Associate Investigator Athinoula A. Martinos Center for Biomedical Imaging, Mass General Research Institute

Associate Professor of Radiology Harvard Medical School

7-tesla mri; aging; alzheimer's disease; biomarkers; brainstem nuclei; cognition disorders; dementia; functional mri; locus coeruleus; pet imaging The Jacobs lab focuses on the function and structure of various neuromodulatory nuclei (e.g. locus coeruleus (latin for blue spot)) in the brainstem and subcortical regions to ultimately improve early detection of cognitive decline and neurodegenerative disorders. We also develop neuroimaging methodologies to improve the in vivo investigation of these nuclei, and evaluate novel interventions aiming to delay cognitive decline by targeting the function of neuromodulatory nuclei.

Research themes

• Optimizing neuroimaging methods (3T, 7T and PET) to investigate the neuromodulatory nuclei

 Many of these neuromodulatory nuclei are tiny and difficult to detect with standard imaging methods. Our group has developed and validated the first 7T MRI sequence to visualize the locus coeruleus in vivo. We also work on unravelling the source of this contrast in vivo and ex vivo and develop optimal pipelines that take physiological noise, partial volume effects as well as modelling the hemodynamic response function into account. 

• Investigate the functional and structural role of neuromodulatory nuclei in age-related cognitive changes

Norepinephrine, dopamine, acetylcholine and other neurotransmitters modulate various cognitive functions (attention, memory,..) and behaviors (sleep, mood, arousal,..) in a global and at the same time specific way. We recently demonstrated that greater functional connectivity between the locus coeruleus and nucleus basalis of Meynert or the ventral tegmental area were associated with lower memory performance in individuals older than 40 years of age. We also combine MRI data with other data modalities (physiological data, fluid data, PET data, pupil measurements) to determine how these nuclei fit into current disease models.

• Mapping contributions of the function and structure of neuromodulatory nuclei to neuropathological changes in neurodegenerative disorders

These neuromodulatory nuclei are among the first to be affected by Alzheimer’s pathology (amyloid, tau). We recently showed that increased turnover of norepinephrine is associated with greater levels of amyloid and tau and worse cognitive performance.  Currently, we work on combining our developed MRI methodologies with amyloid, tau and FDG-PET, CSF and blood measurements in healthy individuals and patients to investigate regional patterns, temporal sequences as well as examining what makes these nuclei vulnerable to pathological events. 

• Explore the potential to modulate neuromodulatory nuclei to delay cognitive decline

As these neuromodulatory nuclei plays an important role in cognition and behavior and are vulnerable to pathology early in life, it is our goal to delay cognitive decline as early as possible by modulating the function of these nuclei. We recently provided proof of concept evidence that transcutaneous vagus nerve stimulation, a non-invasive neurostimulation method that increases norepinephrine and targets the brainstem, can improve memory performance in older individuals. Establishing the underlying neural correlates and individual factors that contribute to a successful outcome is an important aim of the group.