The anatomy of apathy: a neurocognitive framework for amotivated behaviour
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Apathy is a debilitating syndrome associated with many neurological disorders, including several common neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, and focal lesion syndromes such as stroke. Here, we review neuroimaging studies to identify anatomical correlates of apathy, across brain disorders. Our analysis reveals that apathy is strongly associated with disruption particularly of dorsal anterior cingulate cortex (dACC), ventral striatum (VS) and connected brain regions. Remarkably, these changes are consistent across clinical disorders and imaging modalities. Review of the neuroimaging findings allows us to develop a neurocognitive framework to consider potential mechanisms underlying apathy. According to this perspective, an interconnected group of brain regions - with dACC and VS at its core - plays a crucial role in normal motivated behaviour. Specifically we argue that motivated behaviour requires a willingness to work, to keep working, and to learn what is worth working for. We propose that deficits in any one or more of these processes can lead to the clinical syndrome of apathy, and outline specific approaches to test this hypothesis. A richer neurobiological understanding of the mechanisms underlying apathy should ultimately facilitate development of effective therapies for this disabling condition.
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Apathy is a well-recognized feature of strokes affecting the medial frontal cortex and the medial and anterior thalamus.
“In addition, apathy is a well-recognized feature of strokes affecting similar portions of the medial frontal cortex (Kang & Kim, 2008; Le Heron et al., 2018) and the medial and anterior thalamus (Carrera & Bogousslavsky, 2006; Krause et al., 2012; Serra et al., 2013) respectively.”
From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as Le Heron et al., 2018
Across differing underlying pathologies and neuroimaging methods, the anterior cingulate cortex, orbital frontal cortex, and medial thalamus exhibit some of the most robust changes associated with apathy.
“Across differing underlying pathologies and neuroimaging methods, the anterior cingulate cortex, orbital frontal cortex, and medial thalamus exhibit some of the most robust changes associated with apathy (Le Heron et al., 2018).”
From The cingulum bundle: Anatomy, function, and dysfunction (2018) · cites this paper as Le Heron et al., 2018
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“We do not discuss psychiatric disorders, where there is also a body of work that examines the structural or functional basis of apathy (Foussias et al., 2014; Holroyd and Umemoto, 2016; Treadway and Zald, 2011).”
BackgroundReijnders, J., Scholtissen, B., Weber, W., Aalten, P., Verhey, F., & Leentjens, A. (2010) · Movement Disorders · doi:10.1002/mds.23268 · Cited by 192 · see citing works
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The research domain criteria framework: The case for anterior cingulate cortex
Holroyd, C. B., & Umemoto, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.021 · Cited by 187 · cited 1× · see citing works
“We do not discuss psychiatric disorders, where there is also a body of work that examines the structural or functional basis of apathy (Foussias et al., 2014; Holroyd and Umemoto, 2016; Treadway and Zald, 2011).”
BackgroundThe organization of the descending ventral pallidal projections in the monkey
Haber, S., Lynd-Balta, E., & Mitchell, S. (1993) · The Journal of comparative neurology · doi:10.1002/cne.903290108 · Cited by 184 · see citing works
Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies
Wen, M., Chan, L. L., Tan, L. C. S., & Tan, E. (2016) · European Journal of Neurology · doi:10.1111/ene.13002 · Cited by 183 · see citing works
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Anterior cerebral artery infarction: Stroke mechanism and clinical-imaging study in 100 patients
Kang, S. Y., & Kim, J. S. (2008) · Neurology · doi:10.1212/01.wnl.0000314686.94007.d0 · Cited by 177 · see citing works
Dorsal anterior cingulate cortex integrates reinforcement history to guide voluntary behavior
Holroyd, C. B., & COLES, M. G. H. (2007) · Cortex · doi:10.1016/j.cortex.2007.08.013 · Cited by 171 · see citing works
Parabolic discounting of monetary rewards by physical effort
Hartmann, M. N., Hager, O. M., Tobler, P. N., & Kaiser, S. (2013) · Behavioural Processes · doi:10.1016/j.beproc.2013.09.014 · Cited by 169 · see citing works
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Self-citationIndividual Differences in Premotor Brain Systems Underlie Behavioral Apathy
Bonnelle, V., Manohar, S., Behrens, T., & Husain, M. (2015) · Cerebral Cortex · doi:10.1093/cercor/bhv247 · Cited by 163 · see citing works
Self-citationNeuropsychiatric features of corticobasal degeneration
Litvan, I., Cummings, J., & Mega, M. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.65.5.717 · Cited by 160 · see citing works
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Apathy Secondary to Stroke: A Systematic Review and Meta-Analysis
Caeiro, L., Ferro, J. M., & Costa, J. N. (2013) · Cerebrovascular Diseases · doi:10.1159/000346076 · Cited by 156 · see citing works
Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease
Benoit, M., Clairet, S., Koulibaly, P. M., Darcourt, J., & Robert, P. H. (2004) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1163 · Cited by 147 · see citing works
Carrière, N., Besson, P., Dujardin, K., Duhamel, A., Defebvre, L., Delmaire, C., & Devos, D. (2014) · Movement Disorders · doi:10.1002/mds.25904 · Cited by 147 · see citing works
The role of cognitive effort in subjective reward devaluation and risky decision-making
Apps, M. A. J., Grima, L. L., Manohar, S., & Husain, M. (2015) · Scientific Reports · doi:10.1038/srep16880 · Cited by 145 · see citing works
Self-citationWittmann, M. K., Kolling, N., Akaishi, R., Chau, B. K. H., Brown, J. W., Nelissen, N., & Rushworth, M. F. S. (2016) · Nature Communications · doi:10.1038/ncomms12327 · Cited by 142 · see citing works
Neurons in Dorsal Anterior Cingulate Cortex Signal Postdecisional Variables in a Foraging Task
Blanchard, T. C., & Hayden, B. Y. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.3151-13.2014 · Cited by 141 · see citing works
Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson’s disease
Muhammed, K., Manohar, S., Yehuda, M. B., Chong, T. T. ‐., Tofaris, G. K., Lennox, G. G., Bogdanovic, M. D., Hu, M., & Masud Husain, B. (2016) · Brain · doi:10.1093/brain/aww188 · Cited by 133 · see citing works
Self-citationScahill, R. I., Hobbs, N. Z., Say, M. J., Bechtel, N., Henley, S. M. D., Hyare, H., Langbehn, D. R., Jones, R., Leavitt, B. R., Roos, R. A. C., et al. (2011) · Human Brain Mapping · doi:10.1002/hbm.21449 · Cited by 132 · cited 1× · see citing works
“A study in pre-symptomatic and early HD did not find any associations between apathy and either GM or WM changes (Scahill et al., 2011).”
BackgroundNeuroimaging Correlates of Apathy and Depression in Alzheimer's Disease
STARKSTEIN, S. E., Mizrahi, R., Capizzano, A. A., Ación, L., Brockman, S., & Power, B. (2009) · Journal of Neuropsychiatry · doi:10.1176/jnp.2009.21.3.259 · Cited by 132 · see citing works
Resting-state frontostriatal functional connectivity in Parkinson's disease-related apathy
Baggio, H. C., Segura, B., Garrido‐Millan, J. L., Marti, M., Compta, Y., Valldeoriola, F., Tolosa, E., & Junque, C. (2015) · Movement Disorders · doi:10.1002/mds.26137 · Cited by 131 · see citing works
A SPECT study of apathy in Alzheimer's disease
Lanctôt, K. L., Moosa, S., Herrmann, N., Leibovitch, F. S., Rothenburg, L., Cotter, A., & Black, S. E. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000103633 · Cited by 126 · see citing works
Apathy in frontotemporal dementia: Behavioral and neuroimaging correlates
Eslinger, P., Moore, P., Antani, S., Anderson, C., & Grossman, M. (2012) · Behavioural Neurology · doi:10.3233/ben-2011-0351 · Cited by 126 · see citing works
Adaptive coding of action values in the human rostral cingulate zone
Jocham, G., Neumann, J., Klein, T., Danielmeier, C., & Ullsperger, M. (2009) · Journal of Neuroscience · doi:10.1016/s1053-8119(09)72093-2 · Cited by 126 · see citing works
Reyes, S., Viswanathan, A. C., Godin, O., Dufouil, C., Benisty, S., Hernandez, K., Kurtz, A., Jouvent, E., O'Sullivan, M., Czernecki, V., et al. (2009) · Neurology · doi:10.1212/01.wnl.0000344166.03470.f8 · Cited by 125 · see citing works
Separate and overlapping brain areas encode subjective value during delay and effort discounting
Massar, S. A. A., Libedinsky, C., Weiyan, C., Huettel, S. A., & Chee, M. W. L. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.06.080 · Cited by 123 · see citing works
Basal forebrain infarction. A clinicopathologic correlation.
Phillips, S., Sangalang, V., & Sterns, G. L. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520230024008 · Cited by 121 · cited 1× · see citing works
“Subcortically, basal ganglia lesions, particularly those involving the caudate nucleus or nucleus accumbens, are associated with the development of apathy (Bhatia and Marsden, 1994; Gerace et al., 2013; Maeda et al., 2012; Phillips et al., 1987).”
BackgroundAdaptive effort investment in cognitive and physical tasks: A neurocomputational model
Verguts, T., Vassena, E., & Silvetti, M. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00057 · Cited by 118 · see citing works
Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients.
Santangelo, G., Vitale, C., Picillo, M., Cuoco, S., Moccia, M., Pezzella, D., Erro, R., Longo, K., Vicidomini, C., Pellecchia, M. T., et al. (2015) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2015.02.015 · Cited by 115 · cited 1× · see citing works
“They have reduced striatal dopamine binding capacity even at the time of PD diagnosis, and before they have commenced dopaminergic therapy (Santangelo et al., 2015).”
BackgroundSilvetti, M., Alexander, W., Verguts, T., & Brown, J. W. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.003 · Cited by 114 · see citing works
The Anterior Cingulate Gyrus Signals the Net Value of Others' Rewards
Apps, M. A. J., & Ramnani, N. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2701-13.2014 · Cited by 109 · cited 1× · see citing works
“Neuroimaging studies in healthy human adults have consistently implicated the dACC and VS in signaling the effort costs of a particular behaviour, but also in signaling rewards on offer prior to any action being performed (Apps and Ramnani, 2014; Botvinick et al., 2009; Croxson et al., 2009; Schmidt et al., 2012; Vass…”
BackgroundSelf-citationThe syndrome of combined polar and paramedian thalamic infarction.
Perren, F., Clarke, S., & Bogousslavsky, J. (2005) · Archives of Neurology · doi:10.1001/archneur.62.8.1212 · Cited by 105 · see citing works
Apathy is Associated With Volume of the Nucleus Accumbens in Patients Infected With HIV
Paul, R. H., Brickman, A. M., Navia, B., Hinkin, C., Malloy, P. F., Jefferson, A. L., Cohen, R. A., Tate, D. F., & Flanigan, T. (2005) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.17.2.167 · Cited by 102 · cited 1× · see citing works
“Apathy in HIV is associated with reduced NAc volume (Paul et al., 2005).”
BackgroundApathy and cortical atrophy in Alzheimer's disease
Tunnard, C., Whitehead, D. L., Hurt, C. S., Wahlund, L., Mecocci, P., Tsolaki, M., Vellas, B. J., Spenger, C., Kłoszewska, I., Soininen, H. S., et al. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2603 · Cited by 102 · see citing works
Kos, C., van Tol, M.-J., Marsman, J.-B. C., Knegtering, H., & Aleman, A. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.08.012 · Cited by 101 · see citing works
Dopamine reverses reward insensitivity in apathy following globus pallidus lesions
Adam, R. J., Leff, A. P., Sinha, N., Turner, C., Bays, P. M., Draganski, B., & Husain, M. (2012) · Cortex · doi:10.1016/j.cortex.2012.04.013 · Cited by 100 · cited 1× · see citing works
“Profound apathy is also seen following lesions to the GPi, a crucial output structure of the basal ganglia (Adam et al., 2013).”
BackgroundSelf-citationNeural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits
Moretti, R., & Signori, R. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00289 · Cited by 99 · cited 2× · see citing works
“Yet, to date, few attempts have been made to synthesize findings regarding the neurobiology across different conditions (but see Kos et al., 2016; Moretti and Signori, 2016) and there is particularly limited understanding of the functional anatomy of apathy across disorders.”
BackgroundHuang, C. C., Ravdin, L., Nirenberg, M. J., Piboolnurak, P., Severt, L., Maniscalco, J. S., Sólnes, L. B., Dorfman, B. J., & Henchcliffe, C. (2013) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000345987 · Cited by 99 · see citing works
A review of neuroimaging findings of apathy in Alzheimer's disease
Theleritis, C. G., Politis, A. M., Siarkos, K., & Lyketsos, C. G. (2013) · International Psychogeriatrics · doi:10.1017/s1041610213001725 · Cited by 98 · see citing works
Robert, P. H., Darcourt, G., Koulibaly, M. P., Clairet, S., Benoit, M., Garcia, R., Dechaux, O., & Darcourt, J. (2006) · European Journal of Neurology · doi:10.1111/j.1468-1331.2006.01088.x · Cited by 98 · cited 1× · see citing works
“Research using SPECT has consistently demonstrated that reduced perfusion in ACC and OFC – as well as frontopolar and DLPFC regions in some studies – is associated with apathy in AD (Benoit et al., 2004; Craig et al., 1996; Lanctôt et al., 2007; Migneco et al., 2001; Robert et al., 2006).”
ResultThe structural correlates of functional deficits in early huntington's disease
Delmaire, C., Dumas, E., Sharman, M., van den Bogaard, S. V. D., Valabrègue, R., Jauffret, C., Justo, D., Reilmann, R., Stout, J., Craufurd, D., et al. (2013) · Human Brain Mapping · doi:10.1002/hbm.22055 · Cited by 97 · see citing works
Stanton, B. R., Leigh, P. N., Howard, R. J., Barker, G. J., & Brown, R. G. (2013) · Journal of Neurology · doi:10.1007/s00415-013-6989-9 · Cited by 92 · see citing works
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Neural integration of risk and effort costs by the frontal pole: only upon request
Burke, C. J., Brünger, C., Kahnt, T., Park, S. Q., & Tobler, P. N. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3662-12.2013 · Cited by 87 · cited 4× · see citing works
“Alterations in fronto-striatal circuits may mediate post-stroke apathy Apathy is also a complication of strokes in other cortical locations (Caeiro et al., 2013).”
BackgroundInfluentialScholl, J., Kolling, N., Nelissen, N., Wittmann, M. K., Harmer, C. J., & Rushworth, M. F. S. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0396-15.2015 · Cited by 85 · see citing works
Loss of psychic self-activation after paramedian bithalamic infarction.
Engelborghs, S., Mariën, P., Pickut, B., Verstraeten, S., & de Deyn, P. (2000) · Stroke · doi:10.1161/01.str.31.7.1762 · Cited by 82 · see citing works
Medial prefrontal cortical activity reflects dynamic re-evaluation during voluntary persistence
McGuire, J. T., & Kable, J. W. (2015) · Nature Neuroscience · doi:10.1038/nn.3994 · Cited by 82 · see citing works
Association of Vascular Factors With Apathy in Community-Dwelling Elderly Individuals
Ligthart, S. A., Richard, E., Fransen, N. L., Eurelings, L. S. M., Beem, L., Eikelenboom, P., van Gool, W. A., & Moll van Charante, E. P. (2012) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.1858 · Cited by 79 · see citing works
A Multidimensional Approach to Apathy after Traumatic Brain Injury
Arnould, A., Rochat, L., Azouvi, P., & der Linden, M. V. (2013) · Neuropsychology Review · doi:10.1007/s11065-013-9236-3 · Cited by 79 · see citing works
Microstructural alteration of the anterior cingulum is associated with apathy in Alzheimer disease
Kim, J. W., Lee, D. Y., Choo, I. H., Seo, E. H., Kim, S. G., Park, S. Y., & Woo, J. I. (2011) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e31820dcc73 · Cited by 79 · see citing works
Tighe, S. K., Oishi, K., Mori, S., Smith, G. S., Albert, M., Lyketsos, C. G., & Mielke, M. M. (2012) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.11120375 · Cited by 77 · see citing works
A systematic review of the validity and reliability of apathy scales in neurodegenerative conditions
Radakovic, R., Harley, C., Abrahams, S., & Starr, J. (2014) · International Psychogeriatrics · doi:10.1017/s1041610214002221 · Cited by 77 · cited 1× · see citing works
“On reviewing this literature we have inevitably had to be selective at times due to the considerable variability introduced by different methods of diagnosis and different levels of controlling for comorbidity (Radakovic et al., 2015; Robert et al., 2009).”
BackgroundDissociating behavioral disorders in early dementia—An FDG-PET study
Schroeter, M. L., Vogt, B., Frisch, S., Becker, G., Seese, A., Barthel, H., Mueller, K., Villringer, A., & Sabri, O. (2011) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2011.06.009 · Cited by 77 · cited 2× · see citing works
“Strikingly, when regional metabolism or perfusion is examined across different disorders (including frontotemporal dementia (FTD) and subjective cognitive impairment in one study, and AD and organic personality disorder in another), apathy is strongly correlated with reduced ACC activity (Migneco et al., 2001; Schroet…”
BackgroundBlanchard, T. C., Strait, C. E., & Hayden, B. Y. (2015) · Journal of Neurophysiology · doi:10.1152/jn.00711.2015 · Cited by 76 · see citing works
Distinct Regions within Medial Prefrontal Cortex Process Pain and Cognition
Jahn, A., Nee, D. E., Alexander, W. H., & Brown, J. W. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2180-16.2016 · Cited by 75 · see citing works
Apathy in Parkinson's Disease: Neurophysiological Evidence of Impaired Incentive Processing
Martínez-Horta, S., Riba, J., de Bobadilla, R. F., Pagonabarraga, J., Pascual-Sedano, B., Antonijoan, R., Romero, S., Mañanas, M. A., García-Sánchez, C., & Kulisevsky, J. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0251-14.2014 · Cited by 72 · see citing works
Post-Stroke Apathy and Hypoperfusion in Basal Ganglia: SPECT Study
Onoda, K., Kuroda, Y., Yamamoto, Y., Abe, S., Oguro, H., Nagai, A., Bokura, H., & Yamaguchi, S. (2010) · Cerebrovascular Diseases · doi:10.1159/000319771 · Cited by 64 · cited 1× · see citing works
“One study has in fact concluded that cerebral blood flow within the basal ganglia is reduced in apathetic compared to non-apathetic patients, irrespective of stroke location (Onoda et al., 2011).”
BackgroundAgosta, F., Galantucci, S., Svetel, M., Lukić, M., Copetti, M., Davidovic, K., Tomić, A., Spinelli, E., Kostic, V., & Filippi, M. (2014) · Journal of Neurology · doi:10.1007/s00415-014-7301-3 · Cited by 60 · see citing works
Neuroanatomy of a neurobehavioral disturbance in the left anterior thalamic infarction
Nishio, Y., Hashimoto, M., Ishii, K., & Mori, E. (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.236463 · Cited by 59 · see citing works
White matter correlates of apathy in HIV-positive subjects: a diffusion tensor imaging study.
Hoare, J., Fouche, J., Spottiswoode, B., Joska, J., Schoeman, R., Stein, D. J., & Carey, P. (2010) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.22.3.313 · Cited by 59 · cited 1×
“Limited reports link cerebellar and brainstem involvement with post stroke apathy (Hoffmann and Cases, 2008).”
BackgroundRelationship between apathy and diffusion tensor imaging metrics of the brain in Alzheimer's disease
Ota, M., Sato, N., Nakata, Y., Arima, K., & Uno, M. (2012) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2779 · Cited by 58 · see citing works
Jonsson, M., Edman, Å., Lind, K., Rolstad, S., Sjögren, M., & Wallin, A. (2009) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2379 · Cited by 56 · see citing works
The circuitry of abulia: Insights from functional connectivity MRI
Siegel, J. S., Snyder, A. Z., Metcalf, N. V., Fucetola, R. P., Hacker, C. D., Shimony, J. S., Shulman, G. L., & Corbetta, M. (2014) · NeuroImage Clinical · doi:10.1016/j.nicl.2014.09.012 · Cited by 54 · see citing works
McIntosh, R. C., Rosselli, M., Uddin, L. Q., & Antoni, M. H. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.04.008 · Cited by 50 · cited 1× · see citing works
“…infection Apathy has been recognized as a significant accompaniment of human immunodeficiency virus (HIV) infection, and is thought to arise from the direct result of viral infection, which has a particular affinity for the basal ganglia, rather than as a reactive process (McIntosh et al., 2015).”
BackgroundBalsters, J. H., Mantini, D., Apps, M. A. J., Eickhoff, S. B., & Wenderoth, N. (2016) · NeuroImage: Clinical · doi:10.1016/j.nicl.2016.03.016 · Cited by 50 · cited 1× · see citing works
“These include the amygdala, anterior insula, DLPFC, VTA, and more ventral portions of the medial prefrontal cortex (Balsters et al., 2016; Beckmann et al., 2009; Haber et al., 1995; Mesulam and Mufson, 1982; Mufson and Mesulam, 1982; Neubert et al., 2015; Petrides and Pandya, 1999; Tighe et al.,…”
BackgroundSelf-citationTotal Recovery after Bilateral Paramedian Thalamic Infarct
Krolak-Salmon, P., Croisile, B., Houzard, C., Setiey, A., Girard-Madoux, P., & Vighetto, A. (2000) · European Neurology · doi:10.1159/000008239 · Cited by 50 · see citing works
Kamat, R., Brown, G. G., Bolden, K., Fennema-Notestein, C., Archibald, S., Marcotte, T. D., Letendre, S. L., Ellis, R. J., Woods, S. P., Grant, I., et al. (2014) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2014.950636 · Cited by 47 · see citing works
Apathy blunts neural response to money in Parkinson's disease
Lawrence, A. D., Goerendt, I. K., & Brooks, D. J. (2011) · Social Neuroscience · doi:10.1080/17470919.2011.556821 · Cited by 43 · see citing works
Neuropsychiatry and White Matter Microstructure in Huntington’s Disease
Gregory, S., the Track-HD investigators, Scahill, R. I., Seunarine, K. K., Stopford, C. L., Zhang, H. G., Zhang, J., Orth, M., Dürr, A., Roos, R. A. C., et al. (2015) · Journal of Huntington s Disease · doi:10.3233/jhd-150160 · Cited by 38 · cited 1× · see citing works
“In a heterogeneous group of 60 patients who had suffered traumatic brain injury (TBI), reduced volume within brain regions including medial frontal cortex was associated with greater severity of apathetic features (Guild and Levine, 2015).”
BackgroundDeficiency of brain structural sub‐network underlying post‐ischaemic stroke apathy
Yang, S., Hua, P., Shang, X., Cui, Z., Zhong, S., Gong, G., & Humphreys, G. (2015) · European Journal of Neurology · doi:10.1111/ene.12575 · Cited by 31 · see citing works
Reduced prefrontal N-acetylaspartate in stroke patients with apathy.
Głodzik-Sobańska, L., Słowik, A., Kiełtyka, A., Kozub, J., Sobiecka, B., Urbanik, A., & Szczudlik, A. (2005) · Journal of Neurological Sciences · doi:10.1016/j.jns.2005.06.004 · Cited by 31
Preoperative factors of apathy in subthalamic stimulated Parkinson disease
Robert, G., Jeune, F. L., Lozachmeur, C., Drapier, S., Dondaine, T., Péron, J., Houvenaghel, J.-F., Travers, D., Sauleau, P., Millet, B., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000941 · Cited by 28
Lim, T., & So, Y.-M. (2010) · doi:10.1016/j.jalz.2010.05.1477 · Cited by 27
Etiology of Frontal Network Syndromes in Isolated Subtentorial Stroke
Hoffmann, M., & Cases, L. B. (2009) · Behavioural Neurology · doi:10.3233/ben-2008-0220 · Cited by 23 · cited 1×
“Apathy was associated with reduced FA within WM pathways including the anterior cingulum, uncinate fasciculus and fornix (Hollocks et al., 2015).”
BackgroundTakayanagi, Y., Gerner, G. J., Takayanagi, M., Rao, V., Vannorsdall, T., Sawa, A., Schretlen, D., & Cascella, N. (2013) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.12040093 · Cited by 21 · see citing works
Woodhall, B. (1960) · Cancer chemotherapy reports · doi:10.1097/00000542-197401000-00027 · Cited by 21 · cited 1×
“Research using SPECT has consistently demonstrated that reduced perfusion in ACC and OFC – as well as frontopolar and DLPFC regions in some studies – is associated with apathy in AD (Benoit et al., 2004; Craig et al., 1996; Lanctôt et al., 2007; Migneco et al., 2001; Robert et al., 2006).”
ResultPrefrontal Markers and Cognitive Performance Are Dissociated during Progressive Dopamine Lesion
Wilson, C. R. E., Vezoli, J., Stoll, F. M., Faraut, M. C. M., Leviel, V., Knoblauch, K., & Procyk, E. (2016) · PLoS Biology · doi:10.1371/journal.pbio.1002576 · Cited by 16 · see citing works
Functional Correlates of Midline Brain Volume Loss in Chronic Traumatic Brain Injury
Guild, E. B., & Levine, B. (2015) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617715000600 · Cited by 14 · cited 1× · see citing works
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BackgroundApathetic syndrome from carotid dissection: a dangerous condition
Gerace, C., Corsi, F., & Comanducci, G. (2013) · BMJ Case Reports · doi:10.1136/bcr-2013-009686 · Cited by 4
Micrographia and abulia due to frontal subcortical infarction.
Maeda, K., Idehara, R., & Shiraishi, T. (2012) · Internal medicine · doi:10.2169/internalmedicine.51.7721 · Cited by 4 · cited 1×
“Subcortically, basal ganglia lesions, particularly those involving the caudate nucleus or nucleus accumbens, are associated with the development of apathy (Bhatia and Marsden, 1994; Gerace et al., 2013; Maeda et al., 2012; Phillips et al., 1987).”
BackgroundKhan (2000) · doi:10.1002/1531-8249(200008)48:2
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The cingulum bundle: Anatomy, function, and dysfunction
Bubb, E. J., Metzler-Baddeley, C., & Aggleton, J. P. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.008 · Cited by 740 · see citing works
Neuroscience of apathy and anhedonia: a transdiagnostic approach
Husain, M., & Roiser, J. P. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0029-9 · Cited by 642 · see citing works
Self-citationRobert, P., Lanctôt, K., Agüera-Ortiz, L., Aalten, P., Brémond, F., Defrancesco, M., Hanon, C., David, R., Dubois, B., Dujardin, K., et al. (2018) · European psychiatry · doi:10.1016/j.eurpsy.2018.07.008 · Cited by 283 · see citing works
“, interviews and self-reports; see [17] for a review) but also on new Information and Communication Technologies (ICTs, e.”
BackgroundSelf-citationBehavioral and Psychological Effects of Coronavirus Disease-19 Quarantine in Patients With Dementia
Cagnin, A., Lorenzo, R. D., Marra, C., Bonanni, L., Cupidi, C., Laganà, V., Rubino, E., Vacca, A., Provero, P., Isella, V., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.578015 · Cited by 370 · see citing works
“Apathy, in fact, may have a cognitive, emotional, and physical component and each type of apathy has defined neuro-anatomical correlates targeting prefrontal, dorsolateral, and motor cortex other than striatum (34, 35).”
BackgroundMüller, T., & Apps, M. A. J. (2018) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2018.04.030 · Cited by 239 · see citing works
Self-citationChen, Y., Dang, M., & Zhang, Z. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00456-1 · Cited by 224 · see citing works
Nobis, L., & Masud Husain, B. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.12.007 · Cited by 139 · see citing works
Self-citationBrain mechanisms underlying apathy
Heron, C. J. L., Holroyd, C. B., Salamone, J. D., & Masud Husain, B. (2018) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-318265 · Cited by 190 · see citing works
“Studies examining the neuroimaging correlates of the apathetic syndrome have identified consistent associations between apathy and disruption of specific medial frontal cortex and subcortical structures—see refs 7 8 for reviews.”
Self-citationDiagnostic criteria for apathy in neurocognitive disorders
Miller, D. S., Robert, P., Ereshefsky, L., Adler, L., Bateman, D., Cummings, J., Dekosky, S., Fischer, C. E., Husain, M., Ismail, Z., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12358 · Cited by 168 · see citing works
Self-citationApathy and anxiety are early markers of Alzheimer's disease.
Johansson, M., Stomrud, E., Lindberg, O., Westman, E., Johansson, P., van Westen, D., Mattsson, N., & Hansson, O. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.10.008 · Cited by 156 · see citing works
Müller, H. L., Tauber, M., Lawson, E. A., Özyurt, J., Bison, B., Martinez-Barbera, J.-P., Puget, S., Merchant, T. E., & van Santen, H. M. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00351-z · Cited by 144 · see citing works
Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson’s disease
Heron, C. J. L., Plant, O., Manohar, S., Ang, Y., Jackson, M., Lennox, G. G., Hu, M. T., & Husain, M. (2018) · Brain · doi:10.1093/brain/awy110 · Cited by 162 · see citing works
“…brain network underlying effort-based decision-making is one such candidate system intrinsic to normal motivated behaviour, and indeed a recent neurocognitive framework of apathy emphasizes three core components of it that could potentially underlie the apathetic phenotype (Le Heron et al., 2017).”
BackgroundSelf-citationApathy after stroke: Diagnosis, mechanisms, consequences, and treatment
Tay, J., Morris, R., & Markus, H. (2021) · International Journal of Stroke · doi:10.1177/1747493021990906 · Cited by 124
“These core regions are embedded in large-scale functionally connected networks that underlie GDB-related cognitive functions such as reward-based decision-making, attentional control, and reinforcement learning.(24,28) Disruption to these networks may lead to cognitive deficits that manifest behaviorally as apathy (Su…”
BackgroundBègue, I., Kaiser, S., & Kirschner, M. (2020) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.06.004 · Cited by 108 · see citing works
Steffens, D. C., Fahed, M., Manning, K. J., & Wang, L. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02292-3 · Cited by 114 · see citing works
Salamone, J., Correa, M., Ferrigno, S. M., Yang, J.-H., Rotolo, R., & Presby, R. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.015107 · Cited by 95 · see citing works
“…by a lack of behavioral activation that can be seen across several different disorders, including depression and schizophrenia (Salamone et al., 2006, 2015; Treadway and Zald, 2011; Barch et al., 2014; Dantzer et al., 2014; Whitton et al., 2015; Le Heron et al., 2017; De Doncker et al., 2018).”
BackgroundNeural and computational mechanisms of momentary fatigue and persistence in effort-based choice
Müller, T., Klein-Flügge, M. C., Manohar, S., Husain, M., & Apps, M. A. J. (2021) · Nature Communications · doi:10.1038/s41467-021-24927-7 · Cited by 95 · see citing works
Self-citationHird, E. J., Slanina-Davies, A., Lewis, G., Hamer, M., & Roiser, J. P. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02922-y · Cited by 79 · see citing works
Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease
Prange, S., Météreau, É., Maillet, A., Lhommée, E., Klinger, H., Pélissier, P., Ibarrola, D., Heckemann, R. A., Castrioto, A., Tremblay, L., et al. (2019) · Movement Disorders · doi:10.1002/mds.27793 · Cited by 86 · see citing works
“Interestingly, white-matter abnormalities are remarkably similar to the ones observed in patients suffering from apathy across other neurodegenerative conditions (including frontotemporal dementia,(42) Alzheimer’s disease,(43) and small-vessel disease(44)), which emphasizes the transdiagnostic validity of the conceptu…”
BackgroundAn Integrative Model of Effortful Control
André, N., Audiffren, M. F., & Baumeister, R. F. (2019) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2019.00079 · Cited by 89 · see citing works
Apathy in schizophrenia: A review of neuropsychological and neuroanatomical studies
Bortolon, C., Macgregor, A., Capdevielle, D., & Raffard, S. (2018) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2017.09.033 · Cited by 69 · see citing works
Effort shapes social cognition and behaviour: A neuro-cognitive framework.
Contreras-Huerta, L. S., Pisauro, A., & Apps, M. (2020) · Neuroscience and Biobehavioral Reviews · doi:10.31234/osf.io/mvwqz · Cited by 64
Self-citationIndividual differences in empathy are associated with apathy-motivation
Lockwood, P. L., Ang, Y., Husain, M., & Crockett, M. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-17415-w · Cited by 71 · see citing works
Self-citationAntidepressant medications in dementia: evidence and potential mechanisms of treatment-resistance
Costello, H., Roiser, J. P., & Howard, R. (2023) · Psychological Medicine · doi:10.1017/s003329172200397x · Cited by 60 · see citing works
“Human and animal studies have shown that dopaminergic transmission is crucial in motivated behaviour and reward processing (Le Heron, Apps, & Husain, 2018).”
Dopamine and reward hypersensitivity in Parkinson’s disease with impulse control disorder
Drew, D., Muhammed, K., Baig, F., Kelly, M., Saleh, Y., Sarangmat, N., Okai, D., Hu, M., Manohar, S., & Husain, M. (2020) · Brain : a journal of neurology · doi:10.1093/brain/awaa198 · Cited by 60 · see citing works
Self-citationThe transdiagnostic structure of mental effort avoidance
Patzelt, E. H., Kool, W., Millner, A. J., & Gershman, S. J. (2019) · Scientific Reports · doi:10.1038/s41598-018-37802-1 · Cited by 63 · see citing works
“, cognitive control) that mediates between task demands and task performance5, and/or (3) a preference for greater mental effort.”
BackgroundMultidimensional apathy: evidence from neurodegenerative disease
Radakovic, R., & Abrahams, S. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.12.022 · Cited by 57 · see citing works
Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials.
Mortby, M., Adler, L., Agüera-Ortiz, L., Bateman, D., Brodaty, H., Cantillon, M., Geda, Y., Ismail, Z., Lanctôt, K., Marshall, G., et al. (2021) · The American journal of geriatric psychiatry · doi:10.1016/j.jagp.2021.06.016 · Cited by 55 · see citing works
Distinct neural representations for prosocial and self-benefiting effort
Lockwood, P. L., Wittmann, M. K., Nili, H., Matsumoto-Ryan, M., Abdurahman, A., Cutler, J., Husain, M., & Apps, M. A. J. (2022) · Current Biology · doi:10.1016/j.cub.2022.08.010 · Cited by 73 · see citing works
Self-citationEye movements in Parkinson's disease: from neurophysiological mechanisms to diagnostic tools.
Antoniades, C., & Spering, M. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.11.001 · Cited by 53 · see citing works
The tenacious brain: How the anterior mid-cingulate contributes to achieving goals
Touroutoglou, A., Andreano, J. M., Dickerson, B. C., & Barrett, L. F. (2019) · Cortex · doi:10.1016/j.cortex.2019.09.011 · Cited by 63 · see citing works
Dysfunctional effort-based decision-making underlies apathy in genetic cerebral small vessel disease
Heron, C. J. L., Manohar, S., Plant, O., Muhammed, K., Griffanti, L., Nemeth, A. H., Douaud, G., Markus, H. S., & Husain, M. (2018) · Brain · doi:10.1093/brain/awy257 · Cited by 45 · see citing works
Self-citationSaleh, Y., Heron, C. J. L., Petitet, P., Veldsman, M., Drew, D., Plant, O., Schulz, U. G., Sen, A., Rothwell, P. M., Manohar, S., et al. (2021) · Brain · doi:10.1093/brain/awab013 · Cited by 56 · see citing works
“6, top left) encompass the medial forebrain regions such as the vmPFC and dACC, as well as subcortical structures within the basal ganglia such as the ventral striatum.(17,25,105) That we were able to correlate these changes to our behavioural modelling parameters supports the hypothesis that apathetic behaviour arise…”
Self-citationLang, S., Yoon, E. J., Kibreab, M., Kathol, I., Cheetham, J., Hammer, T., Sarna, J. R., Ismail, Z., & Monchi, O. (2020) · NeuroImage Clinical · doi:10.1016/j.nicl.2020.102252 · Cited by 53 · see citing works
Contreras-Huerta, L. S., Lockwood, P. L., Bird, G., Apps, M. A. J., & Crockett, M. J. (2020) · Emotion · doi:10.1037/emo0000813 · Cited by 55 · see citing works
Self-citationUncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia
Shaw, S. R., El-Omar, H., Roquet, D., Hodges, J. R., Piguet, O., Ahmed, R. M., Whitton, A. E., & Irish, M. (2021) · Brain · doi:10.1093/brain/awab032 · Cited by 55 · see citing works
“Neuroimaging studies in clinical populations converge to reveal commonalities in terms of anterior cingulate cortex and ventral striatum involvement in both apathy and anhedonia.(18,26,27) Importantly, however, divergent neural substrates are evident,”
BackgroundDiagnosis and Management of Neuropsychiatric Symptoms in Alzheimer’s Disease
Wolinsky, D., Drake, K., & Bostwick, J. R. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0978-8 · Cited by 47 · see citing works
Dujardin, K., & Sgambato, V. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00025 · Cited by 46 · see citing works
Saggu, S., Bai, A., Aida, M., Rehman, H., Pless, A., Ware, D., Deák, F., Jiao, K., & Wang, Q. (2024) · GeroScience · doi:10.1007/s11357-024-01359-x · Cited by 47 · see citing works
“These DA-modulated regions are heavily involved in apa-thy and depression, indicating that NPS is partially characterized by hypodopaminergic symptoms [151, 152].”
Saleh, Y., Jarratt-Barnham, I., Petitet, P., Fernandez-Egea, E., Manohar, S. G., & Husain, M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02232-7 · Cited by 45 · see citing works
“One example is the process of option selection, where participants are asked to weigh up the bene fi ts (e.g., potential reward) and costs (e.g., effort required to obtain that reward) of a decision prior to initiating goal-directed action [18, 20, 21].”
BackgroundSelf-citationHuman ventromedial prefrontal cortex is necessary for prosocial motivation
Lockwood, P. L., Cutler, J., Drew, D., Abdurahman, A., Jeyaretna, D. S., Apps, M. A. J., Husain, M., & Manohar, S. (2024) · Nature Human Behaviour · doi:10.1038/s41562-024-01899-4 · Cited by 62 · see citing works
“However, the VLSM analysis also identified specific characterizes apathy, a clinical condition of reduced motivation that is common across multiple psychiatric and neurological disorders 33,34 .”
Self-citationBupropion for the Treatment of Apathy in Alzheimer Disease
Maier, F., Spottke, A., Bach, J., Bartels, C., Buerger, K., Dodel, R., Fellgiebel, A., Fliessbach, K., Frölich, L., Hausner, L., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.6027 · Cited by 44 · see citing works
Martin, G., Mcdonald, K., Allsop, D., Diggle, P., & Leroi, I. (2019) · Journal of Neurology · doi:10.1007/s00415-019-09538-z · Cited by 44 · see citing works
Updating the role of dopamine in human motivation and apathy
Chong, T. T. ‐. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.12.010 · Cited by 50 · see citing works
Brain-based mechanisms of late-life depression: Implications for novel interventions
Gunning, F. M., Oberlin, L. E., Schier, M. M., & Victoria, L. W. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.05.002 · Cited by 47 · see citing works
The VTA dopaminergic system as diagnostic and therapeutical target for Alzheimer's disease
Krashia, P., Spoleti, E., & D’Amelio, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1039725 · Cited by 39 · see citing works
Qiao, J., Lv, Y., Cao, C., Wang, Z., & Li, A. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00417 · Cited by 41 · see citing works
Sleep deprivation, effort allocation and performance
Massar, S. A. A., Lim, J., & Huettel, S. A. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.03.007 · Cited by 55 · see citing works
Apathy and Motivation: Biological Basis and Drug Treatment
Costello, H., Masud Husain, B., & Roiser, J. P. (2023) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-022423-014645 · Cited by 46 · see citing works
Self-citationNeuropsychiatric symptoms in spinocerebellar ataxias and Friedreich ataxia.
Simona, K., Veronika, M., Zahinoor, I., & Martin, V. (2023) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105205 · Cited by 39 · see citing works
Pharmacological Management of Apathy in Dementia
Azhar, L., Kusumo, R. W., Marotta, G., Lanctôt, K., & Herrmann, N. (2022) · CNS Drugs · doi:10.1007/s40263-021-00883-0 · Cited by 39 · see citing works
“Studies have shown that, across the different neurodegenerative disorders, consistent changes are observed mainly in the fronto-striatal circuits, the dorsal anterior cingulate cortex and the ventral striatum (VS), which includes the nucleus accumbens (NAc) [16].”
BackgroundRaimo, S., Santangelo, G., D’Iorio, A., Trojano, L., & Grossi, D. (2018) · Brain Imaging and Behavior · doi:10.1007/s11682-018-9959-0 · Cited by 37 · see citing works
“In particular, frontal regions, that are either directly or indirectly connected to the striatum and implicated in normal motivated behavior (Le Heron et al. 2017), have been subdivided on the basis of the human Brainnetome Atlas (see Fan et al. 2016) in: superior frontal gyrus, middle frontal…”
BackgroundMethodAltered nucleus accumbens functional connectivity precedes apathy in Parkinson’s disease
Morris, L., Harrison, S. J., Melzer, T. R., Dalrymple‐Alford, J. C., Anderson, T., MacAskill, M. R., & Heron, C. J. L. (2023) · Brain · doi:10.1093/brain/awad113 · Cited by 39 · see citing works
“In addition to Parkinson’s disease, neuroimaging of apathy across neurodegenerative and other neurological conditions consistently implicates these same regions.(32) For example, the anterior cingulate cortex is the strongest correlate of apathy in Alzheimer’s disease, as is the basal ganglia for apathy in cerebrovasc…”
Disordered Decision Making: A Cognitive Framework for Apathy and Impulsivity in Huntington’s Disease
Morris, L., O'Callaghan, C., & Le Heron, C. (2022) · Movement Disorders · doi:10.1002/mds.29013 · Cited by 36 · see citing works
The Sense of Effort: a Cost-Benefit Theory of the Phenomenology of Mental Effort
Székely, M., & Michael, J. (2020) · Review of Philosophy and Psychology · doi:10.1007/s13164-020-00512-7 · Cited by 57 · see citing works
Apathy is Associated with Reduced Precision of Prior Beliefs about Action OutcomesPreprint
Hezemans, F., Wolpe, N., & Rowe, J. (2019) · bioRxiv · doi:10.1101/672113 · Cited by 36 · see citing works
“Lesion and neuroimaging studies have also implicated the anterior cingulate cortex and basal ganglia in apathy (Le Heron, Apps, & Husain, 2018; R. Levy & Dubois, 2006).”
Bustamante, L. A., Oshinowo, T., Lee, J. R., Tong, E., Burton, A. R., Shenhav, A., Cohen, J. D., & Daw, N. D. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2221510120 · Cited by 53 · see citing works
Heightened effort discounting is a common feature of both apathy and fatigue
Jurgelis, M., Chong, W. B., Atkins, K. J., Cooper, P. S., Coxon, J. P., & Chong, T. T. ‐. (2021) · Scientific Reports · doi:10.1038/s41598-021-01287-2 · Cited by 42 · see citing works
Apathy: Neurobiology, Assessment and Treatment
Fahed, M., & Steffens, D. C. (2021) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2021.19.2.181 · Cited by 50 · see citing works
“tex (dACC), and ventral striatum (VS) being the most consistently identified [14].”
BackgroundGreen, S., Gignac, G., Watson, P., Brosnan, N., Becerra, R., Pestell, C., & Weinborn, M. (2021) · Neuropsychology Review · doi:10.1007/s11065-021-09501-8 · Cited by 35 · see citing works
The neural basis of neuropsychiatric symptoms in Alzheimer’s disease
Zhang, N. K., Zhang, S. K., Zhang, L. I., Tao, H. W., & Zhang, G. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1487875 · Cited by 35 · see citing works
Fan, Z., Wang, L.-C., Zhang, H.-F., Lv, X., Tu, L., Zhang, M., Zhang, Y., Yan, C., Yu, X., & Wang, H.-L. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.792168 · Cited by 33
“Apathy has been closely associated with components of the frontostriatal circuit (19, 20).”
BackgroundRevisiting Apathy in Alzheimer's Disease: From Conceptualization to Therapeutic Approaches
Teixeira, A. L., Gonzales, M., de Souza, L. D., & Weisenbach, S. (2021) · Behavioural Neurology · doi:10.1155/2021/6319826 · Cited by 33 · see citing works
“To a certain extent, all these neurodegenerative diseases share overlapping neural correlates of apathy [28, 70].”
BackgroundInsula and Amygdala Atrophy Are Associated With Functional Impairment in Subjects With Presbycusis
Belkhiria, C., Vergara, R. C., Martín, S. S., Alexis Leiva, C., Martínez, M., Marcenaro, B., Andrade, M., Delano, P. H., & Delgado, C. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00102 · Cited by 34 · see citing works
Network neuroscience of apathy in cerebrovascular disease
Tay, J., Lisiecka, D. M., Hollocks, M. J., Tuladhar, A. M., Barrick, T. R., Förster, A., O'Sullivan, M. J., Husain, M., de Leeuw, F., Morris, R. G., et al. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101785 · Cited by 37 · see citing works
Self-citationA neuroanatomical and cognitive model of impaired social behaviour in frontotemporal dementia
Rouse, M. A., Binney, R. J., Patterson, K. E., Rowe, J. B., & Ralph, M. A. L. (2024) · Brain · doi:10.1093/brain/awae040 · Cited by 41 · see citing works
“3,117,118 Lateral prefrontal atrophy is associated with impaired executive function, which is the set of processes that control cognition, e.g. in working memory, attentional selection, planning and inhibition.”
BackgroundChang, C. Y. M., Baber, W., Dening, T., & Yates, J. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18126317 · Cited by 32 · see citing works
“Traditionally, apathy is considered the result of neurodegenerative disorder [4] and disease progression, such as cortical changes in the anterior cingulate cortex [5], a region linked to impaired executive functioning in dementia [6].”
BackgroundFrom apathy to addiction: Insights from neurology and psychiatry.
Kirschner, M., Rabinowitz, A. G., Singer, N., & Dagher, A. (2020) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109926 · Cited by 33 · see citing works
Costello, H., Yamamori, Y., Reeves, S., Schrag, A., Howard, R., & Roiser, J. (2022) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2022-330790 · Cited by 31 · see citing works
Apathy in rapid eye movement sleep behaviour disorder is common and under‐recognized
Barber, T., Muhammed, K., Drew, D., Lawton, M., Crabbe, M., Rolinski, M., Quinnell, T., Zaiwalla, Z., Ben-Shlomo, Y., Husain, M., et al. (2017) · European Journal of Neurology · doi:10.1111/ene.13515 · Cited by 31 · see citing works
“The ventral striatum and dorsal anterior cingulate cortex appear to be key regions involved in generating motivated behaviour [34], and dysfunction in striatofrontal functional connectivity has been shown to associate with apathy in patients with PD [35].”
BackgroundSelf-citationRicciardi, L., Apps, M. A. J., & Little, S. (2023) · npj Parkinson's Disease · doi:10.1038/s41531-023-00567-0 · Cited by 28 · see citing works
Self-citationAn Update on Apathy in Alzheimer’s Disease
Dolphin, H., Dyer, A. H., McHale, C., O’Dowd, S., & Kennelly, S. (2023) · Geriatrics · doi:10.3390/geriatrics8040075 · Cited by 34 · see citing works
Neurobehavioral Initiation and Motivation Problems After Acquired Brain Injury
Palmisano, S., Fasotti, L., & Bertens, D. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.00023 · Cited by 28 · see citing works
The relationship between rehabilitation motivation and upper limb motor function in stroke patients
Li, W.-X., Zhu, G.-Y., Lu, Y., Wu, J., Fu, Z., Tang, J.-Y., Zhang, G., & Xu, D. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1390811 · Cited by 27
Berthier, M. L., Edelkraut, L., López‐González, F. J., López-Barroso, D., Mohr, B., Friedemann Pulvermüller, A., STARKSTEIN, S. E., Jorge, R. E., Torres‐Prioris, M. J., & Dávila, G. (2022) · Brain and Language · doi:10.1016/j.bandl.2022.105205 · Cited by 27 · see citing works
“Post-stroke apathy and depression are clinically dissociable and result from disruptions of different subcomponents of networks regulating motivated behavior and mood (Jorge et al., 2010; Kos et al., 2016; Le Heron et al., 2018; Riva-Posse et al., 2019; Starkstein & Brockman, 2018).”
Clement, A., Wiborg, O., & Asuni, A. A. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00056 · Cited by 26 · see citing works
“…this, several studies have mapped apathy to specific brain regions with abnormalities including the anterior cingulate cortex, the prefrontal cortex, and the basal ganglia (Stella et al., 2014; Theleritis et al., 2014; Le Heron et al., 2017), all of which are innervated by dopaminergic pathways.”
BackgroundSelf- and informant-rated apathy in patients with childhood-onset craniopharyngioma
Mehren, A., Özyurt, J., Klampen, P. Z., Boekhoff, S., Thiel, C., & Müller, H. (2018) · Journal of Neuro-Oncology · doi:10.1007/s11060-018-2936-z · Cited by 27
Pharmacotherapy for Neuropsychiatric Symptoms in Frontotemporal Dementia
Le, C., & Finger, E. (2021) · CNS Drugs · doi:10.1007/s40263-021-00854-5 · Cited by 26 · see citing works
Zhou, Y., Yao, X.-Y., Han, W., Wang, Y., Li, Z., & Li, Y. (2022) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5827 · Cited by 26 · see citing works
“Similarly, many researchers considered comorbid apathy and depression as distinct psychiatric syndromes different from depression or apathy alone.(42,43) Therefore, future studies should use functional near‐infrared spectroscopy and magnetic resonance”
BackgroundOzzoude, M., Varriano, B. M., Beaton, D., Ramirez, J., Adamo, S. M., Holmes, M. F., Scott, C. J. M., Gao, F., Sunderland, K. M., McLaughlin, P. M., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01257-y · Cited by 26 · see citing works
Chu, M., Liu, L., Wang, J., Liu, L., Kong, Y., Jing, D., Xie, K.-X., Cui, Y., Cui, B., Zhang, J., et al. (2021) · Journal of Alzheimer's Disease · doi:10.3233/jad-215127 · Cited by 25 · see citing works
“Apathy is a debilitating syndrome that is associated with numerous neurological disorders, and ACC is an anatomical correlate [47].”
BackgroundSoleimani, L., Ravona‐Springer, R., Lin, H., Liu, X., Sano, M. C., Heymann, A. D., & Beeri, M. S. (2021) · Diabetes Care · doi:10.2337/dc20-2031 · Cited by 27 · see citing works
Connors, M. H., Teixeira-Pinto, A., Ames, D., Woodward, M., & Brodaty, H. (2023) · International Psychogeriatrics · doi:10.1017/s1041610222001089 · Cited by 23 · see citing works
Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia
Edelkraut, L., López-Barroso, D., Torres-Prioris, M. J., Starkstein, S., Jorge, R., Aloisi, J., Berthier, M., & Dávila, G. (2022) · World Journal of Psychiatry · doi:10.5498/wjp.v12.i3.450 · Cited by 23 · see citing works
Apathy is associated with parietal cortical-subcortical dysfunction in ALS.
Caga, J., Tu, S.-C., Dharmadasa, T., Tse, N. Y., Zoing, M. C., Huynh, W., Mahoney, C. J., Ahmed, R., & Kiernan, M. (2021) · Cortex; a journal devoted to the study of the nervous system and behavior · doi:10.1016/j.cortex.2021.02.029 · Cited by 23 · see citing works
Kurniawan, I. T., Grueschow, M., & Ruff, C. (2020) · Journal of Neuroscience · doi:10.1101/2020.02.25.964676 · Cited by 23 · see citing works
Exploration Deficits Under Ecological Conditions as a Marker of Apathy in Frontotemporal Dementia
Batrancourt, B., Lecouturier, K., Ferrand-Verdejo, J., Guillemot, V., Azuar, C., Bendetowicz, D., Migliaccio, R., Rametti‐Lacroux, A., Dubois, B., & Lévy, R. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00941 · Cited by 23 · see citing works
“Fourth, the underlying mechanisms of apathy are poorly known in general (18) and in bvFTD in particular (19).”
BackgroundKowalska, K., Droś, J., Mazurek, M., Pasińska, P., Gorzkowska, A., & Klimkowicz-Mrowiec, A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072232 · Cited by 22 · see citing works
Overcoming apathy in frontotemporal dementia: challenges and future directions
Johnson, E., & Kumfor, F. (2018) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2018.01.022 · Cited by 22 · see citing works
Hoy, C. W., de Hemptinne, C., Wang, S. S., Harmer, C. J., Apps, M. A. J., Husain, M., Starr, P. A., & Little, S. J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2322869121 · Cited by 31 · see citing works
Self-citationInsensitivity to loss predicts apathy in huntington's disease
Mclauchlan, D., Lancaster, T., Craufurd, D., Linden, D. E. J., & Rosser, A. (2019) · Movement Disorders · doi:10.1002/mds.27787 · Cited by 21 · see citing works
“A number of cognitive processes are hypothesized to contribute to goal-directed behavior: initiation, including option generation and selection (reward valuation and reward-effort calculations), planning (executive function), and outcome evaluation (learning from loss and reward).(12,13) Deficits in reward valuation,…”
BackgroundA neurometabolic mechanism involving dmPFC/dACC lactate in physical effort-based decision-making
Clairis, N., Barakat, A., Brochard, J., Xin, L., & Sandi, C. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02726-y · Cited by 19 · see citing works
Impaired value-based decision-making in Parkinson’s disease apathy
Gilmour, W., Mackenzie, G. M., Feile, M., Tayler-Grint, L., Suveges, S., Macfarlane, J. A., Macleod, A. D., Marshall, V. L., Grunwald, I. Q., Steele, J. D., et al. (2024) · Brain · doi:10.1093/brain/awae025 · Cited by 23 · see citing works
Chokesuwattanaskul, A., Jiang, H., Bond, R. L., Jiménez, D., Russell, L. L., Sivasathiaseelan, H., Johnson, J. C. S., Benhamou, E., Agustus, J. L., van Leeuwen, J. E. P., et al. (2023) · Brain Communications · doi:10.1093/braincomms/fcad027 · Cited by 24 · see citing works
Cholinergic nucleus 4 grey matter density is associated with apathy in Parkinson’s disease
Sperling, S., Druzgal, J., Blair, J. C., Flanigan, J., Stohlman, S. L., & Barrett, M. (2022) · Clinical Neuropsychologist · doi:10.1080/13854046.2022.2065362 · Cited by 20 · see citing works
“…between the prefrontal cortex and its connections to the ACC and subcortical structures (Bechara et al., 1994; Carmichael & Price, 1995; holroyd & McClure, 2015; Le heron et al., 2018) can contribute to deficits in executive functioning and subsequently a reduction in goal-directed behavior.”
BackgroundMultidimensional Apathy: The Utility of the Dimensional Apathy Scale in Huntington's Disease
Atkins, K. J., Andrews, S. C., Chong, T. T. ‐., & Stout, J. C. (2021) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.13147 · Cited by 21 · see citing works
Nour, A. E. A. M., Jiao, Y., Teng, G., & Initiative, A. D. N. (2020) · Acta Neurologica Belgica · doi:10.1007/s13760-020-01349-8 · Cited by 26 · see citing works
A Transdiagnostic Study of Effort-Cost Decision-Making in Psychotic and Mood Disorders
Culbreth, A. J., Moran, E. K., Mahaphanit, W., Erickson, M. A., Boudewyn, M. A., Frank, M. J., Barch, D. M., MacDonald, A. W., Ragland, J. D., Luck, S. J., et al. (2024) · Schizophrenia Bulletin · doi:10.1093/schbul/sbad155 · Cited by 19 · see citing works
“11,12 However, there are substantial individual differences in the relative contribution of these factors to ECDM.”
BackgroundGonzález-Usigli, H., Ortíz, G. G., Charles‐Niño, C., Mireles-Ramírez, M. A., Pacheco-Moisés, F. P., Torres-Mendoza, B. M., Hernández-Cruz, J. J., Delgado-Lara, D. L. C., & Ramírez-Jirano, L. J. (2023) · Brain Sciences · doi:10.3390/brainsci13030508 · Cited by 27 · see citing works
Armbruster‐Genc, D., Valton, V., Neil, L., Vuong, V., Freeman, Z., Packer, K. C., Kiffin, M. J., Roiser, J. P., Viding, E. M., & McCrory, E. J. P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01284-7 · Cited by 19 · see citing works
- Authors
- Le Heron, C., Apps., M. A. J., & Husain, M.
- Venue
- Neuropsychologia
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 118
- Issue
- Pt B
- Pages
- 54-67
- ISSN
- 0028-3932 (ISSN-L)
- PMC
- PMC6200857
- OpenAlex
- W2726746745
- Cited by
- 380
- References
- 168
- Citations by year
- 2026: 44 · 2025: 43 · 2024: 55 · 2023: 48 · 2022: 55 · 2021: 50 · 2020: 38 · 2019: 20 · 2018: 21 · 2017: 6
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuropsychologia (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- University of Oxford Christopher Welch Scholarship in Biological Sciences
- University of Oxford Clarendon Scholarship
- Green Templeton College Partnership award (GAF1415_CB2_ MSD_758342)
- Biotechnology and Biological Sciences Research Council AFL Fellowship (BB/M013596/1)
- Wellcome Trust (098282)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- apathy, motivated behavior, dorsal anterior cingulate cortex, ventral striatum, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, stroke, neuroimaging correlates, willingness to work
- MeSH terms
- Brain, Brain Mapping, Humans, Motivation, Apathy, Neuroimaging
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