Resting-state MRI Research Articles

Resting-State Functional Connectivity Impairment in Patients with Major Depressive Episode.

This study aims to develop new approaches to characterize brain networks to potentially contribute to a better understanding of mechanisms involved in depression. We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed investigating functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were developed at a functional network level, using a false discovery rate method. Linear discriminant analysis was used to differentiate between the two groups. Significant differences in functional connectivity (FC) between depressed patients vs. healthy controls was demonstrated, with brain regions including the lingual gyrus, cerebellum, midcingulate cortex and thalamus more prominent in healthy subjects as compared to depression where the orbitofrontal cortex emerged as a key node. Linear discriminant analysis demonstrated that full-connectivity matrices were the most precise in differentiating between depression vs. health subjects. The study provides supportive evidence for impaired functional connectivity networks in MDE patients.

Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study.

IntroductionMajor depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment.Materials and methodsTwenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week’s treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients.ResultsThere were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS.ConclusionThe decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy.

The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS.

Associations of lifetime concussion history and repetitive head impact exposure with resting-state functional connectivity in former collegiate American football players: An NCAA 15-year follow-up study.

The objective of this study was to examine associations of lifetime concussion history (CHx) and an advanced metric of lifetime repetitive head impact exposure with resting-state functional connectivity (rsFC) across the whole-brain and among large-scale functional networks (Default Mode; Dorsal Attention; and Frontoparietal Control) in former collegiate football players. Individuals who completed at least one year of varsity collegiate football were eligible to participate in this observational cohort study (n = 48; aged 36-41 years; 79.2% white/Caucasian; 12.5±4.4 years of football played; all men). Individuals were excluded if they reported history/suspicion of psychotic disorder with active symptoms, contraindications to participation in study procedures (e.g., MRI safety concern), or inability to travel. Each participant provided concussion and football playing histories. Self-reported concussion history was analyzed in two different ways based on prior research: dichotomous "High" (≥3 concussions; n = 28) versus "Low" (<3 concussions; n = 20); and four ordinal categories (0-1 concussion [n = 19]; 2-4 concussions [n = 8]; 5-7 concussions [n = 9]; and ≥8 concussions [n = 12]). The Head Impact Exposure Estimate (HIEE) was calculated from football playing history captured via structured interview. Resting-state fMRI and T1-weighted MRI were acquired and preprocessed using established pipelines. Next, rsFC was calculated using the Seitzman et al., (2020) 300-ROI functional atlas. Whole-brain, within-network, and between-network rsFC were calculated using all ROIs and network-specific ROIs, respectively. Effects of CHx and HIEE on rsFC values were examined using separate multivariable linear regression models, with a-priori α set to 0.05. We observed no statistically significant associations between rsFC outcomes and either CHx or HIEE (ps ≥ .12). Neither CHx nor HIEE were associated with neural signatures that have been observed in studies of typical and pathological aging. While CHx and repetitive head impacts have been associated with changes in brain health in older former athletes, our preliminary results suggest that associations with rsFC may not be present in early midlife former football players.

Altered asymmetries of resting-state MRI in the left thalamus of first-episode schizophrenia.

BackgroundSchizophrenia (SCZ) is a complex psychiatric disorder associated with widespread alterations in the subcortical brain structure. Hemispheric asymmetries are a fundamental organizational principle of the human brain and relate to human psychological and behavioral characteristics. We aimed to explore the state of thalamic lateralization of SCZ.MethodsWe used voxel‐based morphometry (VBM) analysis, whole‐brain analysis of low‐frequency fluctuations (ALFF), fractional amplitude of low‐frequency fluctuations (fALFF), and resting‐state seed‐based functional connectivity (FC) analysis to investigate brain structural and functional deficits in SCZ. Also, we applied Pearson's correlation analysis to validate the correlation between Positive and Negative Symptom Scale (PANSS) scores and them.ResultsCompared with healthy controls, SCZ showed increased gray matter volume (GMV) of the left thalamus (t = 2.214, p = 0.029), which positively correlated with general psychosis (r = 0.423, p = 0.010). SCZ also showed increased ALFF in the putamen, the caudate nucleus, the thalamus, fALFF in the nucleus accumbens (NAc), and the caudate nucleus, and decreased fALFF in the precuneus. The left thalamus showed significantly weaker resting‐state FC with the amygdala and insula in SCZ. PANSS negative symptom scores were negatively correlated with the resting‐state FC between the thalamus and the insula (r = −0.414, p = 0.025).ConclusionsCollectively, these results suggest the possibility of aberrant laterality in the left thalamus and its FC with other related brain regions involved in the limbic system.

Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data

BackgroundParkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. MethodsCross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. ResultsOur multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. ConclusionsThree distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.

Exploring the relationship between resting-state intra-network connectivity and accelerometer-measured physical activity in pediatric concussion: a cohort study.

Our objective was to explore the association between resting-state functional connectivity and accelerometer-measured physical activity in pediatric concussion. Fourteen children with concussion (aged 14.54±2.39 years, 8 female) were included in this secondary data analysis of a larger study. Participants had neuroimaging at 15.3±6.7 days postinjury and subsequently a mean of 11.1±5.0 days of accelerometer data. Intra-network connectivity of the default mode network (DMN), sensorimotor network (SMN), salience network (SN), and frontoparietal network (FPN) was computed using resting-state MRI. We found that, per general linear models (GLMs), only intra-network connectivity of the DMN was associated with physical activity levels. More specifically, increased intra-network connectivity of the DMN was significantly associated with higher levels of subsequent accelerometer-measured light physical activity (LPA; F(2, 11)=7.053, p=0.011, Ra2=0.562; β = 0.469), moderate physical activity (MPA; F(2, 11) = 6.159, p = 0.016, Ra2 = 0.528; β = 0.725), and vigorous physical activity (VPA; F(2, 11)=10.855, p=0.002, Ra2=0.664; β = 0.792). Intra-network connectivity of the DMN did not significantly predict sedentary time. Therefore, these preliminary findings suggest that there is a positive association between the intra-network connectivity of the DMN and device-measured physical activity in children with concussion.

0145 Breathing Pattern Estimated By Breathing Rate Variability Correlated With Amplitude Of Low Frequency Resting State MRI Fluctuations May Predict Sleep Quality

Abstract Introduction We recently showed that people with obstructive sleep apnea (OSA) have higher breathing rate (BR) variability (BRV) in population (Pal et al. 2021)1. Simultaneously, Lynch et al. 20202 had assessed impaired breathing in the resting state healthy Human Connectome Dataset, and identified 21 people in each of the three groups of breathing patterns: eupnea (clean), sighs (deep breath) and suspected apnea breathing pattern (burst). During resting state functional MRI recordings, increased amplitude of low frequency fluctuations (ALFF) were found within areas related to hyperarousal such as the midbrain and bilateral extra-nucleus, whereas decreased ALFF were found within areas associated with memory and attention involving the parietal and occipital lobule and others; furthermore, the altered ALFF was associated with sleep efficiency (Ran et al. 20173). Could altered breathing pattern reflect an altered spontaneous neuronal activity state measured by fractional ALFF (fALFF) and associated psycho-physiological markers of sleep quality? Our goal was to characterize BRV and fALFF from the resting state HCP data in the three breathing pattern groups identified in Lynch et al. 2020 along with their psychophysiological states including sleep quality measured by Pittsburg Sleep Quality Index (PSQI). Methods In the three groups (n=21 X 3), clean group (6 males) age (mean±std. dev) 29±4 years, deep breath group (5 males) 29±4 years, burst group (14 males) 30±4 years - we calculated BR, absolute BRV (Interquartile range of BR) and relative BRV% from 15 minutes of resting state respiration belt data; and, fALFF from the minimally preprocessed resting state fMRI data filtered at 0.1-0.08 Hz and smoothed. We correlated fALFF with BR, BRV. Additionally, in the three groups, we report the mean±stdev of PSQI, BMI, systolic and diastolic blood pressure (BP), self-reported anxiety, attention problem, aggression scores along with their correlations with the absolute BRV. Results Absolute BRV was lower in deep breath group 3±3 breaths per minute (bpm) compared to clean (4±2 bpm) and burst (4±3 bpm) groups. BR was also lower in deep breath 14±7 bpm and correlated with BRV at Pearson R = 0.57 (p&amp;lt;0.05), compared to 18±2 bpm, R = -0.51 (p&amp;lt;0.05) in clean group and 18±3 bpm, R = 0.2 in burst group. In the deep breath group, the relative change in BRV 24±14%, correlated less with absolute BRV R = 0.78 (p&amp;lt;0.05) compared to the clean 24±13%, R = 0.98 (p&amp;lt;0.05) and burst groups 24±18%, R = 0.97 (p&amp;lt;0.05) indicating some voluntary sighs in the deep breath group as also validated by visual data inspection. The sleep quality (lower PSQI better sleep quality) was best in the clean 4±2 points, compared to both deep breath 5±3 and burst groups 5±3. Improved psychophysiological state in the clean and deep breath group compared to burst group was indicated by the systolic BP (121±12, 121±13 and 128±14 mmHg), BMI (25±5, 26±5, 28±6 kg/m2), anxiety (5±5, 5±5, 7±7)/attention problems (5±3, 5±4, 7±4)/aggression (3±2, 3±3, 5±2) scores in clean, deep breath and burst groups respectively. Only in the burst group, higher BRV correlated with higher BMI (R = 0.5, p&amp;lt;0.05). fALFF correlated with BRV (p&amp;lt;0.05, FWE corrected), not BR in all three groups at the cerebrospinal fluid (CSF) ventricles. With BRV as co-variate, burst group showed higher fALFF activity (p&amp;lt;0.001, uncorrected) compared to both clean and deep breath groups at the visual and somatosensory regions. Additionally, fALFF at the central executive network (CEN) was higher (p&amp;lt;0.001, uncorrected) for both clean and deep breath groups compared to burst. Interestingly, the clean group as well as the burst group had higher right somatosensory fALFF activity compared to deep breath group, that corresponded to the lower BRV in deep breath group. Conclusion Higher fALFF activity of burst compared to clean and deep breath groups in the visual and somatosensory regions were associated with sleep deprivation states (Dai et al., 20124; Wang et al., 20165 , Ran et al. 20173). Higher CEN fALFF activity indicating better sleep and physiological states (Zeighami et al., 20216, Ran et al. 20173) were found in the clean and deep breath groups compared to burst. Higher right somatosensory fALFF activity in the clean and burst groups compared to deep breath indicating higher breathing related movements in the groups having higher BR and BRV (clean and burst) compared to the deep breath group. The fALFF results are consistent with the indication of breathing coupled hemodynamic and CSF low-frequency oscillations that indicate sleep/wakefulness states during resting state (Fultz 20197). Overall, our study supports that BRV could be a potential indicator of psychophysiology, and taking sighs or deep breaths could potentially improve some psycho-neuro-physiological states but not necessarily sleep quality. As indicated earlier by Lynch et al. 20202, males report more burst breathing pattern while females report more deep breathing pattern indicating the ability to take deep breaths may counteract potential sleep disordered breathing problems. Support (If Any) HL135562

Structural and functional variations in the prefrontal cortex are associated with learning in pre-adolescent common marmosets (Callithrix jacchus)

There is substantial evidence linking the prefrontal cortex (PFC) to a variety of cognitive abilities, with adolescence being a critical period in its development. In the current study, we investigated the neural basis of differences in learning in pre-adolescent common marmosets. At 8 months old, marmosets were given anatomical and resting state MRI scans (n = 24). At 9 months old, association learning and inhibitory control was tested using a ‘go/no go’ visual discrimination (VD) task. Marmosets were grouped into ‘learners’ (n = 12) and “non-learners” (n = 12), and associations between cognitive performance and sub-regional PFC volumes, as well as PFC connectivity patterns, were investigated. “Learners” had significantly (p < 0.05) larger volumes of areas 11, 25, 47 and 32 than ‘non-learners’, although ‘non-learners’ had significantly larger volumes of areas 24a and 8 v than “learners”. There was also a significant correlation between average % correct responses to the ‘punished’ stimulus and volume of area 47. Further, ‘non-learners’ had significantly greater global PFC connections, as well as significantly greater numbers of connections between the PFC and basal ganglia, cerebellum and hippocampus, compared to ‘learners’. These results suggest that larger sub-regions of the orbitofrontal cortex and ventromedial PFC, as well more refined PFC connectivity patterns to other brain regions associated with learning, may be important in successful response inhibition. This study therefore offers new information on the neurodevelopment of individual differences in cognition during pre-adolescence in non-human primates.

Alterations to cognitive abilities and functional networks in rats post broad-band intense noise exposure.

This study aimed to investigate the alterations of cognition and functional connectivity post noise, and find the progress and neural substrates of noise induced hearing loss (NIHL)-associated cognitive impairment. We exposed rats to 122dB broad-band noise for 2h to induce hearing loss and the auditory function was assessed by measuring auditory brainstem response thresholds. Morris water maze test and resting state MRI were computed at 0day, 1, 3, 6months post noise to reveal cognitive ability and neural substrate. The interregional connections in the auditory network and default mode network, as well as the connections using the auditory cortex and cingulate cortex as seeds were also examined addtionally. The deficit in spatial learning/memory was only observed at 6months after noise exposure. The internal connections in the auditory network and default mode network were enhanced at 0day and decreased at 6months post noise. The connectivity using the auditory cortex and cingulate cortex as seeds generally followed the rule of "enhancement-normal-decrease-widely decrease". A new model accounting for arousal, dementia, motor control of NIHL in is proposed. Our study highlights the fundamental flexibility of neural systems, and may also point toward novel therapeutic strategies for treating sensory disorders.

Decreased spontaneous brain activity in the dorsal visual pathway in age-related macular degeneration patients revealed by fractional amplitude of low-frequency fluctuation.

Age-related macular degeneration (AMD) is the leading cause of visual loss in the developed world and damages the central retina. Growing evidences demonstrated that AMD patients were associated with brain structure changes in visual pathway. However, it remains unknown whether alterations of spontaneous brain activity changes occur in AMD patients. The purpose of this study was to investigate the effect of central vision loss on spontaneous brain activity in AMD patients. Seventeen AMD patients and 17 healthy controls (HCs) underwent resting-state MRI scans. The fractional amplitude of low-frequency fluctuations (fALFFs) was applied to investigate the spontaneous brain activity changes in AMD patients. Compared with HC group, AMD patients showed significant decreased fALFF values in the right calcarine/cuneus (brodmann area 17,8) and right superior parietal lobule (brodmann area 7). Our results showed that AMD patients had decreased brain activities in the dorsal visual pathway, which offer important insights into the neural mechanisms of central visual field defect in AMD patients.

Integrating Chronic Obstructive Pulmonary Disease Treatment With 8-Week Tai Chi Chuan Practice: An Exploration of Mind-Body Intervention and Neural Mechanism.

ObjectiveThis study aims to explore the effect of integrating routine treatment with Tai Chi Chuan (TCC) intervention on the clinical symptom of patients with Chronic Obstructive Pulmonary Disease (COPD) from clinical and neurological perspectives.MethodsTwenty patients with COPD were recruited for regular treatment combined with 8-week TCC rehabilitative practice. Clinical symptoms were evaluated by Chronic Obstructive Pulmonary Symptom Assessment Scale (CAT) and Modified Dyspnea Scale (mMRC) at baseline and after treatment. Resting-state MRI scan was also performed with multiline T2-weighted echo-planar imaging (EPI) to acquire their functional images before and after the treatment. TCC rehabilitation involved a total of 8 weeks of practice with 90 min per session, three times a week.ResultsAfter an 8-week integration routine treatment with TCC practice, the patient’s clinical symptoms improved significantly. Imaging analysis showed that COPD patients exhibited decreased Degree of Centrality (DC) in the right inferior frontal gyrus (IFG), right middle frontal gyrus, bilateral cingulate cortex, bilateral precuneus, and right precentral gyrus. Moreover, correlation analysis found that the decreased DC in the right IFG was positively correlated with the CAT improvements.ConclusionThe routine treatment involving TCC rehabilitation practice could improve the clinical symptoms of patients with COPD. The right IFG might be a key brain region to contribute to the neural mechanism underlying integrative intervention on the clinical symptoms in COPD. These findings provide neurological evidence for treating COPD rehabilitation practice with mind-body practice based on Chinese culture to some extent, which also advances the understanding of the efficacy of TCC as the adjuvant technology from a neuroscience perspective.Clinical Trial Registration:[http://www.chictr.org.cn/showproj.aspx?proj=45189], identifier [ChiCTR1900028335].

Menstrual Pain and Visual Sensitivity Are Related to Different Neural Mechanisms in Adolescent Girls

A substantial body of evidence exists demonstrating central pain mechanisms involved in the experience of menstrual pain. Yet, the neurobiological underpinnings are not yet known and have not yet been studied in adolescents. Further, no study has investigated the relationship of menstrual pain to non-physical pain (i.e., noxious visual stimuli) and examined brain connectivity in networks commonly associated with pain. Forty-six adolescent girls (ages 14 to 18) completed a 6-min resting state MRI scan and then completed a visual sensitivity task involving viewing a blue and yellow checkerboard stimulus. Visual unpleasantness ratings and self-reported average menstrual pain ratings were collected. Thirty-five resting-state networks was estimated using a multivariate data-driven method for group Independent Component Analysis (GICA). Cingulo-opercular (CN), prefrontal salience (pfSN) and default mode (DMN) networks were selected as a priori, as they are often associated with pain. Using dual regression approach, we extracted subject-specific network maps corresponding to each a priori network. Statistical models were analyzed using Randomise in FSL to investigate the association of menstrual pain and visual sensitivity scores with the connectivity of these networks. Menstrual pain was negatively associated with connectivity of wide-spread prefrontal areas within the DMN, thalamus, insula, and striatum. In contrast, visual sensitivity was positively associated with connectivity of the medial temporal subnetwork of the DMN. These data suggest that different pain experiences may result from unique neural mechanisms. For visual sensitivity, increased connectivity of medial temporal lobe DMN regions with anterior DMN may be a mechanism in which affective experience of noxious stimuli is linked with self-reported pain. For menstrual pain, dysregulated connectivity within the DMN and between the DMN and pain-related regions might lead to impaired regulation of other pain constructs and put some individuals at risk for chronic pain. Grant support from NIH/NICHD R01 HD093680.

Classification of tic disorders based on functional MRI by machine learning: a study protocol

IntroductionTic disorder (TD) is a common neurodevelopmental disorder in children, and it can be categorised into three subtypes: provisional tic disorder (PTD), chronic motor or vocal TD (CMT or CVT),...

Brain Stimulation for Emotion Regulation in Adolescents With Psychiatric Disorders: Study Protocol for a Clinical-Transdiagnostical, Randomized, Triple-Blinded and Sham-Controlled Neurotherapeutic Trial.

BackgroundAnxiety, conduct and depressive disorders represent three highly prevalent psychiatric conditions in adolescents. A shared underpinning of these disorders is a shortcoming in emotion regulation, connected to the functioning of the ventromedial prefrontal cortex. Thus, an intervention able to target the suggested neural correlate seems to be highly desirable, aiming to hinder a maladaptive development of emotion regulation abilities and chronification of associated psychiatric disorders. As transcranial direct current stimulation (tDCS) was repeatedly demonstrated as a safe and non-invasive method to modulate specific brain activity, research is in demand to evaluate neurotherapeutic applications in adolescents with psychiatric disorders.MethodThis transdiagnostic, randomized, triple-blind and sham-controlled clinical neurostimulation trial primary aims to investigate if emotion regulation abilities are increased after tDCS in adolescents with psychiatric disorders. Secondly, disorder-specific changes in the anxiety, depression or conduct disorder will be investigated, as well as changes in quality of life, and cognitive and emotional functioning after tDCS intervention. We will include 108 adolescents with psychiatric disorders, displaying a substantial deficit in emotion regulation. Of these, one third each has to be primarily diagnosed with a depressive, anxiety or conduct disorder, respectively. Participants will be randomized to the experimental group (n = 54) receiving real anodal tDCS, or to the control group (n = 54) receiving sham tDCS. Brain stimulation will be applied for 20 min on five consecutive days twice targeting the ventromedial prefrontal cortex (vmPFC). Changes in emotion regulation, together with changes in disorder-specific clinical symptoms will be recorded by multi-informant psychological ratings. To inspect changes in behavior and gaze, computerized tasks and an eye tracker system will be used. Changes in brain responses to emotional and cognitive stimuli will be examined with three functional magnetic resonance imaging (fMRI) paradigms. In addition, a resting state MRI will be acquired to investigate possible changes in brain connectivity.DiscussionBy investigating “emotion regulation” as transdiagnostic treatment target, this project is oriented toward the Research Domain Criteria framework with a dimensional view on mental illness. The study aims at investigating the potential of tDCS as non-invasive intervention for depressive, anxiety and conduct disorders in adolescents and broadening the scientific foundation for its clinical application.Clinical Trial RegistrationThe study is ongoing and has been registered in the German Registry of Clinical Trials (DRKS-ID: DRKS00025601X) on the 28.06.2021.

Altered Temporal Variations of Functional Connectivity Associated With Surgical Outcomes in Drug-Resistant Temporal Lobe Epilepsy.

BackgroundCurrently, more than one-third of patients with drug-resistant temporal lobe epilepsy (TLE) continue to develop seizures after resection surgery. Dynamic functional network connectivity (DFNC) analyses, capturing temporal properties of functional connectivity during MRI acquisition, may help us identify unfavorable surgical outcomes. The purpose of this work was to explore the association of DFNC variations of preoperative resting-state MRI and surgical outcomes in patients with drug-resistant TLE.MethodsWe evaluated 61 patients with TLE matched for age and gender with 51 healthy controls (HC). Patients with TLE were classified as seizure-free (n = 39) and not seizure-free (n = 16) based on the Engel surgical outcome scale. Six patients were unable to confirm the postoperative status and were not included in the subgroup analysis. The DFNC was calculated using group spatial independent component analysis and the sliding window approach.ResultsDynamic functional network connectivity analyses suggested two distinct connectivity “States.” The dynamic connectivity state of patients with TLE was different from HC. TLE subgroup analyses showed not seizure-free (NSF) patients spent significantly more time in State II compared to seizure-free (SF) patients and HC. Further, the number of transitions from State II to State I was significantly lower in NSF patients. SF patients had compensatory enhancement of DFNC strengths between default and dorsal attention network, as well as within the default network. While reduced DFNC strengths of within-network and inter-network were both observed in NSF patients, patients with abnormally temporal properties and more extension DFNC strength alterations were less likely to receive seizure freedom.ConclusionsOur study indicates that DFNC could offer a better understanding of dynamic neural impairment mechanisms of drug-resistant TLE functional network, epileptic brain network reorganization, and provide an additional preoperative evaluation support for surgical treatment of drug-resistant TLE.

The predictive value of local to remote functional connectivity changes in comitant exotropia patients.

Comitant exotropia (CE) is a common eye disease with abnormal eye movement, whereas altered synchronous neural activity in CE patients is poorly understood. The purpose of our study was to investigate local to remote functional connectivity of blood oxygen level-dependent (BOLD) signals changes in CE patients. Thirty-four patients and thirty-four healthy controls (HCs) underwent resting-state MRI scans. The ReHo and FC method was applied to investigate the local to remote functional connectivity changes in CE patients. Compared to the HC group, CE patients showed significant increased ReHo values in the left cerebellar_crus2 and left middle frontal gyrus. Meanwhile, CE patients showed significant decreased ReHo values in the right middle temporal gyrus, left postcentral gyrus and right angular. Moreover, CE patients showed an increased FC between the cerebellar network, sensorimotor network (SMN) and default-mode network (DMN). The support vector machine (SVM) classification was up to a total accuracy of 94.12%. The AUC of the classification model was 0.99 on the basis of ReHo map. Our result highlights that CE patients had abnormal local to remote functional connectivity in the cerebellar network, SMN, DMN, which might indicate the neural mechanism of eye movements and stereo vision dysfunction in CE patients. Moreover, the SVM algorithm reveals ReHo maps as a potential biomarker for predicting clinical outcomes in CE patients.

Resting State MRI Amplitude of Low Frequency Fluctuations Associated With Suicidal Ideation in Bipolar Depression.

Objective: Suicidal ideation (SI) is a risk factor for completed suicide. Our previous resting state functional magnetic resonance imaging (fMRI) study found that higher amplitude of low frequency fluctuation (ALFF) in right hippocampus and thalamus was associated with SI in major depressive disorder (MDD). The present study aimed to evaluate that association in participants with bipolar disorder (BD).Methods: Thirty depressed, adult participants with a DSM-IV diagnosis of BD had resting state fMRI scans. Region-of-interest (ROI) analyses used ALFF values within areas that were previously associated with SI in MDD. Spearman rank correlation and ordinal regression analyses were performed to assess associations between ALFF values and the SI item of the Montgomery-Asberg Depression Rating Scale. Exploratory whole-brain analyses identified regions where ALFF was associated with SI.Results: Within the right hippocampus region, SI was positively associated with ALFF (Spearman R = 0.490, P = .0060). Ordinal regression analysis indicated that for every 0.1-unit increase in ALFF in that region, the odds of having higher SI were increased by 35% (odds ratio = 1.35; 95% confidence interval, 1.08-1.73; P = .012). Within the previously identified thalamus cluster, SI was associated with ALFF only at a trend level (Spearman R = 0.310, P = .069). Whole-brain analyses identified 3 clusters of positive association between SI and ALFF, 1 of which was located in the right hippocampus.Conclusions: This study found that our previous finding of positive association between SI and ALFF in the right hippocampus extended to bipolar depression. Future studies should examine the clinical utility of this association, and the role of the hippocampus in SI.Trial Registration: Data used for this secondary analysis came from studies with ClinicalTrials.gov identifiers NCT02239094 (January 2015 through September 2016) and NCT02473250 (January 2015 through December 2019).

First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain

BackgroundWith the high spatial resolution and the potential to reach deep brain structures, ultrasound-based brain stimulation techniques offer new opportunities to non-invasively treat neurological and psychiatric disorders. However, little is known about long-term effects of ultrasound-based brain stimulation. Applying a longitudinal design, we comprehensively investigated neuromodulation induced by ultrasound brain stimulation to provide first sham-controlled evidence of long-term effects on the human brain and behavior.MethodsTwelve healthy participants received three sham and three verum sessions with transcranial pulse stimulation (TPS) focused on the cortical somatosensory representation of the right hand. One week before and after the sham and verum TPS applications, comprehensive structural and functional resting state MRI investigations and behavioral tests targeting tactile spatial discrimination and sensorimotor dexterity were performed.ResultsCompared to sham, global efficiency significantly increased within the cortical sensorimotor network after verum TPS, indicating an upregulation of the stimulated functional brain network. Axial diffusivity in left sensorimotor areas decreased after verum TPS, demonstrating an improved axonal status in the stimulated area.ConclusionsTPS increased the functional and structural coupling within the stimulated left primary somatosensory cortex and adjacent sensorimotor areas up to one week after the last stimulation. These findings suggest that TPS induces neuroplastic changes that go beyond the spatial and temporal stimulation settings encouraging further clinical applications.

HIV-Associated Structural and Functional Brain Alterations in Homosexual Males.

Purpose:Neuroimaging elucidations have shown structural and functional brain alterations in HIV-infected (HIV+) individuals when compared to HIV-negative (HIV–) controls. However, HIV− groups used in previous studies were not specifically considered for sexual orientation, which also affects the brain structures and functions. The current study aimed to characterize the brain alterations associated with HIV infection while controlling for sexual orientation.Methods:Forty-three HIV+ and 40 HIV– homosexual men (HoM) were recruited and underwent resting-state MRI scanning. Group differences in gray matter volume (GMV) were assessed using a voxel-based morphometry analysis. Brain regions with the altered GMV in the HIV+ HoM group were then taken as regions of interest in a seed-based analysis to identify altered functional connectivity. Furthermore, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity values were compared between the two groups to evaluate the HIV-associated functional abnormalities in local brain regions.Results:HIV+ HoM showed significantly increased GMV in the bilateral parahippocampal gyrus and amygdala, and decreased GMV in the right inferior cerebellum, compared with the HIV– HoM. The brain regions with increased GMV were hyper-connected with the left superior cerebellum, right lingual gyrus, and left precuneus in the HIV+ HoM. Moreover, the ALFF values of the right fusiform gyrus, and left parahippocampal gyrus were increased in the HIV+ HoM. The regional homogeneity values of the right anterior cingulate and paracingulate gyri, and left superior cerebellum were decreased in the HIV+ HoM.Conclusion:When the study population was restricted to HoM, HIV+ individuals exhibited structural alterations in the limbic system and cerebellum, and functional abnormalities in the limbic, cerebellum, and visual network. These findings complement the existing knowledge on the HIV-associated neurocognitive impairment from the previous neuroimaging studies by controlling for the potential confounding factor, sexual orientation. Future studies on brain alternations with the exclusion of related factors like sexual orientation are needed to understand the impact of HIV infection on neurocognitive function more accurately.