The subthalamic nucleus modulates the early phase of probabilistic classification learning

Abstract

Previous models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. Thirteen idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, and medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high-probability patterns, and more differentiated strategy analyses were used. The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high-probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention toward unacquainted content. The STN might play a role in balancing the short-term success against strategy optimization for improved long-term outcome. AbstractPrevious models proposed that the subthalamic nucleus (STN) is critical in the early phase of skill acquisition. We hypothesized that subthalamic deep brain stimulation modulates the learning curve in early classification learning. 13 idiopathic Parkinson's disease patients (iPD) with subthalamic deep brain stimulation (STN-DBS), 9 medically treated iPD, and 21 age-matched healthy controls were tested with a probabilistic classification task. STN-DBS patients were tested with stimulation OFF and ON, medically treated patients with medication OFF and ON, respectively. Performance and reaction time were analyzed on the first 100 consecutive trials as early learning phase. Moreover, data were separated for low and high probability patterns, and more differentiated strategy analyses were used.The major finding was a significant modulation of the learning curve in DBS patients with stimulation ON: although overall learning was similar to healthy controls, only the stimulation ON group showed a transient significant performance dip from trials '41-60' that rapidly recovered. Further analysis indicated that this might be paralleled by a modulation of the learning strategy, particularly on the high probability patterns. The reaction time was unchanged during the dip. Our study supports that the STN serves as a relay in early classification learning and directs attention towards unacquainted content.The STN might play a role in balancing the short-term success against strategy optimi...

Subthalamic stimulation modulates cortical motor network activity and synchronization in Parkinson’s disease

“…As local subthalamic beta band activity has been shown to be decreased with DBS (Kuhn et al, 2008;Eusebio et al, 2011), and beta band coupling of STN and cortex has been demonstrated particularly in the resting state and during akinesia (Sharott et al, 2005;Weiss et al, 2012), network effects on cortical beta band activity could be assumed during STN-DBS. Accordingly, beta band rhythm modulations may constitute a network-wide mechanism to balance motor execution and inhibition which is considered a core function of the subthalamo-cortical relay (Aron and Poldrack, 2006;Frank, 2006;Weiss et al, 2014). Similarly, the prefrontal cortices are involved in executive motor functions and include response selection in attentiondemanding motor skills particularly in motor programs that are not well rehearsed (Jahanshahi, 2013).…”

Inverse Relationship between Basal Pacemaker Neuron Activity and Aversive Long-Term Memory Formation in Lymnaea stagnalis

“…As spontaneously active neurons play key roles in motor and reward learning (Nelson et al, 2003, 2005; Pugh and Raman, 2008, 2009; Rueda-Orozco et al, 2009; Mure et al, 2012; Hull et al, 2013; Creed et al, 2014; Ranaldi, 2014; Weiss et al, 2014), better understanding of the full complement of plasticity mechanisms in the brain can have far-reaching impacts on addressing motor disorders and addiction. This study examined the role of basal neuronal activity of spontaneously active neurons in inhibition-induced memory formation.…”

“…Due to the high levels of resting activity, spontaneously active neurons possess several distinct biophysical properties, including higher intracellular Ca 2+ levels (Muri and Knöpfel, 1994) and enhanced activation of Ca 2+ -dependent signaling molecules such as Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) (Nelson et al, 2003, 2005). Accordingly, instead of excitation, synaptic inhibition is found to be a common trigger for neural plasticity in spontaneously active neurons in the cerebellum (Nelson et al, 2003, 2005; Pugh and Raman, 2008, 2009; Hull et al, 2013) and striatum (Rueda-Orozco et al, 2009) in motor learning and the ventral tegmentum area, and subthalamic nucleus in reward- and drug-related learning (Mure et al, 2012; Creed et al, 2014; Ranaldi, 2014; Weiss et al, 2014). In the cerebellar vestibular nucleus (Nelson et al, 2003, 2005) and Golgi neurons (Hull et al, 2013), reduction of tonically elevated CaMKII activity by synaptic inhibition induces persistent enhancement in firing activity.…”