the sensory areas (S1, S2, A1) in three marmosets (Callithrix jacchus) with spontaneous CCD. We also performed rsfMRI in 10 CCD human subjects (six hypoplasic and four agenesic). We observed no differences in the strength of rsFC between homotopic CG and sensory areas in both species when comparing them to healthy controls. However, in CCD marmosets, we found lower strength of quasi-periodic patterns (QPP) correlation in the posterior interhemispheric sensory areas. We also found a significant lag of interhemispheric communication in the medial CG, suggesting asynchrony between the two hemispheres. Correspondingly, in human subjects, we found that the CG of acallosal subjects had a higher QPP correlation than controls. In comparison, hypoplasic subjects had a lower QPP correlation and a delay of 1.6 s in the sensory regions. These results show that CCD affects the interhemispheric synchrony of both CG and sensory areas and that, in both species, its impact on cortical communication varies along the CC development gradient. Our study shines a light on how CCD misconnects homotopic regions and opens a line of research to explain the causes of the symptoms exhibited by CCD patients and how to mitigate them.

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Altered amygdala-based functional connectivity in individuals with attenuated psychosis syndrome and first-episode schizophrenia

Scientific Reports ◽

10.1038/s41598-020-74771-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Woo-Sung Kim ◽

Guangfan Shen ◽

Congcong Liu ◽

Nam-In Kang ◽

Keon-Hak Lee ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Negative Relationship ◽

First Episode ◽

Frontal Pole ◽

Resting State Functional Connectivity ◽

Significant Group ◽

Attenuated Psychosis Syndrome ◽

The Right ◽

First Episode Schizophrenia

Abstract Altered resting-state functional connectivity (FC) of the amygdala (AMY) has been demonstrated to be implicated in schizophrenia (SZ) and attenuated psychosis syndrome (APS). Specifically, no prior work has investigated FC in individuals with APS using subregions of the AMY as seed regions of interest. The present study examined AMY subregion-based FC in individuals with APS and first-episode schizophrenia (FES) and healthy controls (HCs). The resting state FC maps of the three AMY subregions were computed and compared across the three groups. Correlation analysis was also performed to examine the relationship between the Z-values of regions showing significant group differences and symptom rating scores. Individuals with APS showed hyperconnectivity between the right centromedial AMY (CMA) and left frontal pole cortex (FPC) and between the laterobasal AMY and brain stem and right inferior lateral occipital cortex compared to HCs. Patients with FES showed hyperconnectivity between the right superficial AMY and left occipital pole cortex and between the left CMA and left thalamus compared to the APS and HCs respectively. A negative relationship was observed between the connectivity strength of the CMA with the FPC and negative-others score of the Brief Core Schema Scales in the APS group. We observed different altered FC with subregions of the AMY in individuals with APS and FES compared to HCs. These results shed light on the pathogenetic mechanisms underpinning the development of APS and SZ.

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O2.2. EVALUATION OF THE RELATIONSHIP BETWEEN GLUTAMATE AND BRAIN CONNECTIVITY IN ANTIPSYCHOTIC-NAïVE FIRST EPISODE PATIENTS – A COMBINED MAGNETIC RESONANCE SPECTROSCOPY AND RESTING STATE FUNCTIONAL CONNECTIVITY MRI STUDY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa028.007 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S4-S4

Author(s):

Jose Maximo ◽

Frederic Briend ◽

William Armstrong ◽

Nina Kraguljac ◽

Adrienne Lahti

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Group Differences ◽

First Episode ◽

Resonance Spectroscopy ◽

Resting State Functional Connectivity ◽

Positive Correlations ◽

Functional Connectivity Mri

Abstract Background Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used resting state functional connectivity MRI (rs-fcMRI) and magnetic resonance spectroscopy (MRS) to investigate how measurements of glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) relate to rs-fcMRI in medication-naïve first episode psychosis (FEP) subjects compared to healthy controls (HC). Based on our previous findings, we hypothesized that in HC would show correlations between Glx and rs-fMRI in the salience and default mode network, but these relationships would be altered in FEP. Methods Data from 53 HC (age = 24.70 ±6.23, 34M/19F) and 60 FEP (age = 24.08 ±6.29, 38M/22F) were analyzed. To obtain MRS data, a voxel was placed in the ACC (PRESS, TR/TE = 2000/80ms). Metabolite concentrations were quantified with respect to internal water using the AMARES algorithm in jMRUI. rs-fMRI data were processed using a standard preprocessing pipeline in the CONN toolbox. BOLD signal from a priori brain regions of interest from posterior cingulate cortex (default mode network, DMN), anterior cingulate cortex (salience network, SN), and right posterior parietal cortex (central executive network, CEN) were extracted and correlated with the rest of the brain to measure functional connectivity (FC). Group analyses were performed on Glx, FC, and Glx-FC interactions while controlling for age, gender, and motion when applicable. FC and Glx-FC analyses were performed using small volume correction [(p < 0.01, threshold-free cluster enhancement corrected (TFCE)]. Results No significant between-group differences were found in Glx concentration in the ACC [F(1, 108) = 0.34, p = 0.56], but reduced FC was found on each network in FEP compared to HC (pTFCE corrected). Group Glx-FC interactions were found in the form of positive correlations between Glx and FC in DMN and SN in the HC group, but not in FEP; and negative correlations in CEN in HC, but not in FEP. Discussion While we did not find significant group differences in ACC Glx measurements, ACC Glx modulated FC differentially in FEP and HC. Positive correlations between Glx and FC were found in the SN and DMN, suggesting long range modulation of the two networks in HC, but not in FEP. Additionally, negative correlations between Glx and FC were found in CEN in HC, but not in FEP. Overall, these results suggest that even in the absence of group differences in Glx concentration, the long-range modulation of these 3 networks by ACC Glx is altered in FEP.

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