Using connectivity-based real-time fMRI neurofeedback to modulate attentional and resting state networks in people with high trait anxiety.
ABSTRACT: High levels of trait anxiety are associated with impaired attentional control, changes in brain activity during attentional control tasks and altered network resting state functional connectivity (RSFC). Specifically, dorsolateral prefrontal cortex to anterior cingulate cortex (DLPFC - ACC) functional connectivity, thought to be crucial for effective and efficient attentional control, is reduced in high trait anxious individuals. The current study examined the potential of connectivity-based real-time functional magnetic imaging neurofeedback (rt-fMRI-nf) for enhancing DLPFC - ACC functional connectivity in trait anxious individuals. We specifically tested if changes in DLPFC - ACC connectivity were associated with reduced anxiety levels and improved attentional control. Thirty-two high trait anxious participants were assigned to either an experimental group (EG), undergoing veridical rt-fMRI-nf, or a control group (CG) that received sham (yoked) feedback. RSFC (using resting state fMRI), anxiety levels and Stroop task performance were assessed pre- and post-rt-fMRI-nf training. Post-rt-fMRI-nf training, relative to the CG, the EG showed reduced anxiety levels and increased DLPFC-ACC functional connectivity as well as increased RSFC in the posterior default mode network. Moreover, in the EG, changes in DLPFC - ACC functional connectivity during rt-fMRI-nf training were associated with reduced anxiety levels. However, there were no group differences in Stroop task performance. We conclude that rt-fMRI-nf targeting DLPFC - ACC functional connectivity can alter network connectivity and interactions and is a feasible method for reducing trait anxiety.
Project description:INTRODUCTION:Anxiety is known to impair attentional control particularly when Task demands are high. Neuroimaging studies generally support these behavioral findings, reporting that anxiety is associated with increased (inefficient) activity in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) during attentional control Tasks. However, less is known about the relationship between worry (part of the cognitive dimension of trait anxiety) and DLPFC/ACC function and connectivity during attentional control. In the present study, we sought to clarify this relationship. METHODS:Forty-one participants underwent functional magnetic resonance imaging (fMRI) during a composite Faces and Scenes Task with high and low emotional interference conditions. Individual worry levels were assessed using the Penn State Worry Questionnaire. RESULTS:During high but not low emotional interference, worry was associated with increased activity in ACC, DLPFC, insula, and inferior parietal cortex. During high emotional interference, worry was also associated with reduced functional connectivity between ACC and DLPFC. Trait anxiety was not associated with changes in DLPFC/ACC activity or connectivity during either Task condition. CONCLUSIONS:The results are consistent with cognitive models that propose worry competes for limited processing resources resulting in inefficient DLPFC and ACC activity when Tasks demands are high. Limitations of the present study and directions for future work are discussed.
Project description:Intermittent theta burst stimulation (iTBS) delivered to the dorsolateral prefrontal cortex (DLPFC) has been investigated as a promising treatment for stress and stress-related mental disorders such as major depression, yet large individual differences in responsiveness demand further exploration and optimization of its effectiveness. Clinical research suggests that resting-state functional connectivity (rsFC) between the DLPFC and the anterior cingulate cortex (ACC) can predict iTBS treatment response in depression. The present study aimed to investigate whether rsFC between the left DLPFC and ACC subregions could predict the degree to which the stress system is affected by iTBS. After assessment of baseline resting-state fMRI data, 34 healthy female participants performed the Trier Social Stress Test on two separate days, each followed by active or sham iTBS over the left DLPFC. To evaluate iTBS effects on the stress-system, salivary cortisol was measured throughout the procedure. Our results showed that a stronger negative correlation between the left DLPFC and the caudal ACC was linked to a larger attenuation of stress-system sensitivity during active, but not during sham iTBS. In conclusion, based on individual rsFC between left DLPFC and caudal ACC, iTBS could be optimized to more effectively attenuate deregulation of the stress system.
Project description:A central feature of major depression (MDD) is heightened negative self-focused thought (negative-SFT). Neuroscientific research has identified abnormalities in a network of brain regions in MDD, including brain areas associated with SFT such as medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). To our knowledge no studies have investigated the behavioral and neural correlates of negative-SFT using a sentence completion task in a sample of individuals with varying depression histories and severities. We test the following hypotheses: (1) negative-SFT will be associated with depression; and (2) depression and negative-SFT will be related to resting-state functional connectivity (rsFC) for brain regions implicated in SFT. Seventy-nine women with varying depression histories and severities completed a sentence completion task and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Standard seed-based voxelwise rsFC was conducted for self-network regions of interest: dorsomedial PFC (dmPFC) and pregenual ACC (pgACC). We performed linear regression analyses to examine the relationships among depression, negative-SFT, and rsFC for the dmPFC and pgACC. Greater negative-SFT was associated with depression history and severity. Greater negative-SFT predicted increased rsFC between dmPFC and pgACC seeds and dorsolateral prefrontal (dlPFC) and parietal regions; depression group was also associated with increased pgACC-dlPFC connectivity. These findings are consistent with previous literature reporting elevated negative-SFT thought in MDD. Our rs-fMRI results provide novel support linking negative-SFT with increased rsFC between self-network and frontoparietal network regions across different levels of depression. Broadly, these findings highlight a dimension of social-affective functioning that may underlie MDD and other psychiatric conditions.
Project description:Although considerable efforts have been made to understand the neural underpinnings of (state) reactive aggression, which is triggered by provocation or perceived threat, little is known about the neural correlates of proactive aggression, which is driven by instrumental motivations to obtain personal gains through aggressive means and which varies dramatically across individuals in terms of tendency of appealing to such means. Here, by combining structural (grey matter density, GMD) and functional (resting-state functional connection, RSFC) fMRI, we investigated brain structures and functional networks related to trait proactive aggression. We found that individual differences in trait proactive aggression were positively associated with GMD in bilateral dorsolateral prefrontal cortex (DLPFC) and negatively correlated with GMD in posterior cingulate cortex (PCC); they were also negatively correlated with the strength of functional connectivity between left PCC and other brain regions, including right DLPFC, right IPL, right MPFC/ACC, and bilateral precuneus. These findings shed light on the differential brain bases of proactive and reactive aggressions and suggested the neural underpinnings of proactive aggression.
Project description:As a hot research topic in the field of psychology and psychiatry, trait optimism reflects the tendency to expect positive outcomes in the future. Consistent evidence has demonstrated the role of trait optimism in reducing anxiety among different populations. However, less is known about the neural bases of trait optimism and the underlying mechanisms for how trait optimism protects against anxiety in the healthy brain. In this investigation, we examined these issues in 231 healthy adolescent students by assessing resting-state brain activity (i.e., fractional amplitude of low-frequency fluctuations, fALFF) and connectivity (i.e., resting-state functional connectivity, RSFC). Whole-brain correlation analyses revealed that higher levels of trait optimism were linked with decreased fALFF in the right orbitofrontal cortex (OFC) and increased RSFC between the right OFC and left supplementary motor cortex (SMC). Mediation analyses further showed that trait optimism mediated the influence of the right OFC activity and the OFC-SMC connectivity on anxiety. Our results remained significant even after excluding the impact of head motion, positive and negative affect and depression. Taken together, this study reveals that fALFF and RSFC are functional neural markers of trait optimism and provides a brain-personality-symptom pathway for protection against anxiety in which fALFF and RSFC affect anxiety through trait optimism.
Project description:Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD). Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC) may reflect abnormalities within emotional ('hot') and cognitive control ('cold') neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT). Functional Magnetic Resonance Imaging (fMRI) was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC), and pre-frontal cortex (PFC) was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of 'hot' emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of 'cold' cognition.
Project description:Previous functional magnetic resonance imaging (fMRI) studies demonstrated an abnormally coordinated network functioning in Major Depression Disorder (MDD) during rest. The main monoamine-producing nuclei within midbrain/brainstem are functionally integrated within these specific networks. Therefore, we aimed to investigate the resting-state functional connectivity (RSFC) of these nuclei in 45 MDD patients and differences between patients receiving two different classes of antidepressant drugs. Patients showed reduced RSFC from the ventral tegmental area (VTA) to dorsal anterior cingulate cortex (dACC) and stronger RSFC to the left amygdala and dorsolateral prefrontal cortex (DLPFC). Patients treated with antidepressants influencing noradrenergic and serotonergic neurotransmission showed different RSFC from locus coeruleus to DLPFC compared to patients treated with antidepressants influencing serotonergic neurotransmission only. In the opposite contrast patients showed stronger RSFC from dorsal raphe to posterior brain regions. Enhanced VTA-RSFC to amygdala as a central region of the salience network may indicate an over-attribution of the affective salience to internally-oriented processes. Significant correlation between decreased VTA-dACC functional connectivity and the BDI-II somatic symptoms indicates an association with diminished volition and behavioral activation in MDD. The observed differences in the FC of the midbrain/brainstem nuclei between two classes of antidepressants suggest differential neural effects of SSRIs and SNRIs.
Project description:Stress-induced changes in functional brain connectivity have been linked to the etiology of stress-related disorders. Resting state functional connectivity (rsFC) is especially informative in characterizing the temporal trajectory of glucocorticoids during stress adaptation. Using the imaging Maastricht Acute Stress Test (iMAST), we induced acute stress in 39 healthy volunteers and monitored the neuroendocrine stress levels during three runs of resting state functional magnetic resonance imaging (rs-fMRI): before (run 1), immediately following (run 2), and 30 min after acute stress (run 3). The iMAST resulted in strong increases in cortisol levels. Whole-brain analysis revealed that acute stress (run 2 - 1) was characterized by changes in connectivity of the amygdala with the ventrolateral prefrontal cortex (vlPFC), ventral posterior cingulate cortex (PCC), cuneus, parahippocampal gyrus, and culmen. Additionally, cortisol responders were characterized by enhanced amygdala - medial prefrontal cortex (mPFC) connectivity. Stress recovery (run 3 - 2) was characterized by altered amygdala connectivity with the dorsolateral prefrontal cortex (dlPFC), ventral and dorsal anterior cingulate cortex (ACC), anterior hippocampal complex, cuneus, and presupplementary motor area (preSMA). Opposite to non-responders, cortisol responders were characterized by enhanced amygdala connectivity with the anterior hippocampal complex and parahippocampal gyrus, and reduced connectivity with left dlPFC, dACC, and culmen during early recovery. Acute stress responding and recovery are thus associated with changes in the functional connectivity of the amygdala network. Our findings show that these changes may be regulated via stress-induced neuroendocrine levels. Defining stress-induced neuronal network changes is pertinent to developing treatments that target abnormal neuronal activity.
Project description:Background: Transcranial stimulation with direct (tDCS) and alternating current (tACS) has increasingly gained interest in various fields, from cognitive neuroscience to clinical investigations. Transcranial current stimulation used alone may modulate brain activity that consequently influences behaviors, without providing information on potentially induced brain activity changes. The combination of transcranial current stimulation and functional magnetic resonance imaging (fMRI) may help to address this. This exploratory study investigated instantaneous and subsequent effects of tDCS and tACS on resting-state functional connectivity (rsFC) in healthy adults. Methods: We conducted a randomized crossover study with 15 healthy subjects receiving three stimulation conditions (tDCS, tACS, and sham) on separate days. Stimulation was applied over the left and right dorsolateral prefrontal cortex (DLPFC) for 30 min (1 mA). rsFC of the targeted prefrontal areas was assessed before, during, and after stimulation using multiband fMRI and using left and right DLPFC as seeds. Results: Both tDCS and tACS increased rsFC during and after the stimulation period, as compared to sham. tDCS-induced changes were observed between the left DLPFC and bilateral parietal regions at the junction of the superior parietal and the inferior parietal lobules. tACS-induced changes were observed between the left DLPFC and the right inferior parietal lobule. Conclusion: Overall, these results suggest that a single session with a low dose, 1 mA, of tDCS or tACS can cause changes in fronto-parietal connectivity that occur rapidly, that is, within the first 15 min. Although exploratory, this work contributes to the discussion of the potential of transcranial current stimulation to modulate resting-state networks and the interest of combining transcranial current stimulation with neuroimaging to identify these changes.
Project description:BACKGROUND:The dorsolateral prefrontal cortex (DLPFC) is the standard stimulation target for the repetitive transcranial magnetic stimulation (rTMS) treatment of major depression disorder (MDD). A retrospective study by Fox and colleagues found that a more negative resting-state functional magnetic resonance imaging (RS-fMRI) functional connectivity (FC) between left DLPFC and the subgenual anterior cingulate cortex (sgACC) in a large group of healthy participants is associated with a better curative effects of rTMS in MDD, suggesting that the sgACC may be an effective region. However, a recent meta-analysis on RS-fMRI studies found that the pregenual ACC (pgACC), rather than the sgACC, of MDD patients showed increased local activity. METHODS:We used the stimulation coordinates in the left DLPFC analyzed by Fox et al. to perform RS-fMRI FC between the stimulation targets obtained from previous rTMS MDD studies and the potential effective regions (sgACC and pgACC, respectively) on the RS-fMRI data from 88 heathy participants. RESULTS:(a) Both the pgACC and the sgACC were negatively connected to the left DLPFC; (b) both FCs of sgACC-DLPFC and pgACC-DLPFC were more negative in responders than in nonresponders; and (c) the associations between DLPFC-sgACC functional connectivity and clinical efficacy were clustered around the midline sgACC. CONCLUSIONS:Both the pgACC and the sgACC may be potential effective regions for rTMS on the left DLPFC for treatment of MDD. However, individualized ACC-DLPFC FC-based rTMS on depression should be performed in the future to test the pgACC or the sgACC as effective regions.