New resting-state fMRI related studies at PubMed

Association of Olfactory Training With Neural Connectivity in Adults With Postviral Olfactory Dysfunction

Thu, 03/18/2021 - 10:00

JAMA Otolaryngol Head Neck Surg. 2021 Mar 18. doi: 10.1001/jamaoto.2021.0086. Online ahead of print.


IMPORTANCE: Viral upper respiratory tract infections are a major cause of olfactory loss. Olfactory training (OT) is a promising intervention for smell restoration; however, a mechanistic understanding of the changes in neural plasticity induced by OT is absent.

OBJECTIVE: To evaluate functional brain connectivity in adults with postviral olfactory dysfunction (PVOD) before and after OT using resting-state functional magnetic resonance imaging.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted from September 1, 2017, to November 30, 2019, recruited adults with clinically diagnosed or self-reported PVOD of 3 months or longer. Baseline olfaction was measured using the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin' Sticks test. Analysis was performed between December 1, 2020, and July 1, 2020.

INTERVENTIONS: Participants completed 12 weeks of OT using 4 essential oils: rose, eucalyptus, lemon, and clove. The resting-state functional magnetic resonance imaging measurements were obtained before and after intervention.

MAIN OUTCOME AND MEASURES: The primary outcome measure was the change in functional brain connectivity before and after OT. Secondary outcome measures included changes in UPSIT and Sniffin' Sticks test scores, as well as patient-reported changes in treatment response as measured by subjective changes in smell and quality-of-life measures.

RESULTS: A total of 16 participants with PVOD (11 female [69%] and 14 White [88%]; mean [SD] age, 60.0 [10.5] years; median duration of smell loss, 12 months [range, 3-240 months]) and 20 control participants (15 [75%] female; 17 [85%] White; mean [SD] age, 55.0 [9.2] years; median UPSIT score, 37 [range, 34-39]) completed the study. At baseline, participants had increased connectivity within the visual cortex when compared with normosmic control participants, a connection that subsequently decreased after OT. Furthermore, 4 other network connectivity values were observed to change after OT, including an increase in connectivity between the left parietal occipital junction, a region of interest associated with olfactory processing, and the cerebellum.

CONCLUSIONS AND RELEVANCE: The use of OT is associated with connectivity changes within the visual cortex. This case-control cohort study suggests that there is a visual connection to smell that has not been previously explored with OT and that further studies examining the efficacy of a bimodal visual and OT program are needed.

PMID:33734298 | DOI:10.1001/jamaoto.2021.0086

Sex differences in functional network dynamics observed using coactivation pattern analysis

Thu, 03/18/2021 - 10:00

Cogn Neurosci. 2021 Mar 18:1-10. doi: 10.1080/17588928.2021.1880383. Online ahead of print.


Sex differences in the organization of large-scale resting-state brain networks have been identified using traditional static measures, which average functional connectivity over extended time periods. In contrast, emerging dynamic measures have the potential to define sex differences in network changes over time, providing additional understanding of neurobiological sex differences. To meet this goal, we used a Coactivation Pattern Analysis (CAP) using resting-state functional magnetic resonance imaging data from 181 males and 181 females from the Human Connectome Project. Significant main effects of sex were observed across two independent imaging sessions. Relative to males, females spent more total time in two transient network states (TNSs) spatially overlapping with the dorsal attention network and occipital/sensory-motor network. Greater time spent in these TNSs was related to females making more frequent transitions into these TNSs compared to males. In contrast, males spent more total time in TNSs spatially overlapping with the salience network, which was related to males staying for longer periods once entering these TNSs compared to females. State-to-state transitions also significantly differed between sexes: females transitioned more frequently from default mode network (DMN) states to the dorsal attention network state, whereas males transitioned more frequently from DMN states to salience network states. Results show that males and females spend differing amounts of time at rest in two distinct attention-related networks and show sex-specific transition patterns from DMN states into these attention-related networks. This work lays the groundwork for future investigations into the cognitive and behavioral implications of these sex-specific network dynamics.

PMID:33734028 | DOI:10.1080/17588928.2021.1880383

Pain stickiness in pediatric complex regional pain syndrome: A role for the nucleus accumbens

Thu, 03/18/2021 - 10:00

Neurobiol Pain. 2021 Feb 19;9:100062. doi: 10.1016/j.ynpai.2021.100062. eCollection 2021 Jan-Jul.


Some individuals with chronic pain experience improvement in their pain with treatment, whereas others do not. The neurobiological reason is unclear, but an understanding of brain structure and functional patterns may provide insights into pain's responsivity to treatment. In this investigation, we used magnetic resonance imaging (MRI) techniques to determine grey matter density alterations on resting functional connectivity (RFC) strengths between pain responders and nonresponders in patients with complex regional pain syndrome. Brain metrics of pediatric patients at admission to an intensive pain rehabilitative treatment program were evaluated. Pain responders reported significant pain improvement at discharge and/or follow-up whereas nonresponders reported no improvements in pain, increases in pain, or emergence of new pain symptoms. The pain (responder/nonresponder) groups were compared with pain-free healthy controls to examine predictors of pain responder status via brain metrics. Our results show: (1) on admission, pain nonresponders had decreased grey matter density (GMD) within the nucleus accumbens (NAc) and reduced RFC strength between the NAc and the dorsolateral prefrontal cortex vs. responders; (2) Connectivity strength was positively correlated with change in pain intensity from admission to discharge; (3) Compared with pain-free controls, grey matter and RFC differences emerged only among pain nonresponders; and (4) Using a discriminative model, combining GMD and RFC strengths assessed at admission showed the highest prediction estimate (87%) on potential for pain improvement, warranting testing in a de novo sample. Taken together, these results support the idea that treatment responsiveness on pain is underpinned by concurrent brain structure and resting brain activity.

PMID:33732954 | PMC:PMC7941018 | DOI:10.1016/j.ynpai.2021.100062

Elamipretide (SS-31) Improves Functional Connectivity in Hippocampus and Other Related Regions Following Prolonged Neuroinflammation Induced by Lipopolysaccharide in Aged Rats

Thu, 03/18/2021 - 10:00

Front Aging Neurosci. 2021 Mar 1;13:600484. doi: 10.3389/fnagi.2021.600484. eCollection 2021.


Neuroinflammation has been recognized as a major cause for neurocognitive diseases. Although the hippocampus has been considered an important region for cognitive dysfunction, the influence of hippocampal neuroinflammation on brain functional connectivity (FC) has been rarely studied. In this study, lipopolysaccharide (LPS) was used to induce systemic inflammation and neuroinflammation in the aged rat brain, while elamipretide (SS-31) was used for treatment. Systemic and hippocampal inflammation were determined using ELISA, while astrocyte responses during hippocampal neuroinflammation were determined by interleukin 1 beta (IL-1β)/tumor necrosis factor alpha (TNFα) double staining immunofluorescence. Oxidative stress was determined by reactive oxidative species (ROS), electron transport chain (ETC) complex, and superoxide dismutase (SOD). Short- (<7 days) and long-term (>30 days) learning and spatial working memory were tested by the Morris water maze (MWM). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to analyze the brain FC by placing seed voxels on the left and right hippocampus. Compared with the vehicle group, rats with the LPS exposure showed an impaired MWM performance, higher oxidative stress, higher levels of inflammatory cytokines, and astrocyte activation in the hippocampus. The neuroimaging examination showed decreased FC on the right orbital cortex, right olfactory bulb, and left hippocampus on day 3, 7, and 31, respectively, after treatment. In contrast, rats with SS-31 treatment showed lower levels of inflammatory cytokines, less astrocyte activation in the hippocampus, and improved MWM performance. Neuroimaging examination showed increased FC on the left-parietal association cortex (L-PAC), left sensory cortex, and left motor cortex on day 7 with the right flocculonodular lobe on day 31 as compared with those without SS-31 treatment. Our study demonstrated that inhibiting neuroinflammation in the hippocampus not only reduces inflammatory responses in the hippocampus but also improves the brain FC in regions related to the hippocampus. Furthermore, early anti-inflammatory treatment with SS-31 has a long-lasting effect on reducing the impact of LPS-induced neuroinflammation.

PMID:33732135 | PMC:PMC7956963 | DOI:10.3389/fnagi.2021.600484

Dorsolateral Prefrontal Functional Connectivity Predicts Working Memory Training Gains

Thu, 03/18/2021 - 10:00

Front Aging Neurosci. 2021 Mar 1;13:592261. doi: 10.3389/fnagi.2021.592261. eCollection 2021.


Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training. Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19). Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task. Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

PMID:33732134 | PMC:PMC7956962 | DOI:10.3389/fnagi.2021.592261

Exosomal MicroRNAs Contribute to Cognitive Impairment in Hypertensive Patients by Decreasing Frontal Cerebrovascular Reactivity

Thu, 03/18/2021 - 10:00

Front Neurosci. 2021 Mar 1;15:614220. doi: 10.3389/fnins.2021.614220. eCollection 2021.


Mechanisms underlying cognitive impairment (CI) in hypertensive patients remain relatively unclear. The present study aimed to explore the relationship among serum exosomal microRNAs (miRNAs), cerebrovascular reactivity (CVR), and cognitive function in hypertensive patients. Seventy-three hypertensive patients with CI (HT-CI), 67 hypertensive patients with normal cognition (HT-NC), and 37 healthy controls underwent identification of exosomal miRNA, multimodal magnetic resonance imaging (MRI) scans, and neuropsychological tests. CVR mapping was investigated based on resting-state functional MRI data. Compared with healthy subjects and HT-NC subjects, HT-CI subjects displayed decreased serum exosomal miRNA-330-3p. The group difference of CVR was mainly found in the left frontal lobe and demonstrated that HT-CI group had a lower CVR than both HT-NC group and control group. Furthermore, both the CVR in the left medial superior frontal gyrus and the miRNA-330-3p level were significantly correlated with executive function (r = -0.275, P = 0.021, and r = -0.246, P = 0.04, respectively) in HT-CI subjects, and the CVR was significantly correlated with the miRNA-330-3p level (r = 0.246, P = 0.040). Notably, path analysis showed that the CVR mediated the association between miRNA-330-3p and executive function. In conclusion, decreased miRNA-330-3p might contribute to CI in hypertensive patients by decreasing frontal CVR and could be a biomarker of early diagnosis.

PMID:33732103 | PMC:PMC7957933 | DOI:10.3389/fnins.2021.614220

Abnormal Brain Connectivity in Carpal Tunnel Syndrome Assessed by Graph Theory

Thu, 03/18/2021 - 10:00

J Pain Res. 2021 Mar 11;14:693-701. doi: 10.2147/JPR.S289165. eCollection 2021.


INTRODUCTION: Numerous resting-state functional magnetic resonance imaging (fMRI) researches have indicated that large-scale functional and structural remodeling occurs in the whole brain despite an intact sensorimotor network after carpal tunnel syndrome (CTS). Investigators aimed to explore alterations of the global and nodal properties that occur in the whole brain network of patients with CTS based on topographic theory.

METHODS: Standard-compliant fMRI data were collected from 27 patients with CTS in bilateral hands and 19 healthy control subjects in this cross-sectional study. The statistics based on brain networks were calculated the differences between the patients and the healthy. Several topological properties were computed, such as the small-worldness, nodal clustering coefficient, characteristic path length, and degree centrality.

RESULTS: Compared to those of the healthy controls, the global properties of the CTS group exhibited a decreased characteristic path length. Changes in the local-level properties included a decreased nodal clustering coefficient in 6 separate brain regions and significantly different degree centrality in several brain regions that were related to sensorimotor function and pain.

DISCUSSION: The study suggested that CTS reinforces global connections and makes their networks more random. The changed nodal properties were affiliated with basal ganglia-thalamo-cortical circuits and the pain matrix. These results provided new insights for improving our understanding of abnormal topological theory in relation to the functional brain networks of CTS patients.

PERSPECTIVE: This article presents that the CTS patients' brain with a higher global efficiency. And the significant alterations in several brain regions which are more related to pain and motor processes. The results provided effective complements to the neural mechanisms underlying CTS.

PMID:33732015 | PMC:PMC7959208 | DOI:10.2147/JPR.S289165

Repetitive transcranial magnetic stimulation restores altered functional connectivity of central poststroke pain model monkeys

Thu, 03/18/2021 - 10:00

Sci Rep. 2021 Mar 17;11(1):6126. doi: 10.1038/s41598-021-85409-w.


Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP.

PMID:33731766 | DOI:10.1038/s41598-021-85409-w

The additive effect of late-life depression and olfactory dysfunction on the risk of dementia was mediated by hypersynchronization of the hippocampus/fusiform gyrus

Thu, 03/18/2021 - 10:00

Transl Psychiatry. 2021 Mar 17;11(1):172. doi: 10.1038/s41398-021-01291-0.


Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.

PMID:33731679 | DOI:10.1038/s41398-021-01291-0

Predicting Parkinson's disease trajectory using clinical and neuroimaging baseline measures

Wed, 03/17/2021 - 10:00

Parkinsonism Relat Disord. 2021 Mar 7;85:44-51. doi: 10.1016/j.parkreldis.2021.02.026. Online ahead of print.


INTRODUCTION: Predictive biomarkers of Parkinson's Disease progression are needed to expedite neuroprotective treatment development and facilitate prognoses for patients. This work uses measures derived from resting-state functional magnetic resonance imaging, including regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF), to predict an individual's current and future severity over up to 4 years and to elucidate the most prognostic brain regions.

METHODS: ReHo and fALFF are measured for 82 Parkinson's Disease subjects and used to train machine learning predictors of baseline clinical and future severity at 1 year, 2 years, and 4 years follow-up as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Predictive performance is measured with nested cross-validation, validated on an external dataset, and again validated through leave-one-site-out cross-validation. Important predictive features are identified.

RESULTS: The models explain up to 30.4% of the variance in current MDS-UPDRS scores, 55.8% of the variance in year 1 scores, and 47.1% of the variance in year 2 scores (p < 0.0001). For distinguishing high and low-severity individuals at each timepoint (MDS-UPDRS score above or below the median, respectively), the models achieve positive predictive values up to 79% and negative predictive values up to 80%. Higher ReHo and fALFF in several regions, including components of the default motor network, predicted lower severity across current and future timepoints.

CONCLUSION: These results identify an accurate prognostic neuroimaging biomarker which may be used to better inform enrollment in trials of neuroprotective treatments and enable physicians to counsel their patients.

PMID:33730626 | DOI:10.1016/j.parkreldis.2021.02.026

Connective profiles and antagonism between dynamic and static connectivity underlying generalized epilepsy

Wed, 03/17/2021 - 10:00

Brain Struct Funct. 2021 Mar 17. doi: 10.1007/s00429-021-02248-1. Online ahead of print.


This study aims to characterize the connective profiles and the coupling relationship between dynamic and static functional connectivity (dFC and sFC) in large-scale brain networks in patients with generalized epilepsy (GE). Functional, structural and diffuse MRI data were collected from 83 patients with GE and 106 matched healthy controls (HC). Resting-state BOLD time course was deconvolved to neural time course using a blind hemodynamic deconvolution method. Then, five connective profiles, including the structural connectivity (SC) and BOLD/neural time course-derived sFC/dFC networks, were constructed based on the proposed whole brain atlas. Network-level weighted correlation probability (NWCP) were proposed to evaluate the association between dFC and sFC. Both the BOLD signal and neural time course showed highly concordant findings and the present study emphasized the consistent findings between two functional approaches. The patients with GE showed hypervariability and enhancement of FC, and notably decreased SC in the subcortical network. Besides, increased dFC, weaker anatomic links, and complex alterations of sFC were observed in the default mode network of GE. Moreover, significantly increased SC and predominantly increased sFC were found in the frontoparietal network. Remarkably, antagonism between dFC and sFC was observed in large-scale networks in HC, while patients with GE showed significantly decreased antagonism in core epileptic networks. In sum, our study revealed distinct connective profiles in different epileptic networks and provided new clues to the brain network mechanism of epilepsy from the perspective of antagonism between dynamic and static functional connectivity.

PMID:33730218 | DOI:10.1007/s00429-021-02248-1

Fatty acid amide hydrolase binding is inversely correlated with amygdalar functional connectivity: a combined positron emission tomography and magnetic resonance imaging study in healthy individuals

Wed, 03/17/2021 - 10:00

J Psychiatry Neurosci. 2021 Mar 17;46(2):E238-E246. doi: 10.1503/jpn.200010.


BACKGROUND: Upregulation of the endocannabinoid enzyme fatty acid amide hydrolase (FAAH) has been linked to abnormal activity in frontoamygdalar circuits, a hallmark of posttraumatic stress disorder. We tested the hypothesis that FAAH levels in the amygdala were negatively correlated with functional connectivity between the amygdala and prefrontal cortex, subserving stress and affect control.

METHODS: Thirty-one healthy participants completed positron emission tomography (PET) imaging with the FAAH probe [C-11]CURB, and resting-state functional MRI scans. Participants were genotyped for the FAAH polymorphism rs324420, and trait neuroticism was assessed. We calculated amygdala functional connectivity using predetermined regions of interest (including the subgenual ventromedial prefrontal cortex [sgvmPFC] and the dorsal anterior cingulate cortex [dACC]) and a seed-to-voxel approach. We conducted correlation analyses on functional connectivity, with amygdala [C-11]CURB binding as a variable of interest.

RESULTS: The strength of amygdala functional connectivity with the sgvmPFC and dACC was negatively correlated with [C-11]CURB binding in the amygdala (sgvmPFC: r = -0.38, q = 0.04; dACC: r = -0.44; q = 0.03). Findings were partly replicated using the seed-to-voxel approach, which showed a cluster in the ventromedial prefrontal cortex, including voxels in the dACC but not the sgvmPFC (cluster-level, family-wise error rate corrected p < 0.05).

LIMITATIONS: We did not replicate earlier findings of a relationship between an FAAH polymorphism (rs324420) and amygdala functional connectivity.

CONCLUSION: Our data provide preliminary evidence that lower levels of FAAH in the amygdala relate to increased frontoamygdalar functional coupling. Our findings were consistent with the role of FAAH in regulating brain circuits that underlie fear and emotion processing in humans.

PMID:33729738 | DOI:10.1503/jpn.200010

Structural and Functional Brain Changes in Hemodialysis Patients with End-Stage Renal Disease: DTI Analysis Results and ALFF Analysis Results

Wed, 03/17/2021 - 10:00

Int J Nephrol Renovasc Dis. 2021 Mar 9;14:77-86. doi: 10.2147/IJNRD.S295025. eCollection 2021.


INTRODUCTION: The current study aimed to depict intrinsic structural changes and the spontaneous brain activity patterns in voxel level in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD) by using diffusion-tensor imaging and resting-state functional magnetic resonance (MR) imaging with an amplitude of low-frequency fluctuations (ALFF) algorithm and their clinical relevance.

MATERIALS AND METHODS: In the study, the diffusion-tensor imaging and resting-state functional MR imaging were performed in forty-two hemodialysis patients with ESRD and 42 healthy control subjects. Neuropsychological and laboratory tests were performed in all subjects. ALFF, fraction anisotropy (FA), and mean diffusivity (MD) values were compared between the two groups. Correlations between ALFF, FA or MD values, and clinical markers were analyzed.

RESULTS: We found that ESRD patients exhibited significantly lower ALFF values in multiple areas, including medial frontal gyrus, limbic lobe, superior frontal gyrus, bilateral lingual gyri, occipital lobe, parahippocampal gyrus, precuneus, while increased ALFF values in medial frontal gyrus than healthy controls. FA values were decreased in medial frontal gyrus, parietal lobe, and left precuneus regions in the ESRD group compared with controls. Importantly, FA for the frontal and parietal lobes was negatively associated with the dialysis duration of ESRD patients, ALFF z-scores for the medial prefrontal cortex (MPFC) were positively correlated with the dialysis duration of ESRD patients and Serum calcium of ESRD patients negatively correlated with FA values in the frontal and parietal lobes (p<0.05).

CONCLUSION: Our study revealed that both impaired brain structure and function in ESRD patients with routine hemodialysis distributed mainly in the parietal, temporal, and frontal lobes. ESRD patients have cognitive impairment and declined memory ability. Serum calcium and dialysis duration might be associated with the impairment of brain structure and function in patients with ESRD.

PMID:33727853 | PMC:PMC7955761 | DOI:10.2147/IJNRD.S295025

Acute depletion of dopamine precursors in the human brain: effects on functional connectivity and alcohol attentional bias

Wed, 03/17/2021 - 10:00

Neuropsychopharmacology. 2021 Mar 16. doi: 10.1038/s41386-021-00993-9. Online ahead of print.


Individuals who abuse alcohol often show exaggerated attentional bias (AB) towards alcohol-related cues, which is thought to reflect reward conditioning processes. Rodent studies indicate that dopaminergic pathways play a key role in conditioned responses to reward- and alcohol-associated cues. However, investigation of the dopaminergic circuitry mediating this process in humans remains limited. We hypothesized that depletion of central dopamine levels in adult alcohol drinkers would attenuate AB and that these effects would be mediated by altered function in frontolimbic circuitry. Thirty-four male participants (22-38 years, including both social and heavy drinkers) underwent a two-session, placebo-controlled, double-blind dopamine precursor depletion procedure. At each visit, participants consumed either a balanced amino acid (control) beverage or an amino acid beverage lacking dopamine precursors (order counterbalanced), underwent resting-state fMRI, and completed behavioral testing on three AB tasks: an alcohol dot-probe task, an alcohol attentional blink task, and a task measuring AB to a reward-conditioned cue. Dopamine depletion significantly diminished AB in each behavioral task, with larger effects among subjects reporting higher levels of binge drinking. The depletion procedure significantly decreased resting-state functional connectivity among ventral tegmental area, striatum, amygdala, and prefrontal regions. Beverage-related AB decreases were mediated by decreases in functional connectivity between the fronto-insular cortex and striatum and, for alcohol AB only, between anterior cingulate cortex and amygdala. The results support a substantial role for dopamine in AB, and suggest specific dopamine-modulated functional connections between frontal, limbic, striatal, and brainstem regions mediate general reward AB versus alcohol AB.

PMID:33727642 | DOI:10.1038/s41386-021-00993-9

SLC40A1 mediates ferroptosis and cognitive dysfunction in type 1 diabetes

Wed, 03/17/2021 - 10:00

Neuroscience. 2021 Mar 13:S0306-4522(21)00133-0. doi: 10.1016/j.neuroscience.2021.03.009. Online ahead of print.


Cognitive dysfunction often accompanies diabetes. Both hypoglycemia and hyperglycemia cause cognitive dysfunctions. However, the underlying pathophysiology remains unclear. Recent evidence show that ferroptosis primarily triggers nerve cell death, Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). The present study aimed to investigate whether ferroptosis is a vital pathogenic pathway in diabetes-induced cognitive dysfunction. Type 1 diabetic rat model was created by intraperitoneal injection of streptozotocin (STZ). Significant cognitive dysfunction was observed in the diabetic rats as evidenced by increase in latency period to find a hidden platform and decreased cumulative time spent in the target quadrant in the Morris water maze test. We detected the amplitude of low-frequency fluctuation (ALFF) of the BOLD (Blood Oxygenation Level-Dependent) signal using resting-state functional magnetic resonance imaging (rs-fMRI). Consequently, we found that the ALFF values, as well as the T2 relaxation time of the bilateral hippocampus, were reduced in Type 1 diabetic rats. We detected Fe2+ level and lipid peroxidation products (MDA and 4-HNE) in the hippocampus. Mitochondria and neuron injury in the STZ-induced diabetic rats were determined using a Transmission Electron Microscope and Nissl body staining. Iron overload and ferroptosis were detected in the hippocampus. Furthermore, mRNA microarray analysis revealed 201 dysregulated mRNAs in STZ-induced type 1 diabetes (T1D). Pathway enrichment analyses indicated that differentially expressed mRNAs associated-coding genes were associated with ferroptosis. Among ferroptosis signaling pathway genes, Slc40a1 gene (ferroportin) was downregulated. We show that ferroptosis is associated with diabetic cognitive dysfunction and Slc40a1 mediates ferroptosis in Type 1 diabetes.

PMID:33727075 | DOI:10.1016/j.neuroscience.2021.03.009

Segregation of functional networks is associated with cognitive resilience in Alzheimer's disease

Tue, 03/16/2021 - 10:00

Brain. 2021 Mar 16:awab112. doi: 10.1093/brain/awab112. Online ahead of print.


Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal aging, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state-fMRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: First, we included 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls. Second, we included 156 amyloid-PET positive subjects across the spectrum of sporadic Alzheimer's disease as well as 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal-lobe tau-PET (i.e. composite across Braak stage I & III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher fMRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (p = 0.007). Similarly, for sporadic Alzheimer's disease patients, higher fMRI-assessed system segregation was associated with less decrement in global cognition (p = 0.001) and episodic memory (p = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.

PMID:33725114 | DOI:10.1093/brain/awab112

Relationship between dynamic BOLD activity and functional network connectivity: Characterization of schizophrenia subgroups

Tue, 03/16/2021 - 10:00

Brain Connect. 2021 Mar 16. doi: 10.1089/brain.2020.0815. Online ahead of print.


AIM: In this work, we propose a novel use of adaptively constrained independent vector analysis (acIVA) to effectively capture the temporal and spatial properties of dynamic blood-oxygen-level-dependent (BOLD) activity (dBA), and efficiently quantify the spatial property of dBA (sdBA). We also propose to incorporate dBA into the study of brain dynamics to gain insight into activity-connectivity co-evolution patterns.

INTRODUCTION: Studies of the dynamics of human brain using functional magnetic resonance imaging (fMRI) has enabled the identification of unique functional network connectivity (FNC) states and provided new insights into mental disorders. There is evidence showing that both BOLD activity, which is captured by fMRI, and FNC are related to mental and cognitive processes. However, few studies have evaluated the inter-relationships of these two domains of function. Moreover, identification of subgroups of schizophrenia (SZ) has gained significant clinical importance due to a need to study the heterogeneity of SZ.

METHODS: We design a simulation study to verify the effectiveness of acIVA and apply acIVA to the dynamic study of resting-state fMRI data collected from individuals with SZ and healthy controls (HCs) in order to investigate the relationship between dBA and dynamic FNC (dFNC).

RESULTS: The simulation study demonstrates that acIVA accurately captures the spatial variability and provides an efficient quantification of sdBA. The fMRI analysis yields synchronized sdBA-tdBA patterns and shows that the dBA and dFNC are significantly correlated in the spatial domain. Using these dynamic features, we identify subgroups of SZ with significant differences in terms of their clinical symptoms.

CONCLUSION: We find that brain function is less efficiently organized in SZs compared with HCs since there are less synchronized sdBA-tdBA patterns in SZs and SZs prefer a component that merges multiple brain regions. The identification of subgroups of SZ using dynamic features inspires the use of neuroimaging in studying heterogeneity of disorders.

PMID:33724055 | DOI:10.1089/brain.2020.0815

Altered posterior midline activity in patients with jerky and tremulous functional movement disorders

Tue, 03/16/2021 - 10:00

Brain Connect. 2021 Mar 16. doi: 10.1089/brain.2020.0779. Online ahead of print.


OBJECTIVE: To explore changes in resting-state networks in patients with jerky and tremulous functional movement disorders (JT-FMD).

METHODS: Resting-state fMRI data from seventeen patients with JT-FMD and seventeen age-, sex-, and education matched healthy controls was investigated. Independent component analysis was used to examine the frontoparietal network (FPN), dorsal attention network (DAN), salience network (SN), and default mode network (DMN). Frequency distribution of network signal fluctuations, intra- and internetwork functional connectivity were investigated. Symptom severity was measured using the Clinical Global Impression-Severity scale. Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) scores were collected to measure depression and anxiety in FMD, respectively.

RESULTS: Compared with healthy controls, patients with JT-FMD had significantly decreased power of lower-range (0.01-0.10 Hz) frequency fluctuations in a precuneus and posterior cingulate cortex (PCC) component of the DMN, and in the DAN component (FDR-corrected P<0.05). No significant group differences were found for intra- and internetwork functional connectivity. In patients with JT-FMD, symptom severity was not significantly correlated with network measures. Depression scores were weakly correlated with intranetwork functional connectivity in the medial prefrontal cortex, while anxiety was not found to be related to network connectivity.

CONCLUSIONS: Given the changes in the postero-dorsal components of the DMN and DAN, we postulate that the JT-FMD-related functional alterations found in these regions could provide support for the concept that particularly impaired attentional control is a fundamental disturbance in these patients.

PMID:33724053 | DOI:10.1089/brain.2020.0779

Regional brain network and behavioral alterations in EGR3 gene transfected rat model of schizophrenia

Tue, 03/16/2021 - 10:00

Brain Imaging Behav. 2021 Mar 15. doi: 10.1007/s11682-021-00462-3. Online ahead of print.


Schizophrenia is a severe psychiatric disease while its etiology and effective treatment are not completely clear. A rat model of schizophrenia was previously established by transfecting EGR3 gene into the hippocampus of rats. This study aimed to investigate the behavioral and cerebral alterations of the schizophrenic model rats and the risperidone effects. Twenty-six rats were divided into 3 groups: schizophrenia model group (E group), risperidone treatment group (T group), and healthy control group (H group). Morris water maze and open field test were used as behavioral tests, resting-state functional magnetic resonance imaging (fMRI) was performed after EGR3 gene transfection and risperidone therapy. Graph analyses were used for examining cerebral alterations of the rats. Behavioral tests demonstrated reduced spatial working memory and exploring unfamiliar space ability in schizophrenic model rats. Graph analyses revealed reduced regional architectures in the olfactory bulb, nucleus accumbens, and pineal gland in group E compared to group H (p < 0.05), while group T showed increased regional architecture in pineal gland compared to group E (p < 0.05). Besides, the regional architectures in the olfactory bulb, nucleus accumbens were lower in group T than group H, while the hippocampus showed increased regional architecture in group T compared to group H (p < 0.05). Schizophrenia induced several regional alterations in the cerebrum while risperidone can reverse part of these alterations. This study lends support for future research on the pathology of schizophrenia and provides new insights on the role of risperidone in schizophrenia.

PMID:33723811 | DOI:10.1007/s11682-021-00462-3

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement

Tue, 03/16/2021 - 10:00

Neurologia. 2021 Mar 12:S0213-4853(21)00023-2. doi: 10.1016/j.nrl.2021.01.007. Online ahead of print.


INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness.

METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas.

RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas.

CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

PMID:33722455 | DOI:10.1016/j.nrl.2021.01.007