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Pathological gambling (PG) is an impulse control disorder that manifests in 2.2-7% of patients with Parkinson's disease (PD). Although the underlying neural mechanisms remain controversial, parkinsonian patients with PG show enhanced risk propensity, especially when assuming dopamine agonist drugs. The dopaminergic reward circuit, a neural network that participates in developing and monitoring motivated behaviours,1 includes the subthalamic nucleus (STN). Local field potentials (LFPs) recorded from macroelectrodes implanted in the STN for deep brain stimulation (DBS) show specific low-frequency oscillations in patients with PD with impulsive control disorders at rest and in patients with PG during the preparation of conflictual economics decisions.2 ,3 No study has yet investigated STN involvement in monetary reward processing, namely the phase that follows economics decisions, when participants face the outcome of their choice in patients with PD. Besides helping to understand the mechanisms underlying PG, this knowledge could promote the optimisation of therapies for impulse control disorders. We investigated the STN's role in risk-related monetary reward in parkinsonian patients. To do so, we studied the reward-related STN LFPs changes in patients with PD with and without PG engaged in an economics decision task.
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LETTER
Subthalamic involvement in
monetary reward and its
dysfunction in parkinsonian
gamblers
INTRODUCTION
Pathological gambling (PG) is an impulse
control disorder that manifests in 2.27%
of patients with Parkinsons disease (PD).
Although the underlying neural mechan-
isms remain controversial, parkinsonian
patients with PG show enhanced risk pro-
pensity, especially when assuming dopa-
mine agonist drugs.
The dopaminergic reward circuit, a
neural network that participates in devel-
oping and monitoring motivated beha-
viours,
1
includes the subthalamic nucleus
(STN). Local eld potentials (LFPs)
recorded from macroelectrodes implanted
in the STN for deep brain stimulation
(DBS) show specic low-frequency oscilla-
tions in patients with PD with impulsive
control disorders at rest and in patients
with PG during the preparation of con-
ictual economics decisions.
23
No study
has yet investigated STN involvement in
monetary reward processing, namely the
phase that follows economics decisions,
when participants face the outcome of
their choice in patients with PD. Besides
helping to understand the mechanisms
underlying PG, this knowledge could
promote the optimisation of therapies for
impulse control disorders.
We investigated the STNs role in
risk-related monetary reward in parkin-
sonian patients. To do so, we studied the
reward-related STN LFPs changes in
patients with PD with and without PG
engaged in an economics decision task.
MATERIALS AND METHODS
We enrolled 12 patients with PD 4 days
after STN DBS macroelectrode positioning
surgery as described elsewhere
3
(for clinical
details, see table 1 from Ref. 3, patients
number 14, 812, 14, 15, 17). Of the 12
patients, 6 met the criteria for PG according
to the Diagnostic and Statistical Manual of
Mental Disorders (DSM IV-TR). All
patients gave informed consent. The study
was conducted in accordance with the
DeclarationofHelsinkiandwasapproved
by the institutional review board. Patients
were tested with the economics decision
task (gure 1A,C) during bilateral STN LFP
recording from DBS macroelectrode
contact pair 02.
LFPs were preamplied, ltered (band
pass 2512 Hz), differentially amplied
(×100 000) and digitised with a 1024 Hz
sampling rate through the Galileo BE
Light EEG amplication system (EBNeuro
Spa, Florence, Italy). LFPs were analysed
off-line with Matlab software (V.7.10, The
MathWorks, Natick, Massachusetts, USA).
First, to identify the main activated LFP
frequency band during economics feed-
back, we ran a timefrequency analysis.
Then, to obtain the mean frequency band
power in conictual and non-conictual
task conditions during the two task phases
(black screen, feedback) for each type of
feedback (risky positive, risky negative,
non-risky positive, non-risky negative),we
applied the Hilbert transform.
3
For behavioural analyses, the economics
strategy each patient used during task per-
formance was evaluated by calculating the
sum of risky choices in conictual trials.
Differences between economics strategies
in patients with and without PG were
tested in a one-way analysis of variance
(ANOVA) using PG ( presence, absence) as
between factor.
A one-sample Kolmogorov-Smirnov test
was performed with electrophysiological
data to verify whether they have normal
distributions. To assess whether STN LFP
activity recorded during black screen
could be used as the baseline, we rst
compared mean power during the black
screen in conictual and non-conictual
trials using a two-way repeated measures
ANOVA with between factor PG and
within factor type of feedback.
After calculating the percentage power
change from the baseline for each trial,
3
a
three-way repeated measures ANOVA with
between factor PG,rst within factor task
phases and second within factor type of
feedback was run for conictual trials. A
similar three-way ANOVA was run for
non-conictual trials. One patient was
excluded from the analysis on non-
conictual trials for artefacts due to elec-
trode extension cable movement.
Differences were considered signicant at
p<0.05.
RESULTS
During the economics task, patients with
PG adopted a signicantly more risk-
taking behavioural strategy than patients
without PG (F(1,10)=7.99; p=0.017).
The one-sample Kolmogorov-Smirnov
test showed that LFPs in the task phases
and in the types of feedback have a
normal distribution ( p>0.05 for all
variables).
In all patients, the timefrequency plot
for STN LFPs averaged across all trials
showed that the principal power modula-
tions during the feedback phase involved
low-frequency power (from 2.25±0.87 to
12.08±0.29 Hz; gure 1B).
When we applied the Hilbert trans-
form, the two-way ANOVA showed that
the factors PG and feedback type and
their interactions had no signicant effects
on low-frequency power during the black
screen phase in conictual (F(3,66)=1.45;
p>0.05) and non-conictual trials (F
(3,60)=1.38; p>0.05). We therefore con-
sidered the STN LFP low-frequency band
power recorded when we displayed the
black screen as the baseline.
Global three-way ANOVA showed signi-
cantly higher low-frequency power during
feedback than during black screen in con-
ictual (task phases, F(1,22)=9.25;
p=0.005) and non-conictual trials (task
phases, F(1,20)=4.45; p=0.047; gure 1D).
Three-way ANOVA detected a signi-
cant interaction between the three factors
only in conictual trials (PG×task
phases×feedback type, F(3,66)=2.73;
p=0.050). Post hoc ANOVA showed a sig-
nicant interaction (PG×feedback type,F
(1,22)=2.74; p=0.050). Post hoc ANOVA
showed signicant differences between
patients with and without PG only during
risky positive feedback (F(1,22)=5.07;
p=0.034). Specically, when patients
received a positive feedback after a risky
choice, percentage changes in low-
frequency power were signicantly lower
in parkinsonian patients without than with
PG (gure 1E).
DISCUSSION
In general, our results rst provide the
neurophysiological evidence that the
human STN is involved in monetary
reward. Specically, we found that the
reward-related STN neural activity
recorded during an economics decision
task shows distinct patterns in parkinson-
ian patients who gamble and those who
do not: whereas in gamblers, low-
frequency power increases during all types
of monetary feedback, that is, during
winning and losing, in non-gamblers, it
remains unchanged during the risky posi-
tive feedback, a low probable and high
win that in the long run leads to loss. This
neurophysiological pattern reects the
behavioural strategy adopted by patients.
Patients without PG used a risk-avoiding
strategy, for instance, they tended to
choose stimuli associated with small but
more probable positive rewards (in our
economics task, a non-risky positive feed-
back). Conversely, patients with PG used a
risk-taking strategy, and preferred large
and less probable positive rewards (in our
J Neurol Neurosurg Psychiatry Month 2014 Vol 0 No 0 1
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Figure 1 (A) The economics decision task. Each trial comprised two phases: the feedbackphase displaying the money won or lost after the
patients choice, and the black screen. The red letters show the patients choice. (B) The timefrequency plot for the grand average subthalamic
nucleus local eld potential (STN LFP) power in all trials in patients with and without pathological gambling (PG). Note that the principal power
changes during the feedback phase involved the low-frequency band. (C) Feedback obtained during the economics task in conictual and
non-conictual trials. On the left, an example showing a conictual trial between a non-risky stimulus Aand a risky stimulus C. On the right, an
example showing a non-conictual trial between two risky stimuli Band C. We classied four types of feedback according to risk taking: risky
positive (+100), risky negative (70), non-risky positive (+60), non-risky negative (30). The task was designed to reward non-risky stimuli
choices, so that the larger the number of non-risky stimuli choices, the higher was the amount of money earned. (D) On the left, the grand average
of low-frequency power modulations in conictual trials during the feedback phase and the black screen phase in all parkinsonian patients with and
without PG. Low-frequency power modulations are expressed as percentage changes from the black screen phase. Red horizontal lines represent the
mean low-frequency power during the feedback and black screen phases. On the right, the grand average for low-frequency power modulations in
non-conictual trials. Note that in all patients STN LFP low-frequency power increased during feedback in both conictual and non-conictual trials.
(three-way analysis of variance (ANOVA), p<0.05). (E) Histograms represent changes in low-frequency STN LFP power during feedback in patients
with and without PG in conictual trials. Error bars represent the SE of the estimated mean. Below, time-frequency plots for the grand average STN
LFP power during risky positive feedback. Low-frequency power during risky positive feedback is signicantly lower in patients without than in
patients with PG (post hoc ANOVA, *p<0.05).
2J Neurol Neurosurg Psychiatry Month 2014 Vol 0 No 0
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task, a risky positive feedback). These
results suggest that the specic neuro-
physiological activity in non-gamblers that
remains unchanged during risky positive
feedback behaviourally reects their scarce
tendency to choose this option.
Conversely, neurophysiological activity in
patients who gamble is modulated indif-
ferently by reward and gamblers behav-
iourally use a disadvantageous strategy.
Therefore, we conjecture that the spe-
cic STN LFP reward-related pattern in
response to the risky positive feedback
depends on the value that the STN attri-
butesto it in orienting the economics
choice: in patients with PG it suggests an
impaired learning in discriminating eco-
nomics rewards.
To understand the reward circuit better,
future research should also investigate cor-
tical modulation. It should also check
whether the feedback task involves other
cognitive processes related to decision-
making, including inhibition, learning,
probability encoding, stimuli salience and
reward encoding. Nonetheless, in general,
our results conrm previous reports on
STN low-frequency involvement in emo-
tional and decisional processes
4
and agree
with reports that STN DBS can variably
modulate efcacy in using feedback and
regulate impulsivity.
5
Our previous ndings on the prepar-
ation of economics decision in parkinson-
ian patients with PG showed a
subthalamic dysfunction that makes their
decisional threshold highly sensitive to
risky options.
3
In this study, we extend
these results, suggesting that STN activity
is also affected by reward and that PG
could be related to a reward circuit
disorder.
Manuela Fumagalli,
1
Manuela Rosa,
1
Gaia Giannicola,
1
Sara Marceglia,
1
Claudio Lucchiari,
2
Domenico Servello,
3
Angelo Franzini,
4
Claudio Pacchetti,
5
Luigi Romito,
4
Alberto Albanese,
4
Mauro Porta,
3
Gabriella Pravettoni,
2,6
Alberto Priori
1,7
1
Centro Clinico per la Neurostimolazione, le
Neurotecnologie ed i Disordini del Movimento,
Fondazione IRCCS CaGranda, Ospedale Maggiore
Policlinico, Milan, Italy
2
Dipartimento di Economia, Management e Metodi
Quantitativi, Università degli Studi di Milano, Milan,
Italy
3
Neurochirurgia Funzionale e Clinica Tourette, IRCCS
Galeazzi, Milan, Italy
4
Fondazione IRCCS Istituto Nazionale Neurologico
Carlo Besta, Milan, Italy
5
Unità Operativa Parkinson e Disordini del Movimento,
IRCCS Istituto Neurologico Mondino, Pavia, Italy
6
Unità di Ricerca Applicata per le Scienze Cognitive e
Psicologiche, Istituto Europeo di Oncologia, Milan, Italy
7
Dipartimento di Fisiopatologia Medico-Chirurgica e dei
Trapianti, Università degli Studi di Milano, Milan, Italy
Correspondence to Professor Alberto Priori, Centro
Clinico per la Neurostimolazione, le
Neurotecnologie ed i Disordini del Movimento,
Fondazione IRCCS CaGranda, Ospedale Maggiore
Policlinico, Via Francesco Sforza 35, Milan 20122,
Italy; alberto.priori@unimi.it
Contributors MF and MR contributed equally to this
study. MF, MR and GG were involved in conception,
organisation and execution; design and execution and
writing of the rst draft. SM was involved in
conception; review and critique and writing of the rst
draft. CL was involved in conception; review and
critique. DS and AF were involved in conception,
organisation and execution; review and critique. CP and
LR were involved in review and critique. AA, MP, GP
and AP were involved in conception; review and
critique.
Funding ERANET-Neuron Grant PhysiolDBS
(Neuron-48-013).
Competing interests None.
Patient consent Obtained.
Ethics approval Fondazione IRCCS CaGranda
Ospedale Maggiore Policlinico Milano.
Provenance and peer review Not commissioned;
externally peer reviewed.
To cite Fumagalli M, Rosa M, Giannicola G, et al.
J Neurol Neurosurg Psychiatry Published Online First:
[please include Day Month Year] doi:10.1136/jnnp-
2014-307912
Received 18 February 2014
Revised 30 May 2014
Accepted 15 June 2014
J Neurol Neurosurg Psychiatry 2014;0:13.
doi:10.1136/jnnp-2014-307912
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J Neurol Neurosurg Psychiatry Month 2014 Vol 0 No 0 3
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doi: 10.1136/jnnp-2014-307912
published online July 12, 2014J Neurol Neurosurg Psychiatry
Manuela Fumagalli, Manuela Rosa, Gaia Giannicola, et al.
gamblers
reward and its dysfunction in parkinsonian
Subthalamic involvement in monetary
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... Similarly, a recent structural MRI study observed a linear relationship between structural connectivity of a "reward evaluation" circuit and risky gambling in the ICD-group, but not in the ICD+ group, in the absence of differences in gambling behaviour between the groups. 52,53,5 Previous electrophysiological studies found risky strategies in gambling to manifest differently in STN in ICD+ patients. 52,53 Our finding suggests that STN activity relates to how soon ICD-patients stop their risky engagement, but that this relationship is disturbed in ICD+ patients. ...
... 52,53,5 Previous electrophysiological studies found risky strategies in gambling to manifest differently in STN in ICD+ patients. 52,53 Our finding suggests that STN activity relates to how soon ICD-patients stop their risky engagement, but that this relationship is disturbed in ICD+ patients. ...
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... Third, electrophysiological recordings acquired in PD patients while performing cognitive tasks revealed strong relationships between the oscillatory activity of the local field potentials (LFPs) of the STN and the mechanisms of response inhibition and the regulation of decision processes (Cavanagh et al., 2011;Brittain et al., 2012;Zavala et al., 2014). Studying the STN LFP oscillations also revealed that the subjective cost of an action, the subjective value of a reward (Zénon et al., 2016), and the specific motor effort to assign to a motor response are represented at the STN level (Tan et al., 2015) and that this structure is involved in monetary reward processing (Fumagalli et al., 2015) and economic decisions (Rosa et al., 2013). Moreover, electrophysiological data from behaving rodents and nonhuman primates indicate that STN neurons are modulated by cues predicting reward and reward occurrence (Matsumura et al., 1992;Darbaky et al., 2005;Teagarden and Rebec, 2007;Lardeux et al., 2009Lardeux et al., , 2013Espinosa-Parrilla et al., 2013Breysse et al., 2015), and that they could link reward information to the motor output (Espinosa-Parrilla et al., 2013) and differentiate reward types and relative values of reward (Lardeux et al., 2009(Lardeux et al., , 2013Breysse et al., 2015;Espinosa-Parrilla et al., 2015). ...
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Cognitive action control depends on cortical-subcortical circuits, involving notably the subthalamic nucleus (STN), as evidenced by local field potentials recordings (LFPs) studies. The STN consistently shows an increase in theta oscillations power during conflict resolution. Some studies have shown that cognitive action control in Parkinson's disease (PD) could be influenced by the occurrence of monetary reward. In this study, we investigated whether incentive motivation could modulate STN activity, and notably STN theta activity, during response conflict resolution. To achieve this objective, we recorded STN LFPs during a motivated Simon task in PD patients who had undergone deep brain stimulation surgery. Behavioral results revealed that promised rewards increased the difficulty in resolving conflict situations, thus replicating previous findings. Signal analyses locked on the imperative stimulus onset revealed the typical pattern of increased theta power in a conflict situation. However, this conflict-related modulation of theta power was not influenced by the size of the reward cued. We nonetheless identified a significant effect of the reward size on local functional organization (indexed by inter-trial phase clustering) of theta oscillations, with higher organization associated with high rewards while resolving conflict. When focusing on the period following the onset of the reward cue, we unveiled a stronger beta power decrease in higher reward conditions. However, these LFPs results were not correlated to behavioral results. Our study suggests that the STN is involved in how reward information can influence computations during conflict resolution. However, considering recent studies as well as the present results, we suspect that these effects are subtle.
... The studies and the application of deep brain stimulation allowed to deeper understand brain signals through the interpretation of the EEG rhythms, accelerating the development of non-invasive BCI systems (Fumagalli et al., 2014). ...
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Starting from the considerations that new generations communicate and manage social relationships in a different way, thanks to the use of new media, especially Internet, we wanted to study the effects of this communication mode on a neuro-cognitive level. Many studies, especially in sociological and psychological research fields, state that traditional communication among young people is decreasing and that the excessive use of social networking and mobile devices represents a limitation to the development of communication abilities. In this chapter, we present our concept of “sympateia” and show the results of our early-stage experiments addressing our research. Progresses in Neuroscience and current Brain-Computer Interface (BCI) devices enable NeuroInformatics to deeper experiment new Human-machine communication methods and technology. Our aim is to address research efforts in finding new technologies and new IT paradigms to explore the possibility of a direct Human-Human communication mediated by technology. The chapter consists of six sections: in section one, a theoretical background of the cognitive approach to communication and empathy will be defined. In section two, it will be traced the state-of-the-art in Information Technology and Neuroscience studies in human-computer interaction. In section three IT paradigms will be presented to individuate the well-suited ones, with particular attention to AI and learning machine methods. Section four will trace the scenario and the direction of the research, while section five will present some preliminary experiments performed. Finally, in section six will discuss some final considerations and future works.
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Cognitive action control depends on cortical-subcortical circuits, involving notably the subthalamic nucleus (STN), as evidenced by local field potentials recordings (LFPs) studies. The STN consistently shows an increase in theta oscillations power during conflict resolution. Some studies have shown that cognitive action control in Parkinson's disease (PD) could be influenced by the occurrence of monetary reward. In this study, we investigated whether incentive motivation could modulate STN activity, and notably STN theta activity, during response conflict resolution. To achieve this objective, we recorded STN LFPs during a motivated Simon task in PD patients who had undergone deep brain stimulation surgery. Behavioral results revealed that promised rewards increased the difficulty in resolving conflict situations, thus replicating previous findings. Signal analyses locked on the imperative stimulus onset revealed the typical pattern of increased theta power in a conflict situation. However, this conflict-related modulation of theta power was not influenced by the size of the reward cued. We nonetheless identified a significant effect of the reward size on local functional organization (indexed by inter-trial phase clustering) of theta oscillations, with higher organization associated with high rewards while resolving conflict. When focusing on the period following the onset of the reward cue, we unveiled a stronger beta power decrease in higher reward conditions. However, these LFPs results were not correlated to behavioral results. Our study suggests that the STN is involved in how reward information can influence computations during conflict resolution. However, considering recent studies as well as the present results, we suspect that these effects are subtle.
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Economic decision-making is disrupted in individuals with gambling disorder, an addictive behavior observed in Parkinson’s disease (PD) patients receiving dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition of impulsive behaviors; however, its role in impulse control disorders and addiction is still unclear. Here, we recorded STN local field potentials (LFPs) in PD patients with and without gambling disorder during an economic decision-making task. Reaction times analysis showed that for all patients, the decision whether to risk preceded task onset. We compared then for both groups the STN LFP preceding high- and low-risk economic decisions. We found that risk avoidance in gamblers correlated with larger STN LFP low-frequency (<12-Hz) fluctuations preceding task onset. In particular, the amplitude of low-frequency LFP fluctuations carried significant information about future decisions. Decisions of patients not affected by gambling disorder were instead not correlated with pretask STN LFP. Our results suggest that STN activity preceding task onset affects risk decisions by preemptively inhibiting attraction to high but unlikely rewards in favor of a long-term payoff.
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It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying time until the right decision can be made. Using the drift diffusion model of decision making, we found that trial-to-trial increases in mPFC activity (EEG theta power, 4-8 Hz) were related to an increased threshold for evidence accumulation (decision threshold) as a function of conflict. Deep brain stimulation of the STN in individuals with Parkinson's disease reversed this relationship, resulting in impulsive choice. In addition, intracranial recordings of the STN area revealed increased activity (2.5-5 Hz) during these same high-conflict decisions. Activity in these slow frequency bands may reflect a neural substrate for cortico-basal ganglia communication regulating decision processes.
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Deep brain stimulation (DBS) of the subthalamic nucleus markedly improves the motor symptoms of Parkinson's disease, but causes cognitive side effects such as impulsivity. We showed that DBS selectively interferes with the normal ability to slow down when faced with decision conflict. While on DBS, patients actually sped up their decisions under high-conflict conditions. This form of impulsivity was not affected by dopaminergic medication status. Instead, medication impaired patients' ability to learn from negative decision outcomes. These findings implicate independent mechanisms leading to impulsivity in treated Parkinson's patients and were predicted by a single neurocomputational model of the basal ganglia.
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Pathological gambling develops in up to 8% of patients with Parkinson's disease. Although the pathophysiology of gambling remains unclear, several findings argue for a dysfunction in the basal ganglia circuits. To clarify the role of the subthalamic nucleus in pathological gambling, we studied its activity during economics decisions. We analyzed local field potentials recorded from deep brain stimulation electrodes in the subthalamic nucleus while parkinsonian patients with (n = 8) and without (n = 9) pathological gambling engaged in an economics decision-making task comprising conflictual trials (involving possible risk-taking) and non conflictual trials. In all parkinsonian patients, subthalamic low frequencies (2-12 Hz) increased during economics decisions. Whereas, in patients without gambling, low-frequency oscillations exhibited a similar pattern during conflictual and non conflictual stimuli, in those with gambling, low-frequency activity increased significantly more during conflictual than during non conflictual stimuli. The specific low-frequency oscillatory pattern recorded in patients with Parkinson's disease who gamble could reflect a subthalamic dysfunction that makes their decisional threshold highly sensitive to risky options. When parkinsonian patients process stimuli related to an economics task, low-frequency subthalamic activity increases. This task-related change suggests that the cognitive-affective system that drives economics decisional processes includes the subthalamic nucleus. The specific subthalamic neuronal activity during conflictual decisions in patients with pathological gambling supports the idea that the subthalamic nucleus is involved in behavioral strategies and in the pathophysiology of gambling. © 2013 Movement Disorder Society.