Neurovascular coupling alteration in drug-naïve Parkinson's disease: The underlying molecular mechanisms and levodopa's restoration effects.

BACKGROUND: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. MATERIAL AND METHODS: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. RESULTS: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications. CONCLUSION: Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.

Impact of Electric Field Magnitude in the Left Dorsolateral Prefrontal Cortex on Changes in Intrinsic Functional Connectivity Using Transcranial Direct Current Stimulation: A Randomized Crossover Study.

This study investigated whether the electric field magnitude (E-field) delivered to the left dorsolateral prefrontal cortex (L-DLPFC) changes resting-state brain activity and the L-DLPFC resting-state functional connectivity (rsFC), given the variability in tDCS response and lack of understanding of how rsFC changes. Twenty-one healthy participants received either 2 mA anodal or sham tDCS targeting the L-DLPFC for 10 min. Brain imaging was conducted before and after stimulation. The fractional amplitude of low-frequency fluctuation (fALFF), reflecting resting brain activity, and the L-DLPFC rsFC were analyzed to investigate the main effect of tDCS, main effect of time, and interaction effects. The E-field was estimated by modeling tDCS-induced individual electric fields and correlated with fALFF and L-DLPFC rsFC. Anodal tDCS increased fALFF in the left rostral middle frontal area and decreased fALFF in the midline frontal area (FWE p < 0.050), whereas sham induced no changes. Overall rsFC decreased after sham (positive and negative connectivity, p = 0.001 and 0.020, respectively), with modest and nonsignificant changes after anodal tDCS (p = 0.063 and 0.069, respectively). No significant differences in local rsFC were observed among the conditions. Correlations were observed between the E-field and rsFC changes in the L-DLPFC (r = 0.385, p = 0.115), left inferior parietal area (r = 0.495, p = 0.037), and right lateral visual area (r = 0.683, p = 0.002). Single-session tDCS induced resting brain activity changes and may help maintain overall rsFC. The E-field in the L-DLPFC is associated with rsFC changes in both proximal and distally connected brain regions to the L-DLPFC.

Disturbed Dynamic Brain Activity and Neurovascular Coupling in End-Stage Renal Disease Assessed With MRI.

BACKGROUND: Pathophysiological mechanisms underlying cognitive impairment in end-stage renal disease (ESRD) remain unclear, with limited studies on the temporal variability of neural activity and its coupling with regional perfusion. PURPOSE: To assess neural activity and neurovascular coupling (NVC) in ESRD patients, evaluate the classification performance of these abnormalities, and explore their relationships with cognitive function. STUDY TYPE: Prospective. POPULATION: Exactly 33 ESRD patients and 35 age, sex, and education matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: The 3.0T/3D pseudo-continuous arterial spin labeling, resting-state functional MRI, and 3D-T1 weighted structural imaging. ASSESSMENT: Dynamic (dfALFF) and static (sfALFF) fractional amplitude of low-frequency fluctuations and cerebral blood flow (CBF) were assessed. CBF-fALFF correlation coefficients and CBF/fALFF ratio were determined for ESRD patients and HCs. Their ability to distinguish ESRD patients from HCs was evaluated, alongside assessment of cerebral small vessel disease (CSVD) MRI features. All participants underwent blood biochemical and neuropsychological tests to evaluate cognitive decline. STATISTICAL TESTS: Chi-squared test, two-sample t-test, Mann-Whitney U tests, covariance analysis, partial correlation analysis, family-wise error, false discovery rate, Bonferroni correction, area under the receiver operating characteristic curve (AUC) and multivariate pattern analysis. P < 0.05 denoted statistical significance. RESULTS: ESRD patients exhibited higher dfALFF in triangular part of left inferior frontal gyrus (IFGtriang) and left middle temporal gyrus, lower CBF/dfALFF ratio in multiple brain regions, and decreased CBF/sfALFF ratio in bilateral superior temporal gyrus (STG). Compared with CBF/sfALFF ratio, dfALFF, and sfALFF, CBF/dfALFF ratio (AUC = 0.916) achieved the most powerful classification performance in distinguishing ESRD patients from HCs. In ESRD patients, decreased CBF/fALFF ratio correlated with more severe renal impairment, increased CSVD burden, and cognitive decline (0.4 < |r| < 0.6). DATA CONCLUSION: ESRD patients exhibited abnormal dynamic brain activity and impaired NVC, with dynamic features demonstrating superior discriminative capacity and CBF/dfALFF ratio showing powerful classification performance. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Structure-function interrelationships and associated neurotransmitter profiles in drug-naïve benign childhood epilepsy with central-temporal spikes patients.

OBJECTIVES: To explore the interrelationships between structural and functional changes as well as the potential neurotransmitter profile alterations in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients. METHODS: Structural magnetic resonance imaging (sMRI) and resting-state functional MRI data from 20 drug-naïve BECTS patients and 33 healthy controls (HCs) were acquired. Parallel independent component analysis (P-ICA) was used to identify covarying components among gray matter volume (GMV) maps and fractional amplitude of low-frequency fluctuations (fALFF) maps. Furthermore, we explored the spatial correlations between GMV/fALFF changes derived from P-ICA and neurotransmitter maps in JuSpace toolbox. RESULTS: A significantly positive correlation (p < 0.001) was identified between one structural component (GMV_IC6) and one functional component (fALFF_IC4), which showed significant group differences between drug-naïve BECTS patients and HCs (GMV_IC6: p < 0.01; fALFF_IC4: p < 0.001). GMV_IC6 showed increased GMV in the frontal lobe, temporal lobe, thalamus, and precentral gyrus as well as fALFF_IC4 had enhanced fALFF in the cerebellum in drug-naïve BECTS patients compared to HCs. Moreover, significant correlations between GMV alterations in GMV_IC6 and the serotonin (5HT1a: p < 0.001; 5HT2a: p < 0.001), norepinephrine (NAT: p < 0.001) and glutamate systems (mGluR5: p < 0.001) as well as between fALFF alterations in fALFF_IC4 and the norepinephrine system (NAT: p < 0.001) were detected. CONCLUSION: The current findings suggest co-altered structural/functional components that reflect the correlation of language and motor networks as well as associated with the serotonergic, noradrenergic, and glutamatergic neurotransmitter systems. CLINICAL RELEVANCE STATEMENT: The relationship between anatomical brain structure and intrinsic neural activity was evaluated using a multimodal fusion analysis and neurotransmitters which might provide an important window into the multimodal neural and underlying molecular mechanisms of benign childhood epilepsy with central-temporal spikes. KEY POINTS: Structure-function relationships in drug-naïve benign childhood epilepsy with central-temporal spikes (BECTS) patients were explored. The interrelated structure-function components were found and correlated with the serotonin, norepinephrine, and glutamate systems. Co-altered structural/functional components reflect the correlation of language and motor networks and correlate with the specific neurotransmitter systems.

Abnormalities of regional spontaneous brain activity in poststroke aphasia: a meta-analysis.

Poststroke aphasia is an acquired language disorder and has been proven to have adverse effects on patients' social skills and quality of life. However, there are some inconsistencies in the neuroimaging studies investigating poststroke aphasia from the perspective of regional alterations. A meta-analysis has been employed to examine the common pattern of abnormal regional spontaneous brain activity in poststroke aphasia in the current study. Specifically, the Anisotropic effect-size version of seed-based d mapping was utilized, and 237 poststroke aphasia patients and 242 healthy controls (HCs) from 12 resting-state functional magnetic resonance imaging studies using amplitude of low-frequency fluctuations (ALFF), fractional ALFF, or regional homogeneity were included. The results showed that compared with HCs, patients with poststroke aphasia demonstrated increased regional spontaneous brain activity in the right insula, right postcentral gyrus, left cerebellar lobule IX, left angular gyrus, right caudate nucleus, left parahippocampal gyrus, and right supplementary motor area, and decreased regional spontaneous brain activity in the left cerebellar lobule VI, left median cingulate and paracingulate gyri, right cerebellar crus I, and left supplementary motor area. The study could provide further evidence for pathophysiological mechanism of poststroke aphasia and help find targets for treatment.

Decreased dynamic variability of the cerebellum in the euthymic patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a complex mental illness characterized by different mood states, including depression, mania/hypomania, and euthymia. This study aimed to comprehensively evaluate dynamic changes in intrinsic brain activity by using dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic degree centrality (dDC) in patients with BD euthymia or depression and healthy individuals. METHODS: The resting-state functional magnetic resonance imaging data were analyzed from 37 euthymic and 28 depressed patients with BD, as well as 85 healthy individuals. Using the sliding-window method, the dfALFF and dDC were calculated for each participant. These values were compared between the 3 groups using one-way analysis of variance (ANOVA). Additional analyses were conducted using different window lengths, step width, and window type to ensure the reliability of the results. RESULTS: The euthymic group showed significantly lower dfALFF and dDC values of the left and right cerebellum posterior lobe compared with the depressed and control groups (cluster level PFWE < 0.05), while the latter two groups were comparable. Brain regions showing significant group differences in the dfALFF analysis overlapped with those with significant differences in the dDC analysis. These results were consistent across different window lengths, step width, and window type. CONCLUSIONS: These findings suggested that patients with euthymic BD exhibit less flexibility of temporal functional activities in the cerebellum posterior lobes compared to either depressed patients or healthy individuals. These results could contribute to the development of neuropathological models of BD, ultimately leading to improved diagnosis and treatment of this complex illness.

Differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognitive function between untreated major depressive disorder and schizophrenia with depressive mood patients.

BACKGROUND: Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. METHODS: The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. RESULTS: Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. CONCLUSIONS: Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Resting-State Brain Function Alteration in Colorectal Cancer Patients.

BACKGROUND AND PURPOSE: To investigate the abnormal pattern of altered functional activity in the brain and the neuroimaging mechanisms underlying the cognitive impairment of patients with colorectal cancer (CRC) via resting-state functional magnetic resonance imaging (rs-fMRI). MATERIALS AND METHODS: CRC patients (n = 56) and healthy controls (HCs) (n = 50) were studied. The participants underwent rs-fMRI scans and the Montreal Cognitive Assessment (MoCA). The amplitude of low-frequency fluctuations (ALFF), degree centrality (DC), regional homogeneity (ReHo), and MoCA scores, were calculated for participants. RESULTS: The scores of executives, visuospatial, memory, language and attention were lower in CRC patients. ReHo and ALFF values in the left postcentral gyrus, ReHo values in the right postcentral gyrus, ALFF and DC values in the left middle occipital gyrus, ReHo and DC values in the right lingual gyrus, DC values in the right angular gyrus and precuneus, and ALFF values in the left middle temporal gyrus decreased conspicuously in the CRC patients. CONCLUSION: CRC patients have abnormal resting state function, mainly in the brain areas involved in cognitive function. The overlapping brain regions with abnormal functional indicators are in the middle occipital gyrus, postcentral gyrus, and lingual gyrus. This study reveals the potential biological pathways involved in brain impairment and neurocognitive decline in patients with CRC.

Differences in Functional Activity and Connectivity in the Right Frontoparietal Network between Nurses Working Long-Term Shifts and Fixed Day Shifts.

OBJECTIVES: To investigate the differences in functional brain activity and connectivity between nurses working long-term shifts and fixed day shift and explore their correlations with work-related psychological conditions. METHODS: Thirty-five nurses working long-term shifts and 35 nurses working fixed day shifts were recruited. After assessing work-related psychological conditions, such as burnout and perceived stress of these two groups of nurses, amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) analyses were performed to investigate the between-group differences in brain functional activity and connectivity. Furthermore, correlation analysis between the ALFF/FC metrics and psychological conditions was conducted. RESULTS: Compared with nurses working fixed day shifts, nurses working long-term shifts showed higher levels of burnout, perceived stress, and depression scores; lower z-transformed ALFF (zALFF) values in the right dorsolateral prefrontal cortex (dlPFC), right superior parietal lobule (SPL), and right anterior cingulate cortex (ACC); and higher zALFF values in the right middle temporal gyrus (voxel-level p < 0.001, cluster-level p < 0.05, gaussian random field (GRF) correction), as well as lower FC values in the right dlPFC-right SPL and right dlPFC-right ACC (p < 0.05, false discovery rate (FDR) corrected). Moreover, the FC values in the right dlPFC-right SPL were negatively correlated with the perceived stress score in nurses working long-term shifts (p < 0.05, FDR corrected). CONCLUSIONS: This study demonstrated that nurses working long-term shifts had lower functional activity and weaker functional connectivity in the right frontoparietal network, which mainly includes the right dlPFC and right SPL, than those working on regular day shift. The current findings provide new insights into the impacts of long-term shift work on nurses' mental health from a functional neuroimaging perspective.

Alteration of prefrontal cortex and its associations with emotional and cognitive dysfunctions in adolescent borderline personality disorder.

The neurobiological mechanism of borderline personality disorder (BPD) in adolescents remains unclear. The study aimed to assess the alterations in neural activity within prefrontal cortex in adolescents with BPD and investigate the relationship of prefrontal activity with emotional regulation and cognitive function. This study enrolled 50 adolescents aged 12-17 years with BPD and 21 gender and age-matched healthy control (HC) participants. Study assessment for each participant included a brain resting-state functional MRI (rs-fMRI), clinical assessment questionnaires such as Borderline Personality Features Scale (BPFS), Difficulties in Emotion Regulation Scale (DERS), Ottawa Self-Injury Inventory and Childhood Trauma Questionnaire (CTQ) and cognitive testing with Stroop Color-Word Test (SCWT). Fractional amplitude of low-frequency fluctuations (fALFF) and seed-based functional connectivity (FC) were obtained from rs-fMRI analysis. Correlation analysis was also performed to evaluate the associations of the neuroimaging metrics such as fALFF and FC with clinical assessment questionnaire and cognitive testing scores. Adolescents with BPD showed increased fALFF values in the right inferior frontal gyrus and decreased activity in the left middle frontal gyrus as compared to the HC group (p < 0.05, cluster size ≥ 100, FWE correction). In adolescents with BPD, increased fALFF in the right inferior frontal gyrus was related to the BPFS (emotional dysregulation), DERS-F (lacking of emotional regulation strategies) and Ottawa Self-Injury Inventory-4 C scores (internal emotional regulation function of self-injurious behavior). The reduced fALFF in the left middle frontal gyrus was associated with the SCWT-A (reading characters) and the SCWT-B (reading color) scores. Additionally, the fALFF values in the left middle frontal gyrus and the right inferior frontal gyrus were related to the CTQ-D (emotional neglect) (p < 0.05). The left middle frontal gyrus exhibited increased FC with the right hippocampus, left inferior temporal gyrus and right inferior frontal gyrus (voxel p < 0.001, cluster p < 0.05, FWE correction). The increased FC between the left middle frontal gyrus and the right hippocampus was related to the SCWT-C (cognitive flexibility) score. We observed diverging changes in intrinsic brain activity in prefrontal cortex, and neural compensatory changes to maintain function in adolescents with BPD. In addition, decreased neural function was closely associated with emotional dysregulation, while increased neural function as indicated by brain activity and FC was associated with cognitive dysfunction. These results indicated that alterations of intrinsic brain activity may be one of the underlying neurobiological markers for clinical symptoms in adolescents with BPD.

Indirect evidence for altered dopaminergic neurotransmission in very premature-born adults.

While animal models indicate altered brain dopaminergic neurotransmission after premature birth, corresponding evidence in humans is scarce due to missing molecular imaging studies. To overcome this limitation, we studied dopaminergic neurotransmission changes in human prematurity indirectly by evaluating the spatial co-localization of regional alterations in blood oxygenation fluctuations with the distribution of adult dopaminergic neurotransmission. The study cohort comprised 99 very premature-born (<32 weeks of gestation and/or birth weight below 1500 g) and 107 full-term born young adults, being assessed by resting-state functional MRI (rs-fMRI) and IQ testing. Normative molecular imaging dopamine neurotransmission maps were derived from independent healthy control groups. We computed the co-localization of local (rs-fMRI) activity alterations in premature-born adults with respect to term-born individuals to different measures of dopaminergic neurotransmission. We performed selectivity analyses regarding other neuromodulatory systems and MRI measures. In addition, we tested if the strength of the co-localization is related to perinatal measures and IQ. We found selectively altered co-localization of rs-fMRI activity in the premature-born cohort with dopamine-2/3-receptor availability in premature-born adults. Alterations were specific for the dopaminergic system but not for the used MRI measure. The strength of the co-localization was negatively correlated with IQ. In line with animal studies, our findings support the notion of altered dopaminergic neurotransmission in prematurity which is associated with cognitive performance.

Regional abnormalities of spontaneous brain activity in migraine: A coordinate-based meta-analysis.

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have explored abnormal regional spontaneous brain activity in migraine. However, these results are inconsistent. To identify the consistent regions with abnormal neural activity, we meta-analyzed these studies. We gathered whole-brain rs-fMRI studies measuring differences in the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), or regional homogeneity (ReHo) methods. Then, we performed a voxel-wise meta-analysis to identify consistent abnormal neural activity in migraine by anisotropic effect size seed-based d mapping (AES-SDM). To confirm the AES-SDM meta-analysis results, we conducted two meta-analyses: activation likelihood estimation (ALE) and multi-level kernel density analysis (MKDA). We found that migraine showed increased regional neural activities in the bilateral postcentral gyrus (PoCG), left hippocampus (HIP.L), right pons, left superior frontal gyrus (SFG.L), triangular part of right inferior frontal gyrus (IFGtriang.R), right middle frontal gyrus (MFG.R), and left precentral gyrus (PreCG.L) and decreased regional intrinsic brain activities were exhibited in the right angular gyrus (ANG.R), left superior occipital gyrus (SOG.L), right lingual gyrus (LING.R). Moreover, the meta-analysis of ALE further validated the abnormal neural activities in the PoCG, right pons, ANG.R, and HIP. Meta-regression demonstrated that headache intensity was positively associated with the abnormal activities in the HIP.L, ANG.R, and LING.R. These findings suggest that migraine is associated with abnormal spontaneous brain activities of some pain-related regions, which may contribute to a deeper understanding of the neural mechanism of migraine.

Effects of electroacupuncture on imaging and behavior in rats with ischemic stroke through miR-212-5p.

BACKGROUND: Ischemic stroke is a serious disease leading to significant disability in humans worldwide. Increasing evidence suggests that some microRNAs (miRNAs) participate in the pathophysiology of ischemic stroke. A key role for MiR-212 has been found in neuronal function and synaptic plasticity. Ischemic stroke can be effectively treated with electroacupuncture (EA); however, there is a lack of understanding of the relevant mechanisms. In this study, we employed behavioral test and resting-state functional magnetic resonance imaging (rs-fMRI) to detect behavioral and brain function alterations in rats suffering from ischemic stroke. The efficacy of EA therapy and miR-212-5p's role in this process were also evaluated. METHODS AND RESULTS: Forty rats were randomly divided into the following groups: Sham, middle cerebral artery occlusion/reperfusion (MCAO/R), MCAO/R + EA, MCAO/R + EA + antagomir-negative control and MCAO/R + EA + antagomir-212-5p groups. Behavioral changes were assessed by Catwalk gait analysis prior to and after modeling. Rs-fMRI was performed at one week after EA treatment, amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated to reveal neural activity. Furthermore, neuronal apoptosis in the ischemic penumbra was analyzed using a TUNEL assay. Treatment with EA significantly improved the performance of rats in the behavioral test. The motor and cognition-related brain regions showed decreased ALFF and ReHo following focal cerebral ischemia-reperfusion, and EA treatment could reactivate these brain regions. Moreover, EA treatment significantly decreased MCAO/R-induced cell death. However, the transfection of antagomir-212-5p attenuated the therapeutic effect of EA. CONCLUSIONS: In conclusion, the results suggested that EA improved the behavioral and imaging outcomes of ischemic stroke through miR-212-5p.

Altered local spontaneous brain activity pattern in children with right-eye amblyopia of varying degrees: evidence from fMRI.

PURPOSE: To investigate the abnormal changes of local brain activity in children with right-eye amblyopia of varying degrees. METHODS: Data of resting-state functional magnetic resonance imaging were collected from 16 children with severe amblyopia, 17 children with mild to moderate amblyopia, and 15 children with normal binocular vision. Local brain activity was analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). RESULTS: There were extensive ALFF differences among the three groups in 10 brain regions. There were extensive differences in ReHo among the three groups in 11 brain regions. The ALFF and ReHo of the right orbital part of the middle frontal gyrus displayed a significantly positive correlation with the best-corrected visual acuity of the right eye, respectively. The ALFF value and ReHo value of the right orbital part of the middle frontal gyrus followed the pattern of normal control < mild to moderate amblyopia < severe amblyopia. CONCLUSION: This study demonstrated that there were changes in specific patterns of ALFF and ReHo in children with right-eye amblyopia of different degrees in brain regions performing visual sensorimotor and attentional control functions.

Altered time-varying local spontaneous brain activity pattern in patients with high myopia: a dynamic amplitude of low-frequency fluctuations study.

PURPOSE: To investigate the abnormal time-varying local spontaneous brain activity in patients with high myopia (HM) on the basis of the dynamic amplitude of low-frequency fluctuations (dALFF) approach. METHODS: Age and gender matching were performed based on resting-state functional magnetic resonance imaging data from 86 HM patients and 87 healthy controls (HCs). Local spontaneous brain activities were evaluated using the time-varying dALFF method. Support vector machine combined with the radial basis function kernel was used for pattern classification analysis. RESULTS: Inter-group comparison between HCs and HM patients has demonstrated that dALFF variability in the left inferior frontal gyrus (orbital part), left lingual gyrus, right anterior cingulate and paracingulate gyri, and right calcarine fissure and surrounding cortex was decreased in HM patients, while increased in the left thalamus, left paracentral lobule, and left inferior parietal (except supramarginal and angular gyri). Pattern classification between HM patients and HCs displayed a classification accuracy of 85.5%. CONCLUSION: In this study, the findings mentioned above have suggested the association between local brain activities of HM patients and abnormal variability in brain regions performing visual sensorimotor and attentional control functions. Several useful information has been provided to elucidate the mechanism-related alterations of the myopic nervous system. In addition, the significant role of abnormal dALFF variability has been highlighted to achieve an in-depth comprehension of the pathological alterations and neuroimaging mechanisms in the field of HM.

From Molecular to Behavior: Higher Order Occipital Cortex in Major Depressive Disorder.

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.

Frontopolar tDCS Induces Frequency-Dependent Changes of Spontaneous Low-Frequency Fluctuations: A Resting-State fMRI Study.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that can modulate cortical excitability and behavioral performance. However, its effects on spontaneous low-frequency fluctuations of brain activity are still poorly understood. Here, we systematically investigated the frontopolar tDCS effects on resting-state brain activity and connectivity. Twelve healthy participants were recruited and received anode, cathode, and sham stimulation in a randomized order. Resting-state functional magnetic resonance imaging was performed before and after stimulation. Functional connectivity was calculated to examine tDCS effects within and beyond the frontopolar network. To assess the frequency-dependent changes of brain activity, fractional amplitude of low-frequency fluctuations (fALFF) was computed in the slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands. The results showed anodal tDCS-induced widespread connectivity reduction within and beyond the frontopolar network. Regardless of tDCS polarity, stimulation effect on fALFF was significantly larger in slow-5 band compared with the slow-4. Notably, anodal tDCS-induced connectivity changes were associated with pre-tDCS fALFF in slow-4 band, showing positive correlations in the frontal regions and negative correlations in the temporal regions. Our findings imply that tDCS-induced brain alterations may be frequency-dependent, and pre-tDCS regional brain activity could be used to predict post-tDCS connectivity changes.

Frequency-dependent genetic modulation of neuronal oscillations: a combined transcriptome and resting-state functional MRI study.

Neuronal oscillations within certain frequency bands are assumed to associate with specific neural processes and cognitive functions. To examine this hypothesis, transcriptome-neuroimaging spatial correlation analysis was applied to resting-state functional magnetic resonance imaging data from 793 healthy individuals and gene expression data from the Allen Human Brain Atlas. We found that expression measures of 336 genes were correlated with fractional amplitude of low-frequency fluctuations (fALFF) in the slow-4 band (0.027-0.073 Hz), whereas there were no expression-fALFF correlations for the other frequency bands. Furthermore, functional enrichment analyses showed that these slow-4 fALFF-related genes were mainly enriched for ion channel, synaptic function, and neuronal system as well as many neuropsychiatric disorders. Specific expression analyses demonstrated that these genes were specifically expressed in brain tissue, in neurons, and during the late stage of cortical development. Concurrently, the fALFF-related genes were linked to multiple behavioral domains, including dementia, attention, and emotion. In addition, these genes could construct a protein-protein interaction network supported by 30 hub genes. Our findings of a frequency-dependent genetic modulation of spontaneous neuronal activity may support the concept that neuronal oscillations within different frequency bands capture distinct neurobiological processes from the perspective of underlying molecular mechanisms.

[Frequency-Specific Alterations of Spontaneous Brain Activity in First-Episode Drug-Naïve Schizophrenia].

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.

Different sensorimotor mechanism in fast and slow progression amyotrophic lateral sclerosis.

The huge heterogeneity of the disease progression rate may cause inconsistent findings between local activity and functional connectivity of the primary sensorimotor area (PSMA) in amyotrophic lateral sclerosis (ALS). For illustration of this hypothesis, resting-state fMRI (RS-fMRI) data were collected and analyzed on 38 "definite" or "probable" ALS patients (19 fast and 19 slow, cut off median = 0.41) and 37 matched healthy controls. Amplitude of low frequency fluctuations (ALFFs) and functional connectivity strength (FCS) were analyzed within the PSMA. There was a decreased ALFF (pFDR <.05) and FCS (p = .022) in all ALS patients. The two metrics shared about 50% of variance (R = .7) and both showed significant positive correlation with ALS Functional Rating Scale-Revised (ALSFRS-R) in the fast (p values <.034) but not in the slow progression groups. Interestingly, when regressing out the ALFF, the PSMA network FCS, especially the inter-hemisphere FCS, showed negative correlation with the ALSFRS-R score in the slow (R = -.54, p = .026) but not the fast progression group. In summary, the current results suggest that RS-fMRI local activity and network functional connectivity accounts for the severity differently in the slow and fast progression ALS patients.