Research

Bath salts use and mental health

The NIDA sponsored ‘Monitoring the Future’ study reported a prevalence of’ bath salts’ use among 12th graders at 1.1%, with a fifth of these reporting repeated use. In spite of a lower prevalence of synthetic cathinone use compared with drugs such as cannabis, these drugs continue to be a national concern as new molecular variants emerge and become accessible to young recreational users. The bath salt drug methylenedioxypyrovalerone (MDPV) shows high abuse potential and can also cause adverse behavioral effects (3-9), which warrant further investigation. The scientific premise guiding part of our research is that intravenous self-administration (IVSA) of MDPV alters pro-inflammatory signaling, which in turns leads to a dysphoria-like mood state and impairs cognitive behaviors. Alteration in functional and structural interactions between limbic structures mediating negative vs positive valence aspects of behavior will be assessed using high field magnetic resonance imaging (MRI). Thus, our research seeks to understand the mechanism of action of psychoactive synthetic drugs and determine ways to counteract their deleterious effects.

Bath salt drug MDPV increases glial presence and affects functional connectivity

Glial and functional connectivity changes in response to dangerous bath salt drug MDPV

 

Functional network and microstructural changes with amyloid or tau pathology in mouse models

In a separate line of research, we use high field resting state fMRI (rsfMRI) and mouse brain wide functional connectivity analysis to measure neural activity between sensory, motor, affective and cognitive brain areas. To enhance the wealth of data obtained from rsfMRI, we apply network analysis techniques from the field of graph theory to generate quantitative metrics describing distinct properties of functional brain networks, including strength of neural activity, central ‘hubs’, and the arrangement of functional interactions between different brain regions. Because of the critical role of axonal atrophy in various neurodegenerative diseases and in the early course of AD, we anticipate that functional changes as a result of AD pathology adversely affects microstructural intracellular and extracellular environment of major axonal tracts. To fully exploit the capabilities of high field diffusion MRI, we have devised an image acquisition strategy to enhance the sensitivity and precision for measuring water molecule displacements in mouse brain tissue at 11 Tesla. Combining the comprehensive image acquisition strategy with computational techniques for modeling the shape and rates of tissue water displacements offers metrics for geometric aspects of tissue microstructure to uncover the detailed effects of AD pathology. These include measures of the density and degree of dispersion of ‘neurites’, the amount of tissue free water, and indices for axon density and diameter.

Microstructure mapping in rodent brain using high angular resolution diffusion MRI (HARDI) with 8 shells. Acquisition strategy allows the quantitative mapping of orientation dispersion (OD), neurite density (ICVF), axon diameter and density, along with standard fractional anisotropy (FA)

Functional and microstructure imaging in mouse models of Alzheimer’s disease