Most recent paper

Sleep Med. 2024 Aug 8;122:71-83. doi: 10.1016/j.sleep.2024.08.007. Online ahead of print.

ABSTRACT

BACKGROUND: Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear.

METHODS: A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil.

RESULTS: The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus.

CONCLUSIONS: After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.

PMID:39137663 | DOI:10.1016/j.sleep.2024.08.007

Sci Rep. 2024 Aug 13;14(1):18756. doi: 10.1038/s41598-024-68352-4.

ABSTRACT

Heart rate variability (HRV) has been linked to resilience and emotion regulation (ER). How HRV and brain processing interact during ER, however, has remained elusive. Sixty-two subjects completed the acquisition of resting HRV and task HRV while performing an ER functional Magnetic Resonance Imaging (fMRI) paradigm, which included the differential strategies of ER reappraisal and acceptance in the context of viewing aversive pictures. We found high correlations of resting and task HRV across all emotion regulation strategies. Furthermore, individuals with high levels of resting, but not task, HRV showed numerically lower distress during ER with acceptance. Whole-brain fMRI parametrical modulation analyses revealed that higher task HRV covaried with dorso-medial prefrontal activation for reappraisal, and dorso-medial prefrontal, anterior cingulate and temporo-parietal junction activation for acceptance. Subjects with high resting HRV, compared to subjects with low resting HRV, showed higher activation in the pre-supplementary motor area during ER using a region of interest approach. This study demonstrates that while resting and task HRV exhibit a positive correlation, resting HRV seems to be a better predictor of ER capacity. Resting and task HRV were associated with ER brain activation in mid-line frontal cortex (i.e. DMPFC).

PMID:39138266 | DOI:10.1038/s41598-024-68352-4

Alzheimers Dement. 2024 Aug 13. doi: 10.1002/alz.14051. Online ahead of print.

ABSTRACT

INTRODUCTION: In this study, we investigated biomarkers in a midlife, racially diverse, at-risk cohort to facilitate early identification and intervention. We examined neuroimaging measures, including resting state functional magnetic resonance imaging (fMRI), white matter hyperintensity vo (WMH), and hippocampal volumes, alongside cerebrospinal fluid (CSF) markers.

METHODS: Our data set included 76 cognitively unimpaired, middle-aged, Black Americans (N = 29, F/M = 17/12) and Non-Hispanic White (N = 47, F/M = 27/20) individuals. We compared cerebrospinal fluid phosphorylated tau141 and amyloid beta (Aβ)42 to fMRI default mode network (DMN) subnetwork connectivity, WMH volumes, and hippocampal volumes.

RESULTS: Results revealed a significant race × Aβ42 interaction in Black Americans: lower Aβ42 was associated with reduced DMN connectivity and increased WMH volumes regions but not in non-Hispanic White individuals.

DISCUSSION: Our findings suggest that precuneus DMN connectivity and temporal WMHs may be linked to Alzheimer's disease risk pathology during middle age, particularly in Black Americans.

HIGHLIGHTS: Cerebrospinal fluid (CSF) amyloid beta (Aβ)42 relates to precuneus functional connectivity in Black, but not White, Americans. Higher white matter hyperintensity volume relates to lower CSF Aβ42 in Black Americans. Precuneus may be a hub for early Alzheimer's disease pathology changes detected by functional connectivity.

PMID:39136298 | DOI:10.1002/alz.14051

Brain Connect. 2024 Aug 13. doi: 10.1089/brain.2024.0034. Online ahead of print.

ABSTRACT

BACKGROUND: Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are distinguished by whether anxiety is limited to social situations. However, reports on the differences in brain functional networks between GAD and SAD are few. Our objective is to understand the pathogenesis of GAD and SAD by examining the differences in resting brain function between patients with GAD and SAD and healthy controls (HCs).

METHODS: This study included 21 patients with SAD, 17 patients with GAD, and 30 HCs. Participants underwent psychological assessments and resting-state functional magnetic resonance imaging (rsfMRI). Whole-brain analyses were performed to compare resting-state functional connectivity (rsFC) among the groups. Additionally, logistic regression analysis was conducted on the rsFC to identify significant differences between GAD and SAD.

RESULTS: Patients with SAD and GAD had significantly higher rsFC between the bilateral postcentral gyri and bilateral amygdalae/thalami than HCs. Compared with patients with SAD, those with GAD had significantly higher rsFC between the right nucleus accumbens and bilateral thalami and between the left nucleus accumbens and right thalamus. RsFC between the left nucleus accumbens and right thalamus positively correlated with state anxiety in patients with SAD and GAD, respectively. In addition, logistic regression analysis revealed that the right nucleus accumbens and the right thalamus connectivity could distinguish SAD from GAD.

CONCLUSIONS: GAD and SAD were distinguished by the right nucleus accumbens and the right thalamus connectivity. Our findings offer insights into the disease-specific neural basis of SAD and GAD.

PMID:39135472 | DOI:10.1089/brain.2024.0034

Pediatr Radiol. 2024 Aug 13. doi: 10.1007/s00247-024-06022-3. Online ahead of print.

ABSTRACT

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies have revealed extensive functional reorganization in patients with sensorineural hearing loss (SNHL). However, almost no study focuses on the dynamic functional connectivity after hearing loss.

OBJECTIVE: This study aimed to investigate dynamic functional connectivity changes in children with profound bilateral congenital SNHL under the age of 3 years.

MATERIALS AND METHODS: Thirty-two children with profound bilateral congenital SNHL and 24 children with normal hearing were recruited for the present study. Independent component analysis identified 18 independent components composing five resting-state networks. A sliding window approach was used to acquire dynamic functional matrices. Three states were identified using the k-means algorithm. Then, the differences in temporal properties and the variance of network efficiency between groups were compared.

RESULTS: The children with SNHL showed longer mean dwell time and decreased functional connectivity between the auditory network and sensorimotor network in state 3 (P < 0.05), which was characterized by relatively stronger functional connectivity between high-order resting-state networks and motion and perception networks. There was no difference in the variance of network efficiency.

CONCLUSIONS: These results indicated the functional reorganization due to hearing loss. This study also provided new perspectives for understanding the state-dependent connectivity patterns in children with SNHL.

PMID:39134864 | DOI:10.1007/s00247-024-06022-3

AJNR Am J Neuroradiol. 2024 Aug 12:ajnr.A8438. doi: 10.3174/ajnr.A8438. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: The quality of resting-state functional MRI (rs-fMRI) under anesthesia is variable and there are no guidelines on optimal image acquisition or anesthesia protocol. We aim to identify the factors that may lead to compromised clinical rs-fMRI under anesthesia.

MATERIALS AND METHODS: In this cross-sectional study, we analyzed clinical rs-fMRI data acquired under anesthesia from 2009-2023 at Massachusetts General Hospital. Independent component analysis driven resting state networks (RSN) of each patient were evaluated qualitatively and quantitatively and grouped as robust or weak. Overall networks were evaluated using the qualitative method, and motor and language networks were evaluated using the quantitative method. RSN robustness was analyzed in 4 outcome categories: overall, combined Motor-Language, individual motor, and language networks. Predictor variables included rs-fMRI acquisition parameters, anesthesia medications, underlying brain structural abnormalities, age, and sex. Logistic regression was used to examine the effect of the study variables on RSN robustness.

RESULTS: Sixty-nine patients were identified. With qualitative assessment, 40 had robust and 29 had weak overall RSN. Quantitatively, 45 patients had robust, while 24 had weak Motor-Language networks. Among all the predictor variables, only sevoflurane significantly contributed to the outcomes, with sevoflurane administration reducing the odds of having robust RSN in overall (Odds Radio (OR)= 0.2, 95% Confidence Interval (CI) = [0.05;0.79], p = .02), Motor-Language (OR = 0.18, 95% CI = [0.04;0.80], p = .02) and individual motor (OR= 0.1, 95% CI = [0.02;0.64], p= .02) categories. Individual language network robustness was not associated with the tested predictor variables.

CONCLUSIONS: Sevoflurane anesthesia may compromise the visibility of fMRI resting state networks, particularly impacting motor networks. This finding suggests that the type of anesthesia is a critical factor in rs-fMRI quality. We did not observe the association of the MR acquisition technique or underlying structural abnormality with the RSN robustness.

ABBREVIATIONS: BOLD = Blood Oxygen Level-Dependent; ICA = Independent Component Analysis; Rs-fMRI = Resting-State Functional Magnetic Resonance Imaging; RSN = Resting-State Networks; SNR = Signal-to-Noise Ratio.

PMID:39134370 | DOI:10.3174/ajnr.A8438

J Affect Disord. 2024 Aug 10:S0165-0327(24)01242-4. doi: 10.1016/j.jad.2024.08.028. Online ahead of print.

ABSTRACT

BACKGROUND: Depression is a significant public health concern. Identifying biopsychosocial risk factors for depression is important for developing targeted prevention. Studies have demonstrated that blunted striatal activation during reward processing is a risk factor for depression; however, few have prospectively examined whether adolescent reward-related resting-state functional connectivity (rsFC) predicts depression symptoms in adulthood and how this relates to known risk factors (e.g., childhood trauma).

METHODS: At baseline, 66 adolescents (mean age = 14.7, SD = 1.4, 68 % female) underwent rsFC magnetic resonance imaging and completed the Children's Depression Inventory (CDI). At follow-up (mean time between adolescent scan and adult follow-up = 10.1 years, SD = 1.6, mean adult age = 24.8 years, SD = 1.7), participants completed the Childhood Trauma Questionnaire (CTQ) and Beck Depression Inventory (BDI-2). Average rsFC was calculated between nodes in mesocorticolimbic reward circuitry: ventral striatum (VS), rostral anterior cingulate cortex (rACC), medial orbitofrontal cortex, and ventral tegmental area. Linear regressions assessed associations between rsFC, BDI-2, and CTQ, controlling for adolescent CDI, sex assigned at birth, and scan age (Bonferroni corrected).

RESULTS: Greater childhood trauma was associated with higher adulthood depression symptoms. Stronger VS-rACC rsFC during adolescence was associated with greater depression symptoms in adulthood and greater childhood trauma.

LIMITATIONS: The small sample size, limited depression severity, and seed-based approach are limitations.

CONCLUSIONS: The associations between adolescent striatal-cingulate rsFC and childhood trauma and adult depression symptoms suggest this connectivity may be an early neurobiological risk factor for depression and that early life experience plays an important role. Increased VS-rACC connectivity may represent an over-regulatory response on the striatum, commonly reported in depression, and warrants further investigation.

PMID:39134157 | DOI:10.1016/j.jad.2024.08.028

J Affect Disord. 2024 Aug 10:S0165-0327(24)01238-2. doi: 10.1016/j.jad.2024.08.023. Online ahead of print.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) affects multiple functional neural networks. Neuroimaging studies using resting-state functional connectivity (FC) have focused on the amygdala but did not assess changes in connectivity between the left and right amygdala. The current study aimed to examine the inter-hemispheric functional connectivity (homotopic FC, HoFC) between different amygdalar sub-regions in patients with MDD compared to healthy controls, and to examine whether amygdalar sub-regions' HoFC also predicts response to Serotonin Selective Reuptake Inhibitors (SSRIs).

METHOD: Sixty-seven patients with MDD and 64 matched healthy controls were recruited. An MRI scan focusing on resting state fMRI and clinical and cognitive evaluations were performed. An atlas seed-based approach was used to identify the lateral and medial sub-regions of the amygdala. HoFC of these sub-regions was compared between groups and correlated with severity of depression, and emotional processing performance. Baseline HoFC levels were used to predict response to SSRIs after 2 months of treatment.

RESULTS: Patients with MDD demonstrated decreased inter-hemispheric FC in the medial (F3,120 = 4.11, p = 0.008, η2 = 0.096) but not in the lateral (F3,119 = 0.29, p = 0.82, η2 = 0.008) amygdala compared with healthy controls. The inter-hemispheric FC of the medial sub-region correlated with symptoms severity (r = -0.33, p < 0.001) and emotional processing performance (r = 0.38, p < 0.001). Moreover, it predicted treatment response to SSRIs 65.4 % of the cases.

LIMITATIONS: The current study did not address FC changes in MDD biotypes. In addition, structural connectivity was not examined.

CONCLUSIONS: Using a unique perspective of the amygdalar distinct areas elucidated differential inter-hemispheric FC patterns in MDD patients, emphasizing the role of interhemispheric communication in depression.

PMID:39134155 | DOI:10.1016/j.jad.2024.08.023

bioRxiv [Preprint]. 2024 Jul 31:2024.07.31.606025. doi: 10.1101/2024.07.31.606025.

ABSTRACT

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized as functional networks. These areas show stronger internal and weaker external functional connectivity (FC) and exhibit similar FC profiles within rather than between networks. Previous studies have demonstrated the development of these networks from nascent forms present before birth to their mature, adult-like topography in childhood. However, analyses often still use definitions based on adult functional networks. We aim to assess how this might lead to the misidentification of functional networks and explore potential consequences and solutions. Our findings suggest that even though adult networks provide only a marginally better than-chance description of the infant FC organization, misidentification was largely driven by specific areas. By restricting functional networks to areas showing adult-like network clustering, we observed consistent within-network FC both within and across scans and throughout development. Additionally, these areas were spatially closer to locations with low variability in network identity among adults. Our analysis aids in understanding the potential consequences of using adult networks "as is" and provides guidance for future research on selecting and utilizing functional network models based on the research question and scenario.

HIGHLIGHTS: Specialized functional networks in the human cerebral cortex, evident in resting-state fMRI, support sensory, motor, cognitive, and affective functions and evolve throughout the lifespan.Existing studies have focused on age-specific networks for infants, but less on to what extent adult networks can describe infant functional connectivity (FC).Analysis revealed a subset of areas in infants showing adult-like network organization, with within-network FC exhibiting less variation across age and higher reliability across scans.These areas are posited near locations with low variability in functional network identity in adults, suggestive of the relationship between developmental sequence and interindividual variability in functional network organization.

PMID:39131337 | PMC:PMC11312607 | DOI:10.1101/2024.07.31.606025

bioRxiv [Preprint]. 2024 Aug 2:2024.08.01.606076. doi: 10.1101/2024.08.01.606076.

ABSTRACT

Mental illnesses extract a high personal and societal cost, and thus explorations of the links between mental illness and functional connectivity in the brain are critical. Investigating major mental illnesses, believed to arise from disruptions in sophisticated neural connections, allows us to comprehend how these neural network disruptions may be linked to altered cognition, emotional regulation, and social interactions. Although neuroimaging has opened new avenues to explore neural alterations linked to mental illnesses, the field still requires precise and sensitive methodologies to inspect these neural substrates of various psychological disorders. In this study, we employ a hierarchical methodology to derive double functionally independent primitives (dFIPs) from resting state functional magnetic resonance neuroimaging data (rs-fMRI). These dFIPs encapsulate canonical overlapping patterns of functional network connectivity (FNC) within the brain. Our investigation focuses on the examination of how combinations of these dFIPs relate to different mental disorder diagnoses. The central aim is to unravel the complex patterns of FNC that correspond to the diverse manifestations of mental illnesses. To achieve this objective, we used a large brain imaging dataset from multiple sites, comprising 5805 total individuals diagnosed with schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), and controls. The key revelations of our study unveil distinct patterns associated with each mental disorder through the combination of dFIPs. Notably, certain individual dFIPs exhibit disorder-specific characteristics, while others demonstrate commonalities across disorders. This approach offers a novel, data-driven synthesis of intricate neuroimaging data, thereby illuminating the functional changes intertwined with various mental illnesses. Our results show distinct signatures associated with psychiatric disorders, revealing unique connectivity patterns such as heightened cerebellar connectivity in SCZ and sensory domain hyperconnectivity in ASD, both contrasted with reduced cerebellar-subcortical connectivity. Utilizing the dFIP concept, we pinpoint specific functional connections that differentiate healthy controls from individuals with mental illness, underscoring its utility in identifying neurobiological markers. In summary, our findings delineate how dFIPs serve as unique fingerprints for different mental disorders.

PMID:39131299 | PMC:PMC11312551 | DOI:10.1101/2024.08.01.606076

bioRxiv [Preprint]. 2024 Jul 29:2023.01.19.524818. doi: 10.1101/2023.01.19.524818.

ABSTRACT

The brain is closely attuned to visceral signals from the body's internal environment, as evidenced by the numerous associations between neural, hemodynamic, and peripheral physiological signals. We show that these brain-body co-fluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo fMRI data acquisition sequences, we identify widespread co-fluctuations in the low-frequency range (0.01 - 0.1 Hz) between resting-state global fMRI signals, neural activity, and a host of autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain-body co-fluctuations observed at rest are elicited by arousal induced by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Further, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide (PETCO2) variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot explain the origin of these signals in the brain. These findings establish the global fMRI signal as a significant component of the arousal response governed by the autonomic nervous system.

PMID:39131291 | PMC:PMC11312447 | DOI:10.1101/2023.01.19.524818

Cereb Cortex. 2024 Aug 1;34(8):bhae322. doi: 10.1093/cercor/bhae322.

ABSTRACT

The functional organization of the frontal lobe is a source of debate, focusing on broad functional subdivisions, large-scale networks, or local refined specificities. Multiple neurocognitive models have tried to explain how functional interactions between cingulate and lateral frontal regions contribute to decision making and cognitive control, but their neuroanatomical bases remain unclear. We provide a detailed description of the functional connectivity between cingulate and lateral frontal regions using resting-state functional MRI in rhesus macaques. The analysis focuses on the functional connectivity of the rostral part of the cingulate sulcus with the lateral frontal cortex. Data-driven and seed-based analysis revealed three clusters within the cingulate sulcus organized along the rostro-caudal axis: the anterior, mid, and posterior clusters display increased functional connectivity with, respectively, the anterior lateral prefrontal regions, face-eye lateral frontal motor cortical areas, and hand lateral frontal motor cortex. The location of these clusters can be predicted in individual subjects based on morphological landmarks. These results suggest that the anterior cluster corresponds to the anterior cingulate cortex, whereas the posterior clusters correspond to the face-eye and hand cingulate motor areas within the anterior midcingulate cortex. These data provide a comprehensive framework to identify cingulate subregions based on functional connectivity and local organization.

PMID:39129533 | DOI:10.1093/cercor/bhae322

Neurourol Urodyn. 2024 Aug 12. doi: 10.1002/nau.25569. Online ahead of print.

ABSTRACT

PURPOSE: The study aims to analyze alterations in dynamic functional connectivity density (dFCD) and effective connectivity (dEC) patterns using functional magnetic resonance imaging (fMRI), hypothesizing that overactive bladder (OAB) patients will exhibit distinct dFCD and dEC patterns, reflecting altered neural communication underlying the OAB.

METHODS: Forty-three female OAB patients and 40 female healthy controls (HC) underwent resting-state fMRI. Sliding window correlation was used to calculate the variability of the dFCD. The changes in dFCD-based dEC between the two groups were examined using Granger causal analysis. To describe the time-varying Granger causality, a sliding-window approach was utilized to divide time courses into a group of windows. We adopted a k-means clustering method to cluster all matrices into discrete connectivity states.

RESULTS: Compared with HC, OAB females consistently had a dFCD (decreased) in the left anterior cingulate cortex (ACC) and left medial prefrontal cortex (mPFC) (p < 0.05, GRF corrected). In state 1, OAB patients had excitatory effective connections from bilateral ACC to left mPFC in comparison to HC. In state 2, there was an increase in dEC from the SMA to the mPFC. Participants with OAB showed significantly more inhibitory dorsolateral prefrontal cortex (dlPFC) connections between the left ACC and the right ACC in state 4, as well as an excitatory dEC connection between the right dlPFC and the left ACC in state 2 (p < 0.05, GRF corrected).

CONCLUSION: OAB patients demonstrate significant alterations in dFCD and dEC patterns, which may be indicative of the neural mechanisms involved in OAB pathophysiology.

PMID:39129436 | DOI:10.1002/nau.25569

Alcohol Alcohol. 2024 Jul 21;59(5):agae056. doi: 10.1093/alcalc/agae056.

ABSTRACT

AIMS: Previous neuroimaging research in alcohol use disorder (AUD) has found altered functional connectivity in the brain's salience, default mode, and central executive (CEN) networks (i.e. the triple network model), though their specific associations with AUD severity and heavy drinking remains unclear. This study utilized resting-state fMRI to examine functional connectivity in these networks and measures of alcohol misuse.

METHODS: Seventy-six adult heavy drinkers completed a 7-min resting-state functional MRI scan during visual fixation. Linear regression models tested if connectivity in the three target networks was associated with past 12-month AUD symptoms and number of heavy drinking days in the past 30 days. Exploratory analyses examined correlations between connectivity clusters and impulsivity and psychopathology measures.

RESULTS: Functional connectivity within the CEN network (right and left lateral prefrontal cortex [LPFC] seeds co-activating with 13 and 15 clusters, respectively) was significantly associated with AUD symptoms (right LPFC: β = .337, p-FDR = .016; left LPFC: β = .291, p-FDR = .028) but not heavy drinking (p-FDR > .749). Post-hoc tests revealed six clusters co-activating with the CEN network were associated with AUD symptoms-right middle frontal gyrus, right inferior parietal gyrus, left middle temporal gyrus, and left and right cerebellum. Neither the default mode nor the salience network was significantly associated with alcohol variables. Connectivity in the left LPFC was correlated with monetary delay discounting (r = .25, p = .03).

CONCLUSIONS: These findings support previous associations between connectivity within the CEN network and AUD severity, providing additional specificity to the relevance of the triple network model to AUD.

PMID:39129375 | DOI:10.1093/alcalc/agae056

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Aug 8:S2451-9022(24)00215-5. doi: 10.1016/j.bpsc.2024.07.026. Online ahead of print.

ABSTRACT

BACKGROUND: The prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear.

METHODS: Youth from the Adolescent Brain and Cognitive DevelopmentSM Study (ages 9-10 years at baseline) with a resting-state fMRI scan and mental health data were eligible for inclusion. Internalizing subscale scores from the Brief Problem Monitor - Youth Form were combined across two years of follow-up to generate a cumulative measure of internalizing symptoms. The total sample (n = 6521) was split into a large discovery dataset and a smaller validation dataset. Brain-behavior associations of resting-state functional connectivity (RSFC) with internalizing symptoms were estimated in the discovery dataset. The weighted contributions of each functional connection were aggregated using multivariate statistics to generate a polyneuro risk score (PNRS). The predictive power of the PNRS was evaluated in the validation dataset.

RESULTS: The PNRS explained 10.73% of the observed variance in internalizing symptom scores in the validation dataset. Model performance peaked when the top 2% functional connections identified in the discovery dataset (ranked by absolute β-weight) were retained. The RSFC networks that were implicated most prominently were the default mode, dorsal attention, and cingulo-parietal networks. These findings were significant (p < 1*10-6) as accounted for by permutation testing (n = 7000).

CONCLUSIONS: These results suggest that the neural phenotype associated with internalizing symptoms during adolescence is functionally distributed. The PNRS approach is a novel method for capturing relationships between RSFC and behavior.

PMID:39127423 | DOI:10.1016/j.bpsc.2024.07.026

J Clin Med. 2024 Jul 23;13(15):4284. doi: 10.3390/jcm13154284.

ABSTRACT

Background: The alternations of brain responses to a strong desire to void were unclear, and the gender differences under the strong desire to void remain controversial. The present study aims to identify the functional brain network's topologic property changes evoked by a strong desire to void in healthy male and female adults with synchronous urodynamics using a graph theory analysis. Methods: The bladders of eleven healthy males and eleven females were filled via a catheter using a specific infusion and withdrawal pattern. A resting-state functional magnetic resonance imaging (fMRI) was performed on the enrolled subjects, scanning under both the empty bladder and strong desire to void states. An automated anatomical labeling (AAL) atlas was used to identify the ninety cortical and subcortical regions. Pearson's correlation calculations were performed to establish a brain connection matrix. A paired t-test (p < 0.05) and Bonferroni correction were applied to identify the significant statistical differences in topological properties between the two states, including small-world network property parameters [gamma (γ) and lambda (λ)], characteristic path length (Lp), clustering coefficient (Cp), global efficiency (Eglob), local efficiency (Eloc), and regional nodal efficiency (Enodal). Results: The final data suggested that females and males had different brain response patterns to a strong desire to void, compared with an empty bladder state. Conclusions: More brain regions involving emotion, cognition, and social work were active in females, and males might obtain a better urinary continence via a compensatory mechanism.

PMID:39124552 | DOI:10.3390/jcm13154284

J Psychiatry Neurosci. 2024 Aug 9;49(4):E252-E262. doi: 10.1503/jpn.240031. Print 2024 Jul-Aug.

ABSTRACT

BACKGROUND: Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network.

METHODS: Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus.

RESULTS: We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with inter-regional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation.

LIMITATION: Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language.

CONCLUSION: As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis.

PMID:39122409 | DOI:10.1503/jpn.240031

Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Aug 6:S2451-9022(24)00212-X. doi: 10.1016/j.bpsc.2024.07.024. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals with schizophrenia (SZ) experience impairments in social cognition that contribute to poor functional outcomes. However, mechanisms of social cognitive dysfunction in SZ remain poorly understood, which impedes the design of novel interventions to improve outcomes. This pre-registered project (https://doi.org/10.17605/OSF.IO/JH5FC) examines the representation of social cognition in the brain's functional architecture across early and chronic SZ.

METHODS: The study contains two parts: a confirmatory and an exploratory portion. In the confirmatory portion, we identified resting-state connectivity disruptions evident in early and chronic SZ. We performed a connectivity analysis using regions associated with social cognitive dysfunction in early and chronic SZ to test whether aberrant connectivity observed in chronic SZ (N=47; HC=52) was also present in early SZ (N=71, HC=47). In the exploratory portion, we assessed the out-of-sample generalizability and precision of predictive models of social cognition. We used machine learning to predict social cognition and established generalizability with out-of-sample testing and confound control.

RESULTS: Results reveal decreases between left inferior frontal gyrus and intraparietal sulcus in early and chronic SZ, which are significantly associated with social and general cognition and global functioning in chronic SZ and with general cognition and global functioning in early SZ. Predictive modeling reveals the importance of out-of-sample evaluation and confound control.

CONCLUSION: This work provides insights into the functional architecture in early and chronic SZ and suggests that IFG-IPS connectivity could be a prognostic biomarker of social impairments and a target for future interventions (e.g. neuromodulation) focused on improved social functioning.

PMID:39117275 | DOI:10.1016/j.bpsc.2024.07.024

J Cogn Neurosci. 2024 Aug 5:1-38. doi: 10.1162/jocn_a_02230. Online ahead of print.

ABSTRACT

Trait self-report mindfulness scales measure one's disposition to pay nonjudgmental attention to the present moment. Concerns have been raised about the validity of trait mindfulness scales. Despite this, there is extensive literature correlating mindfulness scales with objective brain measures, with the goal of providing insight into mechanisms of mindfulness, and insight into associated positive mental health outcomes. Here, we systematically examined the neural correlates of trait mindfulness. We assessed 68 correlational studies across structural magnetic resonance imaging, task-based fMRI, resting-state fMRI, and EEG. Several consistent findings were identified, associating greater trait mindfulness with decreased amygdala reactivity to emotional stimuli, increased cortical thickness in frontal regions and insular cortex regions, and decreased connectivity within the default-mode network. These findings converged with results from intervention studies and those that included mindfulness experts. On the other hand, the connections between trait mindfulness and EEG metrics remain inconclusive, as do the associations between trait mindfulness and between-network resting-state fMRI metrics. ERP measures from EEG used to measure attentional or emotional processing may not show reliable individual variation. Research on body awareness and self-relevant processing is scarce. For a more robust correlational neuroscience of trait mindfulness, we recommend larger sample sizes, data-driven, multivariate approaches to self-report and brain measures, and careful consideration of test-retest reliability. In addition, we should leave behind simplistic explanations of mindfulness, as there are many ways to be mindful, and leave behind simplistic explanations of the brain, as distributed networks of brain areas support mindfulness.

PMID:39116268 | DOI:10.1162/jocn_a_02230

Alzheimers Dement. 2024 Aug 8. doi: 10.1002/alz.14155. Online ahead of print.

ABSTRACT

INTRODUCTION: Whether brain functional connectivity (FC) is consistently disrupted in individuals with mild cognitive impairment (MCI) with isolated language impairment (ilMCI), and its potential to differentiate between MCI subtypes remains uncertain.

METHODS: Cross-sectional data from 404 participants in two cohorts (the Chinese Preclinical Alzheimer's Disease Study and the Alzheimer's Disease Neuroimaging Initiative) were analyzed, including neuropsychological tests, resting-state functional magnetic resonance imaging (fMRI), cerebral amyloid positivity, and apolipoprotein E (APOE) status.

RESULTS: Temporo-frontoparietal FC, particularly between the bilateral superior temporal pole and the left inferior frontal/supramarginal gyri, was consistently decreased in ilMCI compared to amnestic MCI (aMCI) and normal controls, which was correlated with semantic impairment. Using mean temporo-frontoparietal FC as a classifier could improve accuracy in identifying ilMCI subgroups with positive cerebral amyloid deposition and APOE risk alleles.

DISCUSSION: Temporal-frontoparietal hypoconnectivity was observed in individuals with ilMCI, which may reflect semantic impairment and serve as a valuable biomarker to indicate potential mechanisms of underlying neuropathology.

HIGHLIGHTS: Temporo-frontoparietal hypoconnectivity was observed in impaired language mild cognitive impairment (ilMCI). Temporo-frontoparietal hypoconnectivity may reflect semantic impairment. Temporo-frontoparietal functional connectivity can classify ilMCI subtypes.

PMID:39115942 | DOI:10.1002/alz.14155