Functional connectivity within MTL

There is a ton of work looking at BOLD functional connectivity (FC) in Alzheimer’s Disease, and one consensus that has emerged is that this is a disconnection syndrome, with most studies finding weaker connectivity within the default mode network (DMN), including connectivity to DMN cortex from the hippocampus and/or MTL. But what happens inside the MTL ? There is intricate feedback circuitry within the MTL, highlighted by the perforant path that connects extra-hippocampal cortex to the hippocampus. Thanks to our automated MTL subregion labeling technique (implemented in the publicly available ASHS software), we are in a position to carefully label MTL subregions and measure connectivity between these. That’s what we did in a paper published in Hippocampus last year. This work was in collaboration with David Wolk¬†at the Penn Memory Center.


This figure summarizes the findings. We found increased FC of MTL subregions to Entorhinal cortex (one of the first areas to show tangle pathology in the disease) in prodromal AD patients, but also evidence of the aforementioned, widely reported disconnection between MTL and neocortex.

  • [DOI] S. R. Das, J. Pluta, L. Mancuso, D. Kliot, S. Orozco, B. C. Dickerson, P. A. Yushkevich, and D. A. Wolk, “Increased functional connectivity within medial temporal lobe in mild cognitive impairment.,” Hippocampus, vol. 23, iss. 1, pp. 1-6, 2013.
    author = {Das, Sandhitsu R. and Pluta, John and Mancuso, Lauren and Kliot,
    Dasha and Orozco, Sylvia and Dickerson, Bradford C. and Yushkevich,
    Paul A. and Wolk, David A.},
    title = {{I}ncreased functional connectivity within medial temporal lobe in
    mild cognitive impairment.},
    journal = {{H}ippocampus},
    year = {2013},
    volume = {23},
    pages = {1-6},
    number = {1},
    month = {1},
    abstract = {Pathology at preclinical and prodromal stages of Alzheimer's disease
    (AD) may manifest itself as measurable functional change in neuronal
    networks earlier than detectable structural change. Functional connectivity
    as measured using resting-state functional magnetic resonance imaging
    has emerged as a useful tool for studying disease effects on baseline
    states of neuronal networks. In this study, we use high resolution
    MRI to label subregions within the medial temporal lobe (MTL), a
    site of early pathology in AD, and report an increase in functional
    connectivity in amnestic mild cognitive impairment between entorhinal
    cortex and subregions of the MTL, with the strongest effect in the
    anterior hippocampus. However, our data also replicated the effects
    of decreased connectivity of the MTL to other nodes of the default
    mode network reported by other researchers. This dissociation of
    changes in functional connectivity within the MTL versus the MTL's
    connection with other neocortical structures can help enrich the
    characterization of early stages of disease progression in AD},
    address = {United States},
    citation_identifier = {Das 2013},
    doi = {10.1002/hipo.22051},
    endnote_reference_number = {157},
    issn = {1098-1063},
    keywords = {Disease Progression;Humans;Middle Aged;Neural Pathways;Female;Entorhinal
    Cortex;Hippocampus;Cohort Studies;Male;Aged;Magnetic Resonance Imaging;Aged,
    80 and over;Temporal Lobe;research support, n.i.h., extramural;Mild
    Cognitive Impairment},
    mid = {NIHMS452636},
    organization = {Penn Image Computing and Science Laboratory (PICSL), Department of
    Radiology, University of Pennsylvania, Philadelphia, Pennsylvania,
    USA. sudas\},
    owner = {srdas},
    pmcid = {PMC3642853},
    pubmedid = {22815064},
    timestamp = {2014.02.19},
    us_nlm_id = {9108167},
    uuid = {17492B62-593F-41CB-A94C-DE69BB0F2D7B},
    web_data_source = {PubMed}