New resting-state fMRI related studies at PubMed

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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.

ABSTRACT

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

Distinct Neural Processing of Acute Stress in Major Depression and Borderline Personality Disorder

Mon, 03/15/2021 - 10:00

J Affect Disord. 2021 Feb 26;286:123-133. doi: 10.1016/j.jad.2021.02.055. Online ahead of print.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) and borderline personality disorder (BPD) are highly prevalent and often comorbid psychiatric conditions, with abnormal processing of negative affect resulting from psychological stress. Characteristics of central processing of autonomic response to stress in each disorder are not clearly settled.

METHODS: We obtained whole brain 3T fMRI with concurrent skin conductance, respiration rate, and heart rate variability measures in a cohort of MDD (N=19), BPD (N=19) patients, and healthy (N=20) individuals. Experiments were conducted in resting conditions, during a control mental arithmetic task, during highly stressful mental arithmetic, and in the period immediately following psychological stress.

RESULTS: Widespread activation of central autonomic network (CAN) structures was observed during stress compared to a control task in the group of healthy participants, whereas CAN activation during stress was less intense in both BPD and MDD. Both patient groups displayed increased sympathetic and decreased parasympathetic activation compared to healthy subjects, as previously reported. The relationship between peripheral sympathetic or parasympathetic activity and simultaneous regional brain BOLD activity was similar in BPD patients and healthy subjects, and markedly different from that seen in MDD patients.

LIMITATIONS: The sample size, the fact it belonged to a single study site, and low grade affective symptomatology in both patient groups limit the generalizability of the present findings.

CONCLUSIONS: The diverging neurobiological signature in the homeostatic response to stress in MDD and BPD possibly represents a heuristically valuable candidate biomarker to help discern MDD and BPD patients.

PMID:33721739 | DOI:10.1016/j.jad.2021.02.055

Functional Connectivity and Response Inhibition: A Secondary Analysis of an 8-Week Randomized Controlled Trial of Computerized Cognitive Training

Mon, 03/15/2021 - 10:00

J Alzheimers Dis. 2021 Mar 9. doi: 10.3233/JAD-200844. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence suggests that computerized cognitive training (CCT) can improve cognitive function in older adults, particularly executive functions. However, the underlying mechanisms by which CCT may improve executive functions are not well established.

OBJECTIVE: To determine: 1) inter-network functional connectivity correlates of changes in executive functions; and 2) the effect of CCT on these functional connectivity correlates.

METHODS: This secondary analysis included a subset of 124 adults aged 65-85 years enrolled in an 8-week randomized controlled trial of CCT. Participants were randomized to either: 1) group-based CCT 3x/week for 1 hour plus 3x/week home-based training; 2) group-based CCT preceded by brisk walking (Ex-CCT) 3x/week for 1 hour plus 3x/week home-based training (exercise+CCT); or 3) group-based balanced and toned (BAT) classes 3x/week for 1 hour (control). At baseline and trial completion, 65 of the 124 participants completed resting-state functional magnetic resonance imaging and neuropsychological tests of executive functions, specifically the Stroop Colour-Word Test and Flanker Test.

RESULTS: Improved performance on the Stroop Colour-Word Test and Flanker Test were associated with decreased correlation between the default mode network (DMN) and the fronto-parietal network (FPN) (p < 0.05). Compared with BAT, CCT alone significantly decreased correlation between the left dorsolateral prefrontal cortex and both the left and right medial temporal gyrus (-0.143, 95%CI [-0.256,-0.030], p = 0.014, and -0.123, 95%CI [-0.242,-0.004], p = 0.043, respectively).

CONCLUSION: Decreased correlation between DMN and FPN, indicating less connection between these networks, may be an underlying mechanism by which CCT improves executive functions. Future studies are needed to replicate this finding.

PMID:33720882 | DOI:10.3233/JAD-200844

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

Mon, 03/15/2021 - 10:00

J Vis Exp. 2021 Feb 24;(168). doi: 10.3791/62267.

ABSTRACT

Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity measure of the cerebral blood volume achieved by ultrafast doppler angiography. As brain perfusion is strongly linked to local neuronal activity, this technique allows the whole-brain 3D mapping of task-induced regional activation as well as resting-state functional connectivity, non-invasively, with unmatched spatio-temporal resolution and operational simplicity. In comparison with fMRI (functional magnetic resonance imaging), a main advantage of fUS imaging consists in enabling a complete compatibility with awake and behaving animal experiments. Moreover, fMRI brain mapping in mice, the most used preclinical model in Neuroscience, remains technically challenging due to the small size of the brain and the difficulty to maintain stable physiological conditions. Here we present a simple, reliable and robust protocol for whole-brain fUS imaging in anesthetized and awake mice using an off-the-shelf commercial fUS system with a motorized linear transducer, yielding significant cortical activation following sensory stimulation as well as reproducible 3D functional connectivity pattern for network identification.

PMID:33720137 | DOI:10.3791/62267

Thalamic dysconnectivity in the psychosis risk syndrome and early illness schizophrenia

Mon, 03/15/2021 - 10:00

Psychol Med. 2021 Mar 15:1-9. doi: 10.1017/S0033291720004882. Online ahead of print.

ABSTRACT

BACKGROUND: Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset.

METHODS: Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups.

RESULTS: Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups.

CONCLUSIONS: PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.

PMID:33719985 | DOI:10.1017/S0033291720004882

The Functional Reorganization of Language Network Modules in Glioma Patients: New Insights From Resting State fMRI Study

Mon, 03/15/2021 - 10:00

Front Oncol. 2021 Feb 26;11:617179. doi: 10.3389/fonc.2021.617179. eCollection 2021.

ABSTRACT

BACKGROUND: Prior investigations of language functions have focused on the response profiles of particular brain regions. However, the specialized and static view of language processing does not explain numerous observations of functional recovery following brain surgery. To investigate the dynamic alterations of functional connectivity (FC) within language network (LN) in glioma patients, we explored a new flexible model based on the neuroscientific hypothesis of core-periphery organization in LN.

METHODS: Group-level LN mapping was determined from 109 glioma patients and forty-two healthy controls (HCs) using independent component analysis (ICA). FC and mean network connectivity (mNC: l/rFCw, FCb, and FCg) were compared between patients and HCs. Correlations between mNC and tumor volume (TV) were calculated.

RESULTS: We identified ten separate LN modules from ICA. Compared to HCs, glioma patients showed a significant reduction in language network functional connectivity (LNFC), with a distinct pattern modulated by tumor position. Left hemisphere gliomas had a broader impact on FC than right hemisphere gliomas, with more reduced edges away from tumor sites (p=0.011). mNC analysis revealed a significant reduction in all indicators of FC except for lFCw in right hemisphere gliomas. These alterations were associated with TV in a double correlative relationship depending on the tumor position across hemispheres.

CONCLUSION: Our findings emphasize the importance of considering the modulatory effects of core-periphery mechanisms from a network perspective. Preoperative evaluation of changes in LN caused by gliomas could provide the surgeon a reference to optimize resection while maintaining functional balance.

PMID:33718172 | PMC:PMC7953055 | DOI:10.3389/fonc.2021.617179

Relation of Decreased Functional Connectivity Between Left Thalamus and Left Inferior Frontal Gyrus to Emotion Changes Following Acute Sleep Deprivation

Mon, 03/15/2021 - 10:00

Front Neurol. 2021 Feb 26;12:642411. doi: 10.3389/fneur.2021.642411. eCollection 2021.

ABSTRACT

Objective: The thalamus is a key node for sleep-wake pathway gate switching during acute sleep deprivation (ASD), and studies have shown that it plays a certain role in emotion changes. However, there are no studies on the association between the thalamus and emotion changes in ASD. In this study, we used resting-state functional magnetic resonance imaging (R-fMRI) to explore whether changes in the functional connections between the thalamus and other brain regions are related to emotion changes and further explored the function of the thalamus under total ASD conditions. Method: Thirty healthy, right-handed adult men underwent emotional assessment according to the Profile of Mood States Scale and R-fMRI scans before and after ASD. The correlations between changes in functional connectivity between the thalamus and other brain regions and emotion changes were then studied. Results: Positive emotions and psychomotor performance were reduced, and negative emotions were increased following ASD. The functional connections between the left thalamus and left middle temporal gyrus, left inferior frontal gyrus, right thalamus, right inferior temporal gyrus, left middle temporal pole gyrus, right calcarine, left cuneus, left rectus and left medial superior frontal gyrus were significantly altered. Decreased functional connectivity between left thalamus and left inferior frontal gyrus related to emotion changes following ASD. Conclusion: This study finds that functional changes in the thalamus are associated with emotion changes during ASD, suggesting that the left thalamus probably plays an essential role in emotion changes under ASD conditions.

PMID:33716944 | PMC:PMC7952868 | DOI:10.3389/fneur.2021.642411

Associations of Serum Liver Function Markers With Brain Structure, Function, and Perfusion in Healthy Young Adults

Mon, 03/15/2021 - 10:00

Front Neurol. 2021 Feb 25;12:606094. doi: 10.3389/fneur.2021.606094. eCollection 2021.

ABSTRACT

Background: Previous neuroimaging studies have demonstrated brain abnormalities in patients with hepatic diseases. However, the identified liver-brain associations are largely limited to disease-affected populations, and the nature and extent of such relations in healthy subjects remain unclear. We hypothesized that serum liver function markers within a normal level would affect brain properties. Method: One hundred fifty-seven healthy young adults underwent structural, resting-state functional, and arterial spin labeling MRI scans. Gray matter volume (GMV), regional homogeneity (ReHo), and cerebral blood flow (CBF) analyses were performed to assess brain structure, function, and perfusion, respectively. Peripheral venous blood samples were collected to measure serum liver function markers. Correlation analyses were conducted to test potential associations between liver function markers and brain imaging parameters. Results: First, serum proteins showed relations to brain structure characterized by higher albumin associated with increased GMV in the parahippocampal gyrus and amygdala and lower globulin and a higher albumin/globulin ratio with increased GMV in the olfactory cortex and parahippocampal gyrus. Second, serum bilirubin was linked to brain function characterized by higher bilirubin associated with increased ReHo in the precuneus, middle cingulate gyrus, inferior parietal lobule, and supramarginal gyrus and decreased ReHo in the caudate nucleus. Third, serum alanine transaminase (ALT) was related to brain perfusion characterized by higher ALT associated with increased CBF in the superior frontal gyrus and decreased CBF in the middle occipital gyrus, angular gyrus, precuneus, and middle temporal gyrus. More importantly, we found that CBF in the superior frontal gyrus was a significant mediator of the association between serum ALT level and working memory performance. Conclusion: These findings may not only expand existing knowledge about the relationship between the liver and the brain but also have clinical implications for studying brain impairments secondary to liver diseases as well as providing potential neural targets for their diagnosis and treatment.

PMID:33716920 | PMC:PMC7947675 | DOI:10.3389/fneur.2021.606094

Case Report: Multimodal Functional and Structural Evaluation Combining Pre-operative nTMS Mapping and Neuroimaging With Intraoperative CT-Scan and Brain Shift Correction for Brain Tumor Surgical Resection

Mon, 03/15/2021 - 10:00

Front Hum Neurosci. 2021 Feb 25;15:646268. doi: 10.3389/fnhum.2021.646268. eCollection 2021.

ABSTRACT

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported. Case Report: A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome. Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery.

PMID:33716700 | PMC:PMC7947337 | DOI:10.3389/fnhum.2021.646268

Structural and Functional Changes Are Related to Cognitive Status in Wilson's Disease

Mon, 03/15/2021 - 10:00

Front Hum Neurosci. 2021 Feb 25;15:610947. doi: 10.3389/fnhum.2021.610947. eCollection 2021.

ABSTRACT

Patients with Wilson's disease (WD) suffer from prospective memory (PM) impairment, and some of patients develop cognitive impairment. However, very little is known about how brain structure and function changes effect PM in WD. Here, we employed multimodal neuroimaging data acquired from 22 WD patients and 26 healthy controls (HC) who underwent three-dimensional T1-weighted, diffusion tensor imaging (DTI), and resting state functional magnetic resonance imaging (RS-fMRI). We investigated gray matter (GM) volumes with voxel-based morphometry, DTI metrics using the fiber tractography method, and RS-fMRI using the seed-based functional connectivity method. Compared with HC, WD patients showed GM volume reductions in the basal ganglia (BG) and occipital fusiform gyrus, as well as volume increase in the visual association cortex. Moreover, whiter matter (WM) tracks of WD were widely impaired in association and limbic fibers. WM tracks in association fibers are significant related to PM in WD patients. Relative to HC, WD patients showed that the visual association cortex functionally connects to the thalamus and hippocampus, which is associated with global cognitive function in patients with WD. Together, these findings suggested that PM impairment in WD may be modulated by aberrant WM in association fibers, and that GM volume changes in the association cortex has no direct effect on cognitive status, but indirectly affect global cognitive function by its aberrant functional connectivity (FC) in patients with WD. Our findings may provide a new window to further study how WD develops into cognitive impairment, and deepen our understanding of the cognitive status and neuropathology of WD.

PMID:33716691 | PMC:PMC7947794 | DOI:10.3389/fnhum.2021.610947

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