New resting-state fMRI related studies at PubMed

Maternal parenting behavior and functional connectivity development in children: A longitudinal fMRI study

Mon, 03/29/2021 - 10:00

Dev Cogn Neurosci. 2021 Mar 22;48:100946. doi: 10.1016/j.dcn.2021.100946. Online ahead of print.


Parenting behavior is associated with internalizing symptoms in children, and cross-sectional research suggests that this association may be mediated by the influence of parenting on the development of frontoamygdala circuitry. However, longitudinal studies are lacking. Moreover, there is a paucity of studies that have investigated parenting and large-scale networks implicated in affective functioning. In this longitudinal study, data from 95 (52 female) children and their mothers were included. Children underwent magnetic resonance imaging that included a 6 min resting state sequence at wave 1 (mean age = 8.4 years) and wave 2 (mean age = 9.9 years). At wave 1, observational measures of positive and negative maternal behavior were collected during mother-child interactions. Region-of-interest analysis of the amygdala, and independent component and dual-regression analyses of the Default Mode Network (DMN), Executive Control Network (ECN) and the Salience Network (SN) were carried out. We identified developmental effects as a function of parenting: positive parenting was associated with decreased coactivation of the superior parietal lobule with the ECN at wave 2 compared to wave 1. Thus our findings provide preliminary longitudinal evidence that positive maternal behavior is associated with maturation of the connectivity between higher-order control networks.

PMID:33780733 | DOI:10.1016/j.dcn.2021.100946

Relationship between GABA levels and task-dependent cortical excitability in children with attention-deficit/hyperactivity disorder

Mon, 03/29/2021 - 10:00

Clin Neurophysiol. 2021 Mar 10;132(5):1163-1172. doi: 10.1016/j.clinph.2021.01.023. Online ahead of print.


OBJECTIVE: Compared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS).

METHODS: Across two sites, 37 children with ADHD and 45 TD children, ages 8-12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models.

RESULTS: In both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms.

CONCLUSIONS: In children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement.

SIGNIFICANCE: Evaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.

PMID:33780723 | DOI:10.1016/j.clinph.2021.01.023

Asthma-Specific Temporal Variability Reveals the Effect of Group Cognitive Behavior Therapy in Asthmatic Patients

Mon, 03/29/2021 - 10:00

Front Neurol. 2021 Mar 12;12:615820. doi: 10.3389/fneur.2021.615820. eCollection 2021.


Background: Group cognitive behavior therapy (GCBT) is a successful therapy for asthma. However, the neural biomarker of GCBT which could be used in clinic remains unclear. The temporal variability is a novel concept to characterize the dynamic functional connectivity (FC), which has many advantages as biomarker. Therefore, the aim of this study is to explore the potential difference of temporal variability between asthmatic patients and healthy controls, then determine the different patterns of temporal variability between pre- and post-treatment group and reveal the relationship between the variability and the symptoms improvement reduced by GCBT. Methods: At baseline, 40 asthmatic patients and 40 matched controls received resting-state functional magnetic resonance imaging (fMRI) scans and clinical assessments. After 8 weeks of GCBT treatment, 17 patients received fMRI scans, and assessments again. Temporal variability at baseline and post-treatment were calculated for further analysis. Results: Compared with controls, asthmatic patients showed widespread decreases in temporal variability. Moreover, the variability in both right caudate and left putamen were positively correlated with asthma control level. After GCBT, asthma control level and depression of patients were improved. Meanwhile, compared with pre-GCBT, patients after treatment showed lower variability in left opercular of Rolandic, right parahippocampal gyrus and right lingual gyrus, as well as higher variability in left temporal pole. Variability in regions which were found abnormal at baseline did not exhibit significant differences between post-GCBT and controls. Conclusions: Asthma-specific changes of dynamic functional connectivity may serve as promising underpinnings of GCBT for asthma. Clinical Trial Registration:, identifier: Chi-CTR-15007442.

PMID:33776882 | PMC:PMC7994749 | DOI:10.3389/fneur.2021.615820

Altered Functional Connectivity Within and Between Salience and Sensorimotor Networks in Patients With Functional Constipation

Mon, 03/29/2021 - 10:00

Front Neurosci. 2021 Mar 11;15:628880. doi: 10.3389/fnins.2021.628880. eCollection 2021.


Functional constipation (FCon) is a common functional gastrointestinal disorder. A considerable portion of patients with FCon is associated with anxiety/depressive status (FCAD). Previous neuroimaging studies mainly focused on patients with FCon without distinguishing FCAD from FCon patients without anxiety/depressive status (FCNAD). Differences in brain functions between these two subtypes remain unclear. Thus, we employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory method to investigate differences in brain network connectivity and topology in 41 FCAD, 42 FCNAD, and 43 age- and gender-matched healthy controls (HCs). FCAD/FCNAD showed significantly lower normalized clustering coefficient and small-world-ness. Both groups showed altered nodal degree/efficiency mainly in the rostral anterior cingulate cortex (rACC), precentral gyrus (PreCen), supplementary motor area (SMA), and thalamus. In the FCAD group, nodal degree in the SMA was negatively correlated with difficulty of defecation, and abdominal pain was positively correlated with nodal degree/efficiency in the rACC, which had a lower within-module nodal degree. The salience network (SN) exhibited higher functional connectivity (FC) with the sensorimotor network (SMN) in FCAD/FCNAD, and FC between these two networks was negatively correlated with anxiety ratings in FCAD group. Additionally, FC of anterior insula (aINS)-rACC was only correlated with constipation symptom (i.e., abdominal pain) in the FCNAD group. In the FCAD group, FCs of dorsomedial prefrontal cortex-rACC, PreCen-aINS showed correlations with both constipation symptom (i.e., difficulty of defecation) and depressive status. These findings indicate the differences in FC of the SN-SMN between FCAD and FCNAD and provide neuroimaging evidence based on brain function, which portrays important clues for improving new treatment strategies.

PMID:33776637 | PMC:PMC7991789 | DOI:10.3389/fnins.2021.628880

The Instant and Sustained Effect of Electroacupuncture in Postgraduate Students with Depression: An fMRI Study

Mon, 03/29/2021 - 10:00

Neuropsychiatr Dis Treat. 2021 Mar 19;17:873-883. doi: 10.2147/NDT.S307083. eCollection 2021.


OBJECTION: This study was a primary study to evaluate the instant and sustained effect of electroacupuncture (EA) at GV20 (Baihui) in postgraduate students with mild depression by using a special flexible head coil.

METHODS: A total of 20 postgraduate students with mild depression underwent EA stimulation at GV20 and 3 phases of resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Phase I: Preparation (before needle insertion); Phase II: during EA; Phase III: 15 minutes after needle removal. The Rs-fMRI data were processed using DPABI and SPSS 25.

RESULTS: 1) ReHo values showed significantly differences in the right posterior cingulate cortex, right calcarine gyrus, right angular gyrus, right precuneus, right cuneus, and bilateral postcentral gyri among Phase I, Phase II and Phase III; 2) Relative to the Phase I, increased brain activity in the Phase II was observed in the bilateral postcentral gyri, right calcarine gyrus, right cuneus. Compared with the Phase II, decreased brain activity in the Phase III was observed in the right precuneus, right posterior cingulate cortex, right angular gyrus. Relative to the Phase I, Significantly increased brain activity in the Phase III was observed in the right calcarine gyrus, right cuneus, and bilateral postcentral gyri. While decreased ReHo values were found in the right posterior cingulate cortex, right angular gyrus, right precuneus; and 3) Correlation analysis showed that the ReHo values of multiple brain regions in Phase I and Phase III were significantly correlated with the VAS and HRSD-17 scores.

CONCLUSION: This study focuses on the instant and sustained effect in postgraduate students with depression. Our study showed that instant effect produced by EA stimulation at GV20 firstly induced changes in somatosensory and visual area, and then, sustained effect (Phase III) have a higher intensity and more extensive than instant effects. Meanwhile, we provide a visualization way to study the instant effects of head acupoints by using a flexible head coil.

PMID:33776442 | PMC:PMC7989050 | DOI:10.2147/NDT.S307083

Influence of anhedonic symptom severity on reward circuit connectivity in PTSD

Mon, 03/29/2021 - 10:00

Behav Brain Res. 2021 Mar 25:113258. doi: 10.1016/j.bbr.2021.113258. Online ahead of print.


Anhedonia, marked by deficits in reward processing, is a prominent symptom of several psychiatric conditions and has been shown to influence functional connectivity between reward-related regions. However, the unique influence of anhedonia severity on reward circuit connectivity in posttraumatic stress disorder (PTSD) remains unclear. To address this, we examined resting-state functional connectivity (rsFC) of the ventral striatum as a function of anhedonia for individuals with PTSD. Resting-state functional MRI scans and behavioral assessments were collected for 71 women diagnosed with PTSD. Seed-based voxelwise rsFC analyses for left and right nucleus accumbens (NAcc) seed regions of interest were performed. Voxelwise regression analyses were conducted to examine the relationship between anhedonia severity and rsFC of left and right NAcc. Results indicated that greater anhedonia severity was associated with reduced rsFC between the left NAcc and a cluster in the left caudate extending to the thalamus. This relationship between anhedonia and rsFC remained significant after controlling for PTSD symptom severity or depression severity. Our findings suggest that reward circuit dysfunction at rest is associated with anhedonia in PTSD. These results further contribute to our understanding of the neural correlates of anhedonia in psychiatric conditions.

PMID:33775774 | DOI:10.1016/j.bbr.2021.113258

Whole-Brain Functional Dynamics Track Depressive Symptom Severity

Sun, 03/28/2021 - 10:00

Cereb Cortex. 2021 Mar 29:bhab047. doi: 10.1093/cercor/bhab047. Online ahead of print.


Depressive symptoms are reported by 20% of the population and are related to altered functional integrity of large-scale brain networks. The link between moment-to-moment brain function and depressive symptomatology, and the implications of these relationships for clinical and community populations alike, remain understudied. The present study examined relationships between functional brain dynamics and subclinical-to-mild depressive symptomatology in a large community sample of adults with and without psychiatric diagnoses. This study used data made available through the Enhanced Nathan Kline Institute-Rockland Sample; 445 participants between 18 and 65 years of age completed a 10-min resting-state functional MRI scan. Coactivation pattern analysis was used to examine the dimensional relationship between depressive symptoms and whole-brain states. Elevated levels of depressive symptoms were associated with increased frequency and dwell time of the default mode network, a brain network associated with self-referential thought, evaluative judgment, and social cognition. Furthermore, increased depressive symptom severity was associated with less frequent occurrences of a hybrid brain network implicated in cognitive control and goal-directed behavior, which may impair the inhibition of negative thinking patterns in depressed individuals. These findings demonstrate how temporally dynamic techniques offer novel insights into time-varying neural processes underlying subclinical and clinically meaningful depressive symptomatology.

PMID:33774654 | DOI:10.1093/cercor/bhab047

Association between functional brain alterations and neuropsychological scales in male chronic smokers using resting-state fMRI

Sat, 03/27/2021 - 10:00

Psychopharmacology (Berl). 2021 Mar 27. doi: 10.1007/s00213-021-05819-6. Online ahead of print.


RATIONALE: Recent studies have demonstrated that cigarette smoking is related to changes in brain structure and function. However, few studies focus on functional brain differences between male chronic smokers and nonsmokers in both local spontaneous activity and whole-brain functional networks.

OBJECTIVES: Our study recruited 67 chronic smokers and 43 nonsmokers who underwent functional magnetic resonance imaging (fMRI) scans to investigate functional activity and connectivity alterations in chronic smokers.

METHODS: We used the mean fractional amplitude of the low-frequency fluctuation (mfALFF) and mean regional homogeneity (mReHo) methods to investigate resting-state spontaneous activity in chronic smokers and nonsmokers. The graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also used to investigate functional connectivity alterations.

RESULTS: Compared with nonsmokers, chronic smokers exhibited higher activation in the reward system and portions of the prefrontal cortex but lower activation in the default mode networks (DMN) and visual-related regions. In addition, correlation analysis was conducted to assess the associations between neuroimaging findings and the severity of nicotine dependence or expectations of smoking effects. Our results showed that certain brain regions correlated with the Fagerström Test for Nicotine Dependence (FTND), the positive aspect of the Drug Use Disorders Identification Test Extended (DUDIT-E), and the negative aspect of the DUDIT-E, especially in the attentional control networks and hippocampus. The graph theoretical analysis (GTA) results indicated chronic smokers exhibited a trend toward increased assortativity. Our network-based statistical (NBS) analysis revealed reduced functional connections between the subnetwork in the prefrontal cortex, olfactory cortex, angular gyrus, and cingulate gyrus of chronic smokers.

CONCLUSIONS: We concluded that chronic smokers have neural adaptations in local spontaneous activity but remain healthy brain functional networks.

PMID:33772331 | DOI:10.1007/s00213-021-05819-6

Using carpet plots to analyze transit times of low frequency oscillations in resting state fMRI

Sat, 03/27/2021 - 10:00

Sci Rep. 2021 Mar 26;11(1):7011. doi: 10.1038/s41598-021-86402-z.


A "carpet plot" is a 2-dimensional plot (time vs. voxel) of scaled fMRI voxel intensity values. Low frequency oscillations (LFOs) can be successfully identified from BOLD fMRI and used to study characteristics of neuronal and physiological activity. Here, we evaluate the use of carpet plots paired with a developed slope-detection algorithm as a means to study LFOs in resting state fMRI (rs-fMRI) data with the help of dynamic susceptibility contrast (DSC) MRI data. Carpet plots were constructed by ordering voxels according to signal delay time for each voxel. The slope-detection algorithm was used to identify and calculate propagation times, or "transit times", of tilted vertical edges across which a sudden signal change was observed. We aim to show that this metric has applications in understanding LFOs in fMRI data, possibly reflecting changes in blood flow speed during the scan, and for evaluating alternative blood-tracking contrast agents such as inhaled CO2. We demonstrate that the propagations of LFOs can be visualized and automatically identified in a carpet plot as tilted lines of sudden intensity change. Resting state carpet plots produce edges with transit times similar to those of DSC carpet plots. Additionally, resting state carpet plots indicate that edge transit times vary at different time points during the scan.

PMID:33772060 | DOI:10.1038/s41598-021-86402-z

Associations between neighborhood disadvantage, resting-state functional connectivity, and behavior in the Adolescent Brain Cognitive Development (ABCD) Study(R): Moderating role of positive family and school environments

Sat, 03/27/2021 - 10:00

Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Mar 23:S2451-9022(21)00085-9. doi: 10.1016/j.bpsc.2021.03.008. Online ahead of print.


OBJECTIVE: Neighborhood disadvantage has consistently been associated with mental health and cognitive function, in addition to alterations in brain function and connectivity. However, positive environmental influences may buffer these effects. The aim of the present study was to examine the association between neighborhood disadvantage and resting-state functional connectivity (rsFC), the moderating role of positive parenting and school environment, and relationships between disadvantage-associated rsFC patterns and mental health and cognition.

METHODS: In this pre-registered study, we tested this hypothesis in a large sample of 7618 children (aged 9-10 years) from the Adolescent Brain Cognitive Development (ABCD) Study. Specifically, we analyzed the relationship between neighborhood disadvantage and system-level FC. We also tested whether positive family and school environmental factors, and sex, moderated effects. Finally, we investigated multivariate relationships between disadvantage-associated rsFC patterns and cognition and mental health.

RESULTS: Disadvantage was associated with widespread alterations in FC across both higher-order (e.g., default mode network and dorsal attention network) and sensorimotor functional systems; some of which were moderated by positive environments. Implicated connections showed multivariate associations with behavior, whereby disadvantage-associated rsFC was generally associated with worse cognition and mental health. Disadvantage-associated connections also predicted variation in cognitive scores using machine learning models.

CONCLUSIONS: Our findings shed light on potential mechanisms (i.e., alteration of neural circuitry) through which neighborhood disadvantage may affect youth cognition and mental wellbeing. This work highlights the importance of positive family and school environments in mitigating some of these effects.

PMID:33771727 | DOI:10.1016/j.bpsc.2021.03.008

The NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty: Protocol and Rationale for Methods and Measures

Sat, 03/27/2021 - 10:00

Neuroimage. 2021 Mar 23:117970. doi: 10.1016/j.neuroimage.2021.117970. Online ahead of print.


Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children.

PMID:33771694 | DOI:10.1016/j.neuroimage.2021.117970

Dysmaturation Observed as Altered Hippocampal Functional Connectivity at Rest Is Associated With the Emergence of Positive Psychotic Symptoms in Patients With 22q11 Deletion Syndrome

Sat, 03/27/2021 - 10:00

Biol Psychiatry. 2021 Jan 18:S0006-3223(21)00045-7. doi: 10.1016/j.biopsych.2020.12.033. Online ahead of print.


BACKGROUND: Hippocampal alterations are among the most replicated neuroimaging findings across the psychosis spectrum. Moreover, there is strong translational evidence that preserving the maturation of hippocampal networks in mice models prevents the progression of cognitive deficits. However, the developmental trajectory of hippocampal functional connectivity (HFC) and its contribution to psychosis is not well characterized in the human population. 22q11 deletion syndrome (22q11DS) offers a unique model for characterizing early neural correlates of schizophrenia.

METHODS: We acquired resting-state functional magnetic resonance imaging in 242 longitudinally repeated scans from 84 patients with 22q11DS (30 with moderate to severe positive psychotic symptoms) and 94 healthy control subjects in the age span of 6 to 32 years. We obtained bilateral hippocampus to whole-brain functional connectivity and employed a novel longitudinal multivariate approach by means of partial least squares correlation to evaluate the developmental trajectory of HFC across groups.

RESULTS: Relative to control subjects, patients with 22q11DS failed to increase HFC with frontal regions such as the dorsal part of the anterior cingulate cortex, prefrontal cortex, and supplementary motor area. Concurrently, carriers of the deletion had abnormally higher HFC with subcortical dopaminergic areas. Remarkably, this aberrant maturation of HFC was more prominent during midadolescence and was mainly driven by patients exhibiting subthreshold positive psychotic symptoms.

CONCLUSIONS: Our findings suggest a critical period of prefrontal cortex-hippocampal-striatal circuit dysmaturation, particularly during late adolescence, which in light of current translation evidence could be a target for short-term interventions to potentially achieve long-lasting rescue of circuit dysfunctions associated with psychosis.

PMID:33771350 | DOI:10.1016/j.biopsych.2020.12.033

A literature review of magnetic resonance imaging sequence advancements in visualizing functional neurosurgery targets

Fri, 03/26/2021 - 10:00

J Neurosurg. 2021 Mar 26:1-14. doi: 10.3171/2020.8.JNS201125. Online ahead of print.


OBJECTIVE: Historically, preoperative planning for functional neurosurgery has depended on the indirect localization of target brain structures using visible anatomical landmarks. However, recent technological advances in neuroimaging have permitted marked improvements in MRI-based direct target visualization, allowing for refinement of "first-pass" targeting. The authors reviewed studies relating to direct MRI visualization of the most common functional neurosurgery targets (subthalamic nucleus, globus pallidus, and thalamus) and summarize sequence specifications for the various approaches described in this literature.

METHODS: The peer-reviewed literature on MRI visualization of the subthalamic nucleus, globus pallidus, and thalamus was obtained by searching MEDLINE. Publications examining direct MRI visualization of these deep brain stimulation targets were included for review.

RESULTS: A variety of specialized sequences and postprocessing methods for enhanced MRI visualization are in current use. These include susceptibility-based techniques such as quantitative susceptibility mapping, which exploit the amount of tissue iron in target structures, and white matter attenuated inversion recovery, which suppresses the signal from white matter to improve the distinction between gray matter nuclei. However, evidence confirming the superiority of these sequences over indirect targeting with respect to clinical outcome is sparse. Future targeting may utilize information about functional and structural networks, necessitating the use of resting-state functional MRI and diffusion-weighted imaging.

CONCLUSIONS: Specialized MRI sequences have enabled considerable improvement in the visualization of common deep brain stimulation targets. With further validation of their ability to improve clinical outcomes and advances in imaging techniques, direct visualization of targets may play an increasingly important role in preoperative planning.

PMID:33770759 | DOI:10.3171/2020.8.JNS201125

A neurodevelopmental signature of parkinsonism in schizophrenia

Fri, 03/26/2021 - 10:00

Schizophr Res. 2021 Mar 23;231:54-60. doi: 10.1016/j.schres.2021.03.004. Online ahead of print.


While sensorimotor abnormalities in schizophrenia (SZ) are of increasing scientific interest, little is known about structural changes and their developmental origins that may underlie parkinsonism. This multimodal magnetic resonance imaging (MRI) study examined healthy controls (HC, n = 20) and SZ patients with (SZ-P, n = 38) and without (SZ-nonP, n = 35) parkinsonism, as defined by Simpson-Angus Scale total scores of ≥4 or ≤1, respectively. Using the Computational Anatomy Toolbox (CAT12), voxel- and surface-based morphometry were applied to investigate cortical and subcortical gray matter volume (GMV) and three cortical surface markers of distinct neurodevelopmental origin: cortical thickness (CTh), complexity of cortical folding (CCF) and sulcus depth. In a subgroup of patients (29 SZ-nonP, 25 SZ-P), resting-state fMRI data were also analyzed using a regions-of-interest approach based on fractional amplitude of low frequency fluctuations (fALFF). SZ-P patients showed increased CCF in the left supplementary motor cortex (SMC) and decreased left postcentral sulcus (PCS) depth compared to SZ-nonP patients (p < 0.05, FWE-corrected at cluster level). In SMC, CCF was associated negatively with activity, which also differed significantly between the patient groups and between patients and HC. In regression models, severity of parkinsonism was associated negatively with left middle frontal CCF and left anterior cingulate CTh. These data provide novel insights into altered trajectories of cortical development in SZ patients with parkinsonism. These cortical surface changes involve the sensorimotor system, suggesting abnormal neurodevelopmental processes tightly coupled with cortical activity and subcortical morphology that convey increased risk for sensorimotor abnormalities in SZ.

PMID:33770626 | DOI:10.1016/j.schres.2021.03.004

Increased brain atrophy and lesion load is associated with stronger lower alpha MEG power in multiple sclerosis patients

Fri, 03/26/2021 - 10:00

Neuroimage Clin. 2021 Mar 17;30:102632. doi: 10.1016/j.nicl.2021.102632. Online ahead of print.


In multiple sclerosis, the interplay of neurodegeneration, demyelination and inflammation leads to changes in neurophysiological functioning. This study aims to characterize the relation between reduced brain volumes and spectral power in multiple sclerosis patients and matched healthy subjects. During resting-state eyes closed, we collected magnetoencephalographic data in 67 multiple sclerosis patients and 47 healthy subjects, matched for age and gender. Additionally, we quantified different brain volumes through magnetic resonance imaging (MRI). First, a principal component analysis of MRI-derived brain volumes demonstrates that atrophy can be largely described by two components: one overall degenerative component that correlates strongly with different cognitive tests, and one component that mainly captures degeneration of the cortical grey matter that strongly correlates with age. A multimodal correlation analysis indicates that increased brain atrophy and lesion load is accompanied by increased spectral power in the lower alpha (8-10 Hz) in the temporoparietal junction (TPJ). Increased lower alpha power in the TPJ was further associated with worse results on verbal and spatial working memory tests, whereas an increased lower/upper alpha power ratio was associated with slower information processing speed. In conclusion, multiple sclerosis patients with increased brain atrophy, lesion and thalamic volumes demonstrated increased lower alpha power in the TPJ and reduced cognitive abilities.

PMID:33770549 | DOI:10.1016/j.nicl.2021.102632

Brainstem functional oscillations across the migraine cycle: A longitudinal investigation

Fri, 03/26/2021 - 10:00

Neuroimage Clin. 2021 Mar 17;30:102630. doi: 10.1016/j.nicl.2021.102630. Online ahead of print.


Although the mechanisms responsible for migraine initiation remain unknown, recent evidence shows that brain function is different immediately preceding a migraine. This is consistent with the idea that altered brain function, particularly in brainstem sites, may either trigger a migraine or facilitate a peripheral trigger that activates the brain, resulting in pain. The aim of this longitudinal study is therefore to expand on the above findings, and to determine if brainstem function oscillates over a migraine cycle in individual subjects. We performed resting state functional magnetic resonance imaging in three migraineurs and five controls each weekday for four weeks. We found that although resting activity variability was similar in controls and interictal migraineurs, brainstem variability increased dramatically during the 24-hour period preceding a migraine. This increase occurred in brainstem areas in which orofacial afferents terminate: the spinal trigeminal nucleus and dorsal pons. These increases were characterized by increased power at infra-slow frequencies, principally between 0.03 and 0.06 Hz. Furthermore, these power increases were associated with increased regional homogeneity, a measure of local signal coherence. The results show within-individual alterations in brain activity immediately preceding migraine onset and support the hypothesis that altered regional brainstem function before a migraine attack is involved in underlying migraine neurobiology.

PMID:33770547 | DOI:10.1016/j.nicl.2021.102630

Differential functional connectivity of insular subdivisions in de novo Parkinson's disease with mild cognitive impairment

Fri, 03/26/2021 - 10:00

Brain Imaging Behav. 2021 Mar 26. doi: 10.1007/s11682-021-00471-2. Online ahead of print.


The insula, consisting of functionally diverse subdivisions, plays a significant role in Parkinson's disease (PD)-related cognitive disorders. However, the functional connectivity (FC) patterns of insular subdivisions in PD remain unclear. Our aim is to investigate the changes in FC patterns of insular subdivisions and their relationships with cognitive domains. Three groups of participants were recruited in this study, including PD patients with mild cognitive impairment (PD-MCI, n = 25), PD patients with normal cognition (PD-NC, n = 13), and healthy controls (HCs, n = 17). Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the FC in insular subdivisions of the three groups. Moreover, all participants underwent a neuropsychological battery to assess cognition so that the relationship between altered FC and cognitive performance could be elucidated. Compared with the PD-NC group, the PD-MCI group exhibited increased FC between the left dorsal anterior insular (dAI) and the right superior parietal gyrus (SPG), and altered FC was negatively correlated with memory and executive function. Compared with the HC group, the PD-MCI group showed significantly increased FC between the right dAI and the right median cingulate and paracingulate gyri (DCG), and altered FC was positively related to attention/working memory, visuospatial function, and language. Our findings highlighted the different abnormal FC patterns of insular subdivisions in PD patients with different cognitive abilities. Furthermore, dysfunction of the dAI may partly contribute to the decline in executive function and memory in early drug-naïve PD patients.

PMID:33770371 | DOI:10.1007/s11682-021-00471-2

Abnormalities of intrinsic brain activity in essential tremor: A meta-analysis of resting-state functional imaging

Fri, 03/26/2021 - 10:00

Hum Brain Mapp. 2021 Mar 26. doi: 10.1002/hbm.25425. Online ahead of print.


Neuroimaging studies using a variety of techniques have demonstrated abnormal patterns of spontaneous brain activity in patients with essential tremor (ET). However, the findings are variable and inconsistent, hindering understanding of underlying neuropathology. We conducted a meta-analysis of whole-brain resting-state functional neuroimaging studies in ET compared to healthy controls (HC), using anisotropic effect-size seed-based d mapping, to identify the most consistent brain activity alterations and their relation to clinical features. After systematic literature search, we included 13 studies reporting 14 comparisons, describing 286 ET patients and 254 HC. Subgroup analyses were conducted considering medication status, head tremor status, and methodological factors. Brain activity in ET is altered not only in the cerebellum and cerebral motor cortex, but also in nonmotor cortical regions including prefrontal cortex and insula. Most of the results remained unchanged in subgroup analyses of patients with head tremor, medication-naive patients, studies with statistical threshold correction, and the large subgroup of studies using functional magnetic resonance imaging. These findings not only show consistent and robust abnormalities in specific brain regions but also provide new information on the biology of patient heterogeneity, and thus help to elucidate the pathophysiology of ET.

PMID:33769638 | DOI:10.1002/hbm.25425

Somatosensory network functional connectivity differentiates clinical pain phenotypes in diabetic neuropathy

Fri, 03/26/2021 - 10:00

Diabetologia. 2021 Mar 25. doi: 10.1007/s00125-021-05416-4. Online ahead of print.


AIMS/HYPOTHESIS: The aim of this work was to investigate whether different clinical pain phenotypes of diabetic polyneuropathy (DPN) are distinguished by functional connectivity at rest.

METHODS: This was an observational, cohort study of 43 individuals with painful DPN, divided into irritable (IR, n = 10) and non-irritable (NIR, n = 33) nociceptor phenotypes using the German Research Network of Neuropathic Pain quantitative sensory testing protocol. In-situ brain MRI included 3D T1-weighted anatomical and 6 min resting-state functional MRI scans. Subgroup differences in resting-state functional connectivity in brain regions involved with somatic (thalamus, primary somatosensory cortex, motor cortex) and non-somatic (insular and anterior cingulate cortices) pain processing were examined. Multidimensional reduction of MRI datasets was performed using a machine-learning approach to classify individuals into each clinical pain phenotype.

RESULTS: Individuals with the IR nociceptor phenotype had significantly greater thalamic-insular cortex (p false discovery rate [FDR] = 0.03) and reduced thalamus-somatosensory cortex functional connectivity (p-FDR = 0.03). We observed a double dissociation such that self-reported neuropathic pain score was more associated with greater thalamus-insular cortex functional connectivity (r = 0.41; p = 0.01) whereas more severe nerve function deficits were more related to lower thalamus-somatosensory cortex functional connectivity (r = -0.35; p = 0.03). Machine-learning group classification performance to identify individuals with the NIR nociceptor phenotype achieved an accuracy of 0.92 (95% CI 0.08) and sensitivity of 90%.

CONCLUSIONS/INTERPRETATION: This study demonstrates differences in functional connectivity in nociceptive processing brain regions between IR and NIR phenotypes in painful DPN. We also establish proof of concept for the utility of multimodal MRI as a biomarker for painful DPN by using a machine-learning approach to classify individuals into sensory phenotypes.

PMID:33768284 | DOI:10.1007/s00125-021-05416-4

Cultivating Affective Resilience: Proof-of-Principle Evidence of Translational Benefits From a Novel Cognitive-Emotional Training Intervention

Fri, 03/26/2021 - 10:00

Front Psychol. 2021 Mar 9;12:585536. doi: 10.3389/fpsyg.2021.585536. eCollection 2021.


Available evidence highlights the importance of emotion regulation (ER) in psychological well-being. However, translation of the beneficial effects of ER from laboratory to real-life remains scarce. Here, we present proof-of-principle evidence from a novel cognitive-emotional training intervention targeting the development of ER skills aimed at increasing resilience against emotional distress. This pilot intervention involved training military veterans over 5-8 weeks in applying two effective ER strategies [Focused Attention (FA) and Cognitive Reappraisal (CR)] to scenarios presenting emotional conflicts (constructed with both external and internal cues). Training was preceded and followed by neuropsychological, personality, and clinical assessments, and resting-state functional MRI data were also collected from a subsample of the participants. Results show enhanced executive function and psychological well-being following training, reflected in increased working memory (WM), post-traumatic growth (PTG), and general self-efficacy (GSE). Brain imaging results showed evidence of diminished bottom-up influences from emotional and perceptual brain regions, along with evidence of normalized functional connectivity in the large-scale functional networks following training. The latter was reflected in increased connectivity among cognitive and emotion control regions and across regions of self-referential and control networks. Overall, our results provide proof-of-concept evidence that resilience and well-being can be learned through ER training, and that training-related improvements manifested in both behavioral change and neuroplasticity can translate into real-life benefits.

PMID:33767643 | PMC:PMC7985085 | DOI:10.3389/fpsyg.2021.585536