The relationship between resting-state functional connectivity, antidepressant discontinuation and depression relapse

AbstractThe risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.

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The relationship between resting-state functional connectivity, antidepressant discontinuation and depression relapse

Scientific Reports ◽

10.1038/s41598-020-79170-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Isabel M. Berwian ◽

Julia G. Wenzel ◽

Leonie Kuehn ◽

Inga Schnuerer ◽

Lars Kasper ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Resting State ◽

Dorsolateral Prefrontal Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Healthy Controls ◽

Resting State Functional Connectivity ◽

Open Label ◽

Dorsolateral Prefrontal

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Effects of unilateral deactivations of dorsolateral prefrontal cortex and anterior cingulate cortex on saccadic eye movements

Journal of Neurophysiology ◽

10.1152/jn.00626.2013 ◽

2014 ◽

Vol 111 (4) ◽

pp. 787-803 ◽

Cited By ~ 12

Author(s):

Michael J. Koval ◽

R. Matthew Hutchison ◽

Stephen G. Lomber ◽

Stefan Everling

Keyword(s):

Prefrontal Cortex ◽

Eye Movements ◽

Functional Connectivity ◽

Anterior Cingulate Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Saccadic Eye Movements ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Dorsolateral Prefrontal ◽

Single Neuron Recording

The dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) have both been implicated in the cognitive control of saccadic eye movements by single neuron recording studies in nonhuman primates and functional imaging studies in humans, but their relative roles remain unclear. Here, we reversibly deactivated either dlPFC or ACC subregions in macaque monkeys while the animals performed randomly interleaved pro- and antisaccades. In addition, we explored the whole-brain functional connectivity of these two regions by applying a seed-based resting-state functional MRI analysis in a separate cohort of monkeys. We found that unilateral dlPFC deactivation had stronger behavioral effects on saccades than unilateral ACC deactivation, and that the dlPFC displayed stronger functional connectivity with frontoparietal areas than the ACC. We suggest that the dlPFC plays a more prominent role in the preparation of pro- and antisaccades than the ACC.

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Mechanisms of transcranial magnetic stimulation in the treatment of anorexia nervosa

BJPsych Open ◽

10.1192/bjo.2021.180 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S49-S50

Author(s):

Lydia Shackshaft

Keyword(s):

Anorexia Nervosa ◽

Prefrontal Cortex ◽

Functional Connectivity ◽

Resting State ◽

High Frequency ◽

Magnetic Stimulation ◽

Dorsolateral Prefrontal Cortex ◽

Resting State Functional Connectivity ◽

Dorsolateral Prefrontal ◽

Neurophysiological Mechanisms

AimsSevere and Enduring Anorexia Nervosa (SE-AN) is a challenging condition to treat, with limited therapeutic options, high morbidity, and the highest mortality rates of any psychiatric illness. Repetitive Transcranial Magnetic Stimulation (rTMS) is an emerging treatment option, as evidence demonstrates promising efficacy in improving mood and reducing core Anorexia Nervosa symptoms, as well as safety and tolerability to patients. We aimed to investigate the neurophysiological mechanisms of rTMS use in SE-AN patients by assessing changes in resting state functional connectivity, in the first functional neuroimaging analysis investigating rTMS effects in Anorexia Nervosa patients.Method26 females with a current diagnosis of SE-AN received 20 sessions of sham or real high frequency rTMS (10 hertz) to the left dorsolateral prefrontal cortex in a randomised double-blind trial. Resting-state functional magnetic resonance imaging was performed before and after rTMS. Neural correlates of rTMS treatment were identified using a seed-based functional connectivity analysis with the left dorsolateral prefrontal cortex and bilateral amygdalae as regions of interest. Functional connectivity differences were analysed using t-contrasts in a mixed ANOVA (flexible factorial analysis) to assess interactions between treatment group (real rTMS vs sham) and time-point (pre or post TMS).ResultNo statistically significant changes in resting-state functional connectivity were observed post-rTMS compared to baseline in participants receiving active rTMS compared to sham. Increased functional connectivity between the left amygdala and left pre-supplementary motor area was observed to reach cluster-wise significance (PFWE < 0.05). However, after Bonferroni correction for multiple comparisons (3 seed regions), this did not reach the significance threshold PFWE <0.017.ConclusionThis study highlights the need for further investigation of neurophysiological mechanisms, including resting-state functional connectivity modulation, resulting from rTMS to the dorsolateral prefrontal cortex in SE-AN patients. This requires higher powered studies to account for heterogeneity in treatment response. We have provided some indication that high frequency rTMS may have therapeutic benefit in SE-AN by modification of functional connectivity between prefrontal and limbic brain regions, resulting in improved top-down cognitive control over emotional processing and ability to enact goal-directed behaviours, enabling secondary reductions in eating disorder behaviours.

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Aberrant resting-state functional connectivity of the dorsolateral prefrontal cortex to the anterior insula and its association with fear avoidance belief in chronic neck pain patients

PLoS ONE ◽

10.1371/journal.pone.0221023 ◽

2019 ◽

Vol 14 (8) ◽

pp. e0221023

Author(s):

Naho Ihara ◽

Kenta Wakaizumi ◽

Daisuke Nishimura ◽

Jungo Kato ◽

Takashige Yamada ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Resting State ◽

Dorsolateral Prefrontal Cortex ◽

Chronic Neck Pain ◽

Anterior Insula ◽

Fear Avoidance ◽

Resting State Functional Connectivity ◽

Dorsolateral Prefrontal ◽

Pain Patients

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Resting-state Functional Connectivity between Dorsolateral Prefrontal Cortex and Left Temporal Language-related Region in Unaffected First-degree Relatives of Schizophrenia Patients

Human Physiology ◽

10.1134/s0362119719050116 ◽

2019 ◽

Vol 45 (6) ◽

pp. 621-627

Author(s):

Ya. R. Panikratova ◽

I. S. Lebedeva ◽

A. N. Pomytkin ◽

U. O. Popovich ◽

P. S. Kananovich ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Resting State ◽

Dorsolateral Prefrontal Cortex ◽

Resting State Functional Connectivity ◽

First Degree Relatives ◽

Dorsolateral Prefrontal ◽

Temporal Language

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Multiple sclerosis–related fatigue: Altered resting-state functional connectivity of the ventral striatum and dorsolateral prefrontal cortex

Multiple Sclerosis Journal ◽

10.1177/1352458518758911 ◽

2018 ◽

Vol 25 (4) ◽

pp. 554-564 ◽

Cited By ~ 22

Author(s):

Sven Jaeger ◽

Friedemann Paul ◽

Michael Scheel ◽

Alexander Brandt ◽

Josephine Heine ◽

...

Keyword(s):

Multiple Sclerosis ◽

Prefrontal Cortex ◽

Functional Connectivity ◽

Caudate Nucleus ◽

Resting State ◽

Dorsolateral Prefrontal Cortex ◽

Ventral Striatum ◽

Resting State Functional Connectivity ◽

Dorsolateral Prefrontal ◽

Fatigue Severity

Objective: Since recent studies suggested a role of the striatum and prefrontal cortex for multiple sclerosis (MS)-related fatigue, we investigated resting-state functional connectivity alterations of striatal subdivisions and the dorsolateral prefrontal cortex (dlPFC). Methods: Resting-state functional magnetic resonance imaging was acquired in 77 relapsing–remitting MS patients (38 fatigued (F-MS), 39 non-fatigued (NF-MS)) and 41 matched healthy controls (HC). Fatigue severity was assessed using the fatigue severity scale. Seed-based connectivity analyses were performed using subregions of the striatum and the dlPFC as regions of interest applying non-parametric permutation testing. Results: Compared to HC and NF-MS patients, F-MS patients showed reduced caudate nucleus and ventral striatum functional connectivity with the sensorimotor cortex (SMC) and frontal, parietal, and temporal cortex regions. Fatigue severity correlated negatively with functional connectivity of the caudate nucleus and ventral striatum with the SMC and positively with functional connectivity of the dlPFC with the rostral inferior parietal gyrus and SMC. Conclusion: MS-related fatigue is associated with reduced functional connectivity between the striatum and sensorimotor as well as attention and reward networks, in which the ventral striatum might be a key integration hub. Together with increased connectivity between the dlPFC and sensory cortical areas, these connectivity alterations shed light on the mechanisms of MS-related fatigue.

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Context-dependency in the Cognitive Bias Task and Resting-state Functional Connectivity of the Dorsolateral Prefrontal Cortex

Journal of the International Neuropsychological Society ◽

10.1017/s1355617720000302 ◽

2020 ◽

Vol 26 (8) ◽

pp. 749-762

Author(s):

Yana Panikratova ◽

Olga Dobrushina ◽

Alexander Tomyshev ◽

Tatiana Akhutina ◽

Ekaterina Pechenkova ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Cognitive Bias ◽

Resting State ◽

Dorsolateral Prefrontal Cortex ◽

Context Dependency ◽

Resting State Functional Connectivity ◽

Whole Brain ◽

Left Dlpfc ◽

Dorsolateral Prefrontal

AbstractObjective:Goldberg, the author of the “novelty-routinization” framework, suggested a new pair of cognitive styles for agent-centered decision-making (DM), context-dependency/independency (CD/CI), quantified by the Cognitive Bias Task (CBT) and supposedly reflecting functional brain hemispheric specialization. To date, there are only three lesion and activation neuroimaging studies on the CBT with the largest sample of 12 participants. The present study is the first to analyze whole-brain functional connectivity (FC) of the dorsolateral prefrontal cortex (DLPFC), involved in contextual agent-centered DM.Method:We compared whole-brain resting-state FC of the DLPFC between CD (n = 24) and CI (n = 22) healthy participants. Additionally, we investigated associations between CD/CI and different aspects of executive functions.Results:CD participants had stronger positive FC of the DLPFC with motor and visual regions; FC of the left DLPFC was more extensive. CI participants had stronger positive FC of the left DLPFC with right prefrontal and parietal-occipital areas and of the left and right DLPFC with ipsilateral cerebellar hemispheres. No sex differences were found. CD/CI had nonlinear associations with working memory.Conclusions:The findings suggest that CD and CI are associated with different patterns of DLPFC FC. While CD is associated with FC between DLPFC and areas presumably involved in storing representations of current situation, CI is more likely to be associated with FC between DLPFC and right-lateralized associative regions, probably involved in the inhibition of the CD response and switching from processing of incoming perceptual information to creation of original response strategies.

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Anodal Transcranial Direct Current Stimulation of Anterior Cingulate Cortex Modulates Subcortical Brain Regions Resulting in Cognitive Enhancement

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2020.584136 ◽

2020 ◽

Vol 14 ◽

Author(s):

Ahsan Khan ◽

Xin Wang ◽

Chun Hang Eden Ti ◽

Chun-Yu Tse ◽

Kai-Yu Tong

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Anterior Cingulate Cortex ◽

Resting State ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Resting State Functional Connectivity ◽

Subcortical Regions ◽

The Impact ◽

Experimental Group

Transcranial direct current stimulation (tDCS) has been widely utilized in research settings and modulates brain activity. The application of anodal tDCS on the prefrontal cortex has indicated improvement in cognitive functioning. The cingulate cortex, situated in the medial aspect of the prefrontal cortex, has been identified as a core region performing cognitive functions. Most of the previous studies investigating the impact of stimulation on the prefrontal cortex stimulated the dorsolateral prefrontal cortex (DLPFC), however, the impact of stimulation on cingulate has not been explored. The current study investigates the effect of stimulation on the resting-state functional connectivity of the anterior cingulate cortex with other regions of the brain and changes in behavioral results in a color-word Stroop task, which has repeatedly elicited activation in different regions of the cingulate. Twenty subjects were randomly assigned to the experimental and sham group, and their medial prefrontal area was stimulated using MRI compatible tDCS. Resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive Stroop task were monitored before, during, and after the stimulation. Neuroimaging results indicated a significant decrease in resting-state functional connectivity in the experimental group during and after stimulation as compared to before stimulation in two clusters including right insular cortex, right central operculum cortex, right frontal operculum cortex and right planum polare with the left anterior cingulate cortex (L-ACC) selected as the seed. The behavioral results indicated a significant decrease in reaction time (RT) following stimulation in the experimental group compared to the sham group. Moreover, the change in functional connectivity in subcortical regions with L-ACC as the seed and change in RT was positively correlated. The results demonstrated that ACC has a close functional relationship with the subcortical regions, and stimulation of ACC can modulate these connections, which subsequently improves behavioral performance, thus, providing another potential target of stimulation for cognitive enhancement.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04318522.

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