Apathy in Frontotemporal Degeneration: Neuroanatomical Evidence of Impaired Goal-directed Behavior

Massimo, Lauren; Powers, John; Evans, Lois K.; McMillan, Corey T.; Rascovsky, Katya; Eslinger, Paul J.; Ersek, Mary; Irwin, David J.; Grossman, Murray

doi:10.3389/fnhum.2015.00611

Cited by 58 publications

(62 citation statements)

References 68 publications

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“…Apathy in FTD has been associated with atrophy in the right ventral striatum, the right temporal cortex, and the left operculum-insula [11]. In other studies, atrophy of the dorsolateral prefrontal and lateral orbitofrontal cortexes, right anterior cingulate cortex, right putamen, and right inferior parietal cortex were associated with apathy in FTD [9,10]. On PET, apathy was associated with decreased orbitofrontal metabolism in FTD [12].…”

Section: Introductionmentioning

confidence: 83%

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Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer’s Disease and Frontotemporal Dementia

Huey

Lee

Cheran

et al. 2016

JAD

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Background: Apathy is a common and problematic symptom of several neurodegenerative illnesses, but its neuroanatomical bases are not understood. Objective: To determine the regions associated with apathy in subjects with mild Alzheimer's disease (AD) using a method that accounts for the significant co-linearity of regional atrophy and neuropsychiatric symptoms. Methods: We identified 57 subjects with mild AD (CDR = 1) and neuropsychiatric symptoms in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We performed a multivariate multiple regression with LASSO regularization on all symptom subscales of the Neuropsychiatric Inventory and the whole-brain ROI volumes calculated from their baseline MRIs with FreeSurfer. We compared our results to those from a previous study using the same method in patients with frontotemporal dementia (FTD) and corticobasal syndrome (CBS). Results: Of neuropsychiatric symptoms, apathy showed the most robust neuroanatomical associations in the AD subjects. Atrophy of the following regions were independently associated with apathy: the ventromedial prefrontal cortex; ventrolateral prefrontal cortex; posterior cingulate cortex and adjacent lateral cortex; and the bank of the superior temporal sulcus. These results replicate previous studies using FTD and CBS patients, mostly agree with the previous literature on apathy in AD, and correspond to the Medial and Orbital Prefrontal Cortex networks identified in non-human primates. Conclusion:The current study, previous studies from our laboratory, and the previous literature suggest that impairment of the same brain networks involved in arousal, threat response, and reward processing are associated with apathy in AD and FTD.

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Section: Introductionmentioning

confidence: 83%

“…Neuropsychiatric symptoms associated with dementia are a major problem that contributes to caregiver stress, cost, and poor patient prognosis [4,5]. Apathy is the most common neuropsychiatric symptom in dementia, occurring in 25 to 88% of patients with AD and the vast majority of FTD patients [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer’s Disease and Frontotemporal Dementia

Huey

Lee

Cheran

et al. 2016

JAD

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“…Similarly, Perry et al showed insensitivity to aversive stimuli but preserved response to rewarding stimuli (noxious and pleasant odors) in frontotemporal dementia. Impaired sensitivity to monetary loss has also been seen in frontotemporal dementia . However, none of these groups looked for an association with apathy in the patient cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Impaired sensitivity to monetary loss has also been seen in frontotemporal dementia. 66 However, none of these groups looked for an association with apathy in the patient cohort. Apathy in Parkinson's disease has shown blunting of response to losses and reward, but no selective deficit in response to loss.…”

Section: Discussionmentioning

confidence: 99%

Insensitivity to loss predicts apathy in huntington's disease

et al. 2019

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Background Apathy is a deficit in goal‐directed behavior that significantly affects quality of life and function. It is common in Huntington's disease and other disorders affecting corticostriatal pathways. Deficits in processing of reward, altered effort, and executive dysfunction are associated with apathy in other disorders, but the cognitive processes leading to apathy in Huntington's disease remain largely unknown. A previously reported deficit in learning from losses in Huntington's disease raises the possibility of a hitherto unrecognized mechanism leading to apathy. This study's objective was to delineate the cognitive processes associated with apathy in HD. Methods We tested 51 Huntington's disease participants and 26 controls on a battery of novel and established measures to assess the contribution to apathy in Huntington's disease of executive function, reward value, reward‐effort calculations, instrumental learning, and response to reward and loss. Results Huntington's disase participants had deficits in instrumental learning with impaired response to loss, but no evidence to suggest altered reward‐related behavior or effort. We also saw an executive dysfunction contribution to apathy in Huntington's disease. Discussion We report the novel finding that apathy in Huntington's disease is associated with blunted responses to losses and impaired instrumental learning. This association is consistent with the known early degeneration of the indirect pathway and amygdala involvement in apathy in Huntington's disease, but is previously unreported in any disorder. In keeping with the comparative preservation of the ventral striatum and orbitofrontal cortex in Huntington's disease, reward valuation and reward‐effort calculations did not contribute to apathy. © 2019 International Parkinson and Movement Disorder Society

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“…The clinical importance of apathy is more and more amplified in neuro-pathological context, especially and at the moment, related specifically to frontal-subcortical circuit alteration (Starkstein et al, 1992; Duffy, 2000; Aarsland et al, 2001; Starkstein and Leentjens, 2008; Massimo et al, 2009; Chase, 2011; Moretti et al, 2012). The overt definition of apathy is that of a reduced motivation, which directly involve the goal-directed behavior (Duffy, 2000) with a diminishment of emotional involvement, and difficulty in the beginning of new actions (Duffy, 2000).…”

Section: Introductionmentioning

confidence: 99%

Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

Moretti

Signori

2016

Front. Aging Neurosci.

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Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; “emotional affective” apathy may be related to the orbitomedial PFC and ventral striatum; “cognitive apathy” may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of “autoactivation” may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies, degenerative or vascular, acute or chronic.

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Apathy in Frontotemporal Degeneration: Neuroanatomical Evidence of Impaired Goal-directed Behavior

Cited by 58 publications

References 68 publications

Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer’s Disease and Frontotemporal Dementia

Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer’s Disease and Frontotemporal Dementia

Insensitivity to loss predicts apathy in huntington's disease

Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

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