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Obsessive compulsive disorder (OCD) is associated with altered processing in brain regions involved in conflict resolution. However, limited research has examined the extent to which conflict from emotional distracters characterizes OCD such that responsiveness to task-irrelevant emotional stimuli is altered compared to controls. In the present study, 16 patients with OCD and 15 healthy controls underwent functional magnetic resonance imaging (fMRI) during resolution of conflict from emotional or nonemotional distracters. Results in healthy controls demonstrated that rostral anterior cingulate cortex (rACC), middle frontal gyrus (MFG), and medial superior frontal gyrus (MSFG) showed greater activation for high conflict versus low conflict. Responses in these regions differed between the emotional and nonemotional distracter tasks, with rACC and MSFG having greater activation for conflict from nonemotional distracters and anterior MFG showing greater activation for conflict from emotional distracters. Furthermore, between-group differences revealed a region in right posterior MFG in which controls similarly exhibited greater activation during high conflict versus low conflict with emotional distracters; however, OCD patients showed the opposite pattern with greater activation during low conflict compared to high conflict. These findings suggest that activity of right posterior MFG may be relevant in better understanding inefficient responding during emotional conflict in OCD.
Copyright © 2019 Elsevier B.V. All rights reserved.
Vascular pathology is common in late-life depression, contributing to changes in cerebral function. We examined whether late-life depression was associated with differences in cerebral blood flow (CBF) and whether such differences were related to vascular risk and cerebrovascular pathology, specifically white matter hyperintensity (WMH) volumes. Twenty-three depressed elders and 20 age- and sex-matched elders with no psychiatric history completed cranial 3T MRI. MRI procedures included a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition obtained while on room air and during a hypercapnia challenge allowing for calculation of cerebrovascular reactivity (CVR). Brain segmentation identified frontal, temporal, parietal and cingulate sub-regions in which CBF and CVR were calculated. The depressed group exhibited an anterior-posterior gradient in CBF, with lower CBF throughout the frontal lobe but higher CBF in the parietal lobe, temporal lobe, thalamus and hippocampus. A similar anterior to posterior gradient was observed in the cingulate cortex, with anterior regions exhibiting lower CBF and posterior regions exhibiting higher CBF. We did not observe any group differences in CVR measures. We did not observe significant relationships between CBF and CVR with vascular risk or WMH volumes, aside from an isolated finding associating higher WMH volumes with lower CBF in the rostral anterior cingulate cortex. Decreased anterior CBF in depressed elders might reflect decreased metabolic activity in these regions, while increased posterior CBF may represent either compensatory processes or different activity of posterior intrinsic functional networks. Future work should examine how these findings are related to compensatory changes with aging.
Copyright © 2017. Published by Elsevier Ltd.
Pain assessments typically depend on self-report of the pain experience. Yet, in individuals with autism spectrum disorders, this can be an unreliable due to communication difficulties. Importantly, observations of behavioral hypo- and hyperresponsivity to pain suggest altered pain sensitivity in autism spectrum disorder. Neuroimaging may provide insight into mechanisms underlying pain behaviors. The neural pain signature reliably responds to painful stimulation and is modulated by other outside regions, affecting the pain experience. In this first functional magnetic resonance imaging study of pain in autism spectrum disorder, we investigated neural responses to pain in 15 adults with autism spectrum disorder relative to a typical comparison group (n = 16). We explored temporal and spatial properties of the neural pain signature and its modulators during sustained heat pain. The two groups had indistinguishable pain ratings and neural pain signature responses during acute pain; yet, we observed strikingly reduced neural pain signature response in autism spectrum disorder during sustained pain and after stimulus offset. The posterior cingulate cortex, a neural pain signature modulating region, mirrored this late signal reduction in autism spectrum disorder. Intact early responses, followed by diminished late responses to sustained pain, may reflect altered pain coping or evaluation in autism spectrum disorder. Evidence of a dichotomous neural response to initial versus protracted pain may clarify the coexistence of both hypo- and hyperresponsiveness to pain in autism spectrum disorder.
BACKGROUND - Vascular pathology is common in late-life depression (LLD) and may contribute to alterations in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). In turn, such hemodynamic deficits may adversely affect brain function and clinical course. The goal of this study was to examine whether altered cerebral hemodynamics in depressed elders predicted antidepressant response.
METHODS - 21 depressed elders completed cranial 3T MRI, including a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition on both room air and during a hypercapnia challenge. Participants then completed 12 weeks of open-label sertraline. Statistical analyses examined the relationship between regional normalized CBF and CVR values and change in Montgomery-Asberg Depression Rating Scale (MADRS) and tested for differences based on remission status.
RESULTS - 10 participants remitted and 11 did not. After controlling for age and baseline MADRS, greater change in MADRS with treatment was associated with lower pre-treatment normalized CBF in the caudal anterior cingulate cortex (cACC) and lateral orbitofrontal cortex (OFC), as well as lower CVR with hypercapnia in the caudal medial frontal gyrus (cMFG). After controlling for age and baseline MADRS score, remitters exhibited lower CBF in the cACC and lower CVR in the cMFG.
LIMITATIONS - Our sample was small, did not include a placebo arm, and we examined only specific regions of interest.
CONCLUSIONS - Our findings suggest that increased perfusion of the OFC and the ACC is associated with a poor antidepressant response. They do not support that vascular pathology as measured by CBF and CVR negatively affects acute treatment outcomes.
Published by Elsevier B.V.
The APOE ε4 allele is associated with cognitive deficits and brain atrophy in older adults, but studies in younger adults are mixed. We examined APOE genotype effects on cognition and brain structure in younger adults and whether genotype effects differed by age and with presence of depression. 157 adults (32 % ε4 carriers, 46 % depressed) between 20 and 50 years of age completed neuropsychological testing, 131 of which also completed 3 T cranial MRI. We did not observe a direct effect of APOE genotype on cognitive performance or structural MRI measures. A significant genotype by age interaction was observed for executive function, where age had less of an effect on executive function in ε4 carriers. Similar interactions were observed for the entorhinal cortex, rostral and caudal anterior cingulate cortex and parahippocampal gyrus, where the effect of age on regional volumes was reduced in ε4 carriers. There were no significant interactions between APOE genotype and depression diagnosis. The ε4 allele benefits younger adults by allowing them to maintain executive function performance and volumes of cingulate and temporal cortex regions with aging, at least through age fifty years.
Depression remains a great societal burden and a major treatment challenge. Most antidepressant medications target serotonergic raphé nuclei. Acute tryptophan depletion (ATD) modulates serotonin function. To better understand the raphé's role in mood networks, we studied raphé functional connectivity in depression. Fifteen depressed patients were treated with sertraline for 12 weeks and scanned during ATD and sham conditions. Based on our previous findings in a separate cohort, resting state MRI functional connectivity between raphé and other depression-related regions (ROIs) was analyzed in narrow frequency bands. ATD decreased raphé functional connectivity with the bilateral thalamus within 0.025-0.05 Hz, and also decreased raphé functional connectivity with the right pregenual anterior cingulate cortex within 0.05-0.1 Hz. Using the control broadband filter 0.01-0.1 Hz, no significant differences in raphé-ROI functional connectivity were observed. Post-hoc analysis by remission status suggested increased raphé functional connectivity with left pregenual anterior cingulate cortex in remitters (n=10) and decreased raphé functional connectivity with left thalamus in non-remitters (n=5), both within 0.025-0.05 Hz. Reducing serotonin function appears to alter coordination of these mood-related networks in specific, low frequency ranges. For examination of effects of reduced serotonin function on mood-related networks, specific low frequency BOLD fMRI signals can identify regions implicated in neural circuitry and may enable clinically-relevant interpretation of functional connectivity measures. The biological significance of these low frequency signals detected in the raphé merits further study.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
The goal of this pilot study is to use complementary MRI strategies to quantify and relate cerebrovascular reactivity, resting cerebral blood flow and functional connectivity alterations in the first week following sports concussion in college varsity athletes. Seven college athletes (3F/4M, age = 19.7 ± 1.2 years) were imaged 3-6 days following a diagnosed sports related concussion and compared to eleven healthy controls with no history of concussion (5M/6F, 18-23 years, 7 athletes). Cerebrovascular reactivity and functional connectivity were measured using functional MRI during a hypercapnia challenge and via resting-state regional partial correlations, respectively. Resting cerebral blood flow was quantified using arterial spin labeling MRI methods. Group comparisons were made within and between 18 regions of interest. Cerebrovascular reactivity was increased after concussion when averaged across all regions of interest (p = 0.04), and within some default-mode network regions, the anterior cingulate and the right thalamus (p < 0.05) independently. The FC was increased in the concussed athletes within the default-mode network including the left and right hippocampus, precuneus and ventromedial prefrontal cortex (p < 0.01), with measures being linearly related to cerebrovascular reactivity in the hippocampus in the concussed athletes. Significant resting cerebral blood flow changes were not detected between the two groups. This study provides evidence for increased cerebrovascular reactivity and functional connectivity in the medial regions of the default-mode network within days of a single sports related concussion in college athletes. Our findings emphasize the utility of complementary cerebrovascular measures in the interpretation of alterations in functional connectivity following concussion.
Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.
BACKGROUND - Late-life depression is associated with white matter hyperintense lesions (WMLs) occurring in specific fiber tracts. In this study, we sought to determine if greater WML severity in the cingulum bundle or uncinate fasciculus was associated with poor short-term antidepressant response.
METHODS - Eleven depressed elders completed a baseline cranial 3T MRI and received antidepressant treatment following a medication algorithm. MRIs were analyzed to measure the fraction of each fiber tract׳s volume occupied by WMLs. Statistical analyses examined the effect of dichotomized fiber tract WML severity on three- and six-month depression severity after controlling for age and baseline depression severity.
RESULTS - Greater WML severity in the left hemispheric cingulum bundle adjacent to the hippocampus was associated with greater post-treatment depression severity at three- (F1,7=6.42, p=0.0390) and six-month assessments (F1,5=9.62, p=0.0268). Other fiber tract WML measures were not significantly associated with outcomes.
LIMITATIONS - The study had a small sample size and analyses were limited to only a priori fiber tracts.
CONCLUSIONS - This pilot study supports the hypothesis that focal damage to the cingulum bundle may contribute to poor short-term antidepressant response. These findings warrant further investigation with a larger, more definitive study.
Copyright © 2014 Elsevier B.V. All rights reserved.
The tendency to approach or avoid novel people is a fundamental human behavior and is a core dimension of social anxiety. Resting state fMRI was used to test for an association between social inhibition and intrinsic connectivity in 40 young adults ranging from low to high in social inhibition. Higher levels of social inhibition were associated with specific patterns of reduced amygdala-cingulate cortex connectivity. Connectivity was reduced between the superficial amygdala and the rostral cingulate cortex and between the centromedial amygdala and the dorsal anterior cingulate cortex. Social inhibition also modulated connectivity in several well-established intrinsic networks; higher social inhibition correlated with reduced connectivity with default mode and dorsal attention networks and enhanced connectivity in salience and executive control networks. These findings provide important preliminary evidence that social inhibition reflects differences in the underlying intrinsic connectivity of the brain in the absence of social stimuli or stressors.
Copyright © 2014 Elsevier B.V. All rights reserved.