Apathy in Frontotemporal Degeneration: Neuroanatomical Evidence of Impaired Goal-directed Behavior
Open accessAbstract
BACKGROUND: Apathy, the major manifestation of impaired goal-directed behavior (GDB), is the most common neuropsychiatric syndrome associated with behavioral variant frontotemporal degeneration (bvFTD). The behavioral and biological mechanisms of apathy, however, are not well understood. We hypothesized that GDB has multiple components-including at least initiation, planning and motivation-and that GDB is supported by a network of multiple frontal brain regions. In this study, we examined this hypothesis by evaluating the selective breakdown of GDB in bvFTD, and relating these deficits to gray matter (GM) atrophy and white matter (WM) integrity. METHODS: Eighteen apathetic bvFTD participants and 17 healthy controls completed the Philadelphia Apathy Computerized Test (PACT). This test quantifies each of three components of GDB hypothesized to contribute to apathy. We then used regression analyses to relate PACT scores to GM atrophy and reduced white matter (WM) fractional anisotropy (FA) in bvFTD. RESULTS: Compared to controls, bvFTD participants demonstrated significant impairments in each of the three hypothesized components of GDB that contribute to apathy. Regression analyses related each component to disease in specific GM structures and associated WM tracts. Poor initiation thus was related to GM atrophy in anterior cingulate and reduced FA in the cingulum. Planning impairment was related to GM atrophy in dorsolateral prefrontal cortex and reduced FA in superior longitudinal fasciculus. Poor motivation was related to GM atrophy in orbitofrontal cortex (OFC) and reduced FA in uncinate fasciculus (UNC). CONCLUSIONS: bvFTD patients have difficulty with initiation, planning and motivation components of GDB. These findings are consistent with the hypotheses that GDB encompasses at least three processes, that these are supported by a large-scale neural network within specific portions of the frontal lobe, and that degradation of any one of these prefrontal regions in bvFTD may contribute to apathy.
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The fronto-insular cortex, part of the salience network, has been structurally and functionally linked to FTD syndromes, particularly bvFTD.
“The fronto‐insular cortex, part of the salience network, has been structurally and functionally linked to FTD syndromes, particularly bvFTD, 58 and this is suggested by our MRI analysis.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [58]
The Results (Imaging results; page unavailable) show frontal and temporal gray-matter atrophy and reduced white-matter integrity in bvFTD, supporting a structural link for frontal regions. Our copy does not identify the fronto-insular cortex as an affected region, describe it as part of the salience network, or establish the claimed functional link. (LLM, conf=0.78)
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Cingulate-centered large-scale networks: Normal functions, aging, and neurodegenerative disease
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Insensitivity to loss predicts apathy in huntington's disease
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Anhedonia in Neurodegenerative Diseases
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Exploration Deficits Under Ecological Conditions as a Marker of Apathy in Frontotemporal Dementia
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Measurement Challenges in Research With Individuals With Cognitive Impairment
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Self-citationCoexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD
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Automatic classification of AD pathology in FTD phenotypes using natural speech
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Shaping perceptual learning of synthetic speech through feedback
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Computerized assessment of goal-directed behavior in Parkinson’s disease
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Post-stroke apathy: A case series investigation of neuropsychological and lesion characteristics.
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- Authors
- Massimo, L., Powers, J. P., Evans, L. K., McMillan, C. T., Rascovsky, K., Eslinger, P., Ersek, M., Irwin, D. J., & Grossman, M.
- Affiliations
- University of Pennsylvania (US)
- Pennsylvania State University (US)
- Corresponding author
- Massimo, Lauren
- ORCID
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2015-11-10
- Volume
- 9
- Pages
- 611-611
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC4639601
- OpenAlex
- W2192986043
- Cited by
- 69
- References
- 66
- Citations by year
- 2026: 6 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 10 · 2017: 6 · 2016: 3
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (F31NR013306, AG017586, AG010124, AG043503, NS053488, NS044266)
- John A. Hartford Foundation
- Wyncote Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
- Keywords
- apathy, goal-directed behavior, gray matter atrophy, white matter integrity, fractional anisotropy, anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex, cingulum, superior longitudinal fasciculus, uncinate fasciculus, motivation, action initiation, planning
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