Talk 1:

Cognitive Functions of the Rat Subthalamic Nucleus

Christelle Baunez
 ^{CNRS INT UMR7289 / Aix-Marseille University, Marseille, France}

Within the basal ganglia, the subthalamic nucleus (STN) has long been considered a relay structure on the so-called ‘indirect pathway’ of the motor loop. For the two last decades, this view has changed when the hyperdirect pathway, connecting directly the cortex to the STN, has been highlighted and when data revealing non-motor deficits induced by manipulation of the STN started to accumulate. Here, our data obtained in the rat using STN lesions, high frequency stimulation or electrophysiological recording, will be summarized, demonstrating a critical role for the STN in attention (Baunez and Robbins, 1997; Baunez et al., 2007), control of inhibition (Baunez et al., 1995; Eagle and Baunez, 2010) and encoding of error in execution or in reward prediction (Lardeux et al., 2009).

Talk 2:

Deep Brain Stimulation Impairs On-line Executive Control in Parkinson’s Disease Patients

Fluchère, F.¹, Burle, B.², Vidal, F.², Azulay, J.-P.¹, Hasbroucq, T.^2
1 Pôle de Neurosciences Cliniques de la Timone, AP-HM and Aix-Marseille Université, Marseille, France
² Laboratoire de Neurosciences Cognitives, CNRS and Aix-Marseille Université, Marseille, France

High frequency DBS is thought to inactivate the subthalamic nuclei (STNs) and to restore the thalamo-cortical projections impaired by PD. This therapy dramatically improves PD motor symptoms. Recent fMRI data collected in healthy volunteers suggest that the STNs are involved in the urgent inhibition of ongoing actions. We reasoned that a side effect of DBS could be to impair this ability in PD patients. 16 PD patients treated by DBS for performed a conflict reaction time (RT) task involving thumb responses in 4 treatment conditions: Stimulator ON – Medication ON, Stimulator OFF – Medication ON, Stimulator ON – Medication OFF, Stimulator OFF – Medication OFF. The electromyographic activity of the response agonists was recorded and analysed, allowing the detection of partial errors, that is of subliminal activations of the muscles involved in erroneous responses. Responses were thus classified in 3 categories: correct, partial errors and overt errors. The medication exerted no notable effect on the patients’ performance. DBS shortened correct RT but increased the overt error rate and decreased the number of partial errors. Analyses of the temporal distribution of the 3 response categories revealed that the increase in overt error rate observed when the stimulator was ON was specifically due to a failure to detect, inhibit and correct partial errors before they resulted in overt erroneous responses. While it improves motor performance and shortens RT, DBS impairs the patients’ faculty to suppress erroneous response activations as revealed by their inability to counteract partial errors when the stimulator was ON.

Talk 3:

The Role of the Subthalamic Nucleus in Multiple Alternative Perceptual Decision Making
Revealed by 7T Structural and Functional MRI

Forstmann, B.U.¹, Turner, R.², van Maanen, L.¹, Bogacz, R.³, Schäfer, A.², Neumann, J.², Keuken, M.C.^1,2
¹ Cognitive Science Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
² Max-Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
³ Department of Computer Science, University of Bristol, Bristol, United Kingdom

Recently, quantitative mathematical and neuro-computational models have been developed that make predictions about the latent psychological processes and brain structures involved in multiple alternative decision-making. In particular, the subthalamic nucleus (STN), a small structure in the basal ganglia (BG), is hypothesized to become more active with an increasing amount of choice alternatives. This increase of activity is thought to reflect a decrease in baseline activity causing a delayed response of the output nuclei of the BG so that more evidence can be accumulated in favor of the correct response. In the present study, first the behavioral data were fit with the linear ballistic accumulator (LBA) model to capture the latent psychological processes involved in multiple alternative perceptual decision-making. Secondly, ultra-high resolution 7T functional and structural MRI data were collected to test our STN hypotheses. 7T functional data showed higher stimulus-related activation with an increase of choice alternatives only in the right STN. These results are also captured by the LBA model fits as the drift rate decreases and the threshold increases due to a prolonged decision process. In sum, the present study highlights the functional role of the STN in multiple alternative perceptual decision- making.

Talk 4:

Dopamine Agonists and the Suppression of Impulsive Actions in Parkinson’s Disease

Wylie, S.A.^1,2, Claassen, D.O.¹, Huizenga, H.M.³, Schewel, K.D.², Ridderinkhof, K.R.^3,4, Bashore, T.R.⁵, van den Wildenberg, W.P.M.^3
1 Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
² Neurology Department, University of Virginia Health Systems, Charlottesville, Virginia, USA
³ Amsterdam center for the study of adaptive control in brain and behaviour (Acacia),
Psychology Department, University of Amsterdam, Amsterdam, The Netherlands
⁴ Cognitive Science Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
⁵ School of Psychological Sciences, University of Northern Colorado, Greeley, Colorado, USA

The suppression of impulsive actions is an essential facet of human cognitive control that has been linked to frontal-basal ganglia circuitry. Basal ganglia dysfunction caused by Parkinson’s disease (PD) disrupts the proficiency of action suppression, but how pharmacotherapy for PD impacts impulsive action control is poorly understood. Dopamine agonists improve motor symptoms of PD, but also provoke impulsive-compulsive behaviors (ICB) in a subset of patients. We investigated whether dopamine agonist medication has a beneficial or detrimental effect on impulsive action control in PD. Thirty-eight PD patients, half of whom had current ICB, performed the Simon conflict task both on and withdrawn from their agonist medication. The Simon task measures one’s susceptibility to acting on spontaneous action impulses as well as the proficiency of suppressing these impulses as an act of cognitive control. Compared to the off state, patients on their agonist were no more susceptible to reacting impulsively, but they were less proficient at suppressing the interference caused by the activation of impulsive actions. Importantly, the impact of agonist medication on the suppression of impulsive actions depended on baseline performance in the off agonist state. Patients with active ICB were no more susceptible to making fast, impulsive response errors than patients without ICB, suggesting that problems with rash decision-making and reward-seeking behavior in this vulnerable subset of patients may not be related to impulsivity in the motor domain. Our findings show that agonist medication exerts a direct impact on a key component of action control.

Talk 5:

Deep-Brain Stimulation Improves Overriding
but not Re-engagement of Actions in Parkinson’s Disease

van den Wildenberg, W.P.M.¹, Ridderinkhof, K.R.^1,2, van Wouwe, N.C.³, Lubin, A.⁴, Siegel, A.⁴, Bashore, T.B.⁵, Wylie, S.A.^6
1 Amsterdam center for the study of adaptive control in brain and behaviour (Acacia), Psychology Department, University of Amsterdam, Amsterdam, The Netherlands
² Cognitive Science Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands
³ Department of Psychology, Leiden University, Leiden, The Netherlands
⁴ Neurology Department, University of Virginia Health Systems, Charlottesville, Virginia, USA
⁵ School of Psychological Sciences, University of Northern Colorado, Greeley, Colorado, USA
⁶ Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

Recent fMRI work and patient studies have shown that the basal ganglia play a key role in a distributed brain network that controls the non-specific abortion of motor responses. The aim of the present study was to specify the involvement of the basal ganglia in selective action control of responses as a more fine-grained form of cognitive control. We employed the stop-change task (based on a horse-race model) to investigate the ability to interrupt and change an ongoing overt action. Our sample consisted of 17 patients diagnosed with Parkinson's disease who received deep-brain stimulation (DBS) in the subthalamic nucleus (STN). All patients performed the tasks on and off stimulation to address the question whether stimulation is effective in improving stop-signal RT in the stop-change task. DBS shortened go reaction time (RT) related to generating overt responses. In addition DBS yielded shorter stop-signal RT, pointing toward improved inhibitory control over overt responses. Interestingly stimulation did not shorten response latencies to the change signal. This pattern is interpreted to suggest a functional dissociation of the effects of DBS on generating and inhibiting voluntary actions.