Resting-state Function Research Articles

Impact of network-targeted multichannel transcranial direct current stimulation on intrinsic and network-to-network functional connectivity.

Dynamics within and between functional resting-state networks have a crucial role in determining both healthy and pathological brain functioning in humans. The possibility to noninvasively interact and selectively modulate the activity of networks would open to relevant applications in neuroscience. Here we tested a novel approach for multichannel, network-targeted transcranial direct current stimulation (net-tDCS), optimized to increase excitability of the sensorimotor network (SMN) while inducing cathodal inhibitory modulation over prefrontal and parietal brain regions negatively correlated with the SMN. Using an MRI-compatible multichannel transcranial electrical stimulation (tES) device, 20 healthy participants underwent real and sham tDCS while at rest in the MRI scanner. Changes in functional connectivity (FC) during and after stimulation were evaluated, looking at the intrinsic FC of the SMN and the strength of the negative connectivity between SMN and the rest of the brain. Standard, bifocal tDCS targeting left motor cortex (electrode ~C3) and right frontopolar (~Fp2) regions was tested as a control condition in a separate sample of healthy subjects to investigate network specificity of multichannel stimulation effects. Net-tDCS induced greater FC increase over the SMN compared to bifocal tDCS, during and after stimulation. Moreover, exploratory analysis of the impact of net-tDCS on negatively correlated networks showed an increase in the negative connectivity between SMN and prefrontal/parietal areas targeted by cathodal stimulation both during and after real net-tDCS. Results suggest preliminary evidence of the possibility of manipulating distributed network connectivity patterns through net-tDCS, with potential relevance for the development of cognitive enhancement and therapeutic tES solutions.

Intra and inter: Alterations in functional brain resting-state networks after peripheral nerve injury.

IntroductionNumerous treatments suggest that brain plasticity changes after peripheral nerve injury (PNI), and most studies examining functional magnetic resonance imaging focused on abnormal changes in specific brain regions. However, it is the large‐scale interaction of neuronal networks instead of isolated brain regions contributed to the functional recovery after PNI. In the present study, we examined the intra‐ and internetworks alterations between the related functional resting‐state networks (RSNs) in a sciatic nerve injury rat model.MethodsNinety‐six female rats were divided into a control and model group. Unilateral sciatic nerve transection and direct anastomosis were performed in the latter group. We used an independent component analysis (ICA) algorithm to observe the changes in RSNs and assessed functional connectivity between different networks using the functional networks connectivity (FNC) toolbox.ResultsSix RSNs related to PNI were identified, including the basal ganglia network (BGN), sensorimotor network (SMN), salience network (SN), interoceptive network (IN), cerebellar network (CN), and default mode network (DMN). The model group showed significant changes in whole‐brain FC changes within these resting‐state networks (RSNs), but four of these RSNs exhibited a conspicuous decrease. The interalterations performed that significantly decreased FNC existed between the BGN and SMN, BGN and IN, and BGN and DMN (p < .05, corrected). A significant increase in FNC existed between DMN and CN and between CN and SN (p < .05, corrected).ConclusionThe results showed the large‐scale functional reorganization at the network level after PNI. This evidence reveals new implications to the pathophysiological mechanisms in brain plasticity of PNI.

Associations of Air Pollution and Noise with Local Brain Structure in a Cohort of Older Adults.

Background:Despite the importance of understanding associations of air pollution and noise exposure with loss of neurocognitive performance, studies investigating these exposures and local brain structure are limited.Objective:We estimated associations of residential air pollution and noise exposures with neurocognitive test performance and the local gyrification index (lGI), a marker for local brain atrophy, among older adults.Methods:For participants from the population-based 1000BRAINS study, based on the German Heinz Nixdorf Recall study, we assessed residential exposures to particulate matter (, , ), accumulation mode particle number (), and nitrogen oxides (, ), using land-use regression and chemistry transport models. Weighted 24-h and nighttime noise were modeled according to the European noise directive. We evaluated associations of air pollution and noise exposure at the participants’ 2006–2008 residential addresses with neurocognitive test performance and region-specific lGI values () from magnetic resonance imaging, both assessed in 2011–2015, using linear regression and adjusting for demographic and personal characteristics.Results:Air pollution and noise were associated with language and short-term/working memory and with local atrophy of the fronto–parietal network (FPN), a functional resting-state network associated with these cognitive processes. For example, per , local brain atrophy was more pronounced in the posterior brain regions of the FPN, with a [95% confidence interval (CI): , 0.00] lower lGI. In contrast, in the anterior regions of the FPN, weighted 24-h and nighttime noise were associated with less local brain atrophy [e.g., 0.02 (95% CI: 0.00, 0.04) for (A) 24-h noise].Conclusions:Air pollution and noise exposures were associated in opposite directions with markers of local atrophy of the FPN in the right brain hemisphere in older adults, suggesting that both chronic air pollution and noise exposure may influence the physiological aging process of the brain. https://doi.org/10.1289/EHP5859

Functional Resting-State Connectivity Changes After Post-Operative Delirium in the Elderly

Post-operative delirium (POD) represents a confusional state during days/weeks after surgery and is particularly frequent in elderly patients. Hardly any fMRI studies were conducted to understand the underlying pathophysiology of POD patients. This study aims to examine changes of specific resting-state neuronal networks across different time points (before and 3 months after surgery) in delirious patients compared to no-POD patients.

The developmental trajectory of fronto‐temporoparietal connectivity as a proxy of the default mode network: a longitudinal fNIRS investigation

The default mode network (DMN) is a network of brain regions that is activated while we are not engaged in any particular task. While there is a large volume of research documenting functional connectivity within the DMN in adults, knowledge of the development of this network is still limited. There is some evidence for a gradual increase in the functional connections within the DMN during the first 2 years of life, in contrast to other functional resting‐state networks that support primary sensorimotor functions, which are online from very early in life. Previous studies that investigated the development of the DMN acquired data from sleeping infants using fMRI. However, sleep stages are known to affect functional connectivity. In the current longitudinal study, fNIRS was used to measure spontaneous fluctuations in connectivity within fronto‐temporoparietal areas—as a proxy for the DMN—in awake participants every 6 months from 11 months till 36 months. This study validates a method for recording resting‐state data from awake infants, and presents a data analysis pipeline for the investigation of functional connections with infant fNIRS data, which will be beneficial for researchers in this field. A gradual development of fronto‐temporoparietal connectivity was found, supporting the idea that the DMN develops over the first years of life. Functional connectivity reached its maximum peak at about 24 months, which is consistent with previous findings showing that, by 2 years of age, DMN connectivity is similar to that observed in adults.

Global and regional connectivity analysis of resting-state function MRI brain images using graph theory in Parkinson’s disease

Objectives Parkinson’s disease (PD) is the second most common neurodegenerative disorder which resists around 10 million people worldwide. It develops when nerve cells in a region of the brain that regulates movement become damaged; the symptoms usually begin gradually and become critical over time. In this study, we proposed to investigate the topological properties of functional brain networks within healthy controls (HCs) and PD patients. Also, we evaluated the gender difference among PD patients through graph theoretical approach. Materials and Methods The rs-fMRI (resting-state functional magnetic resonance imaging) data of fifty-one PD patients and healthy controls was applied to generate the brain functional connectome. The functional whole-brain connectome was constructed by thresholding partial correlation matrices of 160 regions from Dosenbach brain atlas. From the graph theory approach, global and nodal metrics were analysed, and we observed considerable changes in PD patients in comparison with healthy controls. Results Findings suggest that there is a significant difference in the topological characteristics of PD patients, and this was found to be evident in the default mode network (DMN) and occipital regions. Conclusion This study provides essential insights from network changes to the clinically relevant information for the PD progression.

Short-Term Effects of Flupentixol-Melitracen on Regional Brain Function in Patients with Irritable Bowel Syndrome: An fMRI Study

Background: The efficacy of the treatment for irritable bowel syndrome (IBS) with the combination of anxiolytic/antidepressant has been confirmed by clinical studies, but the central mechanism is unclear. Objectives: To investigate the effects of flupentixol-melitracen, a mixture of tricyclic antidepressant and a classical antipsychotic component, on resting-state brain function in IBS patients by using functional magnetic resonance imaging (fMRI). Patients and Methods: Thirty-two patients with IBS were randomly divided into an observation group (OG, n = 16) and control group (CG, n = 16). All patients in both groups were given spasmolytic agent (pinaverium bromide). For the OG group, flupentixol-melitracen was added. FMRI scans were performed in all patients before and four weeks after the therapy. The scores of gastrointestinal symptom rating scale (GSRS), Hamilton depression scale (HAMD-17) and anxiety scale (HAMA-14) were evaluated at the same time. FMRI regional homogeneity (ReHo) parameters were compared between the two groups before and after treatment using a 2 (therapy) × 2 (time) mixed model analysis of variance (ANOVA) statistical method, and were correlated with the changes of GSRS, HAMD and HAMA scores in the two groups. Results: The fMRI results of the mixed-model analysis of covariance (ANCOVA) and post analyses were as follows. When the therapeutic factor was the main effect, ReHo was increased in the left superior and middle occipital gyrus, and the left parietal gyrus, and decreased in the left thalamus and the lenticular nucleus in both groups after treatment when compared to the unmedicated state. In addition, the OG group showed decreased ReHo in the left superior temporal gyrus, the right lenticular-putamen nucleus, the right inferior frontal gyrus, the right insula, the right gyrus rectus and subcallosal gyrus. The CG group showed increased ReHo in the right angular gyrus. When the interaction between therapy and time was the main effect, the brain region with different ReHo values was in the left precuneus. In the OG group, the change of ReHo in the left precuneus was negatively correlated with the decrease of HAMD and HAMA scores. Conclusion: Flupentixol-melitracen can effectively improve anxiety, depression and gastrointestinal symptoms in patients with IBS, which may be related to the reversal of abnormal neural activity in the brain regions within the default network and the prefrontal-limbic-temporal emotional circuit in IBS patients.

Resting-state networks of the neonate brain identified using independent component analysis.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been successfully used to probe the intrinsic functional organization of the brain and to study brain development. Here, we implemented a combination of individual and group independent component analysis (ICA) of FSL on a 6-min resting-state data set acquired from 21 naturally sleeping term-born (age 26±6.7 d), healthy neonates to investigate the emerging functional resting-state networks (RSNs). In line with the previous literature, we found evidence of sensorimotor, auditory/language, visual, cerebellar, thalmic, parietal, prefrontal, anterior cingulate as well as dorsal and ventral aspects of the default-mode-network. Additionally, we identified RSNs in frontal, parietal, and temporal regions that have not been previously described in this age group and correspond to the canonical RSNs established in adults. Importantly, we found that careful ICA-based denoising of fMRI data increased the number of networks identified with group-ICA, whereas the degree of spatial smoothing did not change the number of identified networks. Our results show that the infant brain has an established set of RSNs soon after birth.

P119 Brain function and fatigue in patients with inflammatory bowel disease

Abstract Background Fatigue is common in patients with inflammatory bowel diseases (IBD). It occurs in up to 80% of patients with active disease, but also a considerable proportion of patients in remission, and significantly affects quality of life. The underlying mechanisms are still poorly understood, and it is still unclear which patients will suffer from fatigue even in luminally quiescent disease. Task-based brain functional studies have examined neural correlates of fatigueability and found changes in the orbitofrontal cortex (OFC), among other regions. To the best our knowledge, the relationship between brain function and fatigue in IBD has not been investigated. This study aimed to examine the association between fatigue and resting-state brain function in remitted IBD patients. Methods We obtained resting-state-functional MRI (rs-fMRI) data from 45 IBD patients in stable remission without current steroid or biological therapy and 17 healthy controls (HCs). Fatigue was assessed with Würzburger Erschöpfungsinventar Multiple Sklerose (WEIMuS). Preprocessing of rs-fMRI-data and calculation of amplitude of low frequency fluctuations (ALFF) was performed using the Data Processing Assistant for rs-fMRI. The resulting individual maps were analysed via second-level SPM multiple regression models in patients and HC to test for correlations between ALFF data and WEIMuS scores. Age, gender and mean framewise displacement were included as covariates of no interest and results were displayed at p &amp;lt; 0.001 (peak level) with a threshold of spatial extent (k) according to the expected voxels per cluster estimated by SPM. Results Fatigue scores did not differ significantly between patients and controls (mean WEIMuS-scores 17.9 (SD 13.9) vs. 12.3 (SD 16.5), p = .17). Proportions of participants with fatigue scores above the cutoff (&amp;gt;32P.) were nearly identical in patients and HC (8/45 vs. 3/17). In patients, fatigue scores correlated positively with ALFF in the right central operculum and negatively with ALFF in the left OFC and left cerebellum (all p &amp;lt; .001, Figure 1). Fatigue and ALFF in the left cerebellum were also found to correlate in HC. Conclusion This study shows fatigue-associated changes in brain activity in several brain regions. The negative association between fatigue and ALFF in the left OFC of IBD patients was not seen in HC, indicating that reduced ALFF in the OFC may represent a neural correlate of IBD-related fatigue. The OFC is thought to be involved in decision-making, which is described to be impaired in many fatigued IBD patients. If the association between fatigue and brain function detected in our study is confirmed in longitudinal IBD studies, these regions could serve as biomarkers when targeting fatigue in IBD.

Diffusion tensor imaging and resting-state functional magnetic resonance imaging in patients with delirium in intensive care unit

To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium. Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores. A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. (1) No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). (2) fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium (r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. (3) DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.

The functional connection of central executive network in patients with depression after clinical cure

Objective To study the changes in the functional connections of the central executive network in patients with depression after clinical cure. Methods Seventeen depression patients who met the clinical cure standard (patient group) and twenty-two healthy controls (control group) were selected.The baseline rs-fMRI data were collected from the healthy control group and the patient group respectively, and the rs-fMRI data in the patient group were collected again after 6 months.Compared the changes of central executive network function connection between the two groups. Results At baseline, there was a high functional connection in the left inferior parietal lobule(MNI: x, y, z=-39, -69, 33)and right insula(MNI: x, y, z=15, -45, 30) in the patient group compared with the control group.Compared with the baseline, there were high functional connections in part of the left inferior parietal lobe (MNI: x, y, z=-60, -48, 21) and the right dorsolateral prefrontal lobe (MNI: x, y, z=24, 18, 60), and low functional connections in part of the left inferior parietal lobe (MNI: x, y, z=-51, -69, 18) in patient group 6 months after clinical cure.Compared with the control group, there was a high functional connection in the right dorsolateral prefrontal lobe (MNI: x, y, z=45, 51, -6) and the right inferior parietal lobe (MNI: x, y, z=42, -48, 27) in patient group 6 months after clinical cure. Conclusion The functional connection of central executive network of depression patients has not been restored, and the related abnormality is not stable in six months after reaching the clinical cure standard. Key words: Central executive network; Clinical cure; Major depressive disorder; Resting state function connection

Increased soluble amyloid-beta causes early aberrant brain network hypersynchronisation in a mature-onset mouse model of amyloidosis

Alzheimer’s disease (AD) is the most common form of dementia in the elderly. According to the amyloid hypothesis, the accumulation and deposition of amyloid-beta (Aβ) peptides play a key role in AD. Soluble Aβ (sAβ) oligomers were shown to be involved in pathological hypersynchronisation of brain resting-state networks in different transgenic developmental-onset mouse models of amyloidosis. However, the impact of protein overexpression during brain postnatal development may cause additional phenotypes unrelated to AD. To address this concern, we investigated sAβ effects on functional resting-state networks in transgenic mature-onset amyloidosis Tet-Off APP (TG) mice. TG mice and control littermates were raised on doxycycline (DOX) diet from 3d up to 3 m of age to suppress transgenic Aβ production. Thereafter, longitudinal resting-state functional MRI was performed on a 9.4 T MR-system starting from week 0 (3 m old mice) up to 28w post DOX treatment. Ex-vivo immunohistochemistry and ELISA analysis was performed to assess the development of amyloid pathology. Functional Connectivity (FC) analysis demonstrated early abnormal hypersynchronisation in the TG mice compared to the controls at 8w post DOX treatment, particularly across regions of the default mode-like network, known to be affected in AD. Ex-vivo analyses performed at this time point confirmed a 20-fold increase in total sAβ levels preceding the apparition of Aβ plaques and inflammatory responses in the TG mice compared to the controls. On the contrary at week 28, TG mice showed an overall hypoconnectivity, coinciding with a widespread deposition of Aβ plaques in the brain. By preventing developmental influence of APP and/or sAβ during brain postnatal development, we demonstrated FC abnormalities potentially driven by sAβ neurotoxicity on resting-state neuronal networks in mature-induced TG mice. Thus, the Tet-Off APP mouse model could be a powerful tool while used as a mature-onset model to shed light into amyloidosis mechanisms in AD.

Morphological MRI phenotypes of multiple sclerosis differ in resting-state brain function

We aimed to assess differences in resting-state functional connectivity (FC) between distinct morphological MRI-phenotypes in multiple sclerosis (MS). Out of 180 MS patients, we identified those with high T2-hyperintense lesion load (T2-LL) and high normalized brain volume (NBV; a predominately white matter damage group, WMD; N = 37) and patients with low T2-LL and low NBV (N = 37; a predominately grey matter damage group; GMD). Independent component analysis of resting-state fMRI was used to test for differences in the sensorimotor network (SMN) between MS MRI-phenotypes and compared to 37 age-matched healthy controls (HC). The two MS groups did not differ regarding EDSS scores, disease duration and distribution of clinical phenotypes. WMD compared to GMD patients showed increased FC in all sub-units of the SMN (sex- and age-corrected). WMD patients had increased FC compared to HC and GMD patients in the central SMN (leg area). Only in the WMD group, higher EDSS scores and T2-LL correlated with decreased connectivity in SMN sub-units. MS patients with distinct morphological MRI-phenotypes also differ in brain function. The amount of focal white matter pathology but not global brain atrophy affects connectivity in the central SMN (leg area) of the SMN, consistent with the notion of a disconnection syndrome.

Altered spontaneous brain activity in patients with strabismic amblyopia: A resting-state fMRI study using regional homogeneity analysis.

The present study aimed to compare the regional homogeneity (ReHo) of resting-state brain function between subjects with strabismic amblyopia and normal controls. A total of 12 adult patients with strabismic amblyopia and 34 age- and gender-matched normal controls were enrolled in the present study. All patients were subjected to resting-state magnetic resonance imaging using a Siemens Trio 3.0T magnetic resonance scanner. ReHo values of the whole brain were calculated and standardized. An independent-samples t-test was used to analyze the differences in ReHo values between the two groups. Patients with strabismic amblyopia exhibited reduced ReHo values in certain parts of the occipital lobe, including the lingual gyrus, cuneus and superior occipital gyrus. Increased ReHo values were observed in the precuneus and certain parts of the prefrontal cortex of patients with strabismic amblyopia, including the superior frontal gyrus and middle frontal gyrus. The ReHo index of the precuneus was negatively correlated with age. However, there was no correlation between the ReHo values and the visual acuity of patients with strabismic amblyopia. ROC curve analysis demonstrated that the greatest area under curve (AUC) value was in the medial prefrontal cortex (AUC=0.864). The results of the present study suggested that visual information processing may be impaired in visual areas V1 and V2. Furthermore, adult patients with strabismic amblyopia exhibited brain plasticity that compensated for visuomotor coordination and visuospatial imagery deficits.

The brain mechanism of mind popping based on resting-state functional connectivity.

Mind popping is the phenomenon of a word, sentence, image, or melody suddenly coming into the conscious mind. It occurs without any conscious memories, also known as unconscious semantic memory. So far, little is known about the neural basis of this phenomenon. Using the Mind-Popping Questionnaire, we examined the frequency of daily mind popping of 397 healthy college students and related the resting-state functions of the brain with it by means of resting-state functional connectivity analysis. On the basis of previous research, the parahippocampal gyrus and hippocampus were selected as regions of interest. The results showed that the Mind-Popping Questionnaire scores were significantly positively correlated with the functional connectivity strength of parahippocampal gyrus (x = -12, y = -35, z = 0) and supplementary motor area (cluster size = 126 voxels; peak coordinates in MNI: 15, -6, 57; P < 0.005, AlphaSim corrected, t = 2.58). This result, although not very strong, revealed a special connection of a subarea of the default mode network with the medial temporal lobe and the supplementary motor area, indicating that the neural mechanism behind mind popping may be the neural circuit of implicit semantic memory extraction.

Disruption of resting-state functional connectivity of right posterior insula in adolescents and young adults with major depressive disorder

BackgroundThe neural basis of Major Depressive Disorder (MDD) which is a clinical syndrome characterized by emotional and cognitive impairments is poorly understood. Accumulating evidence has suggested that the insula is an important substrate underlying the mechanism of MDD. This study aimed to examine the disrupted resting-state brain regional function in insula and to further investigate the associated resting-state functional connectivity (rs-FC) of insula underlie the MDD in adolescents and young adults. MethodsWe employed 3.0T resting-state functional magnetic resonance imaging (rs-fMRI) to acquire data from 76 adolescents and young adults with MDD and 44 age and sex matched healthy control subjects. We employed a regional Amplitude of Low-Frequency Fluctuation (ALFF) analysis to explore local intrinsic neural oscillation alterations in insula and an ALFF-based functional connectivity (FC) approach to detect the potential changes in remote connectivity with insula in adolescents and young adults with MDD. ResultsBy applying ALFF analysis, significantly decreased activities were detected in bilateral insula, and in particular in right anterior insular gyrus (MNI; ROI1: 42, 24, −3), right posterior insular gyrus (Montreal Neurological Institute, MNI; ROI2: 36, −9, 15) and left anterior insular gyrus (MNI; ROI3: −36, 12, 9) in patients with MDD compared to the healthy controls (p < 0.05, 1000 permutations, TFCE corrected). With ROI2 as the seed in the subsequent ALFF-based rs-FC analysis, patients with MDD were observed to have significantly reduced FC with bilateral middle occipital gyrus, lingual gyrus, calcarine, postcentral gyrus, precentral gyrus, supramarginal area, superior temporal gyrus and middle cingulate gyrus as compared to the healthy controls (p < 0.05, 1000 permutations, TFCE corrected). No significant differences of FC were detected between the patients and healthy controls when using ROI1 and ROI3 as the seeds. We found no correlations between ALFF or rs-FC values and the severity of depression as estimated by Hamilton Depression Rating Scale (HAM-D). LimitationsClinical information were limited and no significant correlations were found between imaging variables and HAM-D scores, which reduces the power to interpret the present findings. A cross-sectional design was employed in this study so that it is not possible to know whether the abnormal ALFF or altered brain FC of insula reflects a state or trait effect in young people with MDD. ConclusionsThis study highlights the regional/network interaction abnormalities of insula in adolescents and young adults with MDD, and could provide further insight into understanding the neural pathomechanism of MDD in young patients.

Resting brain dynamics at different timescales capture distinct aspects of human behavior

Linking human behavior to resting-state brain function is a central question in systems neuroscience. In particular, the functional timescales at which different types of behavioral factors are encoded remain largely unexplored. The behavioral counterparts of static functional connectivity (FC), at the resolution of several minutes, have been studied but behavioral correlates of dynamic measures of FC at the resolution of a few seconds remain unclear. Here, using resting-state fMRI and 58 phenotypic measures from the Human Connectome Project, we find that dynamic FC captures task-based phenotypes (e.g., processing speed or fluid intelligence scores), whereas self-reported measures (e.g., loneliness or life satisfaction) are equally well explained by static and dynamic FC. Furthermore, behaviorally relevant dynamic FC emerges from the interconnections across all resting-state networks, rather than within or between pairs of networks. Our findings shed new light on the timescales of cognitive processes involved in distinct facets of behavior.

Improving brain function of pediatric acute lymphoblastic leukemia patients after induction chemotherapy, a pilot self-contrast study by fractional amplitude of low-frequency fluctuation

Our previous study revealed altered resting-stated brain function in children with acute lymphoblastic leukemia (ALL) on new-onset stage. To investigate the effects after induction chemotherapy, a pilot self-contrast study was conducted to compare the difference in resting-stated brain function between pre- and post-induction chemotherapy of ALL. Fractional amplitude of low-frequency fluctuation (fALFF) was employed for fMRI data analysis. Clinical and resting state functional magnetic resonance imaging (RS-fMRI) data of 14 new-onset pediatric ALL patients were collected before and after 3 months of induction chemotherapy. Fourteen age- and gender-matched healthy controls (HCs) were recruited for comparison. Before induction chemotherapy, fALFF values of ALL patients decreased globally, especially in the default mode network (DMN), left frontal lobe, left occipital lobe, and bilateral postcentral gyri as compared to HCs. After induction chemotherapy, fALFF values of ALL patients decreased significantly in the bilateral cuneus, left lingual and calcarine gyri, and left mid frontal gyrus. Paired-sample t-tests and self-contrast analysis showed fALFF increased in the left precuneus, bilateral cuneus, left occipital lobe, bilateral frontal gyri, and bilateral temporal lobes, whereas fALFF in the bilateral precuneus decreased in the ALL patients after induction, which suggests potential side-effects of the treatment. The alteration of fALFF values suggested that resting brain function was impaired before induction chemotherapy and mostly recovered after treatment. This study suggested that fALFF is a reliable and feasible tool in detecting spontaneous brain activity to monitor early neurocognitive impairments in pediatric ALL to better understand the underlying neurobiological mechanisms of chemotherapy on the brain.

The Association between DRD3 Ser9Gly Polymorphism and Depression Severity in Parkinson's Disease.

More and more evidence suggests that dopamine receptor D3 gene (DRD3) plays an important role in the clinical manifestations and the treatment of Parkinson's disease (PD). DRD3 Ser9Gly polymorphism is the most frequently studied variant point. Our aim was to investigate the potential effect of DRD3 Ser9Gly polymorphism on modulating resting-state brain function and associative clinical manifestations in PD patients. We consecutively recruited 61 idiopathic PD patients and 47 healthy controls (HC) who were evaluated by clinical scales, genotyped for variant Ser9Gly in DRD3, and underwent resting-state functional magnetic resonance imaging. Based on DRD3 Ser9Gly polymorphism, PD patients and HCs were divided into four subgroups. Then, two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions of PD and DRD3 Ser9Gly polymorphism on the brain function via amplitude of low-frequency fluctuations (ALFF) approach. The association between DRD3 Ser9Gly-modulated significantly different brain regions, and clinical manifestations were detected by Spearman's correlations. PD patients exhibited decreased ALFF values in the right inferior occipital gyrus, lingual gyrus, and fusiform gyrus. A significant difference in the interaction of “groups × genotypes” was observed in the right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positively correlated with HAMD-17 scores (r=0.489, p=0.011) and anhedonia scores (r=0.512, p=0.008) in PD patients with the Ser/Gly or Gly/Gly genotypes. Therefore, D3 gene Ser9Gly polymorphism might be associated with the severity of depression characterized by anhedonia in PD patients.

Cerebral Blood Perfusion Predicts Response to Sertraline versus Placebo for Major Depressive Disorder in the EMBARC Trial

BackgroundMajor Depressive Disorder (MDD) has been associated with brain-related changes. However, biomarkers have yet to be defined that could “accurately” identify antidepressant-responsive patterns and reduce the trial-and-error process in treatment selection. Cerebral blood perfusion, as measured by Arterial Spin Labelling (ASL), has been used to understand resting-state brain function, detect abnormalities in MDD, and could serve as a marker for treatment selection. As part of a larger trial to identify predictors of treatment outcome, the current investigation aimed to identify perfusion predictors of treatment response in MDD. MethodsFor this secondary analysis, participants include 231 individuals with MDD from the EMBARC study, a randomised, placebo-controlled trial investigating clinical, behavioural, and biological predictors of antidepressant response. Participants received sertraline (n = 114) or placebo (n = 117) and response was monitored for 8 weeks. Pre-treatment neuroimaging was completed, including ASL. A whole-brain, voxel-wise linear mixed-effects model was conducted to identify brain regions in which perfusion levels differentially predict (moderate) treatment response. Clinical effectiveness of perfusion moderators was investigated by composite moderator analysis and remission rates. Composite moderator analysis combined the effect of individual perfusion moderators and identified which contribute to sertraline or placebo as the “preferred” treatment. Remission rates were calculated for participants “accurately” treated based on the composite moderator (lucky) versus “inaccurately” treated (unlucky). FindingsPerfusion levels in multiple brain regions differentially predicted improvement with sertraline over placebo. Of these regions, perfusion in the putamen and anterior insula, inferior temporal gyrus, fusiform, parahippocampus, inferior parietal lobule, and orbital frontal gyrus contributed to sertraline response. Remission rates increased from 37% for all those who received sertraline to 53% for those who were lucky to have received it and sertraline was their perfusion-preferred treatment. InterpretationThis large study showed that perfusion patterns in brain regions involved with reward, salience, affective, and default mode processing moderate treatment response favouring sertraline over placebo. Accurately matching patients with defined perfusion patterns could significantly increase remission rates. FundingNational Institute of Mental Health, the Hersh Foundation, and the Center for Depression Research and Clinical Care, Peter O'Donnell Brain Institute at UT Southwestern Medical Center.Trial Registration.Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMARC) Registration Number: NCT01407094 (https://clinicaltrials.gov/ct2/show/NCT01407094).