Apathy: A pathology of goal-directed behaviour. A new concept of the clinic and pathophysiology of apathy

doi:10.1016/j.neurol.2012.05.003

Revue Neurologique

Volume 168, Issues 8–9, August–September 2012, Pages 585-597

https://doi.org/10.1016/j.neurol.2012.05.003 Get rights and content

Abstract

We propose to defined apathy as a quantitative reduction of goal-directed behaviour. As such, the neural bases of apathy rely on lesions or dysfunctions of the brain structures that generate and control goal-directed behaviour: the frontal lobes, the basal ganglia and the frontal-basal ganglia circuits. Lesions or dysfunctions of the limbic territories of the frontal lobes (the orbital-mesial prefrontal cortex) and the basal ganglia (e.g., the ventral striatum) lead to apathy through difficulties to provide the affective value of a given behavioural context. We also suggest that lesions or dysfunctions of the associative (“cognitive”) territories of the frontal lobes (the dorsal prefrontal cortex) and the basal ganglia (e.g., the dorsal caudate) contribute to apathy via a “cognitive inertia” — an inability to generate or activate strategies required to successfully complete a given program of actions. The most severe forms of apathy (“auto-activation deficit” syndrome), due to bilateral lesions in the prefrontal-basal ganglia circuits can be explained either by the addition of lesions in the cognitive and limbic territories or by a more general and elementary impairment that mirrored the presumed normal functions of the prefrontal-basal ganglia circuits, that is to selectively amplified the behaviour that one considers as the most adapted to one's personal needs or environmental demands. These lesions may limit the selective amplification of the signal that represents relevant thoughts and actions, leading to difficulties to disambiguate decision-making at the level of the prefrontal cortex.

Résumé

L’apathie peut être définie par la réduction quantitative des comportements volontaires (ou dirigés vers un but). Elle apparaît quand les circuits cérébraux sous-tendant la génération et le contrôle de ces comportements sont atteints. Ces circuits sont principalement représentés par le cortex frontal et ses régions cibles dans les ganglions de la base. Ces circuits étant fonctionnellement et anatomiquement distincts, nous proposons que l’apathie résulte de mécanismes divers, sources de réduction des comportements volontaires. Ainsi, nous isolons au moins trois mécanismes d’apathie : 1) une difficulté à attribuer correctement une valeur affective à un comportement donné (« a-motivation »). Cette forme d’apathie serait secondaire à une altération de boucles reliant les régions ventro-médiales du cortex frontal aux régions limbiques des ganglions de la base (striatum ventral, pallidum ventral, entre autres) ; 2) une difficulté à élaborer la séquence d’actions à effectuer alors que la motivation est normale (« inertie cognitive »). Les lésions siègeraient plutôt dans le système dorsal (cortex préfrontal dorsolatéral, noyau caudé, pallidum dorsal) ; 3) une déconnexion entre la motivation et le système exécutif cognitif, empêchant les systèmes motivationnel et cognitif d’interagir. Les lésions seraient situées à l’interface entre les deux systèmes (cortex préfrontal médial) ou affecteraient les deux systèmes (atteintes des systèmes associatif et limbique des ganglions de la base). Cette synthèse a pour but de passer en revue les arguments étayant cette nouvelle conception clinique et physiopathologique de l’apathie.

Section snippets

Of the importance of apathy in brain diseases

Apathy is a frequent syndrome in brain diseases. It can be observed in neurodegenerative diseases such as Alzheimer's disease (AD) for which its prevalence is about 60% (Robert et al., 2006a) at the dementia stage and about 50% at the podromal (pre-dementia) phase of the disease (Robert et al., 2006b, Geda et al., 2008). It is also a common clinical feature of many pathological states, involving lesions or dysfunctions mostly, located within the prefrontal-basal ganglia system. For instance, it

Definition

Apathy is viewed as a clinical syndrome due to an “absence or lack of feeling, emotion, interest or concern”. For practical medical purposes, apathy is defined by a “lack of motivation not attributable to diminished level of consciousness, cognitive impairment or emotional distress” (Marin, 1991, Marin, 1996). In this definition, apathy as a syndrome does not include abulia, akinesia, akinetic mutism, depression, dementia, delirium, despair, and demoralization (Marin, 1990).

However, a major

The frontal lobes, the basal ganglia and the frontal-basal ganglia circuits

One common point of all the pathological situations where apathy occurs is the presence of dysfunctions or lesions of the frontal lobes, the basal ganglia or the frontal-basal ganglia circuits. Direct focal lesions of the frontal lobes are associated with a severe apathy (Luria, 1980, Eslinger and Damasio, 1985, Fuster, 1997, Alexander and Stuss, 2000). Apathy is almost constantly present in fvFTLD (Pasquier et al., 1999, Rosen et al., 2002, Chow et al., 2009). Similarly, focal damage to the

Conclusion

Considering apathy as the direct consequence of difficulties in generating and controlling voluntary actions (GDB) opens the way to a shift in viewing its pathophysiology. We promote the idea that apathy is at the level of cognitive neuroscience a pathology of GDB and at a level of functional neuroanatomy, a pathology of frontal-basal ganglia system. As GDB may be dissected into several steps and processes, it is likely that apathy may be related to different mechanisms and consequently to

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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Basal ganglia and limbic system: a new frontierApathy: A pathology of goal-directed behaviour. A new concept of the clinic and pathophysiology of apathyL’apathie : un modèle pathologique des comportements volontaires

Abstract

Résumé

Section snippets

Of the importance of apathy in brain diseases

Definition

The frontal lobes, the basal ganglia and the frontal-basal ganglia circuits

Conclusion

Disclosure of interest

Brain Lang

Neuropsychologia

Curr Opin Neurobiol

Cognition

Trends Neurosci

Neuropsychologia

Biol Psychiatry

Schizophr Res

Cortex

Neuroscience

J Chem Neuroanat

Neuroimage

Prog Brain Res

Neuroimage

Trends Cogn Sci

Range of neuropsychiatric disturbances in patients with Parkinson's disease

J Neurol Neurosurg Psychiatry

Neuropsychiatric symptoms of patients with progressive supranuclear palsy and Parkinson's disease

J Neuropsychiatry Clin Neurosci

Cognitive, psychiatric and motor response to galantamine in Parkinson's disease with dementia

Int J Geriatr Psychiatry

Parallel organization of functionally segregated circuits linking basal ganglia and cortex

Ann Rev Neurosci

Disorders of frontal lobe functioning

Semin Neurol

Behavior and mental activity disorders after carbon monoxide poisoning. Bilateral pallidal lesions

Rev Neurol (Paris)

Apathy and depressed mood in acquired brain damage: relationship to lesion localization and psychophysiological reactivity

Psychol Med

Akinetic mutism following unilateral anterior cerebral artery occlusion

J Neuropsychiatry Clin Neurosci

Responses to reward in monkey dorsal and ventral striatum

Exp Brain Res

The organization of prefrontocaudate projections and their laminar origin in the macaque monkey: a retrograde study using HRP-gel

J Comp Neurol

Hierarchical cognitive control deficits following damage to the human frontal lobe

Nat Neurosci

Anatomic organization of basoventral and mediodorsal visual recipient prefrontal regions in the rhesus monkey

J Comp Neurol

Comparison of the effect of frontal and caudate lesions on delayed response and alternation in monkeys

J Comp Physiol Psychol

Quality of life and neurobehavioral changes in survivors of malignant middle cerebral artery infarction

J Neurol

Apathy and depression in Alzheimer's disease are associated with functional deficit and psychotropic prescription

Int J Geriatr Psychiatry

The behavioural and motor consequences of focal lesions of the basal ganglia in man

Brain

Loss of psychic self-activation with bithalamic infarction. Neurobehavioural, CT, MRI and SPECT correlates

Acta Neurol Scand

Relationship between positive and negative symptoms and neuropsychological scores in frontotemporal dementia and Alzheimer's disease

J Int Neuropsychol Soc

Do people become more apathetic as they grow older. A longitudinal study in healthy individuals

Int Psychogeriatr

Vergleichende Lokalisationslhere der Grosshirnrinde in ihren Prinzipien dargestelt auf Grund des Zellenbaues

Motor function of the monkey globus pallidus. I. Neuronal discharge and parameter of movement

Brain

Effect of caudate and septal nuclei lesions on resistance to extinction and delayed alternation

J Comp Physiol Psychol

Impaired recognition of anger following damage to the ventral striatum

Brain

Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys

J Comp Neurol

Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys

J Comp Neurol

Apathy symptom profile and behavioral associations in frontotemporal dementia vs dementia of Alzheimer type

Arch Neurol

Habit gambling behaviour caused by ischemic lesions affecting the cognitive territories of the basal ganglia

J Neurol

Bupropion in the management of apathy

J Psychopharmacol

Behavioral changes in Huntington Disease

Basal ganglia and limbic system: a new frontier
Apathy: A pathology of goal-directed behaviour. A new concept of the clinic and pathophysiology of apathyL’apathie : un modèle pathologique des comportements volontaires