The role of the subthalamic nucleus in response inhibition: Evidence from local field potential recordings in the human subthalamic nucleus
Introduction
The unpredictability of every-day life means that changing circumstances can render planned motor actions suddenly inappropriate. The ability to inhibit pre-planned or on-going motor action, known as response inhibition, is therefore essential for the normal control of movement. Response inhibition is frequently tested in the laboratory using countermanding tasks that require participants to ‘stop’ an on-going ‘go’ response. Functional imaging studies show that response inhibition activates areas of frontal cortex and the subthalamic nucleus (STN) of the basal ganglia (Aron and Poldrack, 2006, Aron et al., 2007, Li et al., 2008, Sharp et al., 2010). The importance of the STN in response inhibition has since been demonstrated behaviourally in humans (Ray et al., 2009, van den Wildenberg et al., 2006).
The opportunity to record electrical activity in the form of local field potentials (LFP) directly from the STN arises in Parkinson's disease (PD) patients undergoing surgery to implant deep brain stimulation (DBS) electrodes. Such recordings have revealed that go responses during a go/no-go task are preceded by a decrease in beta power, representing de-synchronised oscillatory activity, while inhibition of go responses during no-go trials are associated with the early termination of beta desynchronisation (Kühn et al., 2004). Voluntary movements are also preceded by an increase in power or synchronisation of higher frequency gamma activity (Androulidakis et al., 2007, Cassidy et al., 2002), but inhibition is not thought to be related to a modulation in gamma. These findings suggest that changes in beta and gamma activity within the STN are associated with the preparation of externally triggered movements, and that synchronised beta activity is involved in the inhibition of voluntary movements in a go/no-go paradigm.
During go/no-go paradigms, no-go trials require movements to be inhibited post preparation but prior to execution. How oscillatory activity in the STN responds to the cancellation of an on-going movement – as required in stop-signal tasks – has not been investigated. We report LFP data acquired from the STN of human participants performing a manual stop-signal task. We were primarily interested in differences in these activities during go- and stop-trials. Previous research on beta and gamma activity in the STN during ‘going’ and ‘stopping’ (Androulidakis et al., 2007, Cassidy et al., 2002, Kühn et al., 2004) leads us to expect beta synchrony to decrease after go-signals in both go- and stop-trials, but to re-emerge more quickly during stop-trials (i.e. following presentation of the stop-signal). We also expect, based on previous data in the internal globus pallidus (GPi), in which gamma-band activity is coherent with the STN (Cassidy et al., 2002), that gamma activity is decreased during stop-trials compared to go-trials (Brücke et al., 2008).
Section snippets
Participants
Participants were nine right-handed PD patients undergoing surgery to implant DBS electrodes into the STN. Seven of the patients received bilateral electrodes, while the remaining two patients received electrodes implanted unilaterally into the left STN. Recordings were made in the peri-operative period, prior to implantation of the DBS pacemaker. During this time the electrodes can be used to record electrical activity in the STN while the patients are awake and performing behavioural tasks.
Behavioural data
In 4 of the 32 runs of the stop-signal task there was a failure to achieve ~ 50% accuracy, due either to impulsivity (failure to stop) or delayed response (withholding). These were removed from further analysis. The data for the remaining 28 runs are summarised in Table 2. The reaction times for the failed (uninhibited) stop-trials were faster than GORTs (t = 5.60, P < 0.001, 1-tailed). GORTs and SSRTs were not correlated (r = 0.07, P = 0.78, 2-tailed).
Beta synchrony and desynchronisation
Figs. 1a and g, show a frequency spectrogram and
The impact of Parkinson's disease on our results
Excessive beta activity in the basal ganglia is a hallmark of basal ganglia activity in PD (Brown et al., 2001, Kühn et al., 2006b, Kühn et al., 2009, Levy et al., 2000, Ray et al., 2008, Weinberger et al., 2006, Weinberger et al., 2009). Patients were studied in the medicated state, which minimises pathological beta activity (Kühn et al., 2006b, Ray et al., 2008). However, as with all studies undertaken during a pathological state, our results may not transfer directly to the normal population
Conclusion
We confirm that beta ERD follows go-signals, and that beta ERS follows stop-signals during a stop-signal task. The degree of beta ERS following stop-signals was different between individuals (those with quicker beta ERS responses had shorter SSRTs), but not within an individual (beta ERS following stop-signals was not different in timing or in power for failed and successfully inhibited stop-trials when beta activity related to the preceding go-signal was controlled for). Thus, successful
Acknowledgments
The authors acknowledge the financial support from the UK Medical Research Council, The Norman Collisson Foundation, Charles Wolfson Charitable Trust and the Oxford Collaborative Biomedical Research Centre.
References (32)
- et al.
Intra-operative recordings of local field potentials can help localize the subthalamic nucleus in Parkinson's disease surgery
Exp. Neurol.
(2006) - et al.
EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis
J. Neurosci. Methods
(2004) - et al.
The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson’s disease
Exp. Neurol.
(2005) - et al.
Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity
Exp. Neurol.
(2009) - et al.
Spatiotemporal patterns of beta desynchronization and gamma synchronization in corticographic data during self-paced movement
Clin. Neurophysiol.
(2003) - et al.
Local field potential beta activity in the subthalamic nucleus of patients with Parkinson's disease is associated with improvements in bradykinesia after dopamine and deep brain stimulation
Exp. Neurol.
(2008) - et al.
The role of the subthalamic nucleus in response inhibition: evidence from deep brain stimulation for Parkinson's disease
Neuropsychologia
(2009) - et al.
Subthalamic gamma activity in patients with Parkinson's disease
Exp. Neurol.
(2006) - et al.
Pathological subthalamic nucleus oscillations in PD: can they be the cause of bradykinesia and akinesia?
Exp. Neurol.
(2009) - et al.
Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson's disease
Brain
(2007)
Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus
J. Neurosci.
Triangulating a cognitive control network using diffusion-weighted magnetic resonance imaging (MRI) and functional MRI
J. Neurosci.
Multiple Window Time Varying Spectrum Estimation
Inhibitory control in mind and brain: an interactive race model of countermanding saccades
Psychol. Rev.
Single-trial multiwavelet coherence in application to neurophysiological time series
IEEE Trans. Biomed. Eng.
Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson's disease
J. Neurosci.: Off. J. Soc. Neurosci.
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