Faculty Bibliography
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40
Sex differences in brain regional homogeneity during acute abstinence in cocaine use disorder
There are significant sex differences in the clinical characteristics of cocaine use disorder (CUD). As this is a brain disorder that involves changes in functional connectivity, we investigated the existence of sex differences among people with CUD and controls. We used a data-driven method comparing males (n = 20, CK-M) and females with CUD (n = 20, CK-F) and healthy controls (20 males, HC-M and 20 females, HC-F). The participants undertook a resting-state functional magnetic resonance imaging exam. Regional homogeneity (ReHo) was performed to identify group and sex differences. Persons with CUD of both sexes presented lower ReHo parameters than controls, especially within the parietal lobule. Males with CUD showed higher ReHo than females in three right-side brain areas: postcentral gyrus, putamen and fusiform gyrus. It was found that abstinence symptoms severity was associated with lower ReHo values in the right postcentral gyrus and the right fusiform gyrus. Participants with CUD exhibited altered ReHo parameters compared to controls, similar to what is found in ageing-related disorders. Our data also indicate that cocaine has sex-specific effects on brain functioning when analysing ReHo.
PMID: 35470550
ISSN: 1369-1600
CID: 5216982
Toward next-generation primate neuroscience: A collaboration-based strategic plan for integrative neuroimaging
Open science initiatives are creating opportunities to increase research coordination and impact in nonhuman primate (NHP) imaging. The PRIMatE Data and Resource Exchange community recently developed a collaboration-based strategic plan to advance NHP imaging as an integrative approach for multiscale neuroscience.
PMID: 34731649
ISSN: 1097-4199
CID: 5499342
Cortical thickness and subcortical volume abnormalities in male crack-cocaine users
Crack-cocaine offers a higher risk of abuse than intranasal and intravenous use of cocaine. Yet, current treatments remain disappointing and our understanding of the mechanism of crack-cocaine neurotoxicity is still incomplete. Magnetic resonance images studies on brain changes of crack-cocaine addicts show divergent data. The present study investigated gray matter (GM) abnormalities in crack-cocaine dependents (n = 18) compared to healthy controls (n = 17). MRI data was analysed using FreeSurfer and voxel-based morphometry (VBM). FreeSurfer analysis showed that CD had decreased cortical thickness (CT) in the left inferior temporal cortex (lTC), left orbitofrontal cortex (lOFC) and left rostro frontal cortex (lRFC), enlargement in left inferior lateral ventricle, and smaller GM volume in right hippocampus and right ventral diencephalon. VBM analysis showed that CD had significantly decreased GM volume in left Putamen and left nucleus accumbens. Furthermore, we found a negative correlation between duration of crack-cocaine use and lTC CT. These results provide compelling evidence for GM abnormalities in CD and also suggest that duration of crack-cocaine use may be associated with CT alterations.
PMID: 33621927
ISSN: 1872-7506
CID: 4835682
White matter deficits in cocaine use disorder: convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomic analysis
White matter (WM) abnormalities in patients with cocaine use disorder (CUD) have been studied; however, the reported effects on the human brain are heterogenous and most results have been obtained from male participants. In addition, biological data supporting the imaging findings and revealing possible mechanisms underlying the neurotoxic effects of chronic cocaine use (CU) on WM are largely restricted to animal studies. To evaluate the neurotoxic effects of CU in the WM, we performed an in vivo diffusion tensor imaging assessment of male and female cocaine users (n = 75) and healthy controls (HC) (n = 58). Moreover, we performed an ex vivo large-scale proteomic analysis using liquid chromatography-tandem mass spectrometry in postmortem brains of patients with CUD (n = 8) and HC (n = 12). Compared with the HC, the CUD group showed significant reductions in global fractional anisotropy (FA) (p < 0.001), and an increase in global mean (MD) and radial diffusion (RD) (both p < 0.001). The results revealed that FA, RD, and MD alterations in the CUD group were widespread along the major WM tracts, after analysis using the tract-based special statistics approach. Global FA was negatively associated with years of CU (p = 0.0421) and female sex (p < 0.001), but not with years of alcohol or nicotine use. Concerning the fibers connecting the left to the right prefrontal cortex, Brodmann area 9 (BA9), the CUD group presented lower FA (p = 0.006) and higher RD (p < 0.001) values compared with the HC group. A negative association between the duration of CU in life and FA values in this tract was also observed (p = 0.019). Proteomics analyses in BA9 found 11 proteins differentially expressed between cocaine users and controls. Among these, were proteins related to myelination and neuroinflammation. In summary, we demonstrate convergent evidence from in vivo diffusion tensor imaging and ex vivo proteomics analysis of WM disruption in CUD.
PMCID:8081729
PMID: 33911068
ISSN: 2158-3188
CID: 4858852
Journal of the American Academy of Child & Adolescent Psychiatry. 2021:60(2):222-235.DOI: 10.1016/j.jaac.2020.10.013
Systematic Review: Medication Effects on Brain Intrinsic Functional Connectivity in Patients With Attention-Deficit/Hyperactivity Disorder
OBJECTIVE:Resting-state fMRI (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD) have not been systematically reviewed. Systematically identify, assess and summarize within-patient R-fMRI studies of pharmacological-induced changes in patients with ADHD. We critically appraised strengths and limitations, and provide recommendations for future research. METHOD/METHODS:Systematic review of published original reports in English meeting criteria in pediatric and adult patients with ADHD up to July 1, 2020. A thorough search preceded selection of studies matching prespecified criteria. Strengths and limitations of selected studies, regarding design and reporting, were identified based on current best practices. RESULTS:We identified and reviewed 9 studies (5 pediatric and 4 adult studies). Sample sizes were small-medium (16-38 patients), and included few female participants. Medications were methylphenidate, amphetamines, and atomoxetine. Wide heterogeneity was observed in designs, analyses and results, which could not be combined quantitatively. Qualitatively, the multiplicity of brain regions and networks identified, some of which correlated with clinical improvements, do not support a coherent mechanistic hypothesis of medication effects. Overall, reports did not meet current standards to ensure reproducibility. CONCLUSION/CONCLUSIONS:In this emerging field, the few studies using R-fMRI to analyze the neural correlates of medications in patients with ADHD suggest a potential modulatory effect of stimulants and atomoxetine on several intrinsic brain activity metrics. However, methodological heterogeneity and reporting issues need to be addressed in future research to validate findings which may contribute to clinical care. Such a goal is not yet at hand.
PMID: 33137412
ISSN: 1527-5418
CID: 4655932
Resting-State fMRI to Identify the Brain Correlates of Treatment Response to Medications in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Lessons From the CUNMET Study
Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is increasingly being used to characterize functional connectivity in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks in patients with ADHD, which could be the target of pharmacological treatments. We describe the experience and results of the ClÃnica Universidad de Navarra (Spain) Metilfenidato (CUNMET) pilot study. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment vs. treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six brain networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also note the lessons learned, which could help those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine. To advance reproducible open science, our report is accompanied with links providing access to our data and analytic scripts.
PMCID:8635006
PMID: 34867544
ISSN: 1664-0640
CID: 5110082
Is it time to switch your T1W sequence? Assessing the impact of prospective motion correction on the reliability and quality of structural imaging
New large neuroimaging studies, such as the Adolescent Brain Cognitive Development study (ABCD) and Human Connectome Project (HCP) Development studies are adopting a new T1-weighted imaging sequence with prospective motion correction (PMC) in favor of the more traditional 3-Dimensional Magnetization-Prepared Rapid Gradient-Echo Imaging (MPRAGE) sequence. Here, we used a developmental dataset (ages 5-21, NÂ =Â 348) from the Healthy Brain Network (HBN) Initiative to directly compare two widely used MRI structural sequences: one based on the Human Connectome Project (MPRAGE) and another based on the ABCD study (MPRAGE+PMC). We aimed to determine if the morphometric measurements obtained from both protocols are equivalent or if one sequence has a clear advantage over the other. The sequences were also compared through quality control measurements. Inter- and intra-sequence reliability were assessed with another set of participants (NÂ =Â 71) from HBN that performed two MPRAGE and two MPRAGE+PMC sequences within the same imaging session, with one MPRAGE (MPRAGE1) and MPRAGE+PMC (MPRAGE+PMC1) pair at the beginning of the session and another pair (MPRAGE2 and MPRAGE+PMC2) at the end of the session. Intraclass correlation coefficients (ICC) scores for morphometric measurements such as volume and cortical thickness showed that intra-sequence reliability is the highest with the two MPRAGE+PMC sequences and lowest with the two MPRAGE sequences. Regarding inter-sequence reliability, ICC scores were higher for the MPRAGE1 - MPRAGE+PMC1 pair at the beginning of the session than the MPRAGE1 - MPRAGE2 pair, possibly due to the higher motion artifacts in the MPRAGE2 run. Results also indicated that the MPRAGE+PMC sequence is robust, but not impervious, to high head motion. For quality control metrics, the traditional MPRAGE yielded better results than MPRAGE+PMC in 5 of the 8 measurements. In conclusion, morphometric measurements evaluated here showed high inter-sequence reliability between the MPRAGE and MPRAGE+PMC sequences, especially in images with low head motion. We suggest that studies targeting hyperkinetic populations use the MPRAGE+PMC sequence, given its robustness to head motion and higher reliability scores. However, neuroimaging researchers studying non-hyperkinetic participants can choose either MPRAGE or MPRAGE+PMC sequences, but should carefully consider the apparent tradeoff between relatively increased reliability, but reduced quality control metrics when using the MPRAGE+PMC sequence.
PMID: 33248256
ISSN: 1095-9572
CID: 4734762
Measurement reliability for individual differences in multilayer network dynamics: Cautions and considerations
Multilayer network models have been proposed as an effective means of capturing the dynamic configuration of distributed neural circuits and quantitatively describing how communities vary over time. Beyond general insights into brain function, a growing number of studies have begun to employ these methods for the study of individual differences. However, test-retest reliabilities for multilayer network measures have yet to be fully quantified or optimized, potentially limiting their utility for individual difference studies. Here, we systematically evaluated the impact of multilayer community detection algorithms, selection of network parameters, scan duration, and task condition on test-retest reliabilities of multilayer network measures (i.e., flexibility, integration, and recruitment). A key finding was that the default method used for community detection by the popular generalized Louvain algorithm can generate erroneous results. Although available, an updated algorithm addressing this issue is yet to be broadly adopted in the neuroimaging literature. Beyond the algorithm, the present work identified parameter selection as a key determinant of test-retest reliability; however, optimization of these parameters and expected reliabilities appeared to be dataset-specific. Once parameters were optimized, consistent with findings from the static functional connectivity literature, scan duration was a much stronger determinant of reliability than scan condition. When the parameters were optimized and scan duration was sufficient, both passive (i.e., resting state, Inscapes, and movie) and active (i.e., flanker) tasks were reliable, although reliability in the movie watching condition was significantly higher than in the other three tasks. The minimal data requirement for achieving reliable measures for the movie watching condition was 20Â min, and 30Â min for the other three tasks. Our results caution the field against the use of default parameters without optimization based on the specific datasets to be employed - a process likely to be limited for most due to the lack of test-retest samples to enable parameter optimization.
PMID: 33130272
ISSN: 1095-9572
CID: 4684102
Joint embedding: A scalable alignment to compare individuals in a connectivity space
A common coordinate space enabling comparison across individuals is vital to understanding human brain organization and individual differences. By leveraging dimensionality reduction algorithms, high-dimensional fMRI data can be represented in a low-dimensional space to characterize individual features. Such a representative space encodes the functional architecture of individuals and enables the observation of functional changes across time. However, determining comparable functional features across individuals in resting-state fMRI in a way that simultaneously preserves individual-specific connectivity structure can be challenging. In this work we propose scalable joint embedding to simultaneously embed multiple individual brain connectomes within a common space that allows individual representations across datasets to be aligned. Using Human Connectome Project data, we evaluated the joint embedding approach by comparing it to the previously established orthonormal alignment model. Alignment using joint embedding substantially increased the similarity of functional representations across individuals while simultaneously capturing their distinct profiles, allowing individuals to be more discriminable from each other. Additionally, we demonstrated that the common space established using resting-state fMRI provides a better overlap of task-activation across participants. Finally, in a more challenging scenario - alignment across a lifespan cohort aged from 6 to 85 - joint embedding provided a better prediction of age (r2Â =Â 0.65) than the prior alignment model. It facilitated the characterization of functional trajectories across lifespan. Overall, these analyses establish that joint embedding can simultaneously capture individual neural representations in a common connectivity space aligning functional data across participants and populations and preserve individual specificity.
PMID: 32771618
ISSN: 1095-9572
CID: 4572892
Evaluating fMRI-Based Estimation of Eye Gaze During Naturalistic Viewing
The collection of eye gaze information during functional magnetic resonance imaging (fMRI) is important for monitoring variations in attention and task compliance, particularly for naturalistic viewing paradigms (e.g., movies). However, the complexity and setup requirements of current in-scanner eye tracking solutions can preclude many researchers from accessing such information. Predictive eye estimation regression (PEER) is a previously developed support vector regression-based method for retrospectively estimating eye gaze from the fMRI signal in the eye's orbit using a 1.5-min calibration scan. Here, we provide confirmatory validation of the PEER method's ability to infer eye gaze on a TR-by-TR basis during movie viewing, using simultaneously acquired eye tracking data in five individuals (median angular deviation < 2°). Then, we examine variations in the predictive validity of PEER models across individuals in a subset of data (n = 448) from the Child Mind Institute Healthy Brain Network Biobank, identifying head motion as a primary determinant. Finally, we accurately classify which of the two movies is being watched based on the predicted eye gaze patterns (area under the curve = 0.90 ± 0.02) and map the neural correlates of eye movements derived from PEER. PEER is a freely available and easy-to-use tool for determining eye fixations during naturalistic viewing.
PMID: 31595961
ISSN: 1460-2199
CID: 4150762
