Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach.

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Modulating the default mode network: Antidepressant efficacy of transcutaneous electrical cranial-auricular acupoints stimulation targeting the insula.

BACKGROUND: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy for major depressive disorder (MDD) that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. However, there are few neuroimaging studies involving the TECAS for the treatment of MDD. Therefore, this study aimed to investigate the treatment response and neurological effects of TECAS using resting-state functional magnetic resonance imaging (rs-fMRI). METHOD: A total of 34 patients with mild-to-moderate MDD and 34 demographically matched healthy controls (HCs) were recruited. After an eight-week treatment the primary outcome was clinical response, defined as a baseline-to-endpoint ≥ 50 % reduction in the 17-item Hamilton Depression Rating Scale (HAMD-17). The low-frequency fluctuations (ALFF) method were used to investigate the brain abnormalities of MDD patients and HCs, and altered brain networks were analyzed between pre- and post-treatment using seed-based functional connectivity (FC) analysis. RESULTS: We found no significant differences in terms of gender, age, and years of education between the two groups. After treatment, the response rate was 58.82 %. Compared to HCs, MDD patients showed lower ALFF values in the left insula(t = -4.298,P < 0.005), the insula-based FC revealed in the right middle frontal gyrus (MFG)/ right superior frontal gyrus, orbital part (ORBsupmed) (t = -5.29,P < 0.005) and the right anterior cingulate gyrus (ACC)were decreased (t = -6.08,P < 0.005). Furthermore, Compared to pre-treatment, abnormal FC values in the ACC /orbital superior frontal gyrus (SFG) (t = 3.42,P < 0.005) and left superior frontal gyrus (SFG)/ supplement motor area (SMA) were enhanced (t = 3.34,P < 0.005). CONCLUSION: TECAS exhibits antidepressant efficacy, particularly influencing the insula-based functional connections within the Default Mode Network (DMN) related to emotion processing in individuals with MDD.

How Does Meditation Affect the Default Mode Network: A Systematic Review.

This article provides a systematic review of studies evaluating the effect of meditation on the Default Mode Network (DMN). The review was conducted according to PRISMA guidelines. A literature search of PubMed, Scopus, and Embase was conducted up to June 2020. Search terms included default mode network or DMN and meditation.A total of 306 articles were identified, of which 16 controlled trials with a total of 853 experienced (in Mindfulness, Samatha, Raja Yoga, Transcendental Meditation, Vipassana, Insight meditation Theravada tradition) and non-experienced mediators were finally included in this systematic review. The results showed that meditative interventions affect the operation of DMN and there are differences in functional connectivity between networks. Further research should be undertaken to establish meditation as an effective intervention strategy for well-being.

Reducing default mode network connectivity with mindfulness-based fMRI neurofeedback: a pilot study among adolescents with affective disorder history.

Adolescents experience alarmingly high rates of major depressive disorder (MDD), however, gold-standard treatments are only effective for ~50% of youth. Accordingly, there is a critical need to develop novel interventions, particularly ones that target neural mechanisms believed to potentiate depressive symptoms. Directly addressing this gap, we developed mindfulness-based fMRI neurofeedback (mbNF) for adolescents that aims to reduce default mode network (DMN) hyperconnectivity, which has been implicated in the onset and maintenance of MDD. In this proof-of-concept study, adolescents (n = 9) with a lifetime history of depression and/or anxiety were administered clinical interviews and self-report questionnaires, and each participant's DMN and central executive network (CEN) were personalized using a resting state fMRI localizer. After the localizer scan, adolescents completed a brief mindfulness training followed by a mbNF session in the scanner wherein they were instructed to volitionally reduce DMN relative to CEN activation by practicing mindfulness meditation. Several promising findings emerged. First, mbNF successfully engaged the target brain state during neurofeedback; participants spent more time in the target state with DMN activation lower than CEN activation. Second, in each of the nine adolescents, mbNF led to significantly reduced within-DMN connectivity, which correlated with post-mbNF increases in state mindfulness. Last, a reduction of within-DMN connectivity mediated the association between better mbNF performance and increased state mindfulness. These findings demonstrate that personalized mbNF can effectively and non-invasively modulate the intrinsic networks associated with the emergence and persistence of depressive symptoms during adolescence.

Posterior cingulate cortex targeted real-time fMRI neurofeedback recalibrates functional connectivity with the amygdala, posterior insula, and default-mode network in PTSD.

BACKGROUND: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. METHODS: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. RESULTS: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. CONCLUSION: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.

Disentangling self from pain: mindfulness meditation-induced pain relief is driven by thalamic-default mode network decoupling.

ABSTRACT: For millenniums, mindfulness was believed to diminish pain by reducing the influence of self-appraisals of noxious sensations. Today, mindfulness meditation is a highly popular and effective pain therapy that is believed to engage multiple, nonplacebo-related mechanisms to attenuate pain. Recent evidence suggests that mindfulness meditation-induced pain relief is associated with the engagement of unique cortico-thalamo-cortical nociceptive filtering mechanisms. However, the functional neural connections supporting mindfulness meditation-based analgesia remain unknown. This mechanistically focused clinical trial combined functional magnetic resonance imaging with psychophysical pain testing (49°C stimulation and pain visual analogue scales) to identify the neural connectivity supporting the direct modulation of pain-related behavioral and neural responses by mindfulness meditation. We hypothesized that mindfulness meditation-based pain relief would be reflected by greater decoupling between brain mechanisms supporting appraisal (prefrontal) and nociceptive processing (thalamus). After baseline pain testing, 40 participants were randomized to a well-validated, 4-session mindfulness meditation or book-listening regimen. Functional magnetic resonance imaging and noxious heat (49°C; right calf) were combined during meditation to test study hypotheses. Mindfulness meditation significantly reduced behavioral and neural pain responses when compared to the controls. Preregistered (NCT03414138) whole-brain analyses revealed that mindfulness meditation-induced analgesia was moderated by greater thalamus-precuneus decoupling and ventromedial prefrontal deactivation, respectively, signifying a pain modulatory role across functionally distinct neural mechanisms supporting self-referential processing. Two separate preregistered seed-to-seed analyses found that mindfulness meditation-based pain relief was also associated with weaker contralateral thalamic connectivity with the prefrontal and primary somatosensory cortex, respectively. Thus, we propose that mindfulness meditation is associated with a novel self-referential nociceptive gating mechanism to reduce pain.

Meditation reduces brain activity in the default mode network in children with active cancer and survivors.

BACKGROUND: Mounting evidence demonstrates that meditation can lower pain and emotional distress in adults, and more recently, in children. Children may benefit from meditation given its accessibility across a variety of settings (e.g., surgical preparation). Recent neuroimaging studies in adults suggest that meditation techniques are neurobiologically distinct from other forms of emotion regulation, such as distraction, that rely on prefrontal control mechanisms, which are underdeveloped in youth. Rather, meditation techniques may not rely on "top-down" prefrontal control and may therefore be utilized across the lifespan. PROCEDURE: We examined neural activation in children with cancer, a potentially distressing diagnosis. During neuroimaging, children viewed distress-inducing video clips while using martial arts-based meditation (focused attention, mindful acceptance) or non-meditation (distraction) emotion regulation techniques. In a third condition (control), participants passively viewed the video clip. RESULTS: We found that meditation techniques were associated with lower activation in default mode network (DMN) regions, including the medial frontal cortex, precuneus, and posterior cingulate cortex, compared to the control condition. Additionally, we found evidence that meditation techniques may be more effective for modulating DMN activity than distraction. There were no differences in self-reported distress ratings between conditions. CONCLUSION: Together, these findings suggest that martial arts-based meditation modulates negative self-referential processing associated with the DMN, and may have implications for the management of pediatric pain and negative emotion.

Is Mindfulness Associated With Lower Pain Reactivity and Connectivity of the Default Mode Network? A Replication and Extension Study in Healthy and Episodic Migraine Participants.

Formal training in mindfulness-based practices promotes reduced experimental and clinical pain, which may be driven by reduced emotional pain reactivity and undergirded by alterations in the default mode network, implicated in mind-wandering and self-referential processing. Recent results published in this journal suggest that mindfulness, defined here as the day-to-day tendency to maintain a non-reactive mental state in the absence of training, associates with lower pain reactivity, greater heat-pain thresholds, and resting-state default mode network functional connectivity in healthy adults in a similar manner to trained mindfulness. The extent to which these findings extend to chronic pain samples and replicate in healthy samples is unknown. Using data from healthy adults (n = 36) and episodic migraine patients (n = 98) and replicating previously published methods, we observed no significant association between mindfulness and heat-pain threshold, pain intensity or unpleasantness, or pain catastrophizing in healthy controls, or between mindfulness and headache frequency, severity, impactor pain catastrophizing in patients. There was no association between default mode network connectivity and mindfulness in either sample when probed via seed-based functional connectivity analyses. In post-hoc whole brain exploratory analyses, a meta-analytically derived default mode network node (ie, posterior cingulate cortex) showed connectivity with regions unassociated with pain processing as a function of mindfulness, such that healthy adults higher in mindfulness showed greater functional connectivity between the posterior cingulate cortex-and cerebellum. Collectively, these findings suggest that the relationship between mindfulness and default mode network functional connectivity may be nuanced or non-robust, and encourage further investigation of how mindfulness relates to pain. PERSPECTIVE: This study found few significant associations between dispositional mindfulness and pain, pain reactivity and default mode connectivity in healthy adults and migraine patients. The relationship between mindfulness and default mode network connectivity may be nuanced or non-robust.

Meta-analytic evidence that mindfulness training alters resting state default mode network connectivity.

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to control, with the hypothesis that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of mindfulness-based training interventions. RsFC effects were extracted from twelve studies (mindfulness n = 226; control n = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate (Hedge's g = .234, p = 0.0288, I2 = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger's test for publication bias was nonsignificant, bias = 2.17, p = 0.162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

[Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia].

OBJECTIVE: To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI). METHODS: A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO15) and Shen (CO10) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain. RESULTS: After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01). CONCLUSION: taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.

Restoration of default mode network and task positive network anti-correlation associated with mindfulness-based cognitive therapy for bipolar disorder.

Individuals with bipolar disorder (BP) show abnormalities in the default mode network (DMN), a brain network active at rest and during self-referential cognition. In healthy individuals, the DMN is anti-correlated (strongly negatively correlated) with the task positive network (TPN), a brain network that is active during attention demanding tasks. Mindfulness has been linked to changes in DMN connectivity. We investigated the effects of mindfulness-based cognitive therapy (MBCT) versus supportive psychotherapy (SP) on the relationship between these two networks in individuals with BP. We identified differences in BOLD resting state DMN-TPN connectivity between healthy controls (HC; n = 22) and individuals with DSM-IV BP before treatment (n = 22) using a seed region in the dorsolateral prefrontal cortex (DLPFC), a key TPN node. We then explored changes in DMN-TPN connectivity after 12 weeks of MBCT or SP. Before treatment, BP individuals showed positively correlated activity and the HC group showed negatively correlated activity between the DLPFC and the posterior cingulate cortex (PCC). After treatment, BP individuals who received MBCT showed negatively correlated DLPFC-PCC activity. BP individuals who received SP did not show a significant change. Mindfulness-based cognitive therapy can restore the anti-correlation between the DMN and TPN in individuals with BP.

Musical memories in newborns: A resting-state functional connectivity study.

Music is known to induce emotions and activate associated memories, including musical memories. In adults, it is well known that music activates both working memory and limbic networks. We have recently discovered that as early as during the newborn period, familiar music is processed differently from unfamiliar music. The present study evaluates music listening effects at the brain level in newborns, by exploring the impact of familiar or first-time music listening on the subsequent resting-state functional connectivity in the brain. Using a connectome-based framework, we describe resting-state functional connectivity (RS-FC) modulation after music listening in three groups of newborn infants, in preterm infants exposed to music during their neonatal-intensive-care-unit (NICU) stay, in control preterm, and full-term infants. We observed modulation of the RS-FC between brain regions known to be implicated in music and emotions processing, immediately following music listening in all newborn infants. In the music exposed group, we found increased RS-FC between brain regions known to be implicated in familiar and emotionally arousing music and multisensory processing, and therefore implying memory retrieval and associative memory. We demonstrate a positive correlation between the occurrence of the prior music exposure and increased RS-FC in brain regions implicated in multisensory and emotional processing, indicating strong engagement of musical memories; and a negative correlation with the Default Mode Network, indicating disengagement due to the aforementioned cognitive processing. Our results describe the modulatory effect of music listening on brain RS-FC that can be linked to brain correlates of musical memory engrams in preterm infants.

Mapping the subcortical connectivity of the human default mode network.

The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical DMN nodes. However, the subcortical connectivity of the DMN has not been fully mapped, and optimal subcortical targets for therapeutic neuromodulation of consciousness have not been identified. In this work, we created a comprehensive map of DMN subcortical connectivity by combining high-resolution functional and structural datasets with advanced signal processing methods. We analyzed 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy volunteers acquired in the Human Connectome Project. The rs-fMRI blood-oxygen-level-dependent (BOLD) data were temporally synchronized across subjects using the BrainSync algorithm. Cortical and subcortical DMN nodes were jointly analyzed and identified at the group level by applying a novel Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method to the synchronized dataset. The subcortical connectivity map was then overlaid on a 7 Tesla 100 µm ex vivo MRI dataset for neuroanatomic analysis using automated segmentation of nuclei within the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia. We further compared the NASCAR subcortical connectivity map with its counterpart generated from canonical seed-based correlation analyses. The NASCAR method revealed that BOLD signal in the central lateral nucleus of the thalamus and ventral tegmental area of the midbrain is strongly correlated with that of the DMN. In an exploratory analysis, additional subcortical sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei were correlated with the cortical DMN. We also found that the putamen and globus pallidus are negatively correlated (i.e., anti-correlated) with the DMN, providing rs-fMRI evidence for the mesocircuit hypothesis of human consciousness, whereby a striatopallidal feedback system modulates anterior forebrain function via disinhibition of the central thalamus. Seed-based analyses yielded similar subcortical DMN connectivity, but the NASCAR result showed stronger contrast and better spatial alignment with dopamine immunostaining data. The DMN subcortical connectivity map identified here advances understanding of the subcortical regions that contribute to human consciousness and can be used to inform the selection of therapeutic targets in clinical trials for patients with disorders of consciousness.

[Effect of acupuncture on default mode network in patients with migraine based on functional Magnetic Resonance Imaging: a preliminary study].

OBJECTIVE: To investigate the effect of acupuncture on default mode network (DMN) in migraine patients without aura based on functional Magnetic Resonance Imaging (fMRI). METHODS: Fifteen patients with migraine were included and treated with acupuncture based on "root-knot" theory (Zuqiaoyin [GB 44] for shaoyang headache, Lidui [ST 45] for yangming headache, Zhiyin [BL 67] for taiyang headache, and ashi point), once every other day, three times a week for 4 weeks. The patients received fMRI scanning before and after acupuncture treatment, the effect of acupuncture on DMN in patients with migraine was observed; the frequency of migraine attack, visual analogue scale (VAS) score and the using of analgesic medication before and after treatment were recorded to evaluate the curative effect of acupuncture; the migraine-specific quality of life questionnaire (MSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the improvements of quality of life and emotional state. RESULTS: Compared before acupuncture, the functional connections of left parahippocampal cortex (PHC) and anterior medial prefrontal cortex (aMPFC), dorsal medial prefrontal cortex (dMPFC) and lateral temporal cortex (LTC) in DMN after acupuncture were weakened (P<0.05), and the functional connections of bilateral posterior cingulate cortex (PCC) and dMPFC were weakened (P<0.05). Compared before treatment, the frequency of migraine attack, VAS, SAS and SDS scores after treatment were decreased (P<0.05), and MSQ score was increased (P<0.05). CONCLUSION: Acupuncture shows good clinical efficacy for migraine without aura, and could adjust the functional connection of DMN.

Mindfulness and Attention Deficit Hyperactivity Disorder: A Neuropsychological Perspective.

ABSTRACT: Understanding the underlying mechanisms of mindfulness has been a hot topic in recent years, not only in clinical fields but also in neuroscience. Most neuroimaging findings demonstrate that critical brain regions involved in mindfulness are responsible for cognitive functions and mental states. However, the brain is a complex system operating via multiple circuits and networks, rather than isolated brain regions solely responsible for specific functions. Mindfulness-based treatments for attention deficit hyperactivity disorder (ADHD) have emerged as promising adjunctive or alternative intervention approaches. We focus on four key brain circuits associated with mindfulness practices and effects on symptoms of ADHD and its cognitive dysfunction, including executive attention circuit, sustained attention circuit, impulsivity circuit, and hyperactivity circuit. We also expand our discussion to identify three key brain networks associated with mindfulness practices, including central executive network, default mode network, and salience network. We conclude by suggesting that more research efforts need to be devoted into identifying putative neuropsychological mechanisms of mindfulness on how it alleviates ADHD symptoms.

Pretreatment intranetwork connectivity can predict the outcomes in idiopathic tinnitus patients treated with sound therapy.

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network-level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting-state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory-related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory-related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network-level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.

Tracking spatial dynamics of functional connectivity during a task.

Functional connectivity (FC) measured from functional magnetic resonance imaging (fMRI) provides a powerful tool to explore brain organization. Studies of the temporal dynamics of brain organization have shown a large temporal variability of the functional connectome, which may be associated with mental status transitions and/or adaptive process. Most dynamic studies, e.g. functional connectome and functional network connectivity (FNC), have focused on the macroscopic FC changes, i.e. the changes of temporal coherence across various brain network sources, nodes and/or regions of interest, where it is assumed within the network or node that the FC is static. In this paper, we develop a novel method to examine the spatial dynamics of FC, without the assumption of its intra-network stationarity. We applied our approach to fMRI data during an auditory oddball task (AOD) from twenty-two subjects, in an attempt to capture/validate the approach by evaluating whether spatial connectivity varies with task condition. The results showed that connectivity networks exhibit spatial variability over time, in addition to participating in conventional temporal dynamics, i.e. cross-network variability or dynamic functional network connectivity (dFNC). Furthermore, we studied the relationship of spatial dynamic in FC to cognitive processes, by performing a cluster analysis to evaluate an individual's functional correspondence towards the 'target' (oddball) detection from AOD task, and extracting cognitive task correspondence states as well as their dynamic FC spatial maps segregated by such states. We found a clear trend in different task-guided states, particularly, a prominent reduction of task stimulus synchrony state along with strong anticorrelation between default mode network (DMN) and cognitive attentional networks. We also observed an increasing occurrence of the task desynchrony state which showed an absence of DMN anticorrelation. The results highlight the impact of a well-studied cognitive task on the observed spatial dynamic structure. We also showed that the FC spatial dynamic pattern from our method largely corresponds to macroscopic dFNC patterns, but with more details and specifications over space, meanwhile the connectivity within the source itself provides novel information and varies over time. Overall, we demonstrate clear evidence of the presence of the (usually ignored) spatial dynamics of connectivity, its links to the task and implications of cognition/mental status.

Selective vulnerability to atrophy in sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: Identification of brain regions susceptible to quantifiable atrophy in sporadic Creutzfeldt-Jakob disease (sCJD) should allow for improved understanding of disease pathophysiology and development of structural biomarkers that might be useful in future treatment trials. Although brain atrophy is not usually present by visual assessment of MRIs in sCJD, we assessed whether using voxel-based morphometry (VBM) can detect group-wise brain atrophy in sCJD. METHODS: 3T brain MRI data were analyzed with VBM in 22 sCJD participants and 26 age-matched controls. Analyses included relationships of regional brain volumes with major clinical variables and dichotomization of the cohort according to expected disease duration based on prion molecular classification (i.e., short-duration/Fast-progressors (MM1, MV1, and VV2) vs. long-duration/Slow-progressors (MV2, VV1, and MM2)). Structural equation modeling (SEM) was used to assess network-level interactions of atrophy between specific brain regions. RESULTS: sCJD showed selective atrophy in cortical and subcortical regions overlapping with all but one region of the default mode network (DMN) and the insulae, thalami, and right occipital lobe. SEM showed that the effective connectivity model fit in sCJD but not controls. The presence of visual hallucinations correlated with right fusiform, bilateral thalami, and medial orbitofrontal atrophy. Interestingly, brain atrophy was present in both Fast- and Slow-progressors. Worse cognition was associated with bilateral mesial frontal, insular, temporal pole, thalamus, and cerebellum atrophy. INTERPRETATION: Brain atrophy in sCJD preferentially affects specific cortical and subcortical regions, with an effective connectivity model showing strength and directionality between regions. Brain atrophy is present in Fast- and Slow-progressors, correlates with clinical findings, and is a potential biomarker in sCJD.

Taking the body off the mind: Decreased functional connectivity between somatomotor and default-mode networks following Floatation-REST.

Floatation-Reduced Environmental Stimulation Therapy (REST) is a procedure that reduces stimulation of the human nervous system by minimizing sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational, and proprioceptive channels, in addition to minimizing musculoskeletal movement and speech. Initial research has found that Floatation-REST can elicit short-term reductions in anxiety, depression, and pain, yet little is known about the brain networks impacted by the intervention. This study represents the first functional neuroimaging investigation of Floatation-REST, and we utilized a data-driven exploratory analysis to determine whether the intervention leads to altered patterns of resting-state functional connectivity (rsFC). Healthy participants underwent functional magnetic resonance imaging (fMRI) before and after 90 min of Floatation-REST or a control condition that entailed resting supine in a zero-gravity chair for an equivalent amount of time. Multivariate Distance Matrix Regression (MDMR), a statistically-stringent whole-brain searchlight approach, guided subsequent seed-based connectivity analyses of the resting-state fMRI data. MDMR identified peak clusters of rsFC change between the pre- and post-float fMRI, revealing significant decreases in rsFC both within and between posterior hubs of the default-mode network (DMN) and a large swath of cortical tissue encompassing the primary and secondary somatomotor cortices extending into the posterior insula. The control condition, an active form of REST, showed a similar pattern of reduced rsFC. Thus, reduced stimulation of the nervous system appears to be reflected by reduced rsFC within the brain networks most responsible for creating and mapping our sense of self.

Effect of Acupuncture Stimulation of Hegu (LI4) and Taichong (LR3) on the Resting-State Networks in Alzheimer's Disease: Beyond the Default Mode Network.

It was reported that acupuncture could treat Alzheimer's disease (AD) with the potential mechanisms remaining unclear. The aim of the study is to explore the effect of the combination stimulus of Hegu (LI4) and Taichong (LR3) on the resting-state brain networks in AD, beyond the default network (DMN). Twenty-eight subjects including 14 AD patients and 14 healthy controls (HCs) matched by age, gender, and educational level were recruited in this study. After the baseline resting-state MRI scans, the manual acupuncture stimulation was performed for 3 minutes, and then, another 10 minutes of resting-state fMRI scans was acquired. In addition to the DMN, five other resting-state networks were identified by independent component analysis (ICA), including left frontal parietal network (lFPN), right frontal parietal network (rFPN), visual network (VN), sensorimotor network (SMN), and auditory network (AN). And the impaired connectivity in the lFPN, rFPN, SMN, and VN was found in AD patients compared with those in HCs. After acupuncture, significantly decreased connectivity in the right middle frontal gyrus (MFG) of rFPN (P = 0.007) was identified in AD patients. However, reduced connectivity in the right inferior frontal gyrus (IFG) (P = 0.047) and left superior frontal gyrus (SFG) (P = 0.041) of lFPN and some regions of the SMN (the left inferior parietal lobula (P = 0.004), left postcentral gyrus (PoCG) (P = 0.001), right PoCG (P = 0.032), and right MFG (P = 0.010)) and the right MOG of VN (P = 0.003) was indicated in HCs. In addition, after controlling for the effect of acupuncture on HCs, the functional connectivity of the right cerebellum crus I, left IFG, and left angular gyrus (AG) of lFPN showed to be decreased, while the left MFG of IFPN and the right lingual gyrus of VN increased in AD patients. These findings might have some reference values for the interpretation of the combination stimulus of Hegu (LI4) and Taichong (LR3) in AD patients, which could deepen our understanding of the potential mechanisms of acupuncture on AD.