Modulation of Resting Connectivity Between the Mesial Frontal Cortex and Basal Ganglia

AbstractThe mesial prefrontal cortex, cingulate cortex and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity. In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre-and post-TMS functional connectivity using seed-based and independent components analysis. In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC–ventral striatum showing negative, whereas MCC–ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum. These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesioprefrontal–cingulo–striatal circuit.

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

10.1101/2020.02.06.937268 ◽

2020 ◽

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

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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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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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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Altered corticostriatal functional connectivity in individuals with high social anhedonia

Psychological Medicine ◽

10.1017/s0033291715001592 ◽

2015 ◽

Vol 46 (1) ◽

pp. 125-135 ◽

Cited By ~ 35

Author(s):

Y. Wang ◽

W.-H. Liu ◽

Z. Li ◽

X.-H. Wei ◽

X.-Q. Jiang ◽

...

Keyword(s):

Functional Connectivity ◽

Repeated Measures ◽

Ventral Striatum ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Schizophrenia Spectrum Disorders ◽

Social Anhedonia ◽

Emotional Suppression ◽

Schizophrenia Spectrum ◽

Spectrum Disorders

Background.Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia.Method.Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17–21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect.Results.Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression.Conclusions.Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.

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Aberrant Dynamic Functional Connectivity of Default Mode Network in Schizophrenia and Links to Symptom Severity

Frontiers in Neural Circuits ◽

10.3389/fncir.2021.649417 ◽

2021 ◽

Vol 15 ◽

Author(s):

Mohammad S. E. Sendi ◽

Elaheh Zendehrouh ◽

Charles A. Ellis ◽

Zhijia Liang ◽

Zening Fu ◽

...

Keyword(s):

Functional Connectivity ◽

Default Mode Network ◽

Resting State ◽

Symptom Severity ◽

Transition Probability ◽

Feature Selection Method ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Dynamic Functional Connectivity ◽

Default Mode

Background: Schizophrenia affects around 1% of the global population. Functional connectivity extracted from resting-state functional magnetic resonance imaging (rs-fMRI) has previously been used to study schizophrenia and has great potential to provide novel insights into the disorder. Some studies have shown abnormal functional connectivity in the default mode network (DMN) of individuals with schizophrenia, and more recent studies have shown abnormal dynamic functional connectivity (dFC) in individuals with schizophrenia. However, DMN dFC and the link between abnormal DMN dFC and symptom severity have not been well-characterized.Method: Resting-state fMRI data from subjects with schizophrenia (SZ) and healthy controls (HC) across two datasets were analyzed independently. We captured seven maximally independent subnodes in the DMN by applying group independent component analysis and estimated dFC between subnode time courses using a sliding window approach. A clustering method separated the dFCs into five reoccurring brain states. A feature selection method modeled the difference between SZs and HCs using the state-specific FC features. Finally, we used the transition probability of a hidden Markov model to characterize the link between symptom severity and dFC in SZ subjects.Results: We found decreases in the connectivity of the anterior cingulate cortex (ACC) and increases in the connectivity between the precuneus (PCu) and the posterior cingulate cortex (PCC) (i.e., PCu/PCC) of SZ subjects. In SZ, the transition probability from a state with weaker PCu/PCC and stronger ACC connectivity to a state with stronger PCu/PCC and weaker ACC connectivity increased with symptom severity.Conclusions: To our knowledge, this was the first study to investigate DMN dFC and its link to schizophrenia symptom severity. We identified reproducible neural states in a data-driven manner and demonstrated that the strength of connectivity within those states differed between SZs and HCs. Additionally, we identified a relationship between SZ symptom severity and the dynamics of DMN functional connectivity. We validated our results across two datasets. These results support the potential of dFC for use as a biomarker of schizophrenia and shed new light upon the relationship between schizophrenia and DMN dynamics.

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O2.2. EVALUATION OF THE RELATIONSHIP BETWEEN GLUTAMATE AND BRAIN CONNECTIVITY IN ANTIPSYCHOTIC-NAïVE FIRST EPISODE PATIENTS – A COMBINED MAGNETIC RESONANCE SPECTROSCOPY AND RESTING STATE FUNCTIONAL CONNECTIVITY MRI STUDY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa028.007 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S4-S4

Author(s):

Jose Maximo ◽

Frederic Briend ◽

William Armstrong ◽

Nina Kraguljac ◽

Adrienne Lahti

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Group Differences ◽

First Episode ◽

Resonance Spectroscopy ◽

Resting State Functional Connectivity ◽

Positive Correlations ◽

Functional Connectivity Mri

Abstract Background Schizophrenia is thought to be a disorder of brain dysconnectivity. An imbalance between cortical excitation/inhibition is also implicated, but the link between these abnormalities remains unclear. The present study used resting state functional connectivity MRI (rs-fcMRI) and magnetic resonance spectroscopy (MRS) to investigate how measurements of glutamate + glutamine (Glx) in the anterior cingulate cortex (ACC) relate to rs-fcMRI in medication-naïve first episode psychosis (FEP) subjects compared to healthy controls (HC). Based on our previous findings, we hypothesized that in HC would show correlations between Glx and rs-fMRI in the salience and default mode network, but these relationships would be altered in FEP. Methods Data from 53 HC (age = 24.70 ±6.23, 34M/19F) and 60 FEP (age = 24.08 ±6.29, 38M/22F) were analyzed. To obtain MRS data, a voxel was placed in the ACC (PRESS, TR/TE = 2000/80ms). Metabolite concentrations were quantified with respect to internal water using the AMARES algorithm in jMRUI. rs-fMRI data were processed using a standard preprocessing pipeline in the CONN toolbox. BOLD signal from a priori brain regions of interest from posterior cingulate cortex (default mode network, DMN), anterior cingulate cortex (salience network, SN), and right posterior parietal cortex (central executive network, CEN) were extracted and correlated with the rest of the brain to measure functional connectivity (FC). Group analyses were performed on Glx, FC, and Glx-FC interactions while controlling for age, gender, and motion when applicable. FC and Glx-FC analyses were performed using small volume correction [(p < 0.01, threshold-free cluster enhancement corrected (TFCE)]. Results No significant between-group differences were found in Glx concentration in the ACC [F(1, 108) = 0.34, p = 0.56], but reduced FC was found on each network in FEP compared to HC (pTFCE corrected). Group Glx-FC interactions were found in the form of positive correlations between Glx and FC in DMN and SN in the HC group, but not in FEP; and negative correlations in CEN in HC, but not in FEP. Discussion While we did not find significant group differences in ACC Glx measurements, ACC Glx modulated FC differentially in FEP and HC. Positive correlations between Glx and FC were found in the SN and DMN, suggesting long range modulation of the two networks in HC, but not in FEP. Additionally, negative correlations between Glx and FC were found in CEN in HC, but not in FEP. Overall, these results suggest that even in the absence of group differences in Glx concentration, the long-range modulation of these 3 networks by ACC Glx is altered in FEP.

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