Disconnecting force from money: effects of basal
ganglia damage on incentive motivation
Liane Schmidt,1Baudouin Forgeot d’Arc,1Gilles Lafargue,2Damien Galanaud,3Virginie Czernecki,3
David Grabli,3Michael Schu « pbach,3Andreas Hartmann,3Richard Le ¤vy,1Bruno Dubois1and
1Laboratoire INSERM U610, Institut Fe ¤ de ¤ratif de Recherches en Neurosciences,Universite ¤ Pierre et Marie Curie (Paris 6),
Site Pitie ¤ -Salpe “ trie 're, F-75013 Paris,2Laboratoire URECA,Universite ¤ Charles de Gaulle (Lille 3), F-59659 Villeneuve d’Ascq
and3Centre d’investigation clinique, Fe ¤ de ¤ration des Maladies du syste 'me nerveux, Assistance Publique ^ Ho “ pitaux de Paris,
Groupe Pitie ¤ -Salpe “ trie 're, F-75013 Paris, France
Correspondence to: Mathias Pessiglione, Laboratoire INSERM U610, Ho “ pital Pitie ¤ -Salpe “ trie 're, 47 Boulevard de l’Ho “ pital,
75013, Paris, France
Bilateral basal ganglia lesions have been reported to induce a particular form of apathy, termed auto-activation
deficit (AAD), principally defined as a loss of self-driven behaviour that is reversible with external stimulation.
We hypothesized that AAD reflects a dysfunction of incentive motivation, a process thattranslates an expected
reward (or goal) into behavioural activation.T o investigate this hypothesis, we designed a behavioural paradigm
contrasting an instructed (externally driven) task, in which subjects have to produce different levels of force
by squeezing a hand grip, to an incentive (self-driven) task, in which subjects can win, depending on their hand
grip force, different amounts of money. Skin conductance was simultaneously measured to index affective
evaluation of monetary incentives.Thirteen AAD patients with bilateral striato-pallidal lesions were compared
to thirteen unmedicated patients with Parkinson’s disease (PD), which is characterized by striatal dopamine
depletion and regularly associated with apathy. AAD patients did not differ from PD patients in terms of grip
force response to external instructions or skin conductance response to monetary incentives. However, unlike
PD patients, they failed to distinguish between monetary incentives in their grip force.We conclude that bilat-
eral striato-pallidal damage specifically disconnects motor output from affective evaluation of potential
Keywords: apathy; anoxic/ischaemic damage; Parkinson’s disease; reward; effort
Abbreviations: AAD=auto-activation deficit; GFR=grip force response; MADRS=Montgomery and Asberg depression
rating scale; MMSE=mini mental state examination; MRI=magnetic resonance imaging; MVC=maximal voluntary contrac-
tion; PD=Parkinson’s disease; SCR=skin conductance response;UPDRS III=unified Parkinson’s disease rating scale III
Received November15, 2007 . Revised February14, 2008. Accepted February 20, 2008. Advance Access publication March15, 2008
In 1981, a 25-year-old businessman became dramatically
inactive following encephalopathy caused by a wasp bite.
The patient would spend hours lying awake on his bed,
asking no questions and expressing no interest in anybody.
When stimulated, however, he was able to perform complex
activities, such as playing high-level bridge. This was the
first description of a syndrome characterized by a lack of
self-initiated behaviour with preserved expression of motor
and cognitive abilities when externally driven (Laplane
et al., 1981). Here, following Laplane and Dubois (2001),
we term this syndrome ‘auto-activation deficit’, although
further cases received various names, such as ‘athym-
hormia’, ‘psychic akinesia’ and ‘reversible inertia’ (Luaute
and Saladini, 2001; Habib, 2004). Typically, these patients
do not complain about their situation and do not feel
bored, frustrated or depressed, even if they correctly
acknowledge that their behaviour has radically changed.
When asked about what they think, they may say that their
mind is empty or blank. When receiving good or bad news,
? The Author (2008).Publishedby Oxford University Pressonbehalfofthe Guarantorsof Brain. Allrightsreserved.For Permissions, please email: firstname.lastname@example.org
by guest on June 1, 2013
they may show appropriate emotional reactions, but
without external stimulation they rapidly return to their
habitual neutral state. Brain scans have revealed that such
a syndrome is due to bilateral lesions of the striato-pallidal
complex (Laplane et al., 1989).
Auto-activation deficit (AAD) may shed light on basal
ganglia function. In modern terminology, AAD could
reflect dysfunction of incentive motivation, which refers
to a process that energizes behaviour according to the
expected goal or reward (Berridge, 2004). Indeed, we
recently showed that, in healthy volunteers, basal forebrain
regions surrounding the ventral pallidum activate bilaterally
in proportion to expected rewards, driving physical effort
(Pessiglione et al., 2007). Conversely, we hypothesized that
damage to these regions should prevent patients from
adapting their effort in relation to expected rewards.
However, consistent with AAD reports, patients should
remain able to modulate their effort according to external
instructions. To assess these predictions, we adapted our
original behavioural paradigm, dissociating externally from
self-driven conditions. In the externally driven condition,
subjects are explicitly instructed about how hard they must
squeeze a hand grip. In the self-driven condition, subjects
are free to squeeze the hand grip as they wish, but are
aware that the higher the force exerted the larger the
monetary payoff. The manipulation consists in varying
the instructed force (in the externally driven condition) or
the monetary incentive (in the self-driven condition), to
test whether subjectsvary
Furthermore, to better specify dysfunction of incentive
motivation in the self-driven condition, we also measured
skin conductance, which has been shown to reflect
autonomic sympathetic arousal (Bauer, 1998; Critchley,
2002), and which is considered in our case to reflect
affective evaluation of the monetary incentives. A specific
deficit in incentive motivation would mean that affective
evaluation of the expected reward is preserved (normal skin
conductance response) but does not consistently activate
behaviour (impaired grip force production).
We reasoned that AAD would be interesting to contrast
with Parkinson’s disease (PD), which also affects basal ganglia
functioning (due to striatal dopamine depletion) and reduces
self-initiated behaviour. Indeed, self-initiated movements
were reported to be more impaired than externally guided
movements in PD patients (Jahanshahi et al., 1995; Burleigh-
Jacobs et al., 1997; Kelly et al., 2002). Poverty of movements
(akinesia), a cardinal symptom of PD, is commonly
considered to be a motor symptom, but, interestingly, some
authors have suggested it could result from a motivational
deficit in energizing muscle contractions (Hallett and
Khoshbin, 1980; Agid et al., 2003; Mazzoni et al., 2007).
Furthermore, PD patients score high on apathy scales,
revealing loss of interest and flattening of affect (Starkstein
et al., 1992; Isella et al., 2002; Pluck and Brown, 2002;
Aarsland et al., 2005; Kirsch-Darrow et al., 2006). Apathy in
PD has been proposed to result from dopamine depletion, as
their force accordingly.
it improves with the use of levodopa medication (Czernecki
et al., 2002). This might relate to the well-established role
of dopamine in reward processing in both monkeys (Schultz
et al., 1997; Schultz, 2000, 2007) and humans (Frank et al.,
2004; Knutson et al., 2004; Pessiglione et al., 2006). To further
explore the impact of dopamine depletion on incentive
motivation, we included in our study, in addition to AAD
patients and healthy matched controls, a group of PD patients
in their ‘off state’, following overnight withdrawal from
medication. Using the present behavioural paradigm, we
searched in both groups of patients for dissociations between
performance in instructed (externally driven) and incentive
(self-driven) tasks, and between skin conductance (affective)
and grip force (motor) responses in the incentive condition.
We then searched for correlations between these measures of
behavioural performance and ratings of both apathy, on
Starkstein’s scale (Starkstein et al., 1992), and akinesia, on the
Unified Parkinson’s Disease Rating Scale III (UPDRS-III).
All study procedures were approved by the local ethics committee
and written consent was obtained from all subjects. Subjects were
informed that they would not be paid for their participation and
that the monetary incentives used for behavioural assessment were
fictive. Data were obtained from 26 healthy subjects, 13 patients
with AAD and 13 patients with PD (Table 1).
Healthy subjects were screened for any history of neurological
or psychiatric conditions. Initially, we divided the control group
into two sub-groups of 13 healthy subjects, each matched to one
patient group. However, because their behavioural results were not
significantly different, we pooled all healthy subjects together,
forming an extended control group (n=26) with age ranging from
22 to 80 years. We checked that in this extended control group,
the experimental dependent variables were not significantly
influenced by age, gender or education level.
PD patients were consecutive candidates for deep brain
stimulation, hospitalized for a clinical pre-operative examination.
Inclusion criteria were a diagnosis of idiopathic PD, with a good
response to levodopa (440% improvement on the UPDRS-III
scale), in the absence of dementia (MMS score 425) and
depression (MADRS score 520). The mean disease duration was
9.7?1.3 years (range 7–19 years). PD patients were assessed in
their ‘off’ state, in the morning after overnight (412h) withdrawal
of any medication.
AAD patients were tested during their hospitalization for a
multi-approach investigation of the AAD. Inclusion criteria were
history of AAD and bilateral lesions of the basal ganglia, either
from a vascular or anoxic incident. AAD diagnosis was based on
the symptoms described by Laplane and Dubois (2001), and
quantified using a French rating scale (Habib, 1995), for which we
provide an English version in the Supplementary material. Two
patients had additionallesions
(Supplementary Table 1). AAD patients were undergoing various
treatments (Supplementary Table 2), but were tested as PD
patients in the morning, after overnight withdrawal of any
medication. We checked that the main effects of incentives and
instructions (Table 1) hold when removing from analysis the AAD
outsidethe basal ganglia
1304 Brain (2008),131,1303^1310 L. Schmidt et al.
by guest on June 1, 2013
patients with frontal lesions or those treated with sedative
medication. In addition to the MMS and UPDRS-III examina-
tions, both groups of patients also rated their apathy on
a standard scale (Starkstein et al., 1992). To control for
mood disorders, all patients were also administered the MADRS,
and specificallyratedon the
pooling together the dysphoria and vegetative systems (Suzuki
et al., 2005).
items unrelatedto apathy,
T1-weighted structural scans were acquired using an MRI scanner
(GE Medical Systems, Milwaukee, Wisconsin, USA) of 1.5T for 10
AAD patients and of 3T for the remaining three AAD patients.
The lesions of the 13 patients were manually segmented using
www.sph.sc.edu/comd/rorden/mricro.html). Regions of interest
corresponding to the segmented lesions were normalized to the
MNI space using Statistical Parametric Mapping (SPM5) software
(Wellcome Trust Centre for NeuroImaging, London, UK), then
summed and registered to a canonical T1 template for illustration
All subjects used their dominant hand to perform the tasks. Prior
to performing the tasks, subjects were asked to squeeze the hand
grip as hard as they could. The maximum reached over three trials
was taken as the maximal voluntary contraction (MVC), which
served as individual reference for both the instructed and incentive
force tasks. The two tasks (Fig. 2) were programmed on a PC
using Paradigmaesoftware [Paradigme,
France, www.eye-brain.com]. Levels for instructions and incentives
were selected from a preliminary study, where they were found to
linearly increasegrip force
(Supplementary Fig. 1).
The instructed task was designed to assess whether subjects were
able to modulate their force according to instructions. Subjects
were told to squeeze the hand grip so as to reach the red line
displayed on a computer screen. The red line could correspond to
40, 80 or 120% of MVC. The red line was drawn on a grid
graduated from 0 to 100, which was scaled such that the 50line
corresponded to MVC. Thus, the 40, 80 and 120% were indicated
by red lines drawn at 20, 40 and 60 on the grid. This number was
shown on the screen at the start of every trial, so the subjects
could prepare in advance. At the end of every trial, subjects were
shown a written feedback (correct or incorrect), indicating
whether they succeeded or failed.
The incentive task was designed to assess whether subjects
would modulate their force according to incentives. They were not
told what to do, but only that the more they squeezed the grip,
the more they would win of the monetary incentive, which could
be 1, 10 or 50E. The monetary incentive was assigned to the top
of the grid, which was scaled as in the instructed task. Thus, when
subjects attained their MVC, they reached the midline and won
half of the monetary incentive. The sequence of screenshots was
kept as close as possible to the instructed task: first was shown the
monetary incentive (instead of instructed force), then the
graduated scale with the incentive at the top (instead of the red
line), and finally the feedback (cumulative total instead of correct/
incorrect). The cumulative total (of the money won so far) was
indicated by an arrow pointing on an analogue scale (Fig. 1).
The instructed task included 12 trials, meaning four trials per
instructed force. The incentive task included 45 trials, meaning 15
trials per monetary incentive. The order of trial types (instructed
forces or monetary incentives) was randomized in both tasks. The
instructed task was performed both before and after the incentive
task, to control for fatigue effects on the ability to control one’s
hand grip force. Because no significant difference was found
between the two assessments, we pooled them together for the
analyses presented hereafter.
Force was recorded using a ‘pinch grip’ (MIE medical research
ltd., Leeds, UK), with a sample rate of 25Hz. The recorded signal
was digitalized and fed into the PC running the task program
[Paradigm, e(ye)BRAIN, Paris, France, http://www.eye-brain.com].
The stimuli presentation PC provided subjects with real time
T able1 Demographic, clinical and behavioural data
UPDRS III score
Maximal voluntary contraction?SEM
Instructed grip force (80^40%)?SEM
Incentive grip force (50^1E)?SEM
Incentive skin conductance (50^1E)?SEM
?Behavioural measure showing a significant difference between instructions or incentives (paired t-test, P50.05); NS=non significant.
SEM=standard error mean; MMS=mini mental state;UPDRS III=unified PD rating scale III; MADRS=Montgomery and Asberg depres-
sion rating scale. Note MADRS subscore (max is 36) only includes items related to dysphoria and vegetative symptoms, excluding those
related to apathy.
Apathy and basal ganglia damageBrain (2008),131,1303^13101305
by guest on June 1, 2013
visual feedback of the force being exerted on the grip, as a cursor
moving up and down a grid.
Skin conductance was recorded using Ag/AgCl electrodes (1cm
diameter) taped on the palmar surface of the midfinger and
forearm of the non-dominant hand. The signal was fed into a
skin conductance processing unit (Psylab SC5 Stand Alone
Monitor System, Contact Precision Instruments, London, UK).
The filtered analogue of the skin conductance was displayed online
and recorded digitally, with a sample rate of 200Hz, on a
supplementary PC that received event markers from the PC
running stimuli presentation and recording grip force. Skin
conductance recordings were then down sampled to the frequency
of motor acquisition (25Hz).
To analyse grip force response (GFR), we extracted in every trial
both the maximum reached and the area under the curve over the
0–5s period following onset of the graduated scale. For illustration
purposes, we chose the maximum in the instructed task, to allow
direct comparison with instructions, and the area in the incentive
task, to take into account how long in addition to how hard
subjects tried. We conducted all analyses on both measures; results
did not significantly differ. Skin conductance response (SCR) was
taken as the difference between the maximum reached within
the 2–9s period and the minimum within the 0–2s period
following onset of the graduated scale. Both parameters, grip force
and skin conductance, were expressed in proportion to the highest
measure, to eliminate individual differences in maximal grip force
and skin conductance. Moreover, because grip force and skin
conductance might be compromised in AAD or PD independently
of motivational deficits, we used differential instead of absolute
measures. To assess modulation of grip force in the instructed
task, we compared the 80% to the 40% condition. We chose 80
and 40% because it grossly fits the range of forces produced
during the incentive task, and because subjects tended to stop
Fig. 2 Behavioural tasks. Successive screenshots displayed in one
trial are shown from left to right, with durations in milliseconds.
(A) The instructed task.The trial startsby showing the force to be
exerted on the hand grip (40, 80 or120% of the individual maximal
force).This instructed force is indicated on the subsequent gradu-
ated scale as a red line to reach with the cursor, which represents
online force exerted by the subjects on the hand grip. At the end
of the trial, subjects are given feedback on whether they suc-
ceeded or failed to reach the red line. (B) The incentive task.
At the beginning of the trial, subjects are shown the monetary
incentive (1,10 or 50E), which corresponds to the top of the
subsequent graduated scale.The height reached by the cursor
determines the fraction of the monetary incentive won in the
current trial. At the end of the trial, subjects are given feedback
on their cumulative total, as an arrow pointing on the money
won so far, within an analogue scale.
AAD patient 11AAD patient 1
AAD patient 5
Fig.1 Structural scans of patients with AAD. (A) Coronal and
axial slices from three typical patients showing lesions in caudate
nucleus, putamen or pallidum. Note also atrophy of the caudate
nucleus and enlargement of the lateral ventricles in patient 5.
(B) Superimposition of manually segmented focal lesions from13
patients, normalized in the MNI space.Registration with the
canonical T1template shows that main maxima are located
bilaterally in caudate nucleus, putamen and pallidum.
1306Brain (2008),131,1303^1310L. Schmidt et al.
by guest on June 1, 2013
trying their best in the 120% condition when they realized they
could not reach the red line. To assess modulation of both grip
force and skin conductance in the incentive task, we compared
between the 50E and the 1E conditions. Affective and motor
responses refer to these differences (50–1E) calculated for skin
conductance and grip force, respectively. The null hypothesis was
tested using one-tailed paired t-tests for within-group compar-
isons, two-tailed t-tests for two-group comparisons and analysis of
variance (ANOVA) for three-group comparisons and interactions.
Correlations between behavioural performance and demographic
or clinical factors were searched using Pearson’s correlation
Examination of MRI scans (Fig. 1A) confirmed that all
AAD patients had bilateral basal ganglia damage. More
precisely, lesions were located in the caudate nucleus
(n=6), the putamen (n=8) and the pallidum (n=3). We
also observed bilateral atrophy of the striatum accompanied
by anenlargementof the
Superimposition of individual lesions (Fig. 1B) showed
that damage was heterogeneous across patients, with a low
lesion rate in all voxels: maxima were four in the caudate
nucleus, five in the putamen and three in the pallidum.
There were several significant differences (two-tailed
t-test, P50.05) between AAD and PD patients (Table 1).
As one could expect in a comparison between anoxic–
patients were younger than PD patients. Unfortunately,
chance in the recruitment lead to more males being
included in the PD group. AAD patients had some
Parkinsonian signs as apparent in UPDRS-III ratings, but
much fewer than PD patients. In contrast, they had higher
apathy scores on Starkstein’s scale, as well as lower scores in
the mini mental state examination (MMSE).
Instructed versus incentive tasks
Prior to examining differential effects of instructions and
incentives, we checked that no significant difference in
ANOVA, F2,49=0.015; P40.95).
We first performed a 3-way ANOVA on GFR, including
group (AAD versus PD) as a between factor, task
(instructed versus incentive) and level (80 versus 40% for
instructions or 50 versus 1E for incentives) as within
factors. We found no main effect of group (F1,24=0.32,
P40.5), no interaction
(F1,24=0.01, P40.5) and no interaction between group
and level (F1,24=0.96, P40.25). However, the interaction
between group, task and level was significant (F1,24=5.39,
P50.05). We then performed post hoc t-tests to show that
deficits specifically concerned AAD patients during the
incentive task, where motor activation must be self-driven.
between groupand task
In the instructed task (Fig. 2A), control subjects, PD
patients and AAD patients were equally able to modulate
their force according to the instructions (Fig. 3). The
difference in GFR between the 80% and 40% instructions
was significant for all three groups (one-tailed paired
t-tests; t25=26.4, t12=7.3 and t12=8.4; all P50.001). There
was no difference between the groups compared two by two
(two-tailed t-tests; t37=2.2; t37=1.8 and t24=0.4; all
In the incentive task (Fig. 2B), control subjects and PD
patients modulated their grip force according to the
magnitude of the incentive (Fig. 3). The difference in
GFR between 50 and 1E trials was significant in both
groups (one-tailed paired t-test; t25=9.3 and t12=3.4; both
P50.01), but smaller in PD patients compared to control
subjects (two-tailed t-test; t37=3.6; P50.001). In contrast
to PD patients and control subjects, AAD patients made no
difference between 50 and 1E trials (one-tailed paired
t-test; t12=?0.4; P40.5). Differential GFR between 1 and
50E was significantly lower in AAD than in PD patients
patients produced more force for 1E, and less force for
50E, no post hoc comparison with PD patients, made
separately for the different incentives, was significant (two-
tailed t-test; t24=?1.3, t24=?0.39 and t24=0.4; all P40.1).
40%80% 120% 40% 80% 120%40% 80% 120%
Control subjects PD patientsAAD patients
Fig. 3 Mean effects of instructions and incentives for control
subjects, patients with AAD and patients with PD.Grip force and
skin conductance are expressed as a proportion of the highest
measure. Error bars are ?SEM. Lines joining the histograms were
obtainedby linear regression against the three forces or incentives.
?Indicates a significant difference (paired t-test, P50.01), between
40% and 80% forcesin the instructed task, or between1Eand 50E
in the incentive task. NS=non-significant.
Apathy and basal ganglia damageBrain (2008),131,1303^1310 1307
by guest on June 1, 2013
We therefore cannot know whether AAD patients failed to
exert more force on higher incentives or to retain their
force on lower incentives. More cautiously, we conclude
that AAD patients failed to modulate their force according
to monetary incentives.
Skin conductance versus grip force
We started with a 3-way ANOVA restricted to the incentive
task, including group (AAD versus PD) as a between factor
and response (SCR versus GFR) and level (50 versus 1E) as
within factors. We found no main effect of group
(F1,24=0.09, P40.5), no interaction between group and
response (F1,24=0.08, P40.5) and no interaction between
group and level (F1,24=1.52, P40.25). However, the
interaction between group, response and level was sig-
nificant (F1,24=7.91, P50.01). We then performed post hoc
t-tests to show that deficits specifically concerned the motor
response of AAD patients, without affecting the affective
response to monetary incentives.
In control subjects, as well as in PD and AAD patients,
the amplitude of SCR was greater for higher monetary
incentives (Fig. 3). The difference in SCR between 50 and
1E trials was significant in all three groups (one-tailed
paired t-test; t25=5.8, t12=2.8 and t12=3.6; all P50.01).
With respect to between-group comparisons, the SCR of
both AAD and PD patients was significantly reduced in
comparison to the SCR of control subjects (two tailed
t-tests; t37=2.6 and t37=2.3; both P50.01). There was no
significant difference in SCR between AAD and PD patients
(two-tailed t-tests; t24=0.5; P40.5).
Thus, relative to controls, affective and motor responses
in PD patients were reduced but still in proportion to
monetary incentives. Relative to PD patients, AAD patients
showed similar affective evaluation of monetary incentives,
but failed to translate this affective evaluation into motor
activation. Note this dissociation is also illustrated at the
individual level in Supplementary Fig. 2.
Correlations with demographic and
Correlations were searched between GFR or SCR measured
during the incentive task and demographic (age, gender and
educational level) or clinical (Starkstein, UPDRS-III and
MMSE scores) data, across the two groups of patients. The
only significant correlation was found between GFR and
Starkstein’s apathy score (Pearson’s coefficient=?0.61,
P50.01); all other correlation coefficients were below 0.5.
Thus, the more severe the apathy, the lower the differential
impact of monetary incentives on the force produced.
When considering PD/AAD groups, respectively, correla-
tions of GFR with apathy scores were not significant;
Pearson’s coefficients were ?0.52/?0.45 for GFR, and
?0.57/?0.42 for SCR.
Here, we assessed the behavioural performance of PD
patients (suffering from dopamine depletion) and AAD
patients (suffering from bilateral basal ganglia damage) on
both instructed and incentive force tasks. The instructed
task ensured that all patients were able to normally
modulate their hand grip force according to external
guidance. The incentive task revealed apathy in PD as an
equal flattening of motor and affective responses, but
apathy in AAD as a dissociation of motor activation from
The only significant difference in our behavioural
assessment between PD and AAD patients was found in
the ability to modulate hand grip force according to
monetary incentives. This difference could in principle be
related to other differences noted in the demographic and
clinical data: namely age, sex, UPDRS-III, MMSE and
apathy scores. It seems difficult to conceive why age or sex
Parkinsonian signs might have interfered with the incentive
task, but we controlled for this in the instructed task, where
motor ability was efficient enough to accurately produce
the required levels of force. Cognitive ability might also
play a role in the incentive task, possibly by working out a
strategy to save energy for when the monetary stakes are
higher. However, we previously demonstrated that modula-
tion of grip force occurs even without conscious awareness
of the monetary incentives (Pessiglione et al., 2007), which
suggests that the task involves basic motivational process
rather than sophisticated executive control. In addition to
these arguments, no correlation was observed between age,
sex, UPDRS-III or MMSE scores and differential effect of
monetary incentives on grip force. The only significant
correlation was with apathy scores as measured by
Starkstein’s scale (Starkstein et al., 1992). We therefore
suggest that the incentive force task provides an indepen-
dent, direct and objective assessment of apathy.
Apathy in PD was characterized by a reduction of both
motor and affective responses to monetary incentives. This
finding accords well with clinical descriptions of apathetic
PD patients, which point out loss of interest, flattening of
affect and poor behavioural activity (Pluck and Brown,
2002; Aarsland et al., 2005; Kirsch-Darrow et al., 2006).
A likely cause of such apathetic signs is dopamine deple-
tion, as patients were assessed while off their medication,
although the contribution of other lesions observed in PD
cannot be excluded (Braak et al., 1995). We must remain
cautious, however, of our conclusions regarding the role of
dopamine in incentive motivation, since we do not know
the degree and regional extent of dopamine depletion in
our PD patients. Further investigation of treatment effects
(notably dopaminergic medication and deep brain stimula-
tion) would be necessary to specify the role of dopamine in
the incentive force task. Our data show nonetheless that,
beyond the flattening of affective and motor responses, the
1308 Brain (2008),131,1303^1310 L. Schmidt et al.
by guest on June 1, 2013
process that translates higher expected rewards into harder
physical efforts is relatively preserved in PD. This is
consistent with reports that reward preference still impacts
behavioural performance in a primate model of PD
(Pessiglione et al., 2004). Such functional preservation
might be due to spared dopaminergic innervation of the
limbic circuits passing through the basal ganglia, which was
observed in both Parkinsonian monkeys (Jan et al., 2003)
and PD patients (Kish et al., 1988). These limbic circuits,
originating from the orbital and medial prefrontal cortices,
and including the ventral striatum and ventral pallidum,
have been suggested to play a key role in anticipating
reward and motivating behaviour (Alexander et al., 1986;
Robbins and Everitt, 1996; Brown and Pluck, 2000; Heimer
and Van Hoesen, 2006; Salamone et al., 2007).
Apathy in AAD was chacterized by a dissociation of
motor response to incentives from both motor response to
instructions and affective response to incentives. This
finding accords well with clinical descriptions of AAD
patients, as being able to activate behaviour under external
instructions but not out of their own interests (Laplane
et al., 1982; Ali-Cherif et al., 1984; Habib and Poncet, 1988;
Trillet et al., 1990). In the incentive task, patients are under
external stimulation, as they are asked by the experimenter
to squeeze the hand grip. This they could do, but, crucially,
they failed to differentiate between monetary incentives,
missing the component of motor activation that should be
driven by their financial interests. Because affective evalua-
tion of monetary incentives and motor control of required
forces were both correct, we suggest that the deficit lies
between the two, in the process that translates expected
rewards into motoractivation.
incentive motivation appeared to result from damage to
the striato-pallidum complex. In some cases, current
medication and/or pre-morbid traits may have influenced
the behavioural performance. However, medication and
history were various, whereas basal ganglia damage was
constant, across patients. Furthermore, the link between
striato-pallidal stroke and behavioural changes is supported
by previous clinical reports (Laplane et al., 1989; Habib,
2004). One important feature of AAD is bilaterality of
striato-pallidal damage, as unilateral lesions rarely lead to
behavioural inertia or abulia (Bhatia and Marsden, 1994).
Unfortunately, although we tried a voxel-based morphom-
etry approach, we were unable to find convincing statistical
relationship between a specific cluster and the behavioural
deficit. Neither could we disentangle the contributions of
focal lesions from those of global atrophy of the striato-
pallidal complex. This difficulty relates to the small number
of patients combined with the heterogeneity of damage,
which resulted in a low lesion rate in every voxel of the
striato-pallidal complex. Further studies will be necessary to
specify the anatomical basis of incentive motivation
dysfunction, notably in terms of fronto-striatal circuitry.
Our data show nonetheless that bilateral damage to the
the translation of
expected reward into physical effort. This is consistent
with the general view that the basal ganglia integrate
different domains of information, including those dealing
with reward prediction and motor execution (Mogenson et
al., 1980; Joel and Weiner, 1994; Yelnik, 2002; Haber,
In conclusion, our paradigm has proven useful not only
in assessing severity of apathy following basal ganglia
damage, but also in specifying dysfunction of incentive
motivation, in terms of affective versus motor processing.
Notably, we show that AAD patients assign adapted
affective values to potential rewards, but fail to integrate
these values into their motor behaviour. The reverse
dissociation, meaning impaired affective response with
preserved motor response, could in principle be observed
as well, possibly due to amygdala damage. More generally,
we suggest the present paradigm might also help under-
stand other types of apathy in humans, such as those
observed in depression or schizophrenia.
Supplementary material is available at Brain online.
We thank Serge Kinkingne ´hun (e(ye)BRAIN, Paris, France)
for providing the ‘Paradigmae’ software, Bastien Oliviero
for helping us program the stimuli presentation and data
analysis, and Edith Guilloux and the nursing staff of the
Centre d’Investigation clinique for taking care of the
patients. We appreciate the technical help and thoughtful
suggestions provided by Emmanuelle Volle and Magali
Seassau. Lesion localization benefited from the expertise of
Je ´ro ˆme Yelnik and Eric Bardinet. We are also grateful to
Soledad Jorge for checking the English and to Chris Frith
for helpful comments on the article. This study was
supported by the Institut National de la Sante ´ et de la
Recherche Medicale (INSERM) and the Assistance Publique
– Ho ˆpitaux de Paris (AP-HP). L.S. was supported by the
Ministe `re de la Recherche et de l’Education nationale
(France); B.F.A. received a grant from the Fondation pour
la Recherche Me ´dicale.
Aarsland D, Alves G, Larsen JP. Disorders of motivation, sexual conduct,
and sleep in Parkinson’s disease. Adv Neurol 2005; 96: 56–64.
Agid Y, Arnulf I, Bejjani P, Bloch F, Bonnet AM, Damier P, et al.
Parkinson’s disease is a neuropsychiatric disorder. Adv Neurol 2003; 91:
Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally
segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci
1986; 9: 357–81.
Ali-Cherif A, Royere ML, Gosset A, Poncet M, Salamon G, Khalil R.
[Behavior and mental activity disorders after carbon monoxide
poisoning. Bilateral pallidal lesions]. Rev Neurol 1984; 140: 401–5.
Bauer RM. Physiologic measures of emotion. J Clin Neurophysiol 1998;
Apathy and basal ganglia damageBrain (2008),131,1303^13101309
by guest on June 1, 2013
Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Download full-text
Behav 2004; 81: 179–209.
Bhatia KP, Marsden CD. The behavioural and motor consequences
of focal lesions of the basal ganglia in man. Brain 1994; 117 (Pt 4):
Braak H, Braak E, Yilmazer D, Schultz C, de Vos RA, Jansen EN. Nigral
and extranigral pathology in Parkinson’s disease. J Neural Transm Suppl
1995; 46: 15–31.
Brown RG, Pluck G. Negative symptoms: the ‘pathology’ of motivation
and goal-directed behaviour. Trends Neurosci 2000; 23: 412–7.
Burleigh-Jacobs A, Horak FB, Nutt JG, Obeso JA. Step initiation in
Parkinson’s disease: influence of levodopa and external sensory triggers.
Mov Disord 1997; 12: 206–15.
Critchley HD. Electrodermal responses: what happens in the brain.
Neuroscientist 2002; 8: 132–42.
Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B.
Motivation, reward, and Parkinson’s disease: influence of dopatherapy.
Neuropsychologia 2002; 40: 2257–67.
Frank MJ, Seeberger LC, O’Reilly RC. By carrot or by stick: cognitive
reinforcement learning in Parkinsonism. Science 2004; 306: 1940–3.
Haber SN. The primate basal ganglia: parallel and integrative networks.
J Chem Neuroanat 2003; 26: 317–30.
Habib M. [Activity and motivational disorders in neurology: proposal for
an evaluation scale]. Encephale 1995; 21 (5): 563–70.
Habib M. Athymhormia and disorders of motivation in basal ganglia
disease. J Neuropsychiatry Clin Neurosci 2004; 16: 509–24.
Habib M, Poncet M. Loss of vitality, of interest and of the affect
(athymhormia syndrome) in lacunar lesions of the corpus striatum. Rev
Neurol 1988; 144: 571–7.
Hallett M, Khoshbin S. A physiological mechanism of bradykinesia. Brain
1980; 103: 301–14.
Heimer L, Van Hoesen GW. The limbic lobe and its output channels:
implications for emotional functions and adaptive behavior. Neurosci
Biobehav Rev 2006; 30: 126–47.
Isella V, Melzi P, Grimaldi M, Iurlaro S, Piolti R, Ferrarese C, et al.
Clinical, neuropsychological, and morphometric correlates of apathy in
Parkinson’s disease. Mov Disord 2002; 17: 366–71.
Jahanshahi M, Jenkins IH, Brown RG, Marsden CD, Passingham RE,
Brooks DJ. Self-initiated versus externally triggered movements. I. An
investigation using measurement of regional cerebral blood flow with
PET and movement-related potentials in normal and Parkinson’s disease
subjects. Brain 1995; 118 (Pt 4): 913–33.
Jan C, Pessiglione M, Tremblay L, Tande D, Hirsch EC, Francois C.
functional territories in MPTP-treated monkeys. Eur J Neurosci 2003;
Joel D, Weiner I. The organization of the basal ganglia-thalamocortical
Neuroscience 1994; 63: 363–79.
Kelly VE, Hyngstrom AS, Rundle MM, Bastian AJ. Interaction of levodopa
and cues on voluntary reaching in Parkinson’s disease. Mov Disord
2002; 17: 38–44.
Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D.
Dissociating apathy and depression in Parkinson disease. Neurology
2006; 67: 33–8.
Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopamine loss
in the striatum of patients with idiopathic Parkinson’s disease.
Pathophysiologic and clinical implications. N Engl J Med 1988; 318:
lossin relation to
ratherthan closed segregated.
Knutson B, Bjork JM, Fong GW, Hommer D, Mattay VS, Weinberger DR.
Amphetamine modulates human incentive processing. Neuron 2004; 43:
Laplane D, Baulac M, Pillon B, Panayotopoulou-Achimastos I. [Loss of
psychic self-activation. Compulsive activity of obsessional type. Bilateral
lenticular lesion (author’s transl)]. Rev Neurol 1982; 138: 137–41.
Laplane D, Dubois B. Auto-activation deficit: a basal ganglia related
syndrome. Mov Disord 2001; 16: 810–4.
Laplane D, Levasseur M, Pillon B, Dubois B, Baulac M, Mazoyer B, et al.
Obsessive-compulsive and other behavioural changes with bilateral basal
ganglia lesions. A neuropsychological, magnetic resonance imaging and
positron tomography study. Brain 1989; 112 (Pt 3): 699–725.
Laplane D, Widlocher D, Pillon B, Baulac M, Binoux F. [Obsessional-type
compulsive behavior caused by bilateral circumscribed pallidostriatal
necrosis. Encephalopathy caused by a wasp sting]. Rev Neurol 1981; 137:
Luaute JP, Saladini O. [The French concept of ‘Athymhormie’ (Loss of
vital force) from 1922 to the present]. Can J Psychiatry 2001; 46:
Mazzoni P, Hristova A, Krakauer JW. Why don’t we move faster?
Parkinson’s disease, movement
J Neurosci 2007; 27: 7105–16.
Mogenson GJ, Jones DL, Yim CY. From motivation to action: functional
interface between the limbic system and the motor system. Prog
Neurobiol 1980; 14: 69–97.
Pessiglione M, Guehl D, Jan C, Francois C, Hirsch EC, Feger J, et al.
Disruption of self-organized actions in monkeys with progressive
MPTP-induced Parkinsonism: II. Effects of reward preference. Eur J
Neurosci 2004; 19: 437–46.
Pessiglione M, Schmidt L, Draganski B, Kalisch R, Lau H, Dolan RJ, et al.
How the brain translates money into force: a neuroimaging study of
subliminal motivation. Science 2007; 316: 904–6.
Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-
dependent prediction errors underpin reward-seeking behaviour in
humans. Nature 2006; 442: 1042–5.
Pluck GC, Brown RG. Apathy in Parkinson’s disease. J Neurol Neurosurg
Psychiatry 2002; 73: 636–42.
Robbins TW, Everitt BJ. Neurobehavioural mechanisms of reward and
motivation. Curr Opin Neurobiol 1996; 6: 228–36.
Salamone JD, Correa M, Farrar A, Mingote SM. Effort-related functions of
Psychopharmacol 2007; 191: 461–82.
Schultz W. Multiple reward signals in the brain. Nat Rev Neurosci
2000; 1: 199–207.
Schultz W. Multiple dopamine functions at different time courses. Annu
Rev Neurosci 2007; 30: 259–88.
Schultz W, Dayan P, Montague PR. A neural substrate of prediction and
reward. Science 1997; 275: 1593–9.
Starkstein SE, Mayberg HS, Preziosi TJ, Andrezejewski P, Leiguarda R,
Robinson RG. Reliability, validity, and clinical correlates of apathy in
Parkinson’s disease. J Neuropsychiatry Clin Neurosci 1992; 4: 134–9.
Suzuki A, Aoshima T, Fukasawa T, Yoshida K, Higuchi H, Shimizu T,
et al. A three-factor model of the MADRS in major depressive disorder.
Depress Anxiety 2005; 21: 95–7.
Trillet M, Croisile B, Tourniaire D, Schott B. [Disorders of voluntary
motor activity and lesions of caudate nuclei]. Rev Neurol 1990; 146:
Yelnik J. Functional anatomy of the basal ganglia. Mov Disord 2002; 17
Suppl 3: S15–21.
vigorand implicit motivation.
and associatedforebrain circuits.
1310 Brain (2008),131,1303^1310L. Schmidt et al.
by guest on June 1, 2013