Faculty Bibliography
Searched for:
person:sterne04
in-biosketch:yes
Total Results:
96
Inhibitory control and error processing in Obsessive-Compulsive Disorder: A mega-analysis of task-based fMRI data by the ENIGMA-OCD consortium
OBJECTIVE/UNASSIGNED:Obsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to the maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult and pediatric data from the ENIGMA-OCD consortium and the ABCD study. METHODS/UNASSIGNED:Individual participant data was uniformly processed using HALFpipe to extract statistical maps for response inhibition and error processing contrasts. Bayesian multilevel models were used to assess regional and whole-brain effects of OCD, with additional analyses examining the association between the OCD clinical profile and task-related activation. RESULTS/UNASSIGNED:Across inhibitory control tasks, both individuals with OCD and control participants showed robust activation in regions implicated in response inhibition and error processing. During response inhibition, compared to controls, adults with OCD showed stronger somatomotor cortex activation, while children with OCD showed stronger occipital cortex activation. Children with likely OCD from the ABCD cohort showed reduced activity in the frontoparietal network in the anterior insula/frontal operculum region. During error processing, relative to controls, adults with OCD showed weaker activation in fronto-striatal regions, while children with OCD showed stronger activation in frontoparietal and attention networks. Greater OCD symptom severity was associated with weaker task-related activation in adults and stronger activation in children during response inhibition. CONCLUSION/UNASSIGNED:Case-control differences in brain activation during inhibitory control varied by age group and task contrast. Symptom severity emerged as the main clinical correlate of activation during inhibition, suggesting that inhibitory control deficits in OCD may be both state-dependent and developmentally specific.
PMCID:12636563
PMID: 41279748
ISSN: 2692-8205
CID: 6007212
Negative valence in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium
OBJECTIVE:Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled fMRI data of 633 individuals with OCD and 453 healthy controls from 16 studies using different negatively-valenced tasks across the ENIGMA-OCD Working-Group. METHODS:Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative vs. neutral stimuli. In pre-registered analyses, parameter estimates were entered into Bayesian multilevel models to examine whole-brain and regional effects of OCD and its clinically relevant features - symptom severity, age of onset, and medication status. RESULTS:We provided a proof-of-concept that participant-level data can be combined across several task paradigms and observed one common task activation pattern across individuals with OCD and controls that encompasses fronto-limbic and visual areas implicated in negative valence. Compared to controls, individuals with OCD showed very strong evidence of weaker activation of the bilateral occipital cortex (P+<0.001) and adjacent visual processing regions during negative valence processing that was related to greater OCD severity, late-onset of disease and an unmedicated status. Individuals with OCD also showed stronger activation in the orbitofrontal, subgenual anterior cingulate and ventromedial prefrontal cortex (all P+<0.1) that was related to greater OCD severity and late onset. CONCLUSION/CONCLUSIONS:In the first mega-analysis of this kind, we replicate previous findings of stronger ventral prefrontal activation in OCD during negative valence processing and highlight the lateral occipital cortex as an important region implicated in altered negative valence processing.
PMID: 39725297
ISSN: 1873-2402
CID: 5767792
Effects of KCNQ potassium channel modulation on ventral tegmental area activity and connectivity in individuals with depression and anhedonia
Up to half of individuals with depression do not respond to first-line treatments, possibly due to a lack of treatment interventions informed by neurobiology. A novel therapeutic approach for depression has recently emerged from translational work targeting aberrant activity of ventral tegmental area (VTA) dopamine neurons via modulation of the KCNQ voltage-gated potassium channels. In this study, individuals with major depressive disorder (MDD) with elevated anhedonia were randomized to five weeks of the KCNQ channel opener, ezogabine (up to 900 mg/day) or placebo. Participants completed functional MRI during a monetary anticipation task and resting-state at baseline and at end-of-treatment. The clinical results were reported previously. Here, we examined VTA activity during monetary anticipation and resting-state functional connectivity between the VTA and the ventromedial prefrontal cortex (mesocortical pathway) and ventral striatum (mesolimbic pathway) at baseline and end-of-treatment. Results indicated a significant drug-by-time interaction in VTA activation during anticipation (F(1,34) = 4.36, p = 0.044), where VTA activation was reduced from pre-to-post ezogabine, compared to placebo. Mesocortical functional connectivity was also higher in depressed participants at baseline compared to a healthy control group (t(56) = 2.68, p = 0.01) and associated with VTA hyper-activity during task-based functional MRI at baseline (R = 0.352, p = 0.033). Mesocortical connectivity was also reduced from pre-to-post ezogabine, compared to placebo (significant drug-by-time interaction, F(1,33) = 4.317, p = 0.046). Together this translational work is consistent with preclinical findings highlighting VTA hyper-activity in depression, and suggesting a mechanism of action for KCNQ channel openers in normalizing this hyper-activity in individuals with both depression and anhedonia.
PMID: 40133425
ISSN: 1476-5578
CID: 5815322
Correction: White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group
PMID: 38454086
ISSN: 1476-5578
CID: 5694752
White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group
White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.
PMID: 38326559
ISSN: 1476-5578
CID: 5632312
The Human Affectome
Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomena can be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions-a framework for human affective research. In this capstone paper for the special issue "Towards an Integrated Understanding of the Human Affectome", we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomena collectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research.
PMID: 37925091
ISSN: 1873-7528
CID: 5607222
Correction: The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium
PMID: 37582859
ISSN: 1476-5578
CID: 5619162
Associations Between Suicidality and Interoception in Obsessive-Compulsive Disorder
BACKGROUND/UNASSIGNED:Individuals with obsessive-compulsive disorder (OCD) are at increased risk for suicide. One potential risk factor is interoceptive sensibility (IS), which is one's subjective experience of bodily sensations. The current study examined the relationship between IS and current suicidal ideation and lifetime history of suicide attempt, controlling for relevant covariates. METHODS/UNASSIGNED:= 145) were a clinical sample of individuals with OCD from the New York City area. A clinical rater administered a diagnostic interview and an OCD severity assessment, and participants completed questionnaires about demographics, IS, and suicidality. RESULTS/UNASSIGNED:Current suicidal ideation was associated with reduced trusting of the body, and lifetime history of suicide attempt was related to greater general awareness of sensation. These associations remained significant after controlling for covariates. CONCLUSIONS/UNASSIGNED:These results suggest that specific facets of IS may be associated with specific domains of suicidality. Decreased body trusting may represent a feeling of disconnection from the body that facilitates desire for death. Increased noticing of bodily sensations may lead to greater mental pain, which could interact with deficits in emotion regulation to increase risk for suicide attempt. Further research on the relationships between IS and suicidality in OCD is warranted.
PMCID:10610034
PMID: 37901053
ISSN: 2211-3649
CID: 5736422
Failures of Urge Suppression in Obsessive-Compulsive Disorder: Behavioral Modeling Using a Blink Suppression Task
Many individuals with obsessive-compulsive disorder (OCD) report sensory-based urges (e.g. 'not-just-right experiences') in addition to, or instead of, concrete fear-based obsessions. These sensations may be comparable to normative "urges-for-action" (UFA), such as the urge to blink. While research has identified altered functioning of brain regions related to UFA in OCD, little is known about behavioral patterns of urge suppression in the disorder. Using an urge-to-blink task as a model for sensory-based urges, this study compared failures of urge suppression between OCD patients and controls by measuring eyeblinks during 60-second blocks of instructed blink suppression. Cox shared frailty models estimated the hazard of first blinks during each 60-second block and recurrent blinks following each initial erroneous blink. OCD patients demonstrated a higher hazard of first and recurrent blinks compared to controls, suggesting greater difficulty resisting repetitive sensory-based urges. Within OCD, relationships between task outcomes and symptom severity were inconsistent. Findings provide support for a deficit in delaying initial urge-induced actions and terminating subsequent actions in OCD, which is not clearly related to clinical heterogeneity. Elucidating the nature of behavioral resistance to urges is relevant for informing conceptualizations of obsessive-compulsive psychopathology and optimizing treatment outcomes.
PMCID:10373599
PMID: 37521712
ISSN: 2211-3649
CID: 5545172
Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium
BACKGROUND:Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. METHODS:The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. RESULTS:Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31). CONCLUSIONS:Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.
PMID: 36041582
ISSN: 1573-2517
CID: 5332112
