A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative ...marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.
Background Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), ...depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration. Methods Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA. Results Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was associated with higher FA in the right amygdala-hippocampus complex ( r = 0.400, p = 0.005). Conclusion Veterans with psychiatric disorders and/or mTBI exhibit higher odds of engaging in IPV perpetration. Further, the more severe the symptoms of PTSD, depression, or TBI, and the greater the war zone-related stress, the greater the frequency of IPV perpetration. Moreover, we report a significant association between psychological aggression against an intimate partner and microstructural alterations in the right amygdala-hippocampus complex. These findings suggest the possibility of a structural brain correlate underlying IPV perpetration that requires further research.
AbstractBackgroundThe cingulum bundle (CB) is a major white matter fiber tract of the limbic system that underlies cingulate cortex, passing longitudinally over the corpus callosum. The connectivity ...of this white matter fiber tract plays a major role in emotional expression, attention, motivation, and working memory, all of which are affected in schizophrenia. Myelin related CB abnormalities have also been implicated in schizophrenia. The purpose of this study is to determine whether or not CB abnormalities are evident in individuals at clinical high risk (CHR) for psychosis, and whether or not cognitive deficits in the domains subserved by CB are related to its structural abnormalities. MethodsDiffusion Tensor Imaging (DTI) was performed on a 3 T magnet. DT tractography was used to evaluate CB in 20 individuals meeting CHR criteria (13 males/7 females) and 23 healthy controls (12 males/11 females) group matched on age, gender, parental socioeconomic status, education, and handedness. Fractional anisotropy (FA), a measure of white matter coherence and integrity, radial diffusivity (RD), thought to reflect myelin integrity, trace, a possible marker of atrophy, and axial diffusivity (AD), thought to reflect axonal integrity, were averaged over the entire tract and used to investigate CB abnormalities in individuals at CHR for psychosis compared with healthy controls. ResultsSignificant group differences were found between individuals at CHR for psychosis and controls for FA (p = 0.028), RD (p = 0.03) and trace (p = 0.031), but not for AD (p = 0.09). We did not find any significant correlations between DTI measures and clinical symptoms. ConclusionThese findings suggest abnormalities (possibly myelin related) in the CB in individuals at CHR for psychosis.
The spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in the association cortex, implicated in a broad range of psychiatric disorders. ...However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth.
The authors studied 790 youths ages 8 to 23 years who had 27 minutes of high-quality functional magnetic resonance imaging data as part of the Philadelphia Neurodevelopmental Cohort. Four correlated dimensions were estimated using a confirmatory correlated traits factor analysis on 112 item-level clinical symptoms, and one overall psychopathology factor with 4 orthogonal dimensions were extracted using a confirmatory factor analysis. Spatially regularized nonnegative matrix factorization was used to identify 17 individual-specific functional networks for each participant. Partial least square regression with split-half cross-validation was conducted to evaluate to what extent the topography of personalized functional networks encodes major dimensions of psychopathology.
Personalized functional network topography significantly predicted unseen individuals’ major dimensions of psychopathology, including fear, psychosis, externalizing, and anxious-misery. Reduced representation of association networks was among the most important features for the prediction of all 4 dimensions. Further analysis revealed that personalized functional network topography predicted overall psychopathology (r = 0.16, permutation testing p < .001), which drove prediction of the 4 correlated dimensions.
These results suggest that individual differences in functional network topography in association networks is related to overall psychopathology in youth. Such results underscore the importance of considering functional neuroanatomy for personalized diagnostics and therapeutics in psychiatry.
Diffusion Spectrum Imaging (DSI) using dense Cartesian sampling of q-space has been shown to provide important advantages for modeling complex white matter architecture. However, its adoption has ...been limited by the lengthy acquisition time required. Sparser sampling of q-space combined with compressed sensing (CS) reconstruction techniques has been proposed as a way to reduce the scan time of DSI acquisitions. However prior studies have mainly evaluated CS-DSI in post-mortem or non-human data. At present, the capacity for CS-DSI to provide accurate and reliable measures of white matter anatomy and microstructure in the living human brain remains unclear. We evaluated the accuracy and inter-scan reliability of 6 different CS-DSI schemes that provided up to 80% reductions in scan time compared to a full DSI scheme. We capitalized on a dataset of 26 participants who were scanned over eight independent sessions using a full DSI scheme. From this full DSI scheme, we subsampled images to create a range of CS-DSI images. This allowed us to compare the accuracy and inter-scan reliability of derived measures of white matter structure (bundle segmentation, voxel-wise scalar maps) produced by the CS-DSI and the full DSI schemes. We found that CS-DSI estimates of both bundle segmentations and voxel-wise scalars were nearly as accurate and reliable as those generated by the full DSI scheme. Moreover, we found that the accuracy and reliability of CS-DSI was higher in white matter bundles that were more reliably segmented by the full DSI scheme. As a final step, we replicated the accuracy of CS-DSI in a prospectively acquired dataset (n = 20, scanned once). Together, these results illustrate the utility of CS-DSI for reliably delineating in vivo white matter architecture in a fraction of the scan time, underscoring its promise for both clinical and research applications.
Posterior circulation infarctions (PCI) constitute 5–25% of ischemic strokes. PCI of the occipital lobe present with a panoply of symptoms including quadrantanopsia, topographical disorientation, and ...executive dysfunction. Long-term cognitive recovery after PCI is not well described. However, the adult brain is remarkably plastic, capable of adapting and remodeling.
We describe a 43-year-old right-handed woman who complained of black spots in both eyes, headaches, photophobia, and a feeling she would faint. Initial neurological exam and a CT scan were normal; she was diagnosed with ocular migraine. A second neurological exam a week later showed left superior quadrantopsia; an MRI scan suggested right occipito-temporal infarct. In subsequent months, the patient complained of fatigue, quadrantanopsia, memory problems, and topographical disorientation. The patient participated in multi-modality treatment, and in self-directed arts projects and physical activities. Six years later, she reported noticeable improvements in cognition and daily functioning, which were documented on neurocognitive testing. Comparison between initial and subsequent MRIs using FreeSurfer 5.3 identified neuroplastic brain changes in areas serving similar functions to the areas injured from the stroke.
The case illustrates the neuropsychiatric presentation after right occipito-temporal stroke, the value of formal and self-directed cognitive rehabilitation, the extended time to cognitive recovery, and the ability of the brain to undergo neuroplastic changes.
Military veterans with posttraumatic stress disorder (PTSD) commonly experience posttraumatic guilt. Guilt over commission or omission evolves when responsibility is assumed for an unfortunate ...outcome (e.g., the death of a fellow combatant). Survivor guilt is a state of intense emotional distress experienced by the weight of knowing that one survived while others did not.
This study of the Translational Research Center for TBI and Stress Disorders (TRACTS) analyzed structural and diffusion-weighted magnetic resonance imaging data from 132 male Iraq/Afghanistan veterans with PTSD. The Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) was employed to classify guilt. Thirty (22.7 %) veterans experienced guilt over acts of commission or omission, 34 (25.8 %) experienced survivor guilt, and 68 (51.5 %) had no posttraumatic guilt. White matter microstructure (fractional anisotropy, FA), cortical thickness, and cortical volume were compared between veterans with guilt over acts of commission or omission, veterans with survivor guilt, and veterans without guilt.
Veterans with survivor guilt had significantly lower white matter FA compared to veterans who did not experience guilt (p < .001), affecting several regions of major white matter fiber bundles. There were no significant differences in white matter FA, cortical thickness, or volumes between veterans with guilt over acts of commission or omission and veterans without guilt (p > .050).
This cross-sectional study with exclusively male veterans precludes inferences of causality between the studied variables and generalizability to the larger veteran population that includes women.
Survivor guilt may be a particularly impactful form of posttraumatic guilt that requires specific treatment efforts targeting brain health.
•Posttraumatic guilt is highly common among veterans with PTSD.•Survivor guilt is linked to altered white matter in veterans, potentially impacting moral cognition.•Lower FA in survivor guilt in key brain fiber tracts suggests impaired tissue organization.•Findings highlight the need for comprehensive assessment and intervention for veteran survivor guilt.
The functions of the human brain are metabolically expensive and reliant on coupling between cerebral blood flow (CBF) and neural activity, yet how this coupling evolves over development remains ...unexplored. Here, we examine the relationship between CBF, measured by arterial spin labeling, and the amplitude of low-frequency fluctuations (ALFF) from resting-state magnetic resonance imaging across a sample of 831 children (478 females, aged 8–22 years) from the Philadelphia Neurodevelopmental Cohort. We first use locally weighted regressions on the cortical surface to quantify CBF-ALFF coupling. We relate coupling to age, sex, and executive functioning with generalized additive models and assess network enrichment via spin testing. We demonstrate regionally specific changes in coupling over age and show that variations in coupling are related to biological sex and executive function. Our results highlight the importance of CBF-ALFF coupling throughout development; we discuss its potential as a future target for the study of neuropsychiatric diseases.
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•Cerebral blood flow and amplitude of low-frequency fluctuations are coupled in youth•CBF-ALFF coupling declines during adolescence in the dorsal attention network•Sex differences in CBF-ALFF coupling are prominent in the frontoparietal network•Coupling patterns are associated with individual differences in executive function
The functions of the human brain are metabolically expensive and reliant on neurovascular coupling between cerebral blood flow and neural activity, yet how this coupling evolves over development remains unresolved. Here, Baller et al. show that neurovascular coupling evolves over adolescence, differs by sex, and relates to executive function.
Low reward responsiveness (RR) is associated with poor psychological well-being, psychiatric disorder risk, and psychotropic treatment resistance. Functional MRI studies have reported decreased ...activity within the brain's reward network in individuals with RR deficits, however the neurochemistry underlying network hypofunction in those with low RR remains unclear. This study employed ultra-high field glutamate chemical exchange saturation transfer (GluCEST) imaging to investigate the hypothesis that glutamatergic deficits within the reward network contribute to low RR. GluCEST images were acquired at 7.0 T from 45 participants (ages 15-29, 30 females) including 15 healthy individuals, 11 with depression, and 19 with psychosis spectrum symptoms. The GluCEST contrast, a measure sensitive to local glutamate concentration, was quantified in a meta-analytically defined reward network comprised of cortical, subcortical, and brainstem regions. Associations between brain GluCEST contrast and Behavioral Activation System Scale RR scores were assessed using multiple linear regressions. Analyses revealed that reward network GluCEST contrast was positively and selectively associated with RR, but not other clinical features. Follow-up investigations identified that this association was driven by the subcortical reward network and network areas that encode the salience of valenced stimuli. We observed no association between RR and the GluCEST contrast within non-reward cortex. This study thus provides new evidence that reward network glutamate levels contribute to individual differences in RR. Decreased reward network excitatory neurotransmission or metabolism may be mechanisms driving reward network hypofunction and RR deficits. These findings provide a framework for understanding the efficacy of glutamate-modulating psychotropics such as ketamine for treating anhedonia.
Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) ...microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (
= 38), (2) mTBI (
= 25), (3) comorbid PTSD+mTBI (
= 94), and (4) a control group with neither PTSD nor mTBI (
= 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (
= 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (
< 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (
< 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.
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