Abstract
Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory performance entails ...brain-wide switching between activity states using a combination of functional magnetic resonance imaging in healthy controls and individuals with schizophrenia, pharmacological fMRI, genetic analyses and network control theory. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Individuals with schizophrenia show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations. Our results demonstrate the relevance of dopamine signaling for the steering of whole-brain network dynamics during working memory and link these processes to schizophrenia pathophysiology.
Methods that capture the features of single voxels of resting-state fMRI (RS-fMRI) could precisely localize the abnormal spontaneous activity and hence guide precise brain stimulation. As one of ...these metrics, the amplitude of low-frequency fluctuation (ALFF) has been used in numerous studies, however, it is frequency-dependent and the division of frequency bands is still controversial. Based on the well-accepted power law of time series, this study proposed an approach, namely, power spectrum slope (PSS), to characterize the RS-fMRI time series of single voxels. Two metrics, i.e., linear coefficient b and power-law slope b' were used and compared with ALFF. The reliability and validity of the PSS approach were evaluated on public RS-fMRI datasets (
= 145 in total) of eyes closed (EC) and eyes open (EO) conditions after image preprocessing, with 21 subjects scanned two times for test-retest reliability analyses. Specifically, we used the paired
-test between EC and EO conditions to assess the validity and intra-class correlation (ICC) to assess the reliability. The results included the following: (1) PSS detected similar spatial patterns of validity (i.e., EC-EO differences) and less test-retest reliability with those of ALFF; (2) PSS linear coefficient b showed better validity and reliability than power-law slope b'; (3) While the PPS showed less validity in most regions, PSS linear coefficient b showed exclusive EC-EO difference in the medial temporal lobe which did not show in ALFF. The power spectrum plot in the parahippocampus showed a "cross-over" of power magnitudes between EC and EO conditions in the higher frequency bands (>0.1 Hz). These results demonstrated that PSS (linear coefficient b) is complementary to ALFF for detecting the local spontaneous activity.
Rationale
Aberrant prefrontal-hippocampal (PFC-HC) connectivity is disrupted in several psychiatric and at-risk conditions. Advances in rodent functional imaging have opened the possibility that this ...phenotype could serve as a translational imaging marker for psychiatric research. Recent evidence from functional magnetic resonance imaging (fMRI) studies has indicated an increase in PFC-HC coupling during working-memory tasks in both schizophrenic patients and at-risk populations, in contrast to a decrease in resting-state PFC-HC connectivity. Acute ketamine challenge is widely used in both humans and rats as a pharmacological model to study the mechanisms of
N
-methyl-
d
-aspartate (NMDA) receptor hypofunction in the context of psychiatric disorders.
Objectives
We aimed to establish whether acute ketamine challenge has consistent effects in rats and humans by investigating resting-state fMRI PFC-HC connectivity and thus to corroborate its potential utility as a translational probe.
Methods
Twenty-four healthy human subjects (12 females, mean age 25 years) received intravenous doses of either saline (placebo) or ketamine (0.5 mg/kg body weight). Eighteen Sprague-Dawley male rats received either saline or ketamine (25 mg/kg). Resting-state fMRI measurements took place after injections, and the data were analyzed for PFC-HC functional connectivity.
Results
In both species, ketamine induced a robust increase in PFC-HC coupling, in contrast to findings in chronic schizophrenia.
Conclusions
This translational comparison demonstrates a cross-species consistency in pharmacological effect and elucidates ketamine-induced alterations in PFC-HC coupling, a phenotype often disrupted in pathological conditions, which may give clue to understanding of psychiatric disorders and their onset, and help in the development of new treatments.
Functional MRI studies have achieved promising outcomes in revealing abnormal functional connectivity in Parkinson's disease (PD). The primary sensorimotor area (PSMA) received a large amount of ...attention because it closely correlates with motor deficits. While functional connectivity represents signaling between PSMA and other brain regions, the metabolic mechanism behind PSMA connectivity has rarely been well established. By introducing hybrid PET/MRI scanning, the current study enrolled 33 advanced PD patients during medication-off condition and 25 age-and-sex-matched healthy controls (HCs), aiming to not only identify the abnormal functional connectome pattern of the PSMA, but also to simultaneously investigate how PSMA functional connectome correlates with glucose metabolism. We calculated degree centrality (DC) and the ratio of standard uptake value (SUVr) using resting state fMRI and
F-FDG-PET data. A two-sample t-test revealed significantly decreased PSMA DC (P
< 0.014) in PD patients. The PSMA DC also correlated negatively with H-Y stage (
= 0.031). We found a widespread reduction of H-Y stage associated (
-values < 0.041) functional connectivity between PSMA and the visual network, attention network, somatomotor network, limbic network, frontoparietal network as well as the default mode network. The PSMA DC correlated positively with FDG-uptake in the HCs (
= 0.039) but not in the PD patients (
> 0.44). In summary, we identified disease severity-dependent PSMA functional connectome which in addition uncoupled with glucose metabolism in PD patients. The current study highlighted the critical role of simultaneous PET/fMRI in revealing the functional-metabolic mechanism in the PSMA of PD patients.
•Structural brain networks can be modeled as a trade-off between wiring cost and topological features.•Schizophrenia patients show lower spatial constraints and topological facilitation.•Individual ...model parameters are associated with genetic risk for schizophrenia and cognition.
Alterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of altered brain network formation. We evaluated different generative network models in healthy controls (n=152), schizophrenia patients (n=66), and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated how these factors relate to cognition and to polygenic risk for schizophrenia. Our data show that among the four tested classes of generative network models, structural brain networks were optimally accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation across study groups. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. Further exploratory analyses point to potential associations of the model parameter reflecting spatial constraints with the polygenic risk for schizophrenia and cognitive performance. Our results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to regular brain network formation as well as altered connectomes in schizophrenia and healthy individuals at familial risk for schizophrenia. On an exploratory level, our data further point to the potential relevance of spatial constraints for the genetic risk for schizophrenia and general cognitive functioning, thereby encouraging future studies in following up on these observations to gain further insights into the biological basis and behavioral relevance of model parameters.
Purpose
Perigenual anterior cingulate cortex (pACC) is a neural convergence site for social stress-related risk factors for mental health, including ethnic minority status. Current social status, a ...strong predictor of mental and somatic health, has been related to gray matter volume in this region, but the effects of social mobility over the lifespan are unknown and may differ in minorities. Recent studies suggest a diminished health return of upward social mobility for ethnic minority individuals, potentially due to sustained stress-associated experiences and subsequent activation of the neural stress response system.
Methods
To address this issue, we studied an ethnic minority sample with strong upward social mobility. In a cross-sectional design, we examined 64 young adult native German and 76 ethnic minority individuals with comparable sociodemographic attributes using whole-brain structural magnetic resonance imaging.
Results
Results showed a significant group-dependent interaction between perceived upward social mobility and pACC gray matter volume, with a significant negative association in the ethnic minority individuals. Post-hoc analysis showed a significant mediation of the relationship between perceived upward social mobility and pACC volume by perceived chronic stress, a variable that was significantly correlated with perceived discrimination in our ethnic minority group.
Conclusion
Our findings extend prior work by pointing to a biological signature of the “allostatic costs” of socioeconomic attainment in socially disadvantaged upwardly mobile individuals in a key neural node implicated in the regulation of stress and negative affect.
Previous studies have reliably identified iron deposition in the motor cortex as potential pathogenesis of amyotrophic lateral sclerosis (ALS). Here, we intended to investigate iron deposition, gray ...matter (GM) atrophy, and their associations with disease severity in the motor cortex and the thalamus in patients with ALS.
A total of 34 patients with ALS (age 51.31 ± 8.24 years, 23 males) and 34 nonneurological controls (age 50.96 ± 9.35 years, 19 males) were enrolled between 2018 and 2020. The Revised ALS Functional Rating Scale (ALSFRS-R) and the Penn upper motor neuron (UMN) score were measured. MRI data included quantitative susceptibility mapping (QSM) for iron deposition and three-dimensional (3D) T1 for gray matter volume. After a between-group comparison, Pearson's correlation coefficient was used for identifying correlations of iron deposition, GM volume, and clinical measurements.
The two-sample
-tests revealed increased iron deposition in the left precentral gyrus (peak voxel
= 4.78,
= 0.03) and the thalamus (peak voxel: right:
= 6.38,
< 0.001; left:
= 4.64,
= 0.02) in patients with ALS. GM volume of the precentral gyrus (
= -2.42,
= 0.02) and the bilateral thalamus (
= -4.10,
< 0.001) were reduced. Negative correlations were found between the increased QSM values and the decreased GM volume (
< 0.04, one-tailed) in patients with ALS. Iron deposition in the left precentral gyrus was positively correlated with the UMN score (
= 0.40,
= 0.02) and the GM volume was negatively correlated with the UMN score (
= -0.48,
= 0.004). Negative correlation between thalamic iron deposition and the ALSFRS-R (
= -0.36,
= 0.04) score was observed.
Iron deposition in the thalamus, in addition to the motor cortex, is accompanied by GM atrophy and is associated with disease severity in patients with ALS, indicating that the thalamus is also a pathological region in patients with ALS.
The cerebral cortex is characterized as the integration of distinct functional principles that correspond to basic primary functions, such as vision and movement, and domain‐general functions, such ...as attention and cognition. Diffusion embedding approach is a novel tool to describe transitions between different functional principles, and has been successively applied to investigate pathological conditions in between‐group designs. What still lacking and urgently needed is the efficacy of this method to differentiate within‐subject circumstances. In this study, we applied the diffusion embedding to eyes closed (EC) and eyes on (EO) resting‐state conditions from 145 participants. We found significantly lower within‐network dispersion of visual network (VN) (p = 7.3 × 10−4) as well as sensorimotor network (SMN) (p = 1 × 10−5) and between‐network dispersion of VN (p = 2.3 × 10−4) under EC than EO, while frontoparietal network (p = 9.2 × 10−4) showed significantly higher between‐network dispersion during EC than EO. Test–retest reliability analysis further displayed fair reliability (intraclass correlation coefficient ICC < 0.4) of the network dispersions (mean ICC = 0.116 ± 0.143 standard deviation) except for the within‐network dispersion of SMN under EO (ICC = 0.407). And the reliability under EO was higher but not significantly higher than reliability under EC. Our study demonstrated that the diffusion embedding approach that shows fair reliability is capable of distinguishing EC and EO resting‐state conditions, such that this method could be generalized to other within‐subject designs.
Diffusion embedding can differentiate within‐subject conditions‐eyes closed and open. Visual, sensorimotor and frontoparietal network showed significant differences. Network dispersion showed fair reliability.
Purpose. We investigated the disparate influence of lesion location on functional damage and reorganization of the sensorimotor brain network in patients with thalamic infarction and pontine ...infarction. Methods. Fourteen patients with unilateral infarction of the thalamus and 14 patients with unilateral infarction of the pons underwent longitudinal fMRI measurements and motor functional assessment five times during a 6-month period (<7 days, at 2 weeks, 1 month, 3 months, and 6 months after stroke onset). Twenty-five age- and sex-matched controls underwent MRI examination across five consecutive time points in 6 months. Functional images from patients with left hemisphere lesions were first flipped from the left to the right side. The voxel-wise connectivity analyses between the reference time course of each ROI (the contralateral dorsal lateral putamen (dl-putamen), pons, ventral anterior (VA), and ventral lateral (VL) nuclei of the thalamus) and the time course of each voxel in the sensorimotor area were performed for all five measurements. One-way ANOVA was used to identify between-group differences in functional connectivity (FC) at baseline stage (<7 days after stroke onset), with infarction volume included as a nuisance variable. The family-wise error (FWE) method was used to account for multiple comparison issues using SPM software. Post hoc repeated-measure ANOVA was applied to examine longitudinal FC reorganization. Results. At baseline stage, significant differences were detected between the contralateral VA and ipsilateral postcentral gyrus (cl_VA-ip_postcentral), contralateral VL and ipsilateral precentral gyrus (cl_VL-ip_precentral). Repeated measures ANOVA revealed that the FC change of cl_VA-ip_postcentral differ significantly among the three groups over time. The significant changes of FC between cl_VA and ip_postcentral at different time points in the thalamic infarction group showed that compared with 7 days after stroke onset, there was significantly increased FC of cl_VA-ip_postcentral at 1 month, 3 months, and 6 months after stroke onset. Conclusions. The different patterns of sensorimotor functional damage and reorganization in patients with pontine infarction and thalamic infarction may provide insights into the neural mechanisms underlying functional recovery after stroke.
To explore the structural brain abnormality and its relationship with neuropsychological disorders and electroclinical characteristics in juvenile myoclonic epilepsy (JME) patients.
Sixty-seven ...patients diagnosed with JME and 56 healthy controls were enrolled. All subjects underwent MRI using T1-weighted 3D brain structural images with 1 mm thickness. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were performed. They also underwent a series of neuropsychological tests to assess cognitive function. The correlation analyses were conducted between structural changes, neuropsychological outcomes, and electroclinical features.
The gray matter concentration (GMC) was decreased in the bilateral pre-central and post-central gyrus, right anterior cingulate gyrus, left posterior orbital region, bilateral occipital regions, bilateral hippocampus and bilateral caudate nucleus in the JME groups (corrected
< 0.05). The evaluation of gray matter volume (GMV) showed significant decrease respectively in bilateral pre-central and post-central gyrus, left paracentral lobule, left orbital gyrus, left amygdala, left basal ganglia and left thalamus of JME patients (
< 0.05). The cortex thicknesses of the right inferior temporal gyrus, right insular gyrus, and right cingulate gyrus had negative correlations with the disease duration significantly. At the same time, the whole-brain white matter volume was positively associated with the course of the disease (
< 0.05). Patients with persistent abnormal EEG discharges had significantly less whole-brain gray matter volume than JME patients with normal EEG (
= 0.03). Correlation analyses and linear regression analyses showed that, in addition to the gray matter volumes of frontal and parietal lobe, the temporal lobe, as well as the basal ganglia and thalamus, were also significantly correlated with neuropsychological tests' results (
< 0.05).
The JME patients showed subtle structural abnormalities in multiple brain regions that were not only limited to the frontal lobe but also included the thalamus, basal ganglia, parietal lobe, temporal lobe and some occipital cortex, with significant involvement of the primary somatosensory cortex and primary motor cortex. And we significantly demonstrated a correlation between structural abnormalities and cognitive impairment. In addition, the course of disease and abnormal discharges had a specific negative correlation with the structural changes.
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