Poster No:
473
Submission Type:
Abstract Submission
Authors:
Nelson Descalço1,2,3, Gonçalo Cotovio1,2,4, Jaime Caballero-Insaurriaga1, Ana Maia1,2,4, Francisco Faro Viana1, Nuno Loução1, João Valente Duarte1, Catarina Fonseca2, João Ramos5, José Oliveira1,2, J. Bernardo Barahona-Corrêa1,2, Albino J. Oliveira-Maia1,2
Institutions:
1Champalimaud Research and Clinical Centre, Champalimaud Foundation, Lisbon, Portugal, 2NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisbon, Portugal, 3Psychiatry and Mental Health Department, Hospital Garcia de Orta, Almada, Portugal, 4Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal, 5Department of Neurorradiology, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal
First Author:
Nelson Descalço, MD
Champalimaud Research and Clinical Centre, Champalimaud Foundation|NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa|Psychiatry and Mental Health Department, Hospital Garcia de Orta
Lisbon, Portugal|Lisbon, Portugal|Almada, Portugal
Co-Author(s):
Gonçalo Cotovio
Champalimaud Research and Clinical Centre, Champalimaud Foundation|NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa|Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental
Lisbon, Portugal|Lisbon, Portugal|Lisbon, Portugal
Ana Maia
Champalimaud Research and Clinical Centre, Champalimaud Foundation|NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa|Department of Psychiatry and Mental Health, Centro Hospitalar de Lisboa Ocidental
Lisbon, Portugal|Lisbon, Portugal|Lisbon, Portugal
Francisco Faro Viana
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
Nuno Loução
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
João Valente Duarte
Champalimaud Research and Clinical Centre, Champalimaud Foundation
Lisbon, Portugal
Catarina Fonseca
NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa
Lisbon, Portugal
João Ramos
Department of Neurorradiology, Centro Hospitalar de Lisboa Ocidental
Lisbon, Portugal
José Oliveira
Champalimaud Research and Clinical Centre, Champalimaud Foundation|NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa
Lisbon, Portugal|Lisbon, Portugal
J. Bernardo Barahona-Corrêa
Champalimaud Research and Clinical Centre, Champalimaud Foundation|NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa
Lisbon, Portugal|Lisbon, Portugal
Albino J. Oliveira-Maia
Champalimaud Research and Clinical Centre, Champalimaud Foundation|NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa
Lisbon, Portugal|Lisbon, Portugal
Introduction:
Lesional neuropsychiatric syndromes offer a unique avenue to explore the intricate relationship between structural brain changes and brain function in complex disorders. Techniques such as functional lesion connectivity mapping (fLCM) can be employed for this purpose, using resting-state functional connectivity data from extensive databases of healthy individuals to construct a network of brain regions functionally connected to lesioned areas. Obsessive-compulsive disorder (OCD) cases are predominantly idiopathic but can emerge after brain lesions. In an ongoing work, we have found that lesions associated with OCD-like symptoms are more frequently situated in the bilateral orbitofrontal cortex (OFC) and right middle and superior temporal lobe. Furthermore, these lesions exhibit a distinctive pattern of brain functional connectivity compared to control lesions, with preferential connectivity to the OFC and ventral basal ganglia, bilaterally. However, fLCM predominantly leverages on functional connectivity patterns largely driven by cortical regions, neglecting the characterization of white matter (WM) pathways. Structural disconnections arising from brain lesions can be explored using structural LCM (sLCM) methods resorting to normative connectomes constructed from diffusion imaging data. Here, we aim to 1) examine whether focal brain lesions associated with OCD symptoms converge on a specific structural connectivity network, and whether it is shared with lesional OCD functional connectivity networks; and 2) investigate whether WM regions identified with sLCM exhibit microstructural abnormalities in patients with primary OCD.
Methods:
For aim 1, we performed a systematic literature search following PRISMA guidelines to identify lesion locations associated with OCD and those eligible were traced onto a standard space (N=40). Structural disconnection maps for each brain lesion were computed using BCBToolKit with a structural normative connectome (N=178) and compared to structural disconnection maps from a lesional control cohort (N=608) not selected for a specific neuropsychiatric syndrome. We used a voxel-wise permutation-based two-sample t-test of 5000 permutations, two-tailed and α<0.05, with threshold-free cluster enhancement (TFCE). Voxels were labelled using the JHU WM tractography atlas. For aim 2, we used multishell diffusion images from a multicentric case-control study of age- and sex-matched patients with primary OCD (N=70) and healthy controls (N=69). Diffusion data were preprocessed and reconstructed using generalized q-sampling imaging in DSI Studio. Deterministic tractography was performed for the WM tracts identified in the previous aim. Mean fractional anisotropy (FA), a diffusion tensor metric of WM fiber integrity, was calculated for each tract, and group differences were tested using a two-sample t-test, correcting for multiple comparisons (False Discovery Rate of 10%).
Results:
When looking into sLCM, compared to control lesions, OCD-associated lesions exhibit a significantly higher probability of structural disconnection to the corpus callosum, forceps minor, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulum. Consistently, patients with primary OCD had significantly lower mean FA values than the control cohort for the forceps minor (p=0.022), cingulum (p=0.028), corpus callosum (p=0.044), and right anterior thalamic radiation (p=0.044).
Conclusions:
Our findings support that OCD-associated brain lesions are linked to a pattern of structural dysconnectivity affecting major associative pathways of the frontal lobe with the thalamus, the temporal and occipital lobes, and interhemispheric pathways. Additionally, our study suggests that these pathways are altered in patients with primary OCD, mainly due to abnormal WM integrity compared to healthy controls. This is consistent with the current neurobiological model of dysfunctional cortico-striato-thalamo-cortical circuits in OCD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 2
Novel Imaging Acquisition Methods:
Diffusion MRI
Keywords:
ADULTS
Basal Ganglia
MRI
Obessive Compulsive Disorder
Psychiatric Disorders
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
Provide references using author date format
Yeh, Fang-Cheng, et al. "Deterministic diffusion fiber tracking improved by quantitative anisotropy." (2013): e80713. PLoS ONE 8(11): e80713. doi:10.1371/journal.pone.0080713