Jacobs Lab

About the lab

PI: Heidi Jacobs

The Jacobs lab focuses on the function and structure of various neuromodulatory nuclei (e.g. locus coeruleus) 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.


Our research focuses on the following areas:

  • 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 (Priovoulos et al., 2018). 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.

  • Investigating 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 (Jacobs et al., 2018. 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 (Jacobs et al., 2019).  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.

  • Exploring 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 (Jacobs et al., 2015). Establishing the underlying neural correlates and individual factors that contribute to a successful outcome is an important aim of the group.




      Research Assistants

      Prokopis Prokopiou – Post-doctoral fellow, expected start date: March 1, 2020

      Kelsey Biddle, Clinical Research Coordinator



      Dr. Keith Johnson, MGH
      Dr. Reisa Sperling, MGH
      Dr. Julie Price, MGH
      Dr. Kenneth Kwong, MGH
      Dr. David Salat, MGH
      Dr. Jonathan Polimeni, MGH
      Dr. Vitaly Napadow, MGH
      Dr. Benedikt Poser, Maastricht University
      Dr. Dimo Ivanov, Maastricht University
      Dr. Kamil Uludag, Health Network Toronto

      Selected Publications

      Key publications

      • Pagen LHG, van de Ven VG, Gronenschild EHBM, Priovoulos N, Verhey FRJ, Jacobs HIL. (2020) Contributions of Cerebro-Cerebellar Default Mode Connectivity Patterns to Memory Performance in Mild Cognitive Impairment. J. Alzheimers Dis. 75(2):633-647
      • Riphagen JM, Schmiedek L, Gronenschild EHBM, Yassa MA, Priovoulos N, Sack AT, Verhey FRJ, Jacobs HIL. (2020) Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan: A 7 T imaging study. Sci Rep, 10(1):7572
      • Jacobs HIL, Augustinack JC, Schultz AP, Hanseeuw BJ, Locascio J, Amariglio RE, Papp KV, Rentz DM, Sperling RA, Johnson KA. (2020) The presubiculum links incipient amyloid and tau pathology to memory function in older persons. Neurology, 94(18):e1916-e1928
      • Riphagen JM, Ramakers IHGM, Freeze WM, Pagen LHG, Hanseeuw BJ, Verbeek MM, Verhey FRJ, Jacobs HIL. (2020) Linking APOE-ε4, blood-brain barrier dysfunction, and inflammation to Alzheimer’s pathology. Neurobiol. Aging, 85():96-103
      • Jacobs HIL. Focus on the blue locus for learning. Nature Human Behaviour, (IF 10.586)
      • Priovoulos N, Poser BA, Ivanov D, Verhey FR, Jacobs HIL. (2019). In vivo imaging of the nucleus of the solitary tract with Magnetization Transfer at 7 Tesla. Neuroimage​, 201():116071  (IF 5.812)
      • Jacobs HIL, Riphagen JM, Ramakers IHGB, Verhey FRJ. (2019). Alzheimer’s disease pathology: pathways between central norepinephrine activity, memory and neuropsychiatric symptoms. ​Molecular Psychiatry. accepted (IF 11.973)
      • Jacobs HIL, Müller-Ehrenberg L, Priovoulos N, Roebroeck A. (2018) Curvilinear locus coeruleus functional connectivity trajectories over the adult lifespan: a 7T MRI study. Neurobiology of Aging, 69, 167-176 (IF 4.398)
      • Jacobs HIL, Hedden T, Schultz AP, Sepulcre J, Perea RD, Amariglio RE, Papp KV, Rentz DM, Sperling RA & Johnson KA (2018). Structural tract alterations predict down-stream tau accumulation in amyloid positive older individuals. Nature Neuroscience, 21(3), 424-431 (IF 21.126)
      • Priovoulos N., Jacobs H.I.L., Ivanov D., Ululdag K., Verhey F.R.J., Poser B.A.. (2018). High-resolution in vivo imaging of human locus coeruleus by magnetization transfer MRI at 3T and 7T. Neuroimage, 168, 427-436 (IF 5.812)
      • Jacobs H.I.L.,Hopkins D.A., Mayrhofer H.C., Bruner E., van Leeuwen F.W., Raaijmakers W. & Schmahmann J.D. (2017). The cerebellum in Alzheimer’s disease: evaluating its role in cognitive decline. Brain​, 141(1), 37-47 (IF 11.814)
      • Jacobs, H.I.L.,Riphagen, J.M., Razat, C.M., Wiese, S. & Sack, A.T. (2015) Transcutaneous vagus nerve stimulation boosts associative memory in older individuals. Neurobiology of Aging, 36(6), 1860-7 (IF 4.398)
      • Jacobs, H.I.L.,Wiese, S., van de Ven, V., Gronenschild, E.H.B.M., Verhey, F.R.J. & Matthews, P.M. (2015) Relevance of parahippocampal – locus coeruleus connectivity to memory in early dementia. Neurobiology of Aging, 36(2), 618-26 (IF 4.398)


      Other recent publications

      • Riphagen JM, Ramakers IHGM, Freeze WM, Pagen LHG, Hanseeuw BJ, Verbeek MM, Verhey FRJ, Jacobs HIL(2019). Linking APOE-E4, blood-brain barrier dysfunction and inflammation to Alzheimer’s pathology. Neurobiology of Aging, accepted (IF 4.454)
      • Duecker F, Mayrhofer HC, Jacobs HIL, Sack AT (2019). No effect of cold pressor test-induced arousal on attentional benefits and costs in an endogenous spatial orienting paradigm. Neuropsychologia, accepted.(IF 2.872)
      • Bischof GN, Jacobs HIL. (2019) Subthreshold amyloid and its biological and clinical meaning. Neurology. accepted (IF 8.689)
      • Jacobs H.I.L.,Buckley R.F. (2018).. Where do white matter alterations dovetail with the cascade model of Alzheimer’s disease? Brain. 141 (10), 2830-2833 (IF 11.814)
      • Müller-Ehrenberg L, Riphagen JM, Verhey FRJ, Sack AT, Jacobs HIL(2018). Alzheimer’s disease biomarkers have distinct associations with specific hippocampal subfield volumes. Journal Of Alzheimer’s Disease, 66(2), 811-823 (IF 3.517)
      • van Hooren RWE, Riphagen JM, Jacobs HIL(2018). Internetwork connectivity and amyloid-beta linked to cognitive decline in preclinical Alzheimer’s disease: a longitudinal cohort study. Alzheimer’s Research and Therapy, 10:88 (IF 6.142)
      • Riphagen JM, Gronenschild EHBM, Salat DH, Freeze WM, Ivanov D, Clerx L, Verhey FRJ, Aalten P, Jacobs HIL(2018). Shades of white: diffusion properties of T1- and FLAIR defined white matter signal abnormalities differ in stages from cognitively normal to dementia. Neurobiology of Aging, 68, 48-58 (IF 4.398)
      • Lee CM*, Jacobs HIL*,Marquié M, Becker JA, Andrea NV, Jin DS, Schultz AP, Frosch MP, Gómez-Isla T, Sperling RA, Johnson KA (2018). 18F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus signal. Journal Of Alzheimer’s Disease, 62, 1691-1702 (IF 3.517)

      Funding sources

      Major funding sources:
      NIH/NIA R01: "Tracking the origin of tau pathology"

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