The poster presented at the Parkinson's Foundation 2022 Research Summit @ Boston

White Matter Connectivity in Incident Mild Cognitive Impairment:

A Diffusion Spectrum Imaging Study of World Trade Center Responders at Midlife

J Alzheimers Dis. 2021;80(3):1209-1219. doi: 10.3233/JAD-201237.


Individuals who participated in response efforts at the World Trade Center (WTC) following 9/11/2001 are experiencing elevated incidence of mild cognitive impairment (MCI) at midlife.


We hypothesized that white matter connectivity measured using diffusion spectrum imaging (DSI) would be restructured in WTC responders with MCI versus cognitively unimpaired responders.


Twenty responders (mean age 56; 10 MCI/10 unimpaired) recruited from an epidemiological study were characterized using NIA-AA criteria alongside controls matched on demographics (age/sex/occupation/race/education). Axial DSI was acquired on a 3T Siemen’s Biograph mMR scanner (12-channel head coil) using a multi-band diffusion sequence. Connectometry examined whole-brain tract-level differences in white matter integrity. Fractional anisotropy (FA), mean diffusivity (MD), and quantified anisotropy were extracted for region of interest (ROI) analyses using the Desikan-Killiany atlas.


Connectometry identified both increased and decreased connectivity within regions of the brains of responders with MCI identified in the corticothalamic pathway and cortico-striatal pathway that survived adjustment for multiple comparisons. MCI was also associated with higher FA values in five ROIs including in the rostral anterior cingulate; lower MD values in four ROIs including the left rostral anterior cingulate; and higher MD values in the right inferior circular insula. Analyses by cognitive domain revealed nominal associations in domains of response speed, verbal learning, verbal retention, and visuospatial learning.


WTC responders with MCI at midlife showed early signs of neurodegeneration characterized by both increased and decreased white matter diffusivity in regions commonly affected by early-onset Alzheimer’s disease.

Prediction of lithium treatment response in bipolar depression using 5-HTT and 5-HT 1A PET

Eur J Nucl Med Mol Imaging.

2020 Sep;47(10):2417-2428. doi: 10.1007/s00259-020-04681-6.


  • Binding of the serotonin 1A receptor (5-HT1A) before lithium treatment was predictive of post-treatment clinical response following 8 weeks of lithium treatment with over 85% accuracy.

  • Taken together with our previous work, we find 5-HT1A before treatment could be useful in determining the successful treatment course (either via SSRIs or lithium) in bipolar depression.

Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response

J. Affect. Disord.

Vol. 256, 1 September 2019, Pages 8-16

Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample.


  • FA values were higher in nonremitters than in remitters in raphe-left and right amygdala tracts.

  • Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS scores.

  • While not applicable on an individual level, these results may guide further research on MDD.

Diffusion Entropy:

A Potential Neuroimaging Biomarker of Bipolar Disorder in the Temporal Pole


2018 Feb;72(2):e22015 doi:

Background: Despite much research, bipolar depression remains poorly understood, with no clinically useful biomarkers for its diagnosis.

Purpose: Validate existing findings with traditional diffusion MRI metrics and investigate the utility of a novel diffusion MRI metric, entropy of diffusion, in the search for bipolar depression biomarkers.

Finding: In the temporal pole, we observed significantly lower MD entropy in bipolar patients; this finding suggests a regional difference in MD distributions in the absence of an average difference. This metric allowed us to accurately characterize bipolar patients from controls in leave-one-out (accuracy = 83%) and prediction (accuracy = 73%) analyses.

Conclusion: This novel application of diffusion MRI yielded not only an interesting separation between bipolar patients and healthy controls, but also accurately classified bipolar patients from controls.

Multi-Modal Signatures of Tau Pathology, Neuronal Fiber Integrity, and Functional Connectivity in Traumatic Brain Injury

J. Neurotrauma

2019 Dec 1;36(23):3233-43 doi: 10.1089/neu.2018.6178

Goal: Explore the utility of multimodal imaging via positron-emission tomography (PET) and magnetic resonance imaging (MRI) techniques, such as diffusion tensor imaging (DTI), in a case series based on a population of traumatic brain injury (TBI) patients.

Aims: Probe interrelationship between tau deposition, white matter integrity, and gray matter functional connectivity across the spectrum of TBI.

Summary: We report a novel combination of advanced multi-modal imaging techniques including [F-18]AV-1451 PET, DTI, and fMRI in a heterogenous sample of TBI pathologies. Results suggest that disruptions in white matter integrity and functional connectivity are spatially congruent with tau pathology. These findings demonstrate that synergistic neurobiological information may be gained by interpreting the neuroimaging modalities in unison rather than in isolation. Given that TBI affects 1.5 million people in the United States each year, future research efforts should be aimed at leveraging the multi-modal approach illustrated here to advance our understanding of the full spectrum of TBI to ultimately personalize diagnostic and therapeutic efforts.