Thread by @DavidJonesBrain

1/n 🧵on the brief history of patterns seen on FDG-PET in Alzheimer's disease over the past 40 years. It's a story about a full circle convergence with the past 20 years of functional MRI. AD Heteromodal v primary cortex--> DMN--> AD--> principle gradient--> and the GFSS. #endalz

2/n “This, as well as other recent work, clearly suggests that the abnormal behavior of the demented subject may be related more to the disturbed functioning of surviving tissue than to loss of brain substance itself.” Friedland, et al. J Comput Assist Tomogr. 1983 Aug;7(4):590-8

3/n "In contrast to the association cortices, energy metabolism in the primary cortices and subcortical structures is preserved relatively when compared to that in the parietotemporal and frontal association cortices." Minoshima, et al. Ann Neurol. 1997 Jul;42(1):85-94.

4/n Almost 20 years later, the principle gradient of functional connectivity has the same anatomic description!

5/n“Alzheimer's disease show early reductions ...in this area … posterior cingulate cortex and adjacent precuneus can be posited as a tonically active region of the brain that may continuously gather information about the world around, and possibly within, us.”Raichle, PNAS 2001

6/n The seminal paper describing the default mode of brain function w/ prescient speculation that it models both internal and external data c/w the GFSS description over 20 years later.

7/n DMN 🎂“…several features of the default mode network, that it is widely distributed, internally cued, appears to integrate cognitive and emotional processing, and can be experimentally modulated, should make it an important and rewarding area of study...”Greicius PNAS 2003

8/n The DMN is born and forever linked to resting state fMRI patterns! Back to AD..."That the PCC may be critical to the retrieval of episodic memories is further supported by ... it is consistently among the earliest brain regions to show decreased metabolism in Alzheimer's"

9/n "Our study examining the default-mode network in early AD has generated several important results pertaining both to AD specifically and the default-mode network more generally." Greicius, Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4637-42.

10/n Studying the DMN informs the understanding of AD, and studying AD informs the understanding of the DMN! Many years pass in this cycle (I entered it ~2004 @ the Georgetown Center for Functional and Molecular Imaging)....

11/n "principal gradient corresponds to the intrinsic geometry of the cortex—regions in the DMN have the greatest geodesic distance along the cortical surface from primary sensory/motor areas—further indicates this axis may provide a crucial blueprint for cortical organization"..

12/n Margulies, Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):12574-12579.
... The return of the heteromodal vs primary cortex split, with DMN centered in this pattern!

13/n Full circle Back to FDG and AD with the GFSS model. It's been a long 40 yr journey, but it seems like these things will start making an impact in medical decision making for mental functions with ongoing collaborations w/ clinical, imaging, and computational neuroscientists!

14/n see here for more details:

https://twitter.com/DavidJonesBrain/status/1508419190054653952?s=20&t=zk6Tpl5b7STfW7sHR-qlAQ