Roles of subthalamic nucleus and DBS in reinforcement conflict-based decision making (Frank 2006)

 Download zip file 
Help downloading and running models
Accession:97972
Deep brain stimulation (DBS) of the subthalamic nucleus dramatically improves the motor symptoms of Parkinson's disease, but causes cognitive side effects such as impulsivity. This model from Frank (2006) simulates the role of the subthalamic nucleus (STN) within the basal ganglia circuitry in decision making. The STN dynamically modulates network decision thresholds in proportion to decision conflict. The STN ``hold your horses'' signal adaptively allows the system more time to settle on the best choice when multiple options are valid. The model also replicates effects in Parkinson's patients on and off DBS in experiments designed to test the model (Frank et al, 2007).
Reference:
1 . Frank MJ (2006) Hold your horses: a dynamic computational role for the subthalamic nucleus in decision making. Neural Netw 19:1120-36 [PubMed]
2 . Frank MJ, Samanta J, Moustafa AA, Sherman SJ (2007) Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism Science 318(5854):1309-1312 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Connectionist Network;
Brain Region(s)/Organism:
Cell Type(s): Neostriatum spiny direct pathway neuron; Substantia nigra pars compacta dopaminergic cell; Subthalamus nucleus projection neuron; Globus pallidus neuron;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Dopamine; Gaba; Glutamate;
Simulation Environment: Emergent/PDP++;
Model Concept(s): Simplified Models; Synaptic Plasticity; Rate-coding model neurons; Parkinson's; Reinforcement Learning; Action Selection/Decision Making; Deep brain stimulation; Rebound firing;
Implementer(s): Frank, Michael [mfrank at u.arizona.edu];
Search NeuronDB for information about:  Neostriatum spiny direct pathway neuron; Substantia nigra pars compacta dopaminergic cell; Dopamine; Gaba; Glutamate;
  
For any questions, comments or bug reports please email mfrank@u.arizona.edu

NOTE: The models are set up to run under PDP++ 3.2a08, and the
 analysis scripts configured to work under Linux.  If you are
 running an older version you may have to download and install the
 more recent version of PDP/leabra from
 ftp://grey.colorado.edu/pub/oreilly/pdp++/. If you get error messages
 when you load the project, please let me know or try to download that
 version (newer PDP++ versions should work too -- but this project has
 not yet been converted to emergent). The below instructions assume
 some basic experience with the software; please refer to the O'Reilly
 & Munakata (2000) textbook for an introduction.

----------------------------------------------------------------------------

Simulating effects of Deep Brain Stimulation of the Subthalamic
Nucleus on Probabilistic Decision Making 

leabra++ Conflict_DBS.proj.gz

This project replicates the basic effects of removing the STN from
processing (ie., a "lesion"), and applying external high frequency
activation to the STN (DBS of the STN) on conflict-induced slowing, as
described in Frank et al (2007), Science and Frank (2006), Neural
Networks. (The same models were also used to simulate Parkinson's
disease and dopamine medication effects on Go and NoGo learning, and
performance in the Weather Prediction task and probabilistic reversal,
as described in Frank et al 2004, Science, and Frank (2005), J Cog
Neurosci. For those simulations, please refer to the README file and
associated projects in BG_DA_Learn.zip, also available on ModelDB or
via email).

The network is trained with two stimuli (A and B), associated with
probabilistic feedback, using the Train_Prob process. After each epoch
of training, the network is tested twice using the Epoch_1 and Epoch_4
processes. In both of these tests the network weights are frozen (they
do not change as a function of choice) so as to assess performance of
the network on test trials without allowing them to learn about these
test trials. In this way we can assess conflict based responding after
various stages of training without contaminating subsequent results.
In Epoch_1, the network is tested with the single cues from the
training environment that are associated with 80 or 60% reward
probability. In Epoch_4, the network is tested with a high conflict
combination of the two cues, each associated with a different response
(one is 80% R1 while the other is 60% R2). This is analogous to the
situation in which healthy individuals show slowed reaction times,
relative to low conflict trials. To increase reliability of the
measure, each of the epochs consists of two identical (low or high
conflict) trials -- in principle, the same network with the same
weights could select different responses in these two trials, and with
different reaction times, simply due to noise in unit activity).

***REACTION TIME MEASURES***

To measure each network's reaction time for the different trial types,
 use the Cycle_1 and Cycle_4 Graphlogs, which monitor the activity
 levels of each layer in the network after every cycle of network
 processing within each trial (where again Cycle_1 refers to low
 conflict and Cycle_4 is high conflict). We will keep track of these
 activity levels and compute BG model reaction times in terms of the
 number of cycles until the output activation exceeds a threshold (see
 below). First, make sure that the network is in the desired condition
 (intact, lesion, DBS, meds, etc.) by selecting a setting on the
 "SelectEdit" control panel.  Clicking "intact Run" will put the
 network into its intact state, to simulate normal network
 functioning.  Checking the box marked "STN lesion" will remove the
 STN from processing altogether.  The "DBS" condition adds external
 high frequency stimulation to the STN, functionally reducing its
 ability to respond adaptively to its cortical inputs (see Supplement
 of Frank et al, 2007). The "PD" button will reduce DA in the SNc
 layer, so that only 2 of the 4 units project DA to the Striatum, and
 limiting DA bursts during positive feedback.  And finally, selecting
 "meds" will increase DA relative to the PD networks and also reduce
 the DA dips during negative feedback. These were the same
 manipulations performed in Frank, 2005 and Frank et al 2004. 

Ater selecting the desired model condition, click on LogFile > Set
 Save File in the the Cycle_1 and Cycle_4 graphlogs and name the new
 .log file (e.g., intact_c1.log). This will save all information
 collected into the corresponding file for later analysis. Set the
 number of networks to train (each with its own set of random initial
 weights) in the Batch_Prob control panel by entering a number in
 "batch.max" (25 or 50 should be sufficient), hit "Reinit" and then
 "Run."

(Note: simulations will run considerably faster if you turn off the
network and graphlog updating displays, by checking off the button
marked Display on the top left corner of the network window).


Once all networks have been run, you can analyze the resulting log
file and determine when each response was made. We have provided a css
script which does this for you (css is the scripting language
associated with pdp). The script, called
"anal_rt_thal_e20.css", analyzes model reaction times, in terms of the
number of network processing cycles (where each cycle consists of a
single update of units membrane potentials and activity states) until
a response is selected by BG circuitry. Because the BG (GPi) is
tonically inhibiting the thalamus, the best measure of when a response
is selected is when a given Thalamic unit becomes disinhibited (no
longer has zero activation; in contrast, cortical units have noisy
activation during the entire settling process so if activation exceeds
some value for a single cycle in cortex that should not necessarily be
taken to indicate that a response was selected). Once the thalamus is
disinhibited and a response selected, a single thalamic unit's
activity rises sharply toward maximal firing rate (1.0). We used an
arbitrary threshold of 50% maximal firing rate for a given Thalmus
unit in order to quantify the reaction time -- but this arbitrary
value does not influence the general pattern of results. 

To use this script, type from a console "anal_rt_thal_e20.css
<logfilename.log>". After churning away for a bit, this will produce a
new file with the extension .gort20 (gort refers to the reaction time
at which a "Go" signal facilitated a response).  This file contains
the reaction time information (number of cycles) for every network
that was run in the batch. Note that the script computes reaction
times only after 20 epochs of training (hence the "e20" in the script
name and gort20 in the output filename), once they have learned the
probabilistic associations. Optionally, one can use the
"anal_rt_thal.css" script (ie without the "e20") to compute RT's for
every trial across training, which produces qualitatively similar
results (but as expected, conflict effects are maximal after
learning).
 
 After a .gort20 file is created, another script can be used to
 average these results across all networks in a batch (assuming you
 have the old unixstat package with "dtsem" installed -- otherwise you
 will have to use your own spreadsheet or other analysis tool for
 theses stats).  This script is called "analrt.sh", and the resulting
 file will have the extension .gort20.dt.  For example, type
 "analrt.sh intact_c1.log.gort20."  The .dt output file will contain
 four columns of information.  The first colum is simply the letters
 "GM," and can be ignored.  The three columns of interest, from left
 to right, are the number of trials for which a response was made (ie
 a thalamus unit's activation surpassed the threshold within the
 maximum of 200 cycles -- after this time we consider this to be a
 non-response), followed by the mean number of cycles until the
 response was selected, and finally, the standard error of the
 mean. Your results should show that lesion and DBS nets are
 considerably faster than the other networks when faced with high
 conflict (_c4 results), and also somewhat faster than their low
 conflict reaction times. This high conflict speeding effect was
 observed in patients on DBS. In the model this occurs due to the
 presence of multiple Go signals and simulated DA increases during
 win/win conditions (SNC unit firing rate levels were increased from
 the normal tonic level of 0.5 to 0.7 during the test phase to
 simulate the presence of a rewarding stimulus. As described in the
 supplement of Frank et al (2007), if DA levels are not increased and
 remain at the tonic level, STN dysfunction still reduces
 conflict-induced slowing but does not actually cause high-conflict
 speeding, as we observed for lose/lose high conflict choices in DBS
 patients).

***ACCURACY MEASURES***

 To measure the network's accuracy, again make sure that the network
 is in the desired condition by selecting "intact," "DBS," etc., on
 the control panel as described above. After selecting the desired
 condition, find the Epoch_1 and Epoch_4 Graphlogs.  Select "Save Set
 File" and name the new .log file (e.g, "intact_e1.log" (low conflict)
 and "intact_e4.log" (high conflict)). Then, in the Batch_prob
 process, set the number of networks to run and hit Reinit and Run.
 After the model has finished running the batch, accuracy results can
 be analyzed by using the following scripts: analtst.sh (on the
 Epoch_1 .log file) and analtst_conf.sh (on the Epoch_4 .log file).
 For example, for low conflict accuracy with the intact network, type
 "analtst.sh intact_e1.log." For the high conflict (e4) logs, use
 analtst_conf.sh instead of analtst.sh (simply because network error
 is indexed in a different column in the e4 logs and the analysis
 script has to know which column to average). This will output a list
 of four columns in a new file with the extension ".log.dt".  From
 left to right the columns are: epoch number, number of networks
 averaged across, mean number of errors (out of 2 possible for each
 test), and standard error.  For a general idea of how well a network
 has done, it is easiest to look at the last row in this list, after
 it has received all its training. If the network has an average error
 of roughly 1.0 (out of 2.0 max, this is 50%), it is performing at
 chance.  You should see that the intact network does not suffer
 nearly as much in accuracy from the high conflict (e4) condition,
 whereas the STN lesioned network performs well in low but not high
 conflict trials. DBS networks with external stimulation do not suffer
 as much as STN lesioned networks (for discussion, see supplement of
 Frank et al, 2007).


***PLOTTING LAYER ACTIVITY LEVELS DURING SELECTION***

 One last script that can be run on the .log files is called
 analcycles.sh. This script averages activity levels in the different
 layers of the network as a function of time (cycles), averaging unit
 activity across each layer indpendently, and across all
 networks. This enables you to plot the different layer activity
 levels as a function of time during response selection, using your
 favorite graphing program.  For example, type "analycycles.sh
 intact_c1.log."  This will output a file containing 16 columns, with
 the extension ".cyc.dt".  The first column of the output is cycle
 number, the second column is the number of trials that has been
 averaged across (across different networks and multiple trials for
 each network).  The third and fourth columns are mean and standard
 error of STN activity, respectively. Similarly, columns
 5,7,9,11,13,15 are mean GPe, GPi, Motor cortex, Thalamus, Output
 unit1, and Output unit2, respectively.  Each of these columns is
 followed by a column of the standard error for that layer.


*** SETTING TONIC DA LEVELS; OSCILLATIONS AND PARKINSON"S TREMOR ***


Tonic DA levels are set in the control panel. Default = .03 means that
this is the external input, which translates to around 0.5 activity
levels in the SNc units (but these are also noisy).  You should also
see that if you set tonic levels to 0, some oscillations should be
observed in STN and GP layers on some trials (corresponding to
Parkinson's tremor). You can look at these more carefully in the cycle
graph logs where activity levels of the various layers are
recorded. These oscillations are more reliably observed for high
conflict trials (due to greater overall input from cortex to STN,
which is what causes the rebound STN burst activity associated with
each oscillation (Frank, 2006)). The oscillations can also be more
reliably induced in a network with more competing alternatives, such
as the 4-alternative choice model in Frank (2006). 

Frank MJ (2006) Hold your horses: a dynamic computational role for the subthalamic nucleus in decision making. Neural Netw 19:1120-36[PubMed]

References and models cited by this paper

References and models that cite this paper

Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366-75 [PubMed]

Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:266-71

Alexander GE, Crutcher MD (1990) Preparation for movement: neural representations of intended direction in three motor areas of the monkey. J Neurophysiol 64:133-50 [PubMed]

Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357-81 [PubMed]

Amirnovin R, Williams ZM, Cosgrove GR, Eskandar EN (2004) Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients. J Neurosci 24:11302-6

Aron AR, Poldrack RA (2006) Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J Neurosci 26:2424-33

Ashby FG, Noble S, Filoteo JV, Waldron EM, Ell SW (2003) Category learning deficits in Parkinson's disease. Neuropsychology 17:115-24

Aston-Jones G, Cohen JD (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403-50

Aubert I, Ghorayeb I, Normand E, Bloch B (2000) Phenotypical characterization of the neurons expressing the D1 and D2 dopamine receptors in the monkey striatum. J Comp Neurol 418:22-32 [PubMed]

Bar-Gad I, Morris G, Bergman H (2003) Information processing, dimensionality reduction and reinforcement learning in the basal ganglia. Prog Neurobiol 71:439-73

Basso MA, Wurtz RH (2002) Neuronal activity in substantia nigra pars reticulata during target selection. J Neurosci 22:1883-94

Baunez C, Humby T, Eagle DM, Ryan LJ, Dunnett SB, Robbins TW (2001) Effects of STN lesions on simple vs choice reaction time tasks in the rat: preserved motor readiness, but impaired response selection. Eur J Neurosci 13:1609-16

Baunez C, Robbins TW (1997) Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats. Eur J Neurosci 9:2086-99

Bayer HM, Glimcher PW (2005) Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron 47:129-41 [PubMed]

Beiser DG, Houk JC (1998) Model of cortical-basal ganglionic processing: encoding the serial order of sensory events. J Neurophysiol 79:3168-88 [Journal] [PubMed]

Benazzouz A, Hallett M (2000) Mechanism of action of deep brain stimulation. Neurology 55:S13-6

Bergman H, Feingold A, Nini A, Raz A, Slovin H, Abeles M, Vaadia E (1998) Physiological aspects of information processing in the basal ganglia of normal and parkinsonian primates. Trends Neurosci 21:32-8 [PubMed]

Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436-8 [PubMed]

Bergman H, Wichmann T, Karmon B, DeLong MR (1994) The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 72:507-20 [Journal] [PubMed]

Bevan MD, Magill PJ, Terman D, Bolam JP, Wilson CJ (2002) Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network. Trends Neurosci 25:525-31 [PubMed]

Bogacz R, Brown E, Moehlis J, Holmes P, Cohen JD (2006) The physics of optimal decision making: a formal analysis of models of performance in two-alternative forced-choice tasks. Psychol Rev 113:700-65

Bokura H, Yamaguchi S, Kobayashi S (2005) Event-related potentials for response inhibition in Parkinson's disease. Neuropsychologia 43:967-75

Boraud T, Bezard E, Bioulac B, Gross CE (2002) From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control. Prog Neurobiol 66:265-83

Botvinick MM, Braver TS, Barch DM, Carter CS, Cohen JD (2001) Conflict monitoring and cognitive control. Psychol Rev 108:624-52 [PubMed]

Brown E, Gao J, Holmes P, Bogacz R, Gilzenrat M, Cohen JD (2005) Simple neural networks that optimize decisions Int J Bifurcat Chaos 15:803-826

Brown J, Bullock D, Grossberg S (1999) How the basal ganglia use parallel excitatory and inhibitory learning pathways to selectively respond to unexpected rewarding cues. J Neurosci 19:10502-11 [PubMed]

Brown JW, Bullock D, Grossberg S (2004) How laminar frontal cortex and basal ganglia circuits interact to control planned and reactive saccades. Neural Netw 17:471-510 [PubMed]

Brown RG, Marsden CD (1988) Internal versus external cues and the control of attention in Parkinson's disease. Brain 111 ( Pt 2):323-45

Chamberlain SR, Muller U, Blackwell AD, Clark L, Robbins TW, Sahakian BJ (2006) Neurochemical modulation of response inhibition and probabilistic learning in humans. Science 311:861-3

Charbonneau D, Riopelle RJ, Beninger RJ (1996) Impaired incentive learning in treated Parkinson's disease. Can J Neurol Sci 23:271-8

Choi WY, Balsam PD, Horvitz JC (2005) Extended habit training reduces dopamine mediation of appetitive response expression. J Neurosci 25:6729-33

Clarke HF, Dalley JW, Crofts HS, Robbins TW, Roberts AC (2004) Cognitive inflexibility after prefrontal serotonin depletion. Science 304:878-80

Cools R (2006) Dopaminergic modulation of cognitive function-implications for L-DOPA treatment in Parkinson's disease. Neurosci Biobehav Rev 30:1-23 [PubMed]

Cools R, Barker RA, Sahakian BJ, Robbins TW (2001) Mechanisms of cognitive set flexibility in Parkinson's disease. Brain 124:2503-12 [PubMed]

Cools R, Barker RA, Sahakian BJ, Robbins TW (2001) Enhanced or impaired cognitive function in Parkinson's disease as a function of dopaminergic medication and task demands. Cereb Cortex 11:1136-43 [PubMed]

Cools R, Barker RA, Sahakian BJ, Robbins TW (2003) L-Dopa medication remediates cognitive inflexibility, but increases impulsivity in patients with Parkinson's disease. Neuropsychologia 41:1431-41 [PubMed]

Crutcher MD, Alexander GE (1990) Movement-related neuronal activity selectively coding either direction or muscle pattern in three motor areas of the monkey. J Neurophysiol 64:151-63 [Journal] [PubMed]

Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B (2002) Motivation, reward, and Parkinson's disease: influence of dopatherapy. Neuropsychologia 40:2257-67

Daw ND, Kakade S, Dayan P (2005) Opponent interactions between serotonin and dopamine. Neural Netw 15:603-16 [PubMed]

Delgado MR, Locke HM, Stenger VA, Fiez JA (2003) Dorsal striatum responses to reward and punishment: effects of valence and magnitude manipulations. Cogn Affect Behav Neurosci 3:27-38

Delgado MR, Miller MM, Inati S, Phelps EA (2005) An fMRI study of reward-related probability learning. Neuroimage 24:862-73 [PubMed]

DeLong MR (1990) Primate models of movement disorders of basal ganglia origin. Trends Neurosci 13:281-5 [PubMed]

Desbonnet L, Temel Y, Visser-Vandewalle V, Blokland A, Hornikx V, Steinbusch HW (2004) Premature responding following bilateral stimulation of the rat subthalamic nucleus is amplitude and frequency dependent. Brain Res 1008:198-204

Frank MJ (2005) When and when not to use your subthalamic nucleus: Lessons from a computational model of the basal ganglia Modelling Natural Action Selection: Proceedings of an International Workshop :53-60

Frank MJ (2005) Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. J Cogn Neurosci 17:51-72 [Journal] [PubMed]

   Dynamic dopamine modulation in the basal ganglia: Learning in Parkinson (Frank et al 2004,2005) [Model]

Frank MJ, Claus ED (2006) Anatomy of a decision: striato-orbitofrontal interactions in reinforcement learning, decision making, and reversal. Psychol Rev 113:300-26

Frank MJ, Loughry B, O'Reilly RC (2001) Interactions between frontal cortex and basal ganglia in working memory: a computational model. Cogn Affect Behav Neurosci 1:137-60 [PubMed]

Frank MJ, O'reilly RC (2006) A mechanistic account of striatal dopamine function in human cognition: psychopharmacological studies with cabergoline and haloperidol. Behav Neurosci 120:497-517 [PubMed]

Frank MJ, O'Reilly RC, Curran T (2006) When memory fails, intuition reigns: midazolam enhances implicit inference in humans. Psychol Sci 17:700-7

Frank MJ, Seeberger LC, O`Reilly RC (2004) By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 306:1940-3 [Journal] [PubMed]

   Dynamic dopamine modulation in the basal ganglia: Learning in Parkinson (Frank et al 2004,2005) [Model]

Frank MJ, Woroch BS, Curran T (2005) Error-related negativity predicts reinforcement learning and conflict biases. Neuron 47:495-501 [PubMed]

Gerfen CR (1992) The neostriatal mosaic: multiple levels of compartmental organization in the basal ganglia. Annu Rev Neurosci 15:285-320 [PubMed]

Gerfen CR (2000) Molecular effects of dopamine on striatal-projection pathways. Trends Neurosci 23:S64-70 [PubMed]

Gerfen CR, Keefe KA, Gauda EB (1995) D1 and D2 dopamine receptor function in the striatum: coactivation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons. J Neurosci 15:8167-76 [PubMed]

Gerfen CR, Wilson CJ (1996) The basal ganglia. Handbook of Chemical Neuroanatomy, Swanson LW:Et Al, ed. pp.371

Gold JI, Shadlen MN (2002) Banburismus and the brain: decoding the relationship between sensory stimuli, decisions, and reward. Neuron 36:299-308

Gotham AM, Brown RG, Marsden CD (1988) 'Frontal' cognitive function in patients with Parkinson's disease 'on' and 'off' levodopa. Brain 111 ( Pt 2):299-321

Gurney K, Prescott TJ, Redgrave P (2001) A computational model of action selection in the basal ganglia. I. A new functional anatomy. Biol Cybern 84:401-10 [PubMed]

   Population-level model of the basal ganglia and action selection (Gurney et al 2001, 2004) [Model]

Gurney KN, Humphries M, Wood R, Prescott TJ, Redgrave P (2004) Testing computational hypotheses of brain systems function: a case study with the basal ganglia. Network 15:263-90 [PubMed]

   Population-level model of the basal ganglia and action selection (Gurney et al 2001, 2004) [Model]

Harley T (2004) Does cognitive neuropsychology have a future? Cognitive Neuropsychol 21:3-16

Hazy TE, Frank MJ, O'Reilly RC (2006) Banishing the homunculus: making working memory work. Neuroscience 139:105-18

Hebb DO (1949) The Organization Of Behavior

Hernandez-Lopez S, Bargas J, Surmeier DJ, Reyes A, Galarraga E (1997) D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an L-type Ca2+ conductance. J Neurosci 17:3334-42 [PubMed]

Hernandez-Lopez S, Tkatch T, Perez-Garci E, Galarraga E, Bargas J, Hamm H, Surmeier DJ (2000) D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade. J Neurosci 20:8987-95 [PubMed]

Hikosaka O (1994) Role of basal ganglia in control of innate movements, learned behaviour and cognition The basal ganglia iv: New ideas and data on structure and function, Percheron G:McKenzie J:Feger J, ed. pp.589

Holroyd CB, Coles MG (2002) The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity. Psychol Rev 109:679-709

Houk JC (2005) Agents of the mind. Biol Cybern 92:427-37

Houk JC, Adams JL, Barto AG (1995) A model of how the basal ganglia generate and use neural signals that predict reinforcement Models of information processing in the basal ganglia, Houk JC:Davis JL:Beiser DG, ed. pp.233

Houk JC, Wise SP (2004) Distributed modular architectures linking basal ganglia, cerebellum, and cerebral cortex: their role in planning and controlling action. Cereb Cortex 5:95-110 [PubMed]

Jackson GM, Jackson SR, Harrison J, Henderson L, Kennard C (1995) Serial reaction time learning and Parkinson's disease: evidence for a procedural learning deficit. Neuropsychologia 33:577-93

Jiang H, Stein BE, McHaffie JG (2003) Opposing basal ganglia processes shape midbrain visuomotor activity bilaterally. Nature 423:982-6

Joel D, Weiner I (1999) Striatal contention scheduling and the split circuit scheme of basal ganglia-thalamocortical circuitry: From anatomy to behaviour nceptual advancesin brain research: Brain dynamics and the striatal complex, Miller R:Wickens JR, ed. pp.209

Karachi C, Yelnik J, Tande D, Tremblay L, Hirsch EC, Francois C (2005) The pallidosubthalamic projection: an anatomical substrate for nonmotor functions of the subthalamic nucleus in primates. Mov Disord 20:172-80

Kawaguchi Y, Wilson CJ, Emson PC (1990) Projection subtypes of rat neostriatal matrix cells revealed by intracellular injection of biocytin. J Neurosci 10:3421-38 [PubMed]

Kish SJ, Shannak K, Hornykiewicz O (1988) Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med 318:876-80

Knowlton BJ, Mangels JA, Squire LR (1996) A neostriatal habit learning system in humans. Science 273:1399-402 [PubMed]

Kolomiets BP, Deniau JM, Mailly P, Menetrey A, Glowinski J, Thierry AM (2001) Segregation and convergence of information flow through the cortico-subthalamic pathways. J Neurosci 21:5764-72

Lavoie B, Parent A (1990) Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. J Comp Neurol 299:1-16

Lei W, Jiao Y, Del Mar N, Reiner A (2004) Evidence for differential cortical input to direct pathway versus indirect pathway striatal projection neurons in rats. J Neurosci 24:8289-99

Levesque M, Parent A (2005) The striatofugal fiber system in primates: a reevaluation of its organization based on single-axon tracing studies. Proc Natl Acad Sci U S A 102:11888-93

Levy R, Hutchison WD, Lozano AM, Dostrovsky JO (2000) High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor. J Neurosci 20:7766-75 [PubMed]

Maddox WT, Filoteo JV (2001) Striatal contributions to category learning: quantitative modeling of simple linear and complex nonlinear rule learning in patients with Parkinson's disease. J Int Neuropsychol Soc 7:710-27 [PubMed]

Magill PJ, Bolam JP, Bevan MD (2001) Dopamine regulates the impact of the cerebral cortex on the subthalamic nucleus-globus pallidus network. Neuroscience 106:313-30 [PubMed]

Magill PJ, Sharott A, Bevan MD, Brown P, Bolam JP (2004) Synchronous unit activity and local field potentials evoked in the subthalamic nucleus by cortical stimulation. J Neurophysiol 92:700-14 [Journal]

Mahon S, Casassus G, Mulle C, Charpier S (2003) Spike-dependent intrinsic plasticity increases firing probability in rat striatal neurons in vivo. J Physiol 550:947-59

Maurice N, Deniau JM, Glowinski J, Thierry AM (1998) Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the corticosubthalamic circuits. J Neurosci 18:9539-46 [PubMed]

McAuley JH (2003) The physiological basis of clinical deficits in Parkinson's disease. Prog Neurobiol 69:27-48

Mehta MA, Swainson R, Ogilvie AD, Sahakian J, Robbins TW (2001) Improved short-term spatial memory but impaired reversal learning following the dopamine D(2) agonist bromocriptine in human volunteers. Psychopharmacology (Berl) 159:10-20

Meissner W, Leblois A, Hansel D, Bioulac B, Gross CE, Benazzouz A, Boraud T (2005) Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations. Brain 128:2372-82 [PubMed]

Middleton FA, Strick PL (2000) Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn 42:183-200

Middleton FA, Strick PL (2002) Basal-ganglia 'projections' to the prefrontal cortex of the primate. Cereb Cortex 12:926-35 [PubMed]

Miller W, Delong MR (1987) Altered tonic activity of neurons inthe globus pallidus and subthalamic nucleus in the primate MPTP model of Parkinsonism The Basal Ganglia, Carpenter MB:Jayaraman A, ed. pp.415

Mink JW (1996) The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol 50:381-425 [PubMed]

Nambu A, Kaneda K, Tokuno H, Takada M (2002) Organization of corticostriatal motor inputs in monkey putamen. J Neurophysiol 88:1830-42 [Journal]

Nambu A, Tokuno H, Hamada I, Kita H, Imanishi M, Akazawa T, Ikeuchi Y, Hasegawa N (2000) Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey. J Neurophysiol 84:289-300 [Journal] [PubMed]

Ni Z, Bouali-Benazzouz R, Gao D, Benabid AL, Benazzouz A (2000) Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat. Eur J Neurosci 12:4338-44 [PubMed]

Nocjar C, Roth BL, Pehek EA (2002) Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group. Neuroscience 111:163-76

O'Reilly RC (2001) Generalization in interactive networks: the benefits of inhibitory competition and Hebbian learning. Neural Comput 13:1199-241 [PubMed]

O'Reilly RC, Frank MJ (2006) Making working memory work: a computational model of learning in the prefrontal cortex and basal ganglia. Neural Comput 18:283-328

O'Reilly RC, Frank MJ, Hazy TE, Watz B (2007) PVLV: the primary value and learned value Pavlovian learning algorithm. Behav Neurosci 121:31-49

Oja E (1982) A simplified neuron model as a principal component analyzer. J Math Biol 15:267-73 [PubMed]

Oreilly RC (1996) Biologically plausible error-driven learning using local activation differences: The generalized recirculation algorithm Neural Comput 8:895-938

OReilly RC, Munakata Y (2000) Computational explorations in cognitive neuroscience: understanding the mind by simulating the brain

Orieux G, Francois C, Feger J, Hirsch EC (2002) Consequences of dopaminergic denervation on the metabolic activity of the cortical neurons projecting to the subthalamic nucleus in the rat. J Neurosci 22:8762-70

Pan WX, Schmidt R, Wickens JR, Hyland BI (2005) Dopamine cells respond to predicted events during classical conditioning: evidence for eligibility traces in the reward-learning network. J Neurosci 25:6235-42 [PubMed]

Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 20:128-54 [PubMed]

Parkinson JA, Dalley JW, Cardinal RN, Bamford A, Fehnert B, Lachenal G, Rudarakanchana N, Hal (2002) Nucleus accumbens dopamine depletion impairs both acquisition and performance of appetitive Pavlovian approach behaviour: implications for mesoaccumbens dopamine function. Behav Brain Res 137:149-63

Pasupathy A, Miller EK (2005) Different time courses of learning-related activity in the prefrontal cortex and striatum. Nature 433:873-6 [PubMed]

Picard N, Strick PL (2001) Imaging the premotor areas. Curr Opin Neurobiol 11:663-72

Picard N, Strick PL (2004) Motor areas of the medial wall: a review of their location and functional activation. Cereb Cortex 6:342-53

Pompeiano M, Palacios JM, Mengod G (1994) Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Brain Res Mol Brain Res 23:163-78

Pothos EN, Davila V, Sulzer D (1998) Presynaptic recording of quanta from midbrain dopamine neurons and modulation of the quantal size. J Neurosci 18:4106-18

Ratcliff R, Van Zandt T, McKoon G (1999) Connectionist and diffusion models of reaction time. Psychol Rev 106:261-300 [PubMed]

Raz A, Vaadia E, Bergman H (2000) Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine vervet model of parkinsonism. J Neurosci 20:8559-71

Redgrave P, Prescott TJ, Gurney K (1999) The basal ganglia: a vertebrate solution to the selection problem? Neuroscience 89:1009-23 [PubMed]

Ridley RM, Haystead TA, Baker HF (1981) An analysis of visual object reversal learning in the marmoset after amphetamine and haloperidol. Pharmacol Biochem Behav 14:345-51

Robertson GS, Vincent SR, Fibiger HC (1992) D1 and D2 dopamine receptors differentially regulate c-fos expression in striatonigral and striatopallidal neurons. Neuroscience 49:285-96

Rogers RD, Sahakian BJ, Hodges JR, Polkey CE, Kennard C, Robbins TW (1998) Dissociating executive mechanisms of task control following frontal lobe damage and Parkinson's disease. Brain 121 ( Pt 5):815-42

Rubchinsky LL, Kopell N, Sigvardt KA (2003) Modeling facilitation and inhibition of competing motor programs in basal ganglia subthalamic nucleus-pallidal circuits. Proc Natl Acad Sci U S A 100:14427-32 [PubMed]

Salin P, Hajji MD, Kerkerian-le Goff L (1996) Bilateral 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine pathway reproduces the effects of unilateral lesion on substance P but not on enkephalin expression in rat basal ganglia. Eur J Neurosci 8:1746-57

Samejima K, Ueda Y, Doya K, Kimura M (2005) Representation of action-specific reward values in the striatum. Science 310:1337-40

Sato F, Parent M, Levesque M, Parent A (2000) Axonal branching pattern of neurons of the subthalamic nucleus in primates. J Comp Neurol 424:142-52 [PubMed]

Satoh T, Nakai S, Sato T, Kimura M (2003) Correlated coding of motivation and outcome of decision by dopamine neurons. J Neurosci 23:9913-23 [PubMed]

Schall JD (2003) Neural correlates of decision processes: neural and mental chronometry. Curr Opin Neurobiol 13:182-6

Schultz W (2002) Getting formal with dopamine and reward. Neuron 36:241-63 [PubMed]

Schultz W, Dayan P, Montague PR (1997) A neural substrate of prediction and reward. Science 275:1593-9 [PubMed]

Shohamy D, Myers CE, Geghman KD, Sage J, Gluck MA (2006) L-dopa impairs learning, but spares generalization, in Parkinson's disease. Neuropsychologia 44:774-84 [PubMed]

Shohamy D, Myers CE, Grossman S, Sage J, Gluck MA (2005) The role of dopamine in cognitive sequence learning: evidence from Parkinson's disease. Behav Brain Res 156:191-9

Simen P, Cohen JD, Holmes P (2006) Rapid decision threshold modulation by reward rate in a neural network. Neural Netw 19:1013-26

Smith AG, Neill JC, Costall B (1999) The dopamine D3/D2 receptor agonist 7-OH-DPAT induces cognitive impairment in the marmoset. Pharmacol Biochem Behav 63:201-11

Smith-Roe SL, Kelley AE (2000) Coincident activation of NMDA and dopamine D1 receptors within the nucleus accumbens core is required for appetitive instrumental learning. J Neurosci 20:7737-42 [PubMed]

Stanford IM, Kantaria MA, Chahal HS, Loucif KC, Wilson CL (2005) 5-Hydroxytryptamine induced excitation and inhibition in the subthalamic nucleus: action at 5-HT(2C), 5-HT(4) and 5-HT(1A) receptors. Neuropharmacology 49:1228-34

Sutton RS (1988) Learning to predict by the method of temporal diferences Machine Learning 3:9-44

Swainson R, Rogers RD, Sahakian BJ, Summers BA, Polkey CE, Robbins TW (2000) Probabilistic learning and reversal deficits in patients with Parkinson's disease or frontal or temporal lobe lesions: possible adverse effects of dopaminergic medication. Neuropsychologia 38:596-612 [PubMed]

Terman D, Rubin JE, Yew AC, Wilson CJ (2002) Activity patterns in a model for the subthalamopallidal network of the basal ganglia. J Neurosci 22:2963-76 [Journal] [PubMed]

   Optimal deep brain stimulation of the subthalamic nucleus-a computational study (Feng et al. 2007) [Model]

Usher M, McClelland JL (2001) The time course of perceptual choice: the leaky, competing accumulator model. Psychol Rev 108:550-92 [PubMed]

Walderhaug E, Lunde H, Nordvik JE, Landro NI, Refsum H, Magnusson A (2002) Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals. Psychopharmacology (Berl) 164:385-91

Wichmann T, Bergman H, DeLong MR (1994) The primate subthalamic nucleus. I. Functional properties in intact animals. J Neurophysiol 72:494-506 [Journal] [PubMed]

Winstanley CA, Baunez C, Theobald DE, Robbins TW (2005) Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control. Eur J Neurosci 21:3107-16

Winstanley CA, Theobald DE, Dalley JW, Glennon JC, Robbins TW (2004) 5-HT2A and 5-HT2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion. Psychopharmacology (Berl) 176:376-85

Witt K, Pulkowski U, Herzog J, Lorenz D, Hamel W, Deuschl G, Krack P (2004) Deep brain stimulation of the subthalamic nucleus improves cognitive flexibility but impairs response inhibition in Parkinson disease. Arch Neurol 61:697-700

Wu Y, Richard S, Parent A (2000) The organization of the striatal output system: a single-cell juxtacellular labeling study in the rat. Neurosci Res 38:49-62

Xiang Z, Wang L, Kitai ST (2005) Modulation of spontaneous firing in rat subthalamic neurons by 5-HT receptor subtypes. J Neurophysiol 93:1145-57 [Journal]

Yeung N, Cohen JD, Botvinick MM (2004) The neural basis of error detection: conflict monitoring and the error-related negativity. Psychol Rev 111:931-59

Frank MJ, Samanta J, Moustafa AA, Sherman SJ (2007) Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism Science 318(5854):1309-1312 [Journal] [PubMed]

   Roles of subthalamic nucleus and DBS in reinforcement conflict-based decision making (Frank 2006) [Model]

Frank MJ, Scheres A, Sherman SJ (2007) Understanding decision-making deficits in neurological conditions: insights from models of natural action selection. Philos Trans R Soc Lond B Biol Sci 362:1641-54 [PubMed]

Hazy TE, Frank MJ, O'reilly RC (2007) Towards an executive without a homunculus: computational models of the prefrontal cortex-basal ganglia system. Philos Trans R Soc Lond B Biol Sci 362:1601-13 [PubMed]

Moustafa AA, Cohen MX, Sherman SJ, Frank MJ (2008) A Role for Dopamine in Temporal Decision Making and Reward Maximization in Parkinsonism J. Neurosci. 28(47):12294-12304 [Journal]

(148 refs)

Frank MJ, Samanta J, Moustafa AA, Sherman SJ (2007) Hold Your Horses: Impulsivity, Deep Brain Stimulation, and Medication in Parkinsonism Science 318(5854):1309-1312[PubMed]

References and models cited by this paper

References and models that cite this paper

Aron AR, Behrens TE, Smith S, Frank MJ, Poldrack RA (2007) Triangulating a cognitive control network using diffusion-weighted magnetic resonance imaging (MRI) and functional MRI. J Neurosci 27:3743-52 [PubMed]

Baunez C, Christakou A, Chudasama Y, Forni C, Robbins TW (2007) Bilateral high-frequency stimulation of the subthalamic nucleus on attentional performance: transient deleterious effects and enhanced motivation in both intact and parkinsonian rats. Eur J Neurosci 25:1187-94 [PubMed]

Baunez C, Robbins TW (1997) Bilateral lesions of the subthalamic nucleus induce multiple deficits in an attentional task in rats. Eur J Neurosci 9:2086-99 [PubMed]

Benabid AL (2003) Deep brain stimulation for Parkinson's disease. Curr Opin Neurobiol 13:696-706 [PubMed]

Bergman H, Wichmann T, DeLong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1436-8 [PubMed]

Bogacz R, Brown E, Moehlis J, Holmes P, Cohen JD (2006) The physics of optimal decision making: a formal analysis of models of performance in two-alternative forced-choice tasks. Psychol Rev 113:700-65 [PubMed]

Bogacz R, Gurney K (2007) The basal ganglia and cortex implement optimal decision making between alternative actions. Neural Comput 19:442-77 [PubMed]

Botvinick M, Nystrom LE, Fissell K, Carter CS, Cohen JD (1999) Conflict monitoring versus selection-for-action in anterior cingulate cortex. Nature 402:179-81 [PubMed]

Cools R, Altamirano L, D'Esposito M (2006) Reversal learning in Parkinson's disease depends on medication status and outcome valence. Neuropsychologia 44:1663-73 [PubMed]

Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE (2005) Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 62:1377-81 [PubMed]

Drapier S, Raoul S, Drapier D, Leray E, Lallement F, Rivier I, Sauleau P, Lajat Y, Edan G, Ve (2005) Only physical aspects of quality of life are significantly improved by bilateral subthalamic stimulation in Parkinson's disease. J Neurol 252:583-8 [PubMed]

Frank MJ (2005) Dynamic dopamine modulation in the basal ganglia: a neurocomputational account of cognitive deficits in medicated and nonmedicated Parkinsonism. J Cogn Neurosci 17:51-72 [Journal] [PubMed]

   Dynamic dopamine modulation in the basal ganglia: Learning in Parkinson (Frank et al 2004,2005) [Model]

Frank MJ (2006) Hold your horses: a dynamic computational role for the subthalamic nucleus in decision making. Neural Netw 19:1120-36 [Journal] [PubMed]

   Roles of subthalamic nucleus and DBS in reinforcement conflict-based decision making (Frank 2006) [Model]

Frank MJ, Moustafa AA, Haughey HM, Curran T, Hutchison KE (2007) Genetic triple dissociation reveals multiple roles for dopamine in reinforcement learning. Proc Natl Acad Sci U S A 104:16311-6 [PubMed]

Frank MJ, O`Reilly RC (2006) A mechanistic account of striatal dopamine function in cognition: Psychopharmacological studies with cabergoline and haloperidol Behav Neurosci. 120(3):497-517 [Journal] [PubMed]

Frank MJ, Seeberger LC, O`Reilly RC (2004) By carrot or by stick: cognitive reinforcement learning in parkinsonism. Science 306:1940-3 [Journal] [PubMed]

   Dynamic dopamine modulation in the basal ganglia: Learning in Parkinson (Frank et al 2004,2005) [Model]

Frank MJ, Woroch BS, Curran T (2005) Error-related negativity predicts reinforcement learning and conflict biases. Neuron 47:495-501 [PubMed]

Hershey T, Revilla FJ, Wernle A, Gibson PS, Dowling JL, Perlmutter JS (2004) Stimulation of STN impairs aspects of cognitive control in PD. Neurology 62:1110-4 [PubMed]

Humphries MD, Stewart RD, Gurney KN (2006) A physiologically plausible model of action selection and oscillatory activity in the basal ganglia. J Neurosci 26:12921-42 [Journal] [PubMed]

   Spiking neuron model of the basal ganglia (Humphries et al 2006) [Model]

Liu Y, Postupna N, Falkenberg J, Anderson ME (2008) High frequency deep brain stimulation: what are the therapeutic mechanisms? Neurosci Biobehav Rev 32:343-51 [Journal]

Lo CC, Wang XJ (2006) Cortico-basal ganglia circuit mechanism for a decision threshold in reaction time tasks. Nat Neurosci 9:956-63 [PubMed]

Meissner W, Leblois A, Hansel D, Bioulac B, Gross CE, Benazzouz A, Boraud T (2005) Subthalamic high frequency stimulation resets subthalamic firing and reduces abnormal oscillations. Brain 128:2372-82 [PubMed]

Mink JW (1996) The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol 50:381-425 [PubMed]

Obeso JA, Rodriguez-Oroz MC, Chana P, Lera G, Rodriguez M, Olanow CW (2000) The evolution and origin of motor complications in Parkinson's disease. Neurology 55:S13-20; discussion S21-3 [PubMed]

Orieux G, François C, Feger J, Hirsch EC (2002) Consequences of dopaminergic denervation on the metabolic activity of the cortical neurons projecting to the subthalamic nucleus in the rat. J Neurosci 22:8762-70 [PubMed]

Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 20:128-54 [PubMed]

Ratcliff R, Van Zandt T, McKoon G (1999) Connectionist and diffusion models of reaction time. Psychol Rev 106:261-300 [PubMed]

Saint-Cyr JA, Albanese A (2006) STN DBS in PD: selection criteria for surgery should include cognitive and psychiatric factors. Neurology 66:1799-800 [PubMed]

Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80:1-27 [Journal] [PubMed]

Simen P, Cohen JD, Holmes P (2006) Rapid decision threshold modulation by reward rate in a neural network. Neural Netw 19:1013-26 [PubMed]

Thobois S, Hotton GR, Pinto S, Wilkinson L, Limousin-Dowsey P, Brooks DJ, Jahanshahi M (2007) STN stimulation alters pallidal-frontal coupling during response selection under competition. J Cereb Blood Flow Metab 27:1173-84 [PubMed]

Tversky A, Shafir E (1992) Choice under conflict: The dynamics of deferred decision Psychol Sci 3(6):358-361

Usher M, McClelland JL (2001) The time course of perceptual choice: the leaky, competing accumulator model. Psychol Rev 108:550-92 [PubMed]

Uslaner JM, Robinson TE (2006) Subthalamic nucleus lesions increase impulsive action and decrease impulsive choice- mediation by enhanced incentive motivation? Eur J Neurosci 24:2345-54 [PubMed]

Winstanley CA, Baunez C, Theobald DE, Robbins TW (2005) Lesions to the subthalamic nucleus decrease impulsive choice but impair autoshaping in rats: the importance of the basal ganglia in Pavlovian conditioning and impulse control. Eur J Neurosci 21:3107-16 [PubMed]

Kato A, Morita K (2016) Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation. PLoS Comput Biol 12:e1005145 [Journal] [PubMed]

   Reinforcement Learning with Forgetting: Linking Sustained Dopamine to Motivation (Kato Morita 2016) [Model]

Moustafa AA, Cohen MX, Sherman SJ, Frank MJ (2008) A Role for Dopamine in Temporal Decision Making and Reward Maximization in Parkinsonism J. Neurosci. 28(47):12294-12304 [Journal]

(37 refs)