Strong Association of Depression and Anxiety With the Presence of Back Pain While Impact of Spinal Imaging Findings is Limited: Analysis of an MRI Cohort Study.

Development of back pain is multifactorial, and it is not well understood which factors are the main drivers of the disease. We therefore applied a machine-learning approach to an existing large cohort study data set and sought to identify and rank the most important contributors to the presence of back pain amongst the documented parameters of the cohort. Data from 399 participants in the KORA-MRI (Cooperative health research in the region Augsburg-magnetic resonance imaging) (Cooperative Health Research in the Region Augsburg) study was analyzed. The data set included MRI images of the whole body, including the spine, metabolic, sociodemographic, anthropometric, and cardiovascular data. The presence of back pain was one of the documented items in this data set. Applying a machine-learning approach to this preexisting data set, we sought to identify the variables that were most strongly associated with back pain. Mediation analysis was performed to evaluate the underlying mechanisms of the identified associations. We found that depression and anxiety were the 2 most selected predictors for back pain in our model. Additionally, body mass index, spinal canal width and disc generation, medium and heavy physical work as well as cardiovascular factors were among the top 10 most selected predictors. Using mediation analysis, we found that the effects of anxiety and depression on the presence of back pain were mainly direct effects that were not mediated by spinal imaging. In summary, we found that psychological factors were the most important predictors of back pain in our cohort. This supports the notion that back pain should be treated in a personalized multidimensional framework. PERSPECTIVE: This article presents a wholistic approach to the problem of back pain. We found that depression and anxiety were the top predictors of back pain in our cohort. This strengthens the case for a multidimensional treatment approach to back pain, possibly with a special emphasis on psychological factors.

Sleep dysfunction mediates the relationship between hypothalamic-insula connectivity and anxiety-depression symptom severity bidirectionally in young adults.

BACKGROUND: The hypothalamus plays a crucial role in regulating sleep-wake cycle and motivated behavior. Sleep disturbance is associated with impairment in cognitive and affective functions. However, how hypothalamic dysfunction may contribute to inter-related sleep, cognitive, and emotional deficits remain unclear. METHODS: We curated the Human Connectome Project dataset and investigated how hypothalamic resting state functional connectivities (rsFC) were associated with sleep dysfunction, as evaluated by the Pittsburgh Sleep Quality Index (PSQI), cognitive performance, and subjective mood states in 687 young adults (342 women). Imaging data were processed with published routines and evaluated with a corrected threshold. We examined the inter-relationship amongst hypothalamic rsFC, PSQI score, and clinical measures with mediation analyses. RESULTS: In whole-brain regressions with age and drinking severity as covariates, men showed higher hypothalamic rsFC with the right insula in correlation with PSQI score. No clusters were identified in women at the same threshold. Both hypothalamic-insula rsFC and PSQI score were significantly correlated with anxiety and depression scores in men. Further, mediation analyses showed that PSQI score mediated the relationship between hypothalamic-insula rsFC and anxiety/depression symptom severity bidirectionally in men. CONCLUSIONS: Sleep dysfunction is associated with negative emotions and hypothalamic rsFC with the right insula, a core structure of the interoceptive circuits. Notably, anxiety-depression symptom severity and altered hypothalamic-insula rsFC are related bidirectionally by poor sleep quality. These findings are specific to men, suggesting potential sex differences in the neural circuits regulating sleep and emotional states that need to be further investigated.

[Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI].

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION: The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Exploring the central mechanism of mind-regulation electroacupuncture in treatment of chronic fatigue syndrome with anxiety and depression comorbidity based on functional magnetic resonance imaging. / åŸºäºŽåŠŸèƒ½ç£å ±æŒ¯æŽ¢è®¨è°ƒç¥žæ³•ç”µé’ˆæ²»ç–—æ ¢æ€§ç–²åŠ³ç»¼åˆå¾ä¼´ç„¦è™‘æŠ‘éƒå ±ç— çš„ä¸­æž¢æœºåˆ¶.

OBJECTIVES: To observe the changes in the regional homogeneity (ReHo) and functional brain network in treatment of chronic fatigue syndrome (CFS) with anxiety and depression comorbidity with the mind-regulation electroacupuncture (EA), using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Thirty CFS patients with anxiety and depression comorbidity were enrolled from medical staffs as the observation group. The other 30 healthy subjects were recruited from medical university students as the control group, matching gender, age and education years with the observation group. No any acupuncture intervention was delivered in the control group, and EA for regulating the mind was operated in the observation group. Main points were the emotional area of Sun's scalp acupuncture, the regions 1 and 8 of Sun's abdominal acupuncture. Supplementary acupoints included Baihui (GV 20), Guanyuan (CV 4) and bilateral. RESULTS: The scores of the five domains in MFI-20 (i.e. general fatigue, physical fatigue, mental fatigue, reduced motivation and reduced activity), the total score of MFI-20, and the scores of SDS, SAS and PSQI in the observation group before treatment were higher than those of the control group (P<0.05). Except the score of reduced motivation in MFI-20, the scores of the other domains and the total score of MFI-20, as well as the scores of SDS, SAS and PSQI after treatment were lower than those before treatment in the observation group (P<0.05). Compared with the values before treatment, ReHo value was increased in the the right precuneus and decreased in the left inferior temporal gyrus and the left angular gyrus of the brain in the observation group after treatment. In the observation group, when compared with the control group, ReHo values were increased in the left inferior cerebral lobe, the interhemispheric region, the right occipital lobe and the thalamus; and it was reduced in the left middle temporal gyrus, the right posterior central gyrus, the right middle temporal gyrus, the right orbital middle frontal gyrus, the paracentral lobule and the right fusiform gyrus before treatment. In the observation group, the functional connectivity was decreased between the right thalamus and the left posterior central gyrus, the right hippocampus and the right fusiform gyrus before treatment, respectively; it was re-constructed after treatment between the right thalamus and the left posterior central gyrus, and the right fusiform gyrus. Compared with the control group, the functional connectivity between the right thalamus and the left posterior central gyrus, the right hippocampus, and the right fusiform gyrus was reduced before treatment; while after treatment, the functional connectivity was reduced between the right thalamus and the hippocampus in the observation group. With Spearman correlation analysis between the differential brain regions and the scores of MFI-20, SAS, SDS and PSQI, it was found that the left middle temporal gyrus, the paracentral lobule, the right precuneus, and the left inferior temporal gyrus had a partial positive correlation with the above clinical scales; and the interhemispheric region, the thalamus, the right fusiform gyrus, and the right middle temporal gyrus showed a partial negative correlation. CONCLUSIONS: There is the decrease of ReHo in many brain regions and the numbers of the local brain functional network connectivity in CFS patients with anxiety and depression comorbidity. The mind-regulation electroacupuncture therapy may relieve the clinical symptoms of the patients through adjusting the abnormal brain regions and activating emotion-related brain regions.

Increased insula response to interoceptive attention following mindfulness training is associated with increased body trusting among patients with depression.

Interoceptive dysfunction is often present in anxiety and depression. We investigated the effects of an 8-week intervention, Mindfulness Training for Primary Care (MTPC), on brain mechanisms of interoceptive attention among patients with anxiety and/or depression. We hypothesized that fMRI brain response to interoception in the insula, a region known for interoceptive processing, would increase following the MTPC intervention, and that such increases would be associated with post-intervention changes in self-reported measures of interoceptive awareness. Adults (n = 28) with anxiety and/or depression completed baseline and post-intervention fMRI visits, including a task in which they alternated between focusing on their heartbeat (interoception (INT)) and a control visual attention task (exteroception (EXT)). Following MTPC, we observed increased evoked fMRI response (relative to baseline) in left anterior insula during the INT-EXT task contrast (z > 3.1, p < 0.001 corrected). In patients with moderate-to-severe depression as defined by the Patient Reported Outcomes Measurement Information System (PROMIS), increased post-intervention insula response was associated with increased Body Trusting, a subscale of the Multidimensional Assessment of Interoceptive Awareness (z > 3.1, p = 0.007 corrected). This study demonstrates that patients with mood disorders may respond differentially to mindfulness-based treatment depending on depression severity, and that among those who are more depressed, increased trusting in one's own body sensations and experiencing the body as a safe place to attend to may be necessary components of positive responses to mindfulness-based interventions.

Preliminary single-arm study of brain effects during transcutaneous auricular vagus nerve stimulation treatment of recurrent depression by resting-state functional magnetic resonance imaging.

OBJECTIVE: To examine the brain effects of transcutaneous auricular vagus nerve stimulation (taVNS) treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging (fMRI). METHODS: Twenty-five patients with recurrent depression were enrolled in a single-arm trial of taVNS treatment for eight weeks. Clinical results were assessed by 17-item Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Scale (HAMA), Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Ruminative Response Scale (RRS) scales. Resting-state fMRI was conducted to explore the brain effects before and after treatment. For the functional connectivity (FC) analysis, the bilateral nucleus accumbens, globus pallidus, caudate, and putamen were selected as seeds. Finally, the correlations between FC and the clinical scale scores were calculated. RESULTS: After treatment, the patients' scores of HAMD-17, HAMA, SDS, SAS, and RRS were significantly decreased ( < 0.05). FC was considerably decreased between the following areas: the left globus pallidus and the right postcentral gyrus, inferior parietal gyrus, the right globus pallidus and the left superior marginal gyrus, postcentral gyrus, superior parietal gyrus, inferior parietal gyrus, precuneus, right postcentral gyrus, superior marginal gyrus, and inferior parietal gyrus, between the right caudate and the right lingual gyrus, calcarine gyrus, and cerebellum. Changes in FC between the right globus pallidus and the left inferior parietal gyrus, between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment (before, = 0.003, = -0.6; after, 0.009,= -0.54). The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS (= 0.026,= -0.474). The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS (= 0.016,= -0.513). CONCLUSIONS: Recurrent depression could be effectively treated with taVNS. The changes in brain FC involving the basal ganglia, default mode, and sensorimotor networks provide insight into the effects of taVNS treatment on recurrent depression.

Impact of Tai Chi as an adjunct treatment on brain connectivity in geriatric depression.

BACKGROUND: As an adjunct to antidepressant treatment, Tai Chi Chih (TCC) is superior to health education and wellness (HEW) training in improving the general health of patients with geriatric depression (GD). This study investigated the brain connectivity changes associated with TCC and HEW in combination with antidepressant treatment in patients with GD. METHODS: Forty patients with GD under stable antidepressant treatment underwent TCC training (n = 21) or HEW training (n = 19) for 12 weeks, and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. Within-group and between-group differences in parcel-to-parcel connectivity changes with intervention were evaluated by general linear modeling. Relationships between significant connectivity changes and symptom/resilience improvement were evaluated by partial least squares correlation analysis. RESULTS: Significantly greater increases in connectivity with TCC than with HEW (FDR-corrected p < .05) were observed for 167 pairwise connections, most frequently involving the default mode network (DMN). In both groups, increased connectivity involving largely DMN regions was significantly and positively correlated with improvement in symptoms/resilience. LIMITATIONS: The sample size was relatively small, mainly due to neuroimaging contraindications (e.g., implants). Additionally, the standard antidepressant treatment varied greatly among patients, adding heterogeneity. CONCLUSIONS: Non-pharmacological adjuncts, such as TCC, may enhance DMN connectivity changes associated with improved depressive symptoms and psychological resilience in the treatment of GD.

Effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on depression and neural structural connectivity.

BACKGROUND: Hypertension-related illnesses are a leading cause of disability and death in the United States, where hypertension prevalence in adults is 46%, with only half of those afflicted having it under control. Due to the significant challenges in long-term efficacy and adverse effects associated with pharmacological interventions, there is an eminent need for complimentary approaches for treating hypertension. Although initial studies of the Mindfulness-Based Blood Pressure Reduction program (MB-BP) indicate that this novel 8-week intervention is effective at inducing lasting decreases in blood pressure, the neural correlates are unknown. METHODS: The objectives of this study were to identify structural neural correlates of MB-BP using diffusion tensor magnetic resonance imaging (DTI) and assess potential correlations with key clinical outcomes. RESULTS: In a subset of participants (14 MB-BP, 22 controls) from a larger stage IIa randomized controlled trial, MB-BP participants exhibited increased interoception and decreased depressive symptoms compared to controls. Analyses of DTI data revealed significant group differences in multiple white matter neural tracts associated with the limbic system and/or blood pressure. Specific changes in neural structural connectivity were significantly associated with measures of interoception and depression. LIMITATIONS: Limitations include small sample size (leading to insufficient power in the analysis of blood pressure) and the study duration (3 months). The main MRI limitation is suboptimal resolution in areas of extensive neural tract crossings. CONCLUSIONS: It is concluded that MB-BP induces alterations in brain structural connectivity which could mediate beneficial changes in depression and interoceptive awareness in individuals with hypertension.

Magnetic Resonance Imaging to Evaluate the Recovery Effects of Cerebral Nerve Function in Comprehensive Treatment of Poststroke Depression by Intelligent Algorithm-Based Hyperbaric Oxygen Therapy.

This research was aimed to discuss magnetic resonance imaging (MRI) evaluation of recovery effects of cerebral nerve function in comprehensive treatment of poststroke depression (PSD) by intelligence-based hyperbaric oxygen therapy. Low-rank matrix algorithm was adopted to denoise MRI images of patients with PSD, and mean square error (MSE) and peak signal-to-noise ratio (PSNR) were the evaluation indicators of the results of image denoising. 118 patients were randomly divided into the control group (administered escitalopram oxalate) and the research group (hyperbaric oxygen therapy was implemented based on the treatment in control group). National Institutes of Health Stroke Scale (NIHSS), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), glial fibrillary acidic protein (GFAP), and changes of norepinephrine (NE) level of patients in two groups were compared before and after treatment. The value of MSE of MRI images processed by low-rank matrix algorithm was 92.39, which was higher than that calculated by nonlocal mean (NLM) algorithm (80.54). The PSNR value calculated by low-rank matrix algorithm was 25.35, which was lower than that calculated by NLM algorithm (29.07). In contrast, NIHSS score and HAMD score of the research group after treatment were lower than those of the control group, while PSQI score of the research group was higher than that of the control group. The level of GFAP of the research group was at 852.46 ± 94.47, which was significantly lower than that of the control group, reaching 948.53 ± 98.42. However, the level of NE of the research group was 1478.59 ± 99.85, which was higher than that of the control group (1061.80 ± 98.02). All the comparisons of above indicators had statistical meaning (P < 0.05). The low-rank matrix algorithm can help in clinical diagnosis and treatment to provide more accurate MRI images. In addition, hyperbaric oxygen comprehensive therapy can promote the recovery of neurological function in patients with poststroke depression and significantly improve the depressive state and sleep quality of patients.

Enhanced Temporal Coupling between Thalamus and Dorsolateral Prefrontal Cortex Mediates Chronic Low Back Pain and Depression.

Numerous neuroimaging studies have demonstrated that the brain plasticity is associated with chronic low back pain (cLBP). However, there is a lack of knowledge regarding the underlying mechanisms of thalamic pathways for chronic pain and psychological effects in cLBP caused by lumbar disc herniation (LDH). Combining psychophysics and magnetic resonance imaging (MRI), we investigated the structural and functional brain plasticity in 36 patients with LDH compared with 38 age- and gender-matched healthy controls. We found that (1) LDH patients had increased psychophysical disturbs (i.e., depression and anxiety), and depression (Beck-Depression Inventory, BDI) was found to be an outstanding significant factor to predict chronic pain (short form of the McGill Pain Questionnaire, SF-MPQ); (2) the LDH group showed significantly smaller fractional anisotropy values in the region of posterior corona radiate while gray matter volumes were comparable in both groups; (3) resting state functional connectivity analysis revealed that LDH patients exhibited increased temporal coupling between the thalamus and dorsolateral prefrontal cortex (DLPFC), which further mediate the relationship from chronic pain to depression. Our results emphasized that thalamic pathways underlying prefrontal cortex might play a key role in regulating chronic pain and depression of the pathophysiology of LDH.

[Functional MRI-based study on neuromechanism of trans-auricular vagus nerve stimulation for treatment-resistant depression].

OBJECTIVE: To explore the neuromechanism of trans-auricular vagus nerve stimulation (taVNS) for treatment-resistant depression(TRD) based on functional brain network. METHODS: Twenty-eight patients with TRD were recruited from the psychiatric clinic or by the advertisement. The patients were treated by taVNS (5 Hz/20 Hz, 4-8 mA) at the auricular concha for 30 min, twice daily for 8 weeks. The symptom severity was assessed by 17-Item Hamilton Rating Scale for Depression (HAMD-17, ranging from 0 to 54 points, higher score indicates more severe conditions). Resting state fMRI data of the brain were collected to analyze changes of the regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF) and resting state functional connectivity (rs-FC) before and after 8 weeks' taVNS by using DPARSF toolkit and the correlation between the rs-FC and clinical scale score was analyzed to assess the related brain mechanisms. RESULTS: Twenty-four patients finished the clinical study, and 23 patients finished the fMRI tests. After the treatment, the average score of HAMD-17 was significantly decreased (P<0.01), with the reduction rate being 66.95%; the ALFF and ReHo values of the right insula and putamen, the ReHo values of the right caudate nucleus and thalamus, as well as the rs-FC values of the right insula, left superior frontal gyrus and middle frontal gyrus were all significantly decreased (P<0.05). The reduced ReHo value in the right insular lobe was negatively correlated with the HAMD score reduction (P=0.001, r=-0.633). The rs-FC values of the right insula lobe and the left superior frontal gyrus were significantly negatively correlated with the reduced HAMD score(P=0.012, r=-0.512). CONCLUSION: TaVNS significantly relieves the symptoms of TRD patients, which may be related to its functions in regulating functional changes of the right insular and the left frontal gyrus network, and the limbic area and basal ganglia.

Effects of Mindfulness Training on Emotion Regulation in Patients With Depression: Reduced Dorsolateral Prefrontal Cortex Activation Indexes Early Beneficial Changes.

OBJECTIVE: Mindfulness-based interventions (MBIs) have been found to be a promising approach for the treatment of recurrent courses of depression. However, little is known about their neural mechanisms. This functional magnetic resonance imaging study set out to investigate activation changes in corticolimbic regions during implicit emotion regulation. METHODS: Depressed patients with a recurrent lifetime history were randomized to receive a 2-week MBI (n = 16 completers) or psychoeducation and resting (PER; n = 22 completers). Before and after, patients underwent functional magnetic resonance imaging while labeling the affect of angry, happy, and neutral facial expressions and completed questionnaires assessing ruminative brooding, the ability to decenter from such thinking, and depressive symptoms. RESULTS: Activation decreased in the right dorsolateral prefrontal cortex (dlPFC) in response to angry faces after MBI (p < .01, voxel-wise family-wise error rate correction, T > 3.282; 56 mm3; Montreal Neurological Institute peak coordinate: 32, 24, 40), but not after PER. This change was highly correlated with increased decentring (r = -0.52, p = .033), decreased brooding (r = 0.60, p = .010), and decreased symptoms (r = 0.82, p = .005). Amygdala activation in response to happy faces decreased after PER (p < .01, family-wise error rate corrected; 392 mm3; Montreal Neurological Institute peak coordinate: 28, -4, -16), whereas the MBI group showed no significant change. CONCLUSIONS: The dlPFC is involved in emotion regulation, namely, reappraisal or suppression of negative emotions. Decreased right dlPFC activation might indicate that, after the MBI, patients abstained from engaging in elaboration or suppression of negative affective stimuli; a putatively important mechanism for preventing the escalation of negative mood.Trial Registration: The study is registered at ClinicalTrials.gov (NCT02801513; 16/06/2016).

Clinical Application of Real-Time fMRI-Based Neurofeedback for Depression.

Real-time functional magnetic resonance imaging-based neurofeedback (rt-fMRI NF) is a recent technique used to train self-regulation of circumscribed brain areas or networks. For clinical applications in depression, NF training targets brain areas with disturbed activation patterns, such as heightened reactivity of amygdala in response to negative stimuli, in order to normalize the neurophysiology and their behavioral correlates. Recent studies have targeted emotion processing areas such as the amygdala, the salience network, and top-down control areas such as the lateral prefrontal cortex. Different methods of rt-fMRI-based NF in depression, their potential for clinical improvement, and most recent advancements of this technology are discussed considering their role for future clinical applications. Initial findings of randomized controlled trials show promising results. However, for lasting treatment effects, clinical efficiency and optimal target regions, tasks, control conditions, and duration of training need to be established.

Degeneration of core neural tracts for emotional regulation in a patient with traumatic brain injury: A case report.

RATIONALE: Several brain structures, including the orbital prefrontal cortex, ventrolateral prefrontal cortex, dorsolateral prefrontal cortex, amygdala, and anterior cingulate cortex, are considered key structures in the neural circuitry underlying emotion regulation. We report on a patient showing behavior changes and degeneration of core neural tracts for emotional regulation following traumatic brain injury (TBI). PATIENT CONCERNS: A 51-year-old male patient suffered an in-car accident. The patient lost consciousness for approximately 30 days, and his Glasgow Coma Scale score was 3. He underwent stereotactic drainage for traumatic intraventricular and intracerebral hemorrhages. At approximately 6.5-year after onset, he began to show disinhibition behaviors such as shouting with anger, which worsened over time. At approximately 8-year after onset, he showed severe depression signs and disinhibition, including violence. DIAGNOSES: The patient who showed delayed-onset behavioral changes (disinhibition and depression). INTERVENTIONS: Diffusion tensor imaging data were acquired at 3 months and 8 years after TBI onset. OUTCOMES: The patient showed degeneration of core neural tracts for emotional regulation that was associated with delayed behavioral changes following TBI. On both 3-month and 8-year diffusion tensor tractographies (DTTs), the right dorsolateral prefronto-thalamic tract, ventrolateral prefronto-thalamic tract, orbital prefronto-thalamic tract, uncinate fasciculus, and both cinguli were reconstructed whereas other neural tracts were not reconstructed. Compared with the 3-month DTT, all reconstructed neural tracts on the 8-year DTT were narrow, except for the left cingulum, which showed new transcallosal fibers between both anterior cingula. The fractional anisotropy and tract volume of all reconstructed neural tracts were lower on the 8-year DTT than the 3-month DTT, except for the tract volume of left cingulum. LESSONS: The evaluation of dorsolateral, ventrolateral, and orbital prefronto-thalamic tract, uncinate fasciculus, and cingulum using follow-up DTTs is useful when a patient with TBI shows delayed-onset behavioral problems.

Blockade of Indoleamine 2, 3-dioxygenase 1 ameliorates hippocampal neurogenesis and BOLD-fMRI signals in chronic stress precipitated depression.

Indoleamine 2, 3-dioxygenase 1 (IDO1) has been implicated in the pathogenesis of depression, though its molecular mechanism is still poorly understood. We investigated the molecular mechanism of IDO1 in depression by using the chronic unpredictable mild stress (CUMS) model in Ido1-/- mice and WT mice. The brain blood oxygen level dependent (BOLD) signals in mice were collected by functional magnetic resonance imaging (fMRI) technology. IDO1 inhibitor INCB024360 was intervened in dorsal raphe nucleus (DRN) through stereotactic injection. We found an elevation of serum IDO1 activity and decreased 5-HT in CUMS mice, and the serum IDO1 activity was negatively correlated with 5-HT level. Consistently, IDO1 was increased in hippocampus and DRN regions, accompanied by a reduction of hippocampal BDNF levels in mice with CUMS. Specifically, pharmacological inhibition of IDO1 activity in the DRN alleviated depressive-like behaviour with improving hippocampal BDNF expression and neurogenesis in CUMS mice. Furthermore, ablation of Ido1 exerted stress resistance and decreased the sensitivity of depression in CUMS mice with the stable BOLD signals, BDNF expression and neurogenesis in hippocampus. Thus, IDO1 hyperactivity played crucial roles in modulating 5-HT metabolism and BDNF function thereby impacting outcomes of hippocampal neurogenesis and BOLD signals in depressive disorder.

Brain Networks Connectivity in Mild to Moderate Depression: Resting State fMRI Study with Implications to Nonpharmacological Treatment.

Network mechanisms of depression development and especially of improvement from nonpharmacological treatment remain understudied. The current study is aimed at examining brain networks functional connectivity in depressed patients and its dynamics in nonpharmacological treatment. Resting state fMRI data of 21 healthy adults and 51 patients with mild or moderate depression were analyzed with spatial independent component analysis; then, correlations between time series of the components were calculated and compared between-group (study 1). Baseline and repeated-measure data of 14 treated (psychotherapy or fMRI neurofeedback) and 15 untreated depressed participants were similarly analyzed and correlated with changes in depression scores (study 2). Aside from diverse findings, studies 1 and 2 both revealed changes in within-default mode network (DMN) and DMN to executive control network (ECN) connections. Connectivity in one pair, initially lower in depression, decreased in no treatment group and was inversely correlated with Montgomery-Asberg depression score change in treatment group. Weak baseline connectivity in this pair also predicted improvement on Montgomery-Asberg scale in both treatment and no treatment groups. Coupling of another pair, initially stronger in depression, increased in therapy though was unrelated to improvement. The results demonstrate possible role of within-DMN and DMN-ECN functional connectivity in depression treatment and suggest that neural mechanisms of nonpharmacological treatment action may be unrelated to normalization of initially disrupted connectivity.

The Dynamics of Functional Brain Networks Associated With Depressive Symptoms in a Nonclinical Sample.

Brain function depends on the flexible and dynamic coordination of functional subsystems within distributed neural networks operating on multiple scales. Recent progress has been made in the characterization of functional connectivity (FC) at the whole-brain scale from a dynamic, rather than static, perspective, but its validity for cognitive sciences remains under debate. Here, we analyzed brain activity recorded with functional Magnetic Resonance Imaging from 71 healthy participants evaluated for depressive symptoms after a relationship breakup based on the conventional Major Depression Inventory (MDI). We compared both static and dynamic FC patterns between participants reporting high and low depressive symptoms. Between-group differences in static FC were estimated using a standard pipeline for network-based statistic (NBS). Additionally, FC was analyzed from a dynamic perspective by characterizing the occupancy, lifetime, and transition profiles of recurrent FC patterns. Recurrent FC patterns were defined by clustering the BOLD phase-locking patterns obtained using leading eigenvector dynamics analysis (LEiDA). NBS analysis revealed a brain subsystem exhibiting significantly lower within-subsystem correlation values in more depressed participants (high MDI). This subsystem predominantly comprised connections between regions of the default mode network (i.e., precuneus) and regions outside this network. On the other hand, LEiDA results showed that high MDI participants engaged more in a state connecting regions of the default mode, memory retrieval, and frontoparietal network (p-FDR = 0.012); and less in a state connecting mostly the visual and dorsal attention systems (p-FDR = 0.004). Although both our analyses on static and dynamic FC implicate the role of the precuneus in depressive symptoms, only including the temporal evolution of BOLD FC helped to disentangle over time the distinct configurations in which this region plays a role. This finding further indicates that a holistic understanding of brain function can only be gleaned if the temporal dynamics of FC is included.

Outward subcortical curvature associated with sub-clinical depression symptoms in adolescents.

OBJECTIVE: Subclinical or subthreshold depressive symptoms (StD) are frequent in adolescence and are related to suicidality and onset of depression in adulthood, however, their neurobiology is poorly understood. We examined the relationship between StD and subcortical grey matter structures in unmedicated adolescents with no history of axis I diagnosis. METHODS: 277 youths from Chicago aged 14 years participated, undergoing a structural MRI scan and completing the Revised Children's Anxiety and Depression Scale (RCADS). Blood samples provided a composite of five pro-inflammatory cytokines. Regions of interest (ROI) for vertex-based surface analysis were the left and right amygdala, hippocampus, thalamus, caudate, nucleus accumbens, pallidum and putamen. Covariates were age, pubertal status, socioeconomic disadvantage and intracranial volume. Males and females were analysed separately. RESULTS: StD had positive associations (outward shape) with subcortical morphology in the right amygdala and left hippocampus in females, and the bilateral putamen and the left caudate, hippocampus and thalamus in males. However, we also found negative associations with StD (inward contractions) in the hippocampus in females and the caudate in males. Pro-inflammatory cytokines did not mediate the relationship between StD and outward morphology or volume. CONCLUSION: This is one of the first studies to examine subcortical morphology of basal ganglia and thalamic regions related to StD in adolescents, and the first study to report mostly positive associations between StD, volume and outward morphology in youths. These findings could reflect intact neurogenesis or resilience to depression, however longitudinal research is needed to further understand the neurobiology of StD in adolescents.

Dynamic changes in thalamic connectivity following stress and its association with future depression severity.

INTRODUCTION: Tracking stress-induced brain activity and connectivity dynamically and examining activity/connectivity-associated recovery ability after stress might be an effective way of detecting stress vulnerability. METHODS: Using two widely used stress paradigms, a speech task (social stress) and a mathematical calculation task (mental loading stress), we examined common changes in regional homogeneity (ReHo) and functional connectivity (FC) before, during, and after the two stressful tasks in thirty-nine college students. A counting breath relaxation task was employed as a contrast task. ReHo and FC were compared between subjects with higher versus lower depression symptoms (assessed by the Beck Depression Inventory, BDI). We developed a recovery index (RI) based on dynamic changes of ReHo/FC to evaluate individuals' ability to recover from a stressful state. To assess RI's usefulness in predicting future depression severity, BDI was also measured at one-year follow-up. RESULTS: Our results revealed a ReHo decrease after both stressful tasks and a ReHo increase after the relaxation task in bilateral thalamus. The ReHo decrease after both stressful tasks was more significant in the higher BDI than the lower BDI group. Higher ReHo RI of the right thalamus in the higher BDI groups was significantly correlated with lower BDI severity at one-year follow-up. Bilateral thalamus also showed increased FC with the default mode network and decreased FC with the executive control network after the stressful tasks. CONCLUSION: These findings highlight the importance of tracking resting activity and connectivity of thalamus dynamically for detecting stress vulnerability.

Cerebral patterns of neuropsychological disturbances in hepatitis C patients.

Neuropsychiatric symptoms and cognitive impairment have been consistently reported in patients with hepatitis C virus (HCV) infection. Since the mechanisms behind remain to be established, the present study attempted to assess whether neuropsychological impairments in HCV-infected patients are accompanied by structural alterations in the brain. Therefore, 19 anti-HCV-antibody-positive women with mild liver disease and 16 healthy controls underwent extensive neuropsychological testing and cranial magnetic resonance imaging (MRI) examination. Nine of the patients and five controls were followed up after 6-7 years. Voxel-based morphometry and magnetization transfer imaging were utilized to study HCV-associated structural gray and white matter changes. The HCV-infected patients had significantly worse fatigue and depression scores and significantly poorer performance on attention and memory tests than controls. The patients displayed gray matter (GM) atrophy in the bilateral insula and thalamus and a profound GM volume increases in the cerebellum. Microstructural GM changes in the insula were also evident by a reduced magnetization transfer ratio. Structural white matter changes were observed along several descending and crossing fiber tracts. Follow-up at 7 years revealed increased GM atrophy in the left amygdala and left parahippocampal regions over time. We conclude that our data provide evidence for structural alterations in the brains of patients with chronic HCV infection. Disturbances of cerebellothalamocortical regions and circuits, linking cerebellar projections to the prefrontal cortex through the thalamus, underpin the emotional and cognitive dysfunction characteristically observed in these patients.