Apathy and impulsivity are common traits that affect normal human decision-making. In patients with brain disorders they can have devastating effects on the decisions people make - or don’t make - in daily life. Sometimes they co-exist within the same individual.
We study the mechanisms and neurobiology underlying both apathy and impulsivity in healthy people and neurological patient groups. Our focus is on effort-based decision making. We’ve been inspired by, and work with, researchers who have developed animal models of abnormal motivation (Husain & Roiser (2018) Nature Rev Neurosci; Le Heron et al (2018) JNNP).
A key aspect of effort-based decision making is how individuals evaluate whether potential rewards (benefits) are worth the effort (costs) to obtain them. People differ with respect to whether they value rewards sufficiently to want to work for them, either through physical or cognitive effort. A common set of brain regions, including parts of the anterior cingulate, dorsomedial and dorsolateral prefrontal cortex, and insula are activated when people make such decisions, for physical or cognitive effort (Chong et al (2017) PLoS Biology).
These brain regions, together with parts of the brain implicated in the evaluation of reward - basal ganglia and orbitofrontal cortex - are dysfunctional in patients with apathy, e.g. with Alzheimer’s disease or Parkinson’s disease (Le Heron et al (2018) Neuropsychologia).
Apathy in Parkinson’s disease and in cerebrovascular small vessel disease is associated with blunted sensitivity to rewards (Muhammed et al (2016) Brain; Le Heron et al (2018a) Brain). Apathetic patients with these conditions are unwilling to allocate physical effort for small rewards (Le Heron et al (2018a) Brain; Le Heron et al (2018b) Brain).
Dopamine is an import neurotransmitter that has consistently been implicated in animal studies of effort-based decision-making. In Parkinson’s disease, dopaminergic medication can improve reward sensitivity (Manohar et al (2015) Current Biology) but it does so in both apathetic and non-apathetic individuals (Muhammed et al (2016) Brain). Both apathy and dopaminergic drugs alter effort-based decision-making for physical effort costs in Parkinson’s disease, but they do so in different sectors of the cost-benefit space (Le Heron et al (2018b) Brain), raising the possibility that there may be other neurotransmitters that might be crucial to the development of apathy.
If you want to get involved or find out more about our research at Oxford University and the John Radcliffe Hospital, write to:
Professor Masud Husain, Nuffield Dept Clinical Neurosciences, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU
email: masud.husain@ndcn.ox.ac.uk
You can also find out more about our research by downloading the articles below.
PUBLICATIONS LISTED HERE ARE AVAILABLE FOR PERSONAL USE ONLY
Reviews & Commentaries
Costello H, Husain M, Roiser JP (2024) Apathy and Motivation: Biological Basis and Drug Treatment. Annual Review of Pharmacology and Toxicology 64:313-338. PMID: 37585659
Husain M (2023) Mechanisms underlying apathy in frontotemporal dementia. Brain 146:416-417. PMID: 36567496 [Commentary]
Le Heron C, Holroyd CB, Salamone J, Husain M (2018) Brain mechanisms underlying apathy. J Neurol Neurosurg Psychiatry (Epub ahead of print) [Review]
Husain M, Roiser R (2018) The neuroscience of apathy and anhedonia: A transdiagnostic approach. Nature Reviews Neuroscience 19:470-484. PMID: 29946157 [Review]
Le Heron C, Apps MAJ, Husain M (2017) The anatomy of apathy: A neurocognitive framework for amotivated behaviour. Neuropsychologia (Epub ahead of print) [Review]
Chong T T-J, Bonnelle V, Husain M (2016) Quantifying motivation with effort-based decision-making paradigms in health and disease. Progress in Brain Res 229:71-100 [Review]
Chong T T-J, Husain M (2016) The role of dopamine in the pathophysiology and treatment of apathy. Progress in Brain Res 229: 389-426 [Review]
Muhammed K, Husain M (2016) Clinical significance of apathy in Parkinson's disease. European Medical Journal 4: 56-63 [Review]
Sinha N, Manohar S, Husain M (2013) Impulsivity and apathy in Parkinson's disease. Journal of Neuropsychology. PMID:23621377 [Review]
Norbury A, Husain M (2015) Sensation-seeking: Dopaminergic modulation and risk for psychopathology. Behavioural Brain Research 288:79-93 (Epub ahead of print) PMID: 25907745 [Review]
Research papers
Lanctôt KL, Ismail Z, Bawa KK, Cummings JL, Husain M, Mortby ME, Robert P (2023) Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment‐related aspects of apathy from depression in neurocognitive disorders. Int J Geriatr Psychiatry 2023 Feb; 38: e5882. PMC10107127
Husain M (2023) Mechanisms underlying apathy in frontotemporal dementia. Brain (Epub ahead of print) https://doi.org/10.1093/brain/awac494
Nobis L, Maio MR, Saleh Y, Manohar S, Kienast A, McGann E, Husain M (2023) Role of serotonin in modulation of decision-making in Parkinson's disease. J Psychopharmacol 37: 420–431 PMC10101180
Lockwood PL, Wittmann MK, Nili H, Matsumoto-Ryan M, Abdurahman A, Cutler J, Husain M, Apps MAJ (2022) Distinct neural representations for prosocial and self-benefiting effort. Current Biology 32:4172-4185 PMID: 36376340
Petitet P, Zhao S, Drew D, Manohar SG, Husain M (2022) Dissociable behavioural signatures of co-existing impulsivity and apathy in decision-making. Scientific Reports 12:21476. PMID: 36509827
Wong S, Wei G, Husain M, Hodges JR, Piguet O, Irish M, Kumfor F (2022) Altered reward processing underpins emotional apathy in dementia. Cogn Affect Behav Neurosci doi: 10.3758/s13415-022-01048-2 PMID: 36417157Turner V, Husain M (2022) Anhedonia in Neurodegenerative Diseases. Curr Top Behav Neurosci (Epub ahead of print) PMID: 35435648.
Husain M (2022) Noradrenergic therapies for apathy in Alzheimer’s disease? J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2022-330824 [Commentary]
Müller T, Husain M, Apps MAJ (2022) Preferences for seeking effort or reward information bias the willingness to work. Scientific Reports 12:19486.
Dickson SS, Husain M (2022) Are there distinct dimensions of apathy? The argument for reappraisal. Cortex 149:246-256 PMID: 35181121
Härmson O, Grima LL, Panayi MC, Husain M, Walton ME (2021) 5-HT 2C receptor perturbation has bidirectional influence over instrumental vigour and restraint. Psychopharmacology (Epub ahead of print) PMID: 34762147
Saleh Y, Jarratt-Barnham I, Fernandez-Egea E, Husain M (2021) Mechanisms Underlying Motivational Dysfunction in Schizophrenia. Frontiers in Behavioral Neuroscience 15:709753 PMID: 34566594
van As S, Beckers DGJ, Geurts SAE, Kompier MAJ, Husain M, Veling H (2021) The Impact of Cognitive and Physical Effort Exertion on Physical Effort Decisions: A Pilot Experiment. Frontiers in Psychology 12:645037 PMID: 34795608
Klar VS, Ang Y-S, Lockwood P, Attaallah B, Dickson S, Drew D, Kienast A, Maio MR, Plant O, Slavkova E, Toniolo S, Zambellas, Irani SR, Husain M (2021) Assessment of apathy in neurological patients using the Apathy Motivation Index caregiver version. J Neuropsychol (Epub ahead of print) PMID: 34532963
van Dorst MEG, Rensen YCM, Husain M, Kessels RPC (2021) Behavioral, Emotional and Social Apathy in Alcohol-Related Cognitive Disorders. J Clin Med 10:2447 PMID: 34072955
Miller DS, Robert P, Ereshefsky L, Adler L, Bateman D, Cummings J, DeKosky ST, Fischer CE, Husain M, Ismail Z, Jaeger J, Lerner AJ, Li A, Lyketsos CG, Manera V, Mintzer J, Moebius HJ, Mortby M, Meulien D, Pollentier S, Porsteinsson A, Rasmussen J, Rosenberg PB, Ruthirakuhan MT, Sano M, Zucchero Sarracini C, Lanctôt KL (2021) Diagnostic criteria for apathy in neurocognitive disorders. Alzheimer’s & Dementia (Epub ahead of print) PMID: 33949763
Müller T, Klein-Flügge MC, Manohar SG, Husain M, Apps MAJ (2021) Neural and computational mechanisms of momentary fatigue and persistence in effort-based choice. Nature Communications 12:4593 PMID: 34321478
Muhammed K, Ben Yehuda M, Drew D, Manohar S, Husain M (2021) Reward sensitivity and action in Parkinson's disease patients with and without apathy. Brain Communications 3:fcab022 PMID: 33855297
Quang H, Wong S, Husain M, Piguet O, Hodges JR, Irish M, Kumfor F (2021) Beyond language impairment: Profiles of apathy in primary progressive aphasia. Cortex 139:73-85 PMID: 33836304
Lockwood PL, Abdurahman A, Gabay AS, Drew D, Tamm M, Husain M, Apps MAJ (2021) Aging Increases Prosocial Motivation for Effort. Psychol Sci 32:668-81 PMID: 33860711
Saleh Y, Le Heron C, Petitet P, Veldsman M, Drew D, Plant O, Schulz U, Sen A, Rothwell PM, Manohar S, Husain M (2021) Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making. Brain 144:1247-62. PMID: 33734344
Petitet P, Scholl J, Attaallah B, Drew D, Manohar S, Husain M (2021) The relationship between apathy and impulsivity in large population samples. Scientific Reports 11(1):4830. PMID: 33649399
Drew DS, Muhammed K, Baig F, Kelly M, Saleh Y, Sarangmat N, Okai D, Hu M, Manohar S, Husain M (2020) Dopamine and reward hypersensitivity in Parkinson’s disease with impulse control disorder. Brain 143:2502-18. PMID: 32761061
Tay J, Morris RG, Tuladhar AM, Husain M, de Leeuw FE, Markus HS (2020) Apathy, but not depression, predicts all-cause dementia in small vessel disease. J Neurol Neurosurg Psychiatry 91:953-9. PMID: 32651249
Nachev P, Roberts RE, Husain M, Kennard C (2019) The neural basis of meta-volition. Commun Biol 2:101 PMID:30886910
Tay J, Tuladhar AM, Hollocks MJ, Brookes RL, Tozer DJ, Barrick TR, Husain M, de Leeuw FE, Markus HS (2019) Apathy is associated with large-scale white matter network disruption in small vessel disease. Neurology 92:e1157-e1167
Le Heron C, Manohar S, Plant O, Muhammed K, Griffanti L, Nemeth A, Douaud G, Markus HS, Husain M (2018) Dysfunctional effort-based decision-making underlies apathy in genetic cerebral small vessel disease. Brain 141:3193-3210 PMID:30346491
Manohar SG, Muhammed K, Fallon SJ, Husain M (2018) Motivation dynamically increases noise resistance by internal feedback during movement. Neuropsychologia (Epub ahead of print).
Chong TT, Apps MAJ, Giehl K, Hall S, Clifton CH, Husain M (2018) Computational modelling reveals distinct patterns of cognitive and physical motivation in elite athletes. Scientific Reports 8:11888. PMID:30089782
Ang YS, Manohar S, Plant O, Kienast A, Le Heron C, Muhammed K, Hu M, Husain M (2018) Dopamine modulates option generation for behavior. Current Biology 28:1561-9.
Barber TR, Muhammed K, Drew D, Lawton M, Crabbe M, Rolinski M, Quinnell T, Zaiwalla Z, Ben-Shlomo Y, Husain M, Hu MTM (2018) Apathy in rapid eye movement sleep behaviour disorder is common and under-recognized. Eur J Neurol 25:469-76. PMID:29114969
Robert P, Lanctôt KL, Agüera-Ortiz L, Aalten P, Bremond F, Defrancesco M, Hanon C, David R, Dubois B, Dujardin K, Husain M, König A, Levy R, Mantua V, Meulien D, Miller D, Moebius HJ, Rasmussen J, Robert G, Ruthirakuhan M, Stella F, Yesavage J, Zeghari R, Manera V (2018) Is it time to revise the diagnostic criteria for apathy in brain disorders? The 2018 international consensus group. Eur Psychiatry 54:71-6. PMID: 30125783
Le Heron C, Plant O, Manohar S, Ang YS, Jackson M, Lennox G, Hu MT, Husain M (2018) Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson's disease. Brain 141:1455-69.
Lockwood P, Ang YS, Husain M, Crockett M (2017) Individual differences in empathy are associated with apathy-motivation. Scientific Reports 7:17293 PMID:29229968
Lockwood PL, Hamonet M, Zhang SH, Ratnavel A, Salmony FU, Husain M§, Apps M§ (2017) Prosocial apathy for helping others when effort is required. Nature Human Behaviour 1: 131
Draper A, Koch RM, van der Meers WM, Apps MAJ, Pickers P, Husain M, van der Schaaf ME (2017) Effort but not reward sensitivity is altered by acute sickness induced by experimental endotoxemia in humans. Neuropsychopharmacology (Epub ahead of print) PMID:28948979
Manohar SG, Finzi RD, Drew D, Husain M (2017) Distinct motivational effects of contingent and noncontingent rewards. Psychol Sci (Epub ahead of print).
Chong TT, Bonnelle V, Veromann KR, Juurmaa J, Taba P, Plant O, Husain M (2017) Dissociation of reward and effort sensitivity in methcathinone-induced Parkinsonism. J Neuropsyhcol (Epub ahead of print)
Chong T-J, Apps M, Giehl K, Silence A, Grima L, Husain M (2017) Neurocomputaional mechanisms underlying subjective valuation of effort costs. PLoS Biology 15(2):e1002598. PMID: 28234892
Ang YS, Lockwood P, Apps MA, Muhammed K, Husain M (2017) Distinct subtypes of apathy revealed by the Apathy Motivation Index. PLoS One 12:e0169938. PMID: 28076387
Norbury A, Valton V, Rees G, Roiser JP, Husain M (2016) Shared neural mechanisms for evaluation of intense sensory stimulation and economic reward, dependent on stimulation-seeking behavior. Journal of Neuroscience 36: 10026-38. PMID: 27683900
Muhammed K, Manohar S, Ben Yehuda M, Chong T-J, Tofaris G, Lennox G, Bogdanovic M, Hu M, Husain M (2016) Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson's disease. Brain 139: 2706-21. PMID: 27452600.
Manohar SG, Husain M (2016) Human ventromedial prefrontal lesions alter incentivisation by reward. Cortex 76: 104-20 PMID: 26874940.
Manohar SG, Husain M (2015) Reduced pupillary reward sensitivity in Parkinson's disease. Nature Partner Journals Parkinson's Disease 1, 15026.
Apps MAJ, Grima LL, Manohar S, Husain M (2015) The role of cognitive effort in subjective devaluation and risky decision-making. Scientific Reports 5, 16880. PMID: 26586084
Bonnelle V, Manohar S, Behrens T, Husain M (2015) Individual differences in premotor brain systems underlie behavioural apathy. Cerebral Cortex (Epub ahead of print) PMID: 26564255.
Hollocks MJ, Lawrence AJ, Brookes RL, Barrick TR, Morris RG, Husain M, Markus HS (2015) Differential relationships between apathy and depression with white matter microstructure changes and functional outcomes. Brain (Epub ahead of print) PMID: 26490330.
Manohar SG, Chong TTJ, Apps MAJ, Batla A, Stamelou M, Jarman PR, Bhatia KP, Husain M (2015) Reward pays the cost of noise reduction in motor and cognitive control. Current Biology (Epub ahead of print) PMID: 26096975.
Chong TTJ, Bonnelle V, Manohar S, Veromann K, Muhammed K, Tofaris GK, Hu M, Husain M (2015) Dopamine enhances willingness to exert effort for reward in Parkinson’s disease. Cortex (Epub ahead of print) PMID:
Norbury A, Kurth-Nelson Z, Winston JS, Roiser JP, Husain M (2015) Dopamine regulates approach-avoidance in human sensation-seeking. Internatial Journal of Neuropsychopharmacology (Epub ahead of print) PMID: 25857822.
Roberts RE, Husain M. (2015) A dissociation between stopping and switching actions following a lesion of the pre-supplementary motor area. Cortex 63, 184-195. PMID:25282056
Zokaei N, McNeill A, Proukakis C, Beavan M, Jarman P, Korlipara P, Hughes D, Mehta A, Hu MTM, Schapira AHV, Husain M. (2014) Visual short-term memory deficits associated with GBA mutation and Parkinson’s disease. Brain 137: 2303-2311. PMID:24919969
Norbury A, Manohar S, Rogers RD, Husain M. (2013) Dopamine modulates risk-taking as a function of baseline sensation-seeking trait. The Journal of Neuroscience 33:12982-12986. PMID:23926253
Bunzeck N, Singh-Curry V, Eckart C, Weiskopf N, Perry RJ, Bain PG, Düzel E, Husain M. (2013) Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease. Parkinsonism & Related disorders 19: 1136-1142. PMID:24025315
Adam R, Leff A, Sinha N, Turner C, Bays PM, Draganski B, Husain M. (2012) Dopamine reverses reward insensitivity in apathy following globus pallidus lesions. Cortex 49(5):1292-303. PMID:22721958 PMC3639369
