Abstract WP494: Neuroimaging Correlates of Apathy in Late-Onset Depression

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Irina S Samotaeva ◽  
Alla S Avedisova ◽  
Kseniya V Zakharova ◽  
Inna A Arkusha ◽  
Roman V Luzin ◽  
...  

Apathy is prevalent in older depressed patients and considered to be a predictor of increased dementia risk. Neuroimaging characteristics of late-life depression are being discussed. However, it is unclear whether apathetic (ApD) and nonapathetic depression (D) have different neuroimaging correlates. The objective of this study was to examine structural and functional bases of ApD by using morphometric and functional connectivity MRI analyses. We enrolled 45 consecutive patients with late-onset depression (85% female; mean age=66 (4) years, mean education=14 (2) years) and 22 age and gender-matched healthy elderly. Patients were divided into ApD (n=26) and D (n=19) groups based on Apathy Scale scores. All the participants underwent 1.5 T structural MRI and resting-state fMRI. Fazekas scale was used to quantify white matter hyperintensities. Demographic data, Hamilton Depression Rating Scale (HAMD), Apathy Scale, and MoCA scores for the three groups were compared. Association between apathy, depression and neuroimaging characteristics was assessed using regression analysis with demographic and cognitive variables included as covariates. ApD patients demonstrated nonsignificantly higher HAMD and Fazekas scores and lower MoCA scores compared to D patients. The latter group showed similar Fazekas and slightly lower MoCA scores vs healthy elderly. After controlling for covariates, apathy was significantly associated with volumes of nucleus caudatus and putamen on the right as well as functional connectivity between anterior cingulate and parahippocampal gyrus. Depression correlated with the volumes of the cerebral and cerebellum cortices as well as functional connectivity of salience resting state network. Our study demonstrated an association between volumes of basal ganglia, functional connectivity of anterior cingulate and apathy in late-onset depression.

2020 ◽  
Author(s):  
Nili Solomonov ◽  
Lindsay W. Victoria ◽  
Katharine Dunlop ◽  
Matteo Respino ◽  
Matthew Hoptman ◽  
...  

Background: Problem solving therapy (PST) and “Engage”, a reward-exposure” based therapy, are important treatment options for late-life depression, given modest efficacy of antidepressants in this disorder. Abnormal function of the reward and default mode networks has been observed during depressive episodes. This study examined whether resting state functional connectivity (rsFC) of reward and DMN circuitries is associated with treatment outcomes. Methods: Thirty-two older adults with major depression (mean age = 72.7) were randomized to 9-weeks of either PST or “Engage”. We assessed rsFC at baseline and Week 6. We placed seeds in three a priori regions of interest: subgenual cingulate (sgACC), dorsal anterior cingulate cortex (dACC), and nucleus accumbens (NAcc). Outcome measures included the Hamilton Depression Rating Scale (HAMD) and the Behavioral Activation for Depression Scale (BADS).Results: In both PST and “Engage”, higher rsFC between the sgACC and middle temporal gyrus at baseline was associated with greater improvement in depression severity (HAMD). Preliminary findings suggested that in “Engage” treated participants, lower rsFC between the dACC and DMPFC at baseline was associated with HAM-D improvement. Finally, in Engage only, increased rsFC from baseline to Week 6 between NAcc and Superior Parietal Cortex was associated with increased BADS scores.Conclusion: The results suggest that patients who present with higher rsFC between the sgACC and a structure within the DMN may benefit from behavioral psychotherapies for late life depression. ‘Engage’ may lead to increased rsFC within the reward system reflecting a reconditioning of the reward systems by reward exposure.


2019 ◽  
Vol 3 ◽  
pp. 247054701987366
Author(s):  
Janine Thome ◽  
Maria Densmore ◽  
Georgia Koppe ◽  
Braeden Terpou ◽  
Jean Théberge ◽  
...  

Background Brainstem and midbrain neuronal circuits that control innate, reflexive responses and arousal are increasingly recognized as central to the neurobiological framework of post-traumatic stress disorder (PTSD). The reticular activation system represents a fundamental neuronal circuit that plays a critical role not only in generating arousal but also in coordinating innate, reflexive responding. Accordingly, the present investigation aims to characterize the resting state functional connectivity of the reticular activation system in PTSD and its dissociative subtype. Methods We investigated patterns of resting state functional connectivity of a central node of the reticular activation system, namely, the pedunculopontine nuclei, among individuals with PTSD (n = 77), its dissociative subtype (PTSD+DS; n = 48), and healthy controls (n = 51). Results Participants with PTSD and PTSD+DS were characterized by within-group pedunculopontine nuclei resting state functional connectivity to brain regions involved in innate threat processing and arousal modulation (i.e., midbrain, amygdala, ventromedial prefrontal cortex). Critically, this pattern was most pronounced in individuals with PTSD+DS, as compared to both control and PTSD groups. As compared to participants with PTSD and controls, individuals with PTSD+DS showed enhanced pedunculopontine nuclei resting state functional connectivity to the amygdala and the parahippocampal gyrus as well as to the anterior cingulate and the ventromedial prefrontal cortex. No group differences emerged between PTSD and control groups. In individuals with PTSD+DS, state derealization/depersonalization was associated with reduced resting state functional connectivity between the left pedunculopontine nuclei and the anterior nucleus of the thalamus. Altered connectivity in these regions may restrict the thalamo-cortical transmission necessary to integrate internal and external signals at a cortical level and underlie, in part, experiences of depersonalization and derealization. Conclusions The present findings extend the current neurobiological model of PTSD and provide emerging evidence for the need to incorporate brainstem structures, including the reticular activation system, into current conceptualizations of PTSD and its dissociative subtype.


2017 ◽  
Vol 30 (3) ◽  
pp. 140-150 ◽  
Author(s):  
Filippo Cieri ◽  
Roberto Esposito ◽  
Nicoletta Cera ◽  
Valentina Pieramico ◽  
Armando Tartaro ◽  
...  

Late-life depression (LLD) is a common emotional and mental disability in the elderly population characterized by the presence of depressed mood, the loss of interest or pleasure in daily activities, and other depression symptoms. It has a serious effect on the quality of life of elderly individuals and increases their risk of developing physical and mental diseases. It is an important area of research, given the growing elderly population. Brain functional connectivity modifications represent one of the neurobiological biomarker for LLD even if to date remains poorly understood. In our study, we enrolled 10 elderly patients with depressive symptoms compared to 11 age-matched healthy controls. All participants were evaluated by means of neuropsychological tests and underwent the same functional magnetic resonance imaging (fMRI) protocol to evaluate modifications of brain resting state functional connectivity. Between-group differences were observed for the Geriatric Depression Scale and Hamilton Depression Rating Scale, with higher scores for patients with LLD. Voxel-wise, 1-way analysis of variance revealed between-group differences in left frontoparietal network (lFPN) and sensory motor network (SMN): Increased intrinsic connectivity in the LLD group was observed in the left dorsolateral prefrontal cortex and in the left superior parietal lobule of the lFPN and increased intrinsic connectivity in the LLD group was observed in the bilateral primary somatosensory cortex of the SMN. Our findings support the use of resting state fMRI as a potential biomarker for LLD; even if to confirm the relationship between brain changes and the pathophysiology of LLD, longitudinal neuroimaging studies are required.


2021 ◽  
Vol 15 ◽  
Author(s):  
Mohammad S. E. Sendi ◽  
Elaheh Zendehrouh ◽  
Charles A. Ellis ◽  
Zhijia Liang ◽  
Zening Fu ◽  
...  

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.


2021 ◽  
Author(s):  
Timothy P. Morris ◽  
Aaron Kucyi ◽  
Sheeba Arnold Anteraper ◽  
Maiya Rachel Geddes ◽  
Alfonso Nieto-Castañon ◽  
...  

AbstractInformation about a person’s available energy resources is integrated in daily behavioral choices that weigh motor costs against expected rewards. It has been posited that humans have an innate attraction towards effort minimization and that executive control is required to overcome this prepotent disposition. With sedentary behaviors increasing at the cost of millions of dollars spent in health care and productivity losses due to physical inactivity-related deaths, understanding the predictors of sedentary behaviors will improve future intervention development and precision medicine approaches. In 64 healthy older adults participating in a 6-month aerobic exercise intervention, we use neuroimaging (resting state functional connectivity), baseline measures of executive function and accelerometer measures of time spent sedentary to predict future changes in objectively measured time spent sedentary in daily life. Using cross-validation and bootstrap resampling, our results demonstrate that functional connectivity between 1) the anterior cingulate cortex and the supplementary motor area and 2) the right anterior insula and the left temporoparietal/temporooccipital junction, predict changes in time spent sedentary, whereas baseline cognitive, behavioral and demographic measures do not. Previous research has shown activation in and between the anterior cingulate and supplementary motor area as well as in the right anterior insula during effort avoidance and tasks that integrate motor costs and reward benefits in effort-based decision making. Our results add important knowledge toward understanding mechanistic associations underlying complex sedentary behaviors.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Stephen J. Kohut ◽  
Dionyssios Mintzopoulos ◽  
Brian D. Kangas ◽  
Hannah Shields ◽  
Kelly Brown ◽  
...  

AbstractLong-term cocaine use is associated with a variety of neural and behavioral deficits that impact daily function. This study was conducted to examine the effects of chronic cocaine self-administration on resting-state functional connectivity of the dorsal anterior cingulate (dACC) and putamen—two brain regions involved in cognitive function and motoric behavior—identified in a whole brain analysis. Six adult male squirrel monkeys self-administered cocaine (0.32 mg/kg/inj) over 140 sessions. Six additional monkeys that had not received any drug treatment for ~1.5 years served as drug-free controls. Resting-state fMRI imaging sessions at 9.4 Tesla were conducted under isoflurane anesthesia. Functional connectivity maps were derived using seed regions placed in the left dACC or putamen. Results show that cocaine maintained robust self-administration with an average total intake of 367 mg/kg (range: 299–424 mg/kg). In the cocaine group, functional connectivity between the dACC seed and regions primarily involved in motoric behavior was weaker, whereas connectivity between the dACC seed and areas implicated in reward and cognitive processing was stronger. In the putamen seed, weaker widespread connectivity was found between the putamen and other motor regions as well as with prefrontal areas that regulate higher-order executive function; stronger connectivity was found with reward-related regions. dACC connectivity was associated with total cocaine intake. These data indicate that functional connectivity between regions involved in motor, reward, and cognitive processing differed between subjects with recent histories of cocaine self-administration and controls; in dACC, connectivity appears to be related to cumulative cocaine dosage during chronic exposure.


2013 ◽  
Vol 214 (3) ◽  
pp. 313-321 ◽  
Author(s):  
Carmen Andreescu ◽  
Dana L. Tudorascu ◽  
Meryl A. Butters ◽  
Erica Tamburo ◽  
Meenal Patel ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yasushi Motoyama ◽  
Yoshitetsu Oshiro ◽  
Yumiko Takao ◽  
Hitoaki Sato ◽  
Norihiko Obata ◽  
...  

Abstract Ketamine has been used to treat chronic pain; however, it is still unknown as to what types of chronic pain is ketamine effective against. To identify the effect of administration of subanesthetic-dose ketamine in patients with chronic pain and to clarify the mechanism of the effect, we retrospectively investigated brain functional connectivity using resting-state functional magnetic resonance imaging (rs-fMRI). Patients were divided into responders (Group R: ≥50% improvement on Numerical Rating Scale) and non-responders (Group NR). We compared the differences in terms of brain functional connectivity by seed-to-voxel correlation analysis. Two-sample t-test revealed significant lower connectivity between the medial prefrontal cortex (mPFC) and precuneus in Group R. We also found a significant negative correlation between the improvement rate and functional connectivity strength between the mPFC and precuneus. These findings suggest that subanesthetic-dose ketamine is effective in patients with chronic pain whose brain functional connectivity between the mPFC and precuneus is low. We believe that the current study explored for the first time the correlation between brain functional connectivity and the effect of subanesthetic-dose ketamine for chronic pain and indicated the possibility of use of the predictive marker in pharmacological treatment of chronic pain.


2019 ◽  
Vol 237 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Grant McQueen ◽  
Aderlee Lay ◽  
John Lally ◽  
Anthony S. Gabay ◽  
Tracy Collier ◽  
...  

Abstract Rationale There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. Objectives The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). Methods In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. Results Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). Conclusions These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.


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