Enhanced amygdala-anterior cingulate white matter structural connectivity in Sahaja Yoga Meditators.

OBJECTIVE: To study the white matter connections between anterior cingulate cortex, anterior insula and amygdala as key regions of the frontal-limbic network that have been related to meditation. DESIGN: Twenty experienced practitioners of Sahaja Yoga Meditation and twenty nonmeditators matched on age, gender and education level, were scanned using Diffusion Weighted Imaging, using a 3T scanner, and their white matter connectivity was compared using diffusion tensor imaging analyses. RESULTS: There were five white matter fiber paths in which meditators showed a larger number of tracts, two of them connecting the same area in both hemispheres: the left and right amygdalae and the left and right anterior insula; and the other three connecting left anterior cingulate with the right anterior insula, the right amygdala and the left amygdala. On the other hand, non-meditators showed larger number of tracts in two paths connecting the left anterior insula with the left amygdala, and the left anterior insula with the left anterior cingulate. CONCLUSIONS: The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger white matter tracts strengthening interhemispheric connections between limbic regions and connections between cingulo-amygdalar and cingulo-insular brain regions related to top-down attentional and emotional processes as well as between top-down control functions that could potentially be related to the witness state perceived through the state of mental silence promoted with this meditation. On the other hand, reduced connectivity strength in left anterior insula in the meditation group could be associated to reduced emotional processing affecting top-down processes.

Neural correlates of cognitive behavioral therapy-based interventions for bipolar disorder: A scoping review.

Cognitive Behavioral Therapy (CBT) is among the gold-standard psychotherapeutic interventions for the treatment of psychiatric disorders, including bipolar disorder (BD). While the clinical response of CBT in patients with BD has been widely investigated, its neural correlates remain poorly explored. Therefore, this scoping review aimed to discuss neuroimaging studies on CBT-based interventions in bipolar populations. Particular attention has been paid to similarities and differences between studies to inform future research. The literature search was conducted on PubMed, PsycINFO, and Web of Science databases in June 2023, identifying 307 de-duplicated records. Six studies fulfilled the inclusion criteria and were reviewed. All of them analyzed functional brain activity data. Four studies showed that the clinical response to CBT was associated with changes in the functional activity and/or connectivity of prefrontal and posterior cingulate cortices, temporal parietal junction, amygdala, precuneus, and insula. In two additional studies, a peculiar pattern of baseline activations in the prefrontal cortex, hippocampus, amygdala, and insula predicted post-treatment improvements in depressive symptoms, emotion dysregulation, and psychosocial functioning, although CBT-specific effects were not shown. These results suggest, at the very preliminary level, the potential of CBT-based interventions in modulating neural activity and connectivity of patients with BD, especially in regions ascribed to emotional processing. Nonetheless, the discrepancies between studies concerning aims, design, sample characteristics, and CBT and fMRI protocols do not allow conclusions to be drawn. Further research using multimodal imaging techniques, better-characterized BD samples, and standardized CBT-based interventions is needed.

Neural mechanisms of acceptance-commitment therapy for obsessive-compulsive disorder: a resting-state and task-based fMRI study.

BACKGROUND: There is growing evidence for the use of acceptance-commitment therapy (ACT) for the treatment of obsessive-compulsive disorder (OCD). However, few fully implemented ACT have been conducted on the neural mechanisms underlying its effect on OCD. Thus, this study aimed to elucidate the neural correlates of ACT in patients with OCD using task-based and resting-state functional magnetic resonance imaging (fMRI). METHODS: Patients with OCD were randomly assigned to the ACT (n = 21) or the wait-list control group (n = 21). An 8-week group-format ACT program was provided to the ACT group. All participants underwent an fMRI scan and psychological measurements before and after 8 weeks. RESULTS: Patients with OCD showed significantly increased activation in the bilateral insula and superior temporal gyri (STG), induced by the thought-action fusion task after ACT intervention. Further psycho-physiological interaction analyses with these regions as seeds revealed that the left insular-left inferior frontal gyrus (IFG) connectivity was strengthened in the ACT group after treatment. Increased resting-state functional connectivity was also found in the posterior cingulate cortex (PCC), precuneus, and lingual gyrus after ACT intervention Most of these regions showed significant correlations with ACT process measures while only the right insula was correlated with the obsessive-compulsive symptom measure. CONCLUSIONS: These findings suggest that the therapeutic effect of ACT on OCD may involve the salience and interoception processes (i.e. insula), multisensory integration (i.e. STG), language (i.e. IFG), and self-referential processes (i.e. PCC and precuneus). These areas or their interactions could be important for understanding how ACT works psychologically.

The role of the thalamic subregions in major depressive disorder with childhood maltreatment: Evidences from dynamic and static functional connectivity.

BACKGROUND: Major depressive disorder (MDD) with a history of childhood maltreatment represents a highly prevalent clinical phenotype. Previous studies have demonstrated functional alterations of the thalamus among MDD. However, no study has investigated the static and dynamic changes in functional connectivity (FC) within thalamic subregions among MDD with childhood maltreatment. METHODS: This study included four groups: MDD with childhood maltreatment (n = 48), MDD without childhood maltreatment (n = 30), healthy controls with childhood maltreatment (n = 57), and healthy controls without childhood maltreatment (n = 46). Sixteen thalamic subregions were selected as seed to investigate group-differences in dynamic FC (dFC) and static FC (sFC). Correlation analyses were performed to assess the associations between abnormal FC and maltreatment severity. Eventually, moderation analyses were employed to explore the moderating role of abnormal FC in the relationship between maltreatment and depressive severity. RESULTS: MDD with childhood maltreatment exhibit abnormal thalamic subregions FC compared to MDD without childhood maltreatment, characterized by abnormalities with the sFC of the rostral anterior cingulate cortex, with the dFC of the calcarine, middle cingulate cortex, precuneus cortex and superior temporal gyrus. Furthermore, sFC with the rostral anterior cingulate cortex and dFC with the middle cingulate cortex were correlated with the severity of maltreatment. Additionally, dFC with the superior temporal gyrus moderates the relationship between maltreatment and depression severity. LIMITATIONS: The cross-sectional designs fail to infer causality. CONCLUSIONS: Our findings support thalamic dysfunction as neurobiological features of childhood maltreatment as well as vulnerability to MDD.

Neuroimaging Insights: Kava's (Piper methysticum) Effect on Dorsal Anterior Cingulate Cortex GABA in Generalized Anxiety Disorder.

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

Upregulation of Calhm2 in the anterior cingulate cortex contributes to the maintenance of bilateral mechanical allodynia and comorbid anxiety symptoms in inflammatory pain conditions.

Peripheral inflammation-induced chronic pain tends to evoke concomitant anxiety disorders. It's common knowledge that the anterior cingulate cortex (ACC) plays a vital role in maintaining pain modulation and negative emotions. However, the potential mechanisms of chronic inflammation pain and pain-related anxiety remain elusive. Here, it was reported that injecting complete Freund's adjuvant (CFA) unilaterally resulted in bilateral mechanical allodynia and anxiety-like symptoms in mice via behavioral tests. In addition, CFA induced the bilateral upregulation and activation of calcium homeostasis modulator 2 (Calhm2) in ACC pyramidal neurons by quantitative analysis and double immunofluorescence staining. The knockdown of Calhm2 in the bilateral ACC by a lentiviral vector harboring ribonucleic acid (RNA) interference sequence reversed CFA-induced pain behaviors and neuronal sensitization. Furthermore, the modulating of ACC pyramidal neuronal activities via a designer receptor exclusively activated by designer drugs (DREADD)-hM4D(Gi) greatly changed Calhm2 expression, mechanical paw withdrawal thresholds (PWTs) and comorbid anxiety symptoms. Moreover, it was found that Calhm2 regulates inflammation pain promoting the upregulation of N-methyl-D-aspartic acid (NMDA) receptor 2B (NR2B) subunits. Calhm2 knockdown in ACC exhibited a significant decrease in NR2B expression. These results demonstrated that Calhm2 in ACC pyramidal neurons modulates chronic inflammation pain and pain-related anxiety symptoms, which provides a novel underlying mechanism for the development of inflammation pain.

Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.

Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.

Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents.

BACKGROUND: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. METHODS: Adolescents (N = 90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. DISCUSSION: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).

Mediodorsal thalamus-projecting anterior cingulate cortex neurons modulate helping behavior in mice.

Many species living in groups can perform prosocial behaviors via voluntarily helping others with or without benefits for themselves. To provide a better understanding of the neural basis of such prosocial behaviors, we adapted a preference lever-switching task in which mice can prevent harm to others by switching from using a lever that causes shocks to a conspecific one that does not. We found the harm avoidance behavior was mediated by self-experience and visual and social contact but not by gender or familiarity. By combining single-unit recordings and analysis of neural trajectory decoding, we demonstrated the dynamics of anterior cingulate cortex (ACC) neural activity changes synchronously with the harm avoidance performance of mice. In addition, ACC neurons projected to the mediodorsal thalamus (MDL) to modulate the harm avoidance behavior. Optogenetic activation of the ACC-MDL circuit during non-preferred lever pressing (nPLP) and inhibition of this circuit during preferred lever pressing (PLP) both resulted in the loss of harm avoidance ability. This study revealed the ACC-MDL circuit modulates prosocial behavior to avoid harm to conspecifics and may shed light on the treatment of neuropsychiatric disorders with dysfunction of prosocial behavior.

Functional network of contextual and temporal memory has increased amygdala centrality and connectivity with the retrosplenial cortex, thalamus, and hippocampus.

In fear conditioning with time intervals between the conditioned (CS) and unconditioned (US) stimuli, a neural representation of the CS must be maintained over time to be associated with the later US. Usually, temporal associations are studied by investigating individual brain regions. It remains unknown, however, the effect of the interval at the network level, uncovering functional connections cooperating for the CS transient memory and its fear association. We investigated the functional network supporting temporal associations using a task in which a 5-s interval separates the contextual CS from the US (CFC-5s). We quantified c-Fos expression in forty-nine brain regions of male rats following the CFC-5s training, used c-Fos correlations to generate functional networks, and analyzed them by graph theory. Control groups were trained in contextual fear conditioning, in which CS and US overlap. The CFC-5s training additionally activated subdivisions of the basolateral, lateral, and medial amygdala; prelimbic, infralimbic, perirhinal, postrhinal, and intermediate entorhinal cortices; ventral CA1 and subiculum. The CFC-5s network had increased amygdala centrality and higher amygdala internal and external connectivity with the retrosplenial cortex, thalamus, and hippocampus. Amygdala and thalamic nuclei were network hubs. Functional connectivity among these brain regions could support CS transient memories and their association.

Influence of Inflammatory Pain and Dopamine on Synaptic Transmission in the Mouse ACC.

Dopamine (DA) inhibits excitatory synaptic transmission in the anterior cingulate cortex (ACC), a brain region involved in the sensory and affective processing of pain. However, the DA modulation of inhibitory synaptic transmission in the ACC and its alteration of the excitatory/inhibitory (E/I) balance remains relatively understudied. Using patch-clamp recordings, we demonstrate that neither DA applied directly to the tissue slice nor complete Freund's adjuvant (CFA) injected into the hind paw significantly impacted excitatory currents (eEPSCs) in the ACC, when recorded without pharmacological isolation. However, individual neurons exhibited varied responses to DA, with some showing inhibition, potentiation, or no response. The degree of eEPSC inhibition by DA was higher in naïve slices compared to that in the CFA condition. The baseline inhibitory currents (eIPSCs) were greater in the CFA-treated slices, and DA specifically inhibited eIPSCs in the CFA-treated, but not naïve group. DA and CFA treatment did not alter the balance between excitatory and inhibitory currents. Spontaneous synaptic activity revealed that DA reduced the frequency of the excitatory currents in CFA-treated mice and decreased the amplitude of the inhibitory currents, specifically in CFA-treated mice. However, the overall synaptic drive remained similar between the naïve and CFA-treated mice. Additionally, GABAergic currents were pharmacologically isolated and found to be robustly inhibited by DA through postsynaptic D2 receptors and G-protein activity. Overall, the study suggests that CFA-induced inflammation and DA do not significantly affect the balance between excitatory and inhibitory currents in ACC neurons, but activity-dependent changes may be observed in the DA modulation of presynaptic glutamate release in the presence of inflammation.

Electroacupuncture alleviates mechanical allodynia and anxiety-like behaviors induced by chronic neuropathic pain via regulating rostral anterior cingulate cortex-dorsal raphe nucleus neural circuit.

AIMS: Epidemiological studies in patients with neuropathic pain have demonstrated a strong association between neuropathic pain and psychiatric conditions such as anxiety. Preclinical and clinical work has demonstrated that electroacupuncture (EA) effectively alleviates anxiety-like behaviors induced by chronic neuropathic pain. In this study, a potential neural circuitry underlying the therapeutic action of EA was investigated. METHODS: The effects of EA stimulation on mechanical allodynia and anxiety-like behaviors in animal models of spared nerve injury (SNI) were examined. EA plus chemogenetic manipulation of glutamatergic (Glu) neurons projecting from the rostral anterior cingulate cortex (rACCGlu ) to the dorsal raphe nucleus (DRN) was used to explore the changes of mechanical allodynia and anxiety-like behaviors in SNI mice. RESULTS: Electroacupuncture significantly alleviated both mechanical allodynia and anxiety-like behaviors with increased activities of glutamatergic neurons in the rACC and serotoninergic neurons in the DRN. Chemogenetic activation of the rACCGlu -DRN projections attenuated both mechanical allodynia and anxiety-like behaviors in mice at day 14 after SNI. Chemogenetic inhibition of the rACCGlu -DRN pathway did not induce mechanical allodynia and anxiety-like behaviors under physiological conditions, but inhibiting this pathway produced anxiety-like behaviors in mice at day 7 after SNI; this effect was reversed by EA. EA plus activation of the rACCGlu -DRN circuit did not produce a synergistic effect on mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of EA could be blocked by inhibiting the rACCGlu -DRN pathway. CONCLUSIONS: The role of rACCGlu -DRN circuit may be different during the progression of chronic neuropathic pain and these changes may be related to the serotoninergic neurons in the DRN. These findings describe a novel rACCGlu -DRN pathway through which EA exerts analgesic and anxiolytic effects in SNI mice exhibiting anxiety-like behaviors.

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System.

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit.

Cerebellar control of a unitary head direction sense.

The head-direction (HD) system, a key neural circuit for navigation, consists of several anatomical structures containing neurons selective to the animal's head direction. HD cells exhibit ubiquitous temporal coordination across brain regions, independently of the animal's behavioral state or sensory inputs. Such temporal coordination mediates a single, stable, and persistent HD signal, which is essential for intact orientation. However, the mechanistic processes behind the temporal organization of HD cells are unknown. By manipulating the cerebellum, we identify pairs of HD cells recorded from two brain structures (anterodorsal thalamus and retrosplenial cortex) that lose their temporal coordination, specifically during the removal of the external sensory inputs. Further, we identify distinct cerebellar mechanisms that participate in the spatial stability of the HD signal depending on sensory signals. We show that while cerebellar protein phosphatase 2B-dependent mechanisms facilitate the anchoring of the HD signal on the external cues, the cerebellar protein kinase C-dependent mechanisms are required for the stability of the HD signal by self-motion cues. These results indicate that the cerebellum contributes to the preservation of a single and stable sense of direction.

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.

Medio-dorsal thalamic dysconnectivity in chronic knee pain: A possible mechanism for negative affect and pain comorbidity.

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n = 74) and without (n = 36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.

The thalamus is the causal hub of intervention in patients with major depressive disorder: Evidence from the Granger causality analysis.

Major depressive disorder (MDD) is the leading mental disorder and afflicts more than 350 million people worldwide. The underlying neural mechanisms of MDD remain unclear, hindering the accurate treatment. Recent brain imaging studies have observed functional abnormalities in multiple brain regions in patients with MDD, identifying core brain regions is the key to locating potential therapeutic targets for MDD. The Granger causality analysis (GCA) measures directional effects between brain regions and, therefore, can track causal hubs as potential intervention targets for MDD. We reviewed literature employing GCA to investigate abnormal brain connections in patients with MDD. The total degree of effective connections in the thalamus (THA) is more than twice that in traditional targets such as the superior frontal gyrus and anterior cingulate cortex. Altered causal connections in patients with MDD mainly included enhanced bottom-up connections from the thalamus to various cortical and subcortical regions and reduced top-down connections from these regions to the THA, indicating excessive uplink sensory information and insufficient downlink suppression information for negative emotions. We suggest that the thalamus is the most crucial causal hub for MDD, which may serve as the downstream target for non-invasive brain stimulation and medication approaches in MDD treatment.

Functional specialization of parallel distributed networks revealed by analysis of trial-to-trial variation in processing demands.

Multiple large-scale networks populate human association cortex. Here, we explored the functional properties of these networks by exploiting trial-to-trial variation in component-processing demands. In two behavioral studies (n = 136 and n = 238), participants quantified strategies used to solve individual task trials that spanned remembering, imagining future scenarios, and various control trials. These trials were also all scanned in an independent sample of functional MRI participants (n = 10), each with sufficient data to precisely define within-individual networks. Stable latent factors varied across trials and correlated with trial-level functional responses selectively across networks. One network linked to parahippocampal cortex, labeled Default Network A (DN-A), tracked scene construction, including for control trials that possessed minimal episodic memory demands. To the degree, a trial encouraged participants to construct a mental scene with imagery and awareness about spatial locations of objects or places, the response in DN-A increased. The juxtaposed Default Network B (DN-B) showed no such response but varied in relation to social processing demands. Another adjacent network, labeled Frontoparietal Network B (FPN-B), robustly correlated with trial difficulty. These results support that DN-A and DN-B are specialized networks differentially supporting information processing within spatial and social domains. Both networks are dissociable from a closely juxtaposed domain-general control network that tracks cognitive effort.NEW & NOTEWORTHY Tasks shown to differentially recruit parallel association networks are multifaceted, leaving open questions about network processes. Here, examining trial-to-trial network response properties in relation to trial traits reveals new insights into network functions. In particular, processes linked to scene construction selectively recruit a distributed network with links to parahippocampal and retrosplenial cortices, including during trials designed not to rely on the personal past. Adjacent networks show distinct patterns, providing novel evidence of functional specialization.

Exploring the regulatory effect of acupuncture for Ningshen Tongqiao on the functional connectivity between the anterior cingulate cortex and the whole brain in the patients with subjective tinnitus based on fMRI. / 基于fMRIåˆæŽ¢å®ç¥žé€šçªæ³•é’ˆåˆºå¯¹ä¸»è§‚æ€§è€³é¸£æ‚£è€ å‰æ‰£å¸¦å›žä¸Žå ¨è„‘åŠŸèƒ½è¿žæŽ¥çš„è°ƒæŽ§ä½œç”¨.

OBJECTIVES: To explore the effect of acupuncture for Ningshen Tongqiao (tranquilizing the spirit and unblocking the orifices) on the functional connectivity (FC) between the anterior cingulate cortex (ACC) and the whole brain in the patients with subjective tinnitus using the resting-state functional magnetic resonance imaging (fMRI). METHODS: Forty patients with subjective tinnitus and 40 healthy subjects were recruited. The patients with subjective tinnitus were treated with acupuncture for Ningshen Tongqiao at Yamen (GV 15) and Baihui (GV 20), as well as Tinggong (SI 19), Touqiaoyin (GB 11) and Shuaigu (GB 8) on the affected side; and Tinggong (SI 19) and Touqiaoyin (GB 11) were attached to the electric acupuncture apparatus and stimulated with disperse-dense wave and 2 Hz/50 Hz in frequency. Acupuncture was operated once daily, 3 times a week and 10 treatments were required. Before and after treatment, the scores of tinnitus evaluation questionnaire (TEQ), tinnitus handicap inventory (THI) and tinnitus visual analogue scale (VAS) were evaluated; and the clinical therapeutic effect was assessed. Separately, the patients with subjective tinnitus received one time of fMRI within 2 days before and after treatment, and the healthy subjects underwent one time of fMRI after enrollment. The bilateral ACC was taken as the region of interest (ROI). Using matlab R2017b software, FC between ACC and the whole brain was calculated. RESULTS: After treatment, the scores of THI, TEQ and VAS were reduced in the subjective tinnitus patients compared with those before treatment (P<0.01); and the total effective rate was 92.5% (37/40). Before treatment, compared with the healthy subjects, FC between the right ACC and the left middle temporal gyrus, the left superior temporal gyrus and the left superior frontal gyrus decreased in the subjective tinnitus patients. FC between the right ACC and the left middle frontal gyrus and the bilateral angular gyrus was dropped, while that between the left ACC and the left middle frontal gyrus, the left thalamus, the left angular gyrus and the left middle temporal gyrus was decreased in the subjective tinnitus patients when compared with the healthy subjects after treatment. Compared with those before treatment, FC between the right ACC and the left lingual gyrus and the left thalamus were declined, and that between the left ACC and the right middle frontal gyrus and the right superior frontal gyrus was decreased in the subjective tinnitus patients after treatment. CONCLUSIONS: Acupuncture can effectively relieve the clinical symptoms of subjective tinnitus patients, and promote the functional re-construction of the auditory regions (temporal lobe, frontal lobe and thalamus) and the emotion-related brain regions.

Collateral rostral thalamic projections to prelimbic, infralimbic, anterior cingulate and retrosplenial cortices in the rat brain.

As the functional properties of a cortical area partly reflect its thalamic inputs, the present study compared collateral projections arising from various rostral thalamic nuclei that terminate across prefrontal (including anterior cingulate) and retrosplenial areas in the rat brain. Two retrograde tracers, fast blue and cholera toxin B, were injected in pairs to different combinations of cortical areas. The research focused on the individual anterior thalamic nuclei, including the interanteromedial nucleus, nucleus reuniens and the laterodorsal nucleus. Of the principal anterior thalamic nuclei, only the anteromedial nucleus contained neurons reaching both the anterior cingulate cortex and adjacent cortical areas (prefrontal or retrosplenial), though the numbers were modest. For these same cortical pairings (medial prefrontal/anterior cingulate and anterior cingulate/retrosplenial), the interanteromedial nucleus and nucleus reuniens contained slightly higher proportions of bifurcating neurons (up to 11% of labelled cells). A contrasting picture was seen for collaterals reaching different areas within retrosplenial cortex. Here, the anterodorsal nucleus, typically provided the greatest proportion of bifurcating neurons (up to 15% of labelled cells). While individual neurons that terminate in different retrosplenial areas were also found in the other thalamic nuclei, they were infrequent. Consequently, these thalamo-cortical projections predominantly arise from separate populations of neurons with discrete cortical termination zones, consistent with the transmission of segregated information and influence. Overall, two contrasting medial-lateral patterns of collateral projections emerged, with more midline nuclei, for example, nucleus reuniens and the interoanteromedial nucleus innervating prefrontal areas, while more dorsal and lateral anterior thalamic collaterals innervated retrosplenial cortex.