Neural basis of motivational approach and withdrawal behaviors in neurodegenerative disease

Shunichiro Shinagawa, Adhimoolam Babu, Virginia Sturm, Tal Shany-Ur, Parnian Toofanian Ross, Diana Zackey, Pardis Poorzand, Scott Grossman, Bruce L. Miller, Katherine P. Rankin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Introduction: The Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) have been theorized as neural systems that regulate approach/withdrawal behaviors. Behavioral activation/inhibition balance may change in neurodegenerative disease based on underlying alterations in systems supporting motivation and approach/withdrawal behaviors, which may in turn be reflected in neuropsychiatric symptoms. Method: A total of 187 participants (31 patients diagnosed with behavioral variant of FTD [bvFTD], 13 semantic variant of primary progressive aphasia [svPPA], 14 right temporal variant FTD [rtFTD], 54 Alzheimer's disease [AD], and 75 older healthy controls [NCs]) were included in this study. Changes in behavioral inhibition/activation were measured using the BIS/BAS scale. We analyzed the correlation between regional atrophy pattern and BIS/BAS score, using voxel-based morphometry (VBM). Results: ADs had significantly higher BIS scores than bvFTDs and NCs. bvFTDs activation-reward response (BAS-RR) was significantly lower than ADs and NCs, though their activation-drive (BAS-D) was significantly higher than in ADs. Both AD and rtFTD patients had abnormally low activation fun-seeking (BAS-FS) scores. BIS score correlated positively with right anterior cingulate and middle frontal gyrus volume, as well as volume in the right precentral gyrus and left insula/operculum. Conclusions: AD, bvFTD, and rtFTD patients show divergent patterns of change in approach/withdrawal reactivity. High BIS scores correlated with preservation of right-predominant structures involved in task control and self-protective avoidance of potentially negative reinforcers. Damage to these regions in bvFTD may create a punishment insensitivity that underlies patients' lack of self-consciousness in social contexts.

Original languageAmerican English
Article numbere00350
JournalBrain and Behavior
Issue number9
StatePublished - 1 Sep 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Published by Wiley Periodicals, Inc.


  • Alzheimer's disease
  • Behavior inhibition
  • Dementia
  • Frontotemporal dementia
  • Neurodegeneration
  • Social concern
  • Voxel-based morphometry


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