A human prefrontal-subthalamic circuit for cognitive control

Abstract

The subthalamic nucleus is a key site controlling motor function in humans. Deep brain stimulation of the subthalamic nucleus can improve movements in patients with Parkinson's disease; however, for unclear reasons, it can also have cognitive effects. Here, we show that the human subthalamic nucleus is monosynaptically connected with cognitive brain areas such as the prefrontal cortex. Single neurons and field potentials in the subthalamic nucleus are modulated during cognitive processing and are coherent with 4-Hz oscillations in medial prefrontal cortex. These data predict that low-frequency deep brain stimulation may alleviate cognitive deficits in Parkinson's disease patients. In line with this idea, we found that novel 4-Hz deep brain stimulation of the subthalamic nucleus improved cognitive performance. These data support a role for the human hyperdirect pathway in cognitive control, which could have relevance for brain-stimulation therapies aimed at cognitive symptoms of human brain disease.awx300media15660002226001.

Cognitive control involves theta power within trials and beta power across trials in the prefrontal-subthalamic network

“…To our knowledge, no prior work has shown increased synchrony between these two brain regions when participants are instructed to completely withhold an action. These data therefore lend the strongest support yet to the hypothesis that mPFC-STN theta synchrony conveys an anti-kinetic signal that can either cancel a movement entirely or slow down a response in the presence of conflict (Cavanagh et al, 2011; Cohen and Cavanagh, 2011; Nigbur et al, 2011; Rae et al, 2015; Kelley et al, 2018). …”

“…The STN receives afferent connections from cortical regions involved in cognitive control (Alexander et al, 1986; Aron et al, 2007; Kelley et al, 2018), and projects efferent connections to other basal ganglia structures involved in movement inhibition (Albin et al, 1989; DeLong, 1990). Beta oscillations (10–30 Hz) within the STN regulate both motor and non-motor actions and increase when individuals must cancel or slow down a pre-planned action (Kühn et al, 2004; Brittain et al, 2012; Leventhal et al, 2012; Ray et al, 2012; Alegre et al, 2013; Bastin et al, 2014; Benis et al, 2014; Wessel et al, 2016; Herz et al, 2017; Zavala et al, 2017b).…”

“…Furthermore, high frequency deep brain stimulation (DBS) of the STN appears to disrupt this mPFC-STN network, consequently leading to more conflict-related errors (Frank et al, 2007; Cavanagh et al, 2011). Conversely, low frequency DBS to the STN in the theta band seems to enhance mPFC theta activity and improve response inhibition (Kelley et al, 2018). These anatomical and functional links between the mPFC and the STN therefore suggest that the two structures may intimately interact to mediate cognitive control.…”

Frontal theta and beta oscillations during lower-limb movement in Parkinson’s disease

“…Time-frequency and correlation results suggest the role of frontal theta in motor and cognitive and motor control systems (see figures 4 and 5), which are required to initiate and execute lower-body movements, 20,25 though frontal beta activity is mostly associated with motor control system. 21,22 As proposed by previous reports, frontal regions may play an important role in top-down signaling to guide adjustment of preparatory and execution plans during motor tasks.…”

Event‐related deep brain stimulation of the subthalamic nucleus affects conflict processing

“…50 Our findings point to the prospect of delivering low-frequency (~ 4 Hz) stimulation during periods of increased LFO – indeed, four Hz stimulation was recently shown to improve cognitive control in PD patients. 51 …”