Elsevier

NeuroImage

Volume 75, 15 July 2013, Pages 36-45
NeuroImage

Thalamic gamma oscillations correlate with reaction time in a Go/noGo task in patients with essential tremor

https://doi.org/10.1016/j.neuroimage.2013.02.038Get rights and content

Highlights

  • Neuronal synchronization in the gamma band is important in motor system.

  • Thalamic local field potentials were recorded in patients with tremor.

  • Movement-related gamma activity is lateralized contralateral to the moved side.

  • Gamma activity is predictive of the reaction time.

  • Responses are faster during higher levels of pre-movement gamma activity.

Abstract

Intracerebral recordings of neuronal activity in patients undergoing deep brain stimulation have revealed characteristic movement-related desynchronization at frequencies < 30 Hz and increased activity in the gamma band (~ 30–100 Hz) in the basal ganglia and thalamus. Thalamic gamma activity is also found during arousal. Here, we explore oscillatory gamma band activity recorded from the ventralis intermedius nucleus of the thalamus during motor performance in a Go/noGo task in 10 patients with essential tremor after implantation of deep brain stimulation electrodes. We show that movement-related gamma activity is lateralized to the nucleus contralateral to the moved side similar to previous findings in the globus pallidus internus and the subthalamic nucleus. The onset of contralateral gamma band synchronization following imperative Go cues is positively correlated with reaction time. Remarkably, baseline levels of gamma activity shortly before the Go cue correlated with the reaction times. Here, faster responses occurred in patients with higher levels of pre-cue gamma activity. Our findings support the role of gamma activity as a physiological prokinetic activity in the motor system. Moreover, we suggest that subtle fluctuations in pre-cue gamma band activity may have an impact on task performance and may index arousal-related states.

Introduction

Oscillatory local field potential activity has been used as a surrogate measure of the pattern of underlying neuronal synchronization in the basal ganglia in patients undergoing deep brain stimulation for severe movement disorders. Up to now, most interest in oscillatory activity in the basal ganglia has been focussed on the beta (13–35 Hz) band that is pathologically enhanced in patients with Parkinson's disease (Brown, 2003). This activity shows characteristic patterns of modulation preceding and following movement (Kempf et al., 2007, Kühn et al., 2004, Levy et al., 2002). Oscillatory activity in the gamma frequency range (30–100 Hz) is found in various cortical areas and has been related to visual object binding, cognitive processing, memory retrieval and motor processing (Bauer et al., 2006, Engel et al., 2001, Jensen et al., 2007, Schoffelen et al., 2005; for an overview see Buzsáki, 2006). More recently, gamma band activity has been described in different recordings from the thalamus, globus pallidus internus (GPi) and subthalamic nucleus (STN) irrespective of the underlying disease in patients undergoing deep brain stimulation. In patients with Parkinson's disease gamma synchronization occurs at rest during levodopa treatment (Brown et al., 2001, Cassidy et al., 2002, Pogosyan et al., 2006, Trottenberg et al., 2006, Williams et al., 2002) and has been associated with levodopa induced dyskinesia (Alegre et al., 2005, Alonso-Frech et al., 2006, Fogelson et al., 2006). Gamma synchronization occurs with self-paced (Androulidakis et al., 2007) as well as externally paced movements (Kempf et al., 2007, Liu et al., 2008) and is more prominent contralateral to the moved side (Brücke et al., 2008), similar to synchronized gamma activity over motor cortical areas (Ball et al., 2008, Cheyne et al., 2008, Crone et al., 1998, Pfurtscheller et al., 2003). The degree of motor cortical gamma synchrony has been related to motor parameters such as movement amplitude or speed (Muthukumaraswamy, 2010). Similarly, the event-related gamma synchronization around movement onset recorded in the pallidum in patients with dystonia has been correlated with the scaling of movement and has been associated with response vigor (Brücke et al., 2012). Taken together these findings suggest that motor related gamma activity in the cortex — basal ganglia circuit is not pathological but primarily physiological in nature.

Interestingly, finely tuned gamma activity has been observed in thalamic recordings during wakefulness and REM sleep and is increased with the startle reaction (Kempf et al., 2009) possibly reflecting shifts in arousal levels (Jenkinson et al., in press). If baseline thalamic gamma activity indeed depends on a critical level of arousal related to state modulation of the reticular activating system (Kempf et al., 2009), these activity changes should be predictive of changes in behavioral performance, especially in reaction time tasks. One opportunity to explore this hypothesis is to record neuronal activity from patients undergoing deep brain stimulation in the ventralis intermedius nucleus of the thalamus (VIM) to treat severe essential tremor (Limousin et al., 1999, Schuurman et al., 2000). The human VIM nucleus is considered homologous to the cerebellum-recipient nuclei of the monkey (Sommer, 2003) and thalamic recordings in monkeys have revealed movement-related activity during visually triggered voluntary arm movements (van Donkelaar et al., 1999), whereas interruption of thalamic activity during infusion of lidocaine leads to an alteration of visually triggered movements with increased reaction time (van Donkelaar et al., 2000). Human single unit recordings from the VIM have confirmed movement-related increases in firing rate within the nucleus with a somatotopic distribution of the movement responsive neurons (Crowell et al., 1968, Hua and Lenz, 2005, Lenz et al., 1988, Lenz et al., 1990). Here, we used direct thalamic local field potential recordings in 10 patients with essential tremor to explore the impact of fluctuations in baseline gamma band activity on reaction time and its relation to movement-related changes in thalamic gamma activity during the performance of a visually triggered Go/noGo task.

Section snippets

Patients and surgery

10 patients (3 males, mean age 62.50 ± 18.85 years) undergoing deep brain stimulation for severe essential tremor (ET; for clinical details see Table 1) were included in this study. All patients were diagnosed with essential tremor according to the diagnostic criteria (Deuschl et al., 1998) and none had clinical signs hinting at the presence of Parkinson's disease or dystonia, none had a history of hyperthyroidism or concurrent use of tremor-inducing medications. Intracerebral lesions were

Movement-related changes in thalamic oscillatory activity

The main features that occurred in the time–frequency plots of event related power changes around movement were i) an event-related desynchronization (ERD) starting about 100 ms before movement in the 12–20 Hz range; ii) an increase in synchronized activity (ERS) in the 17–30 Hz band starting around 500 ms after button press in the contralateral VIM, and iii) a movement-related synchronization at 55–80 Hz predominantly in the contralateral VIM starting about 100 ms before movement. Fig. 2 shows the

Discussion

We have demonstrated movement-related increased gamma synchronization in the human thalamus in patients with essential tremor that occurs predominantly contralateral to voluntary movement. Our findings extend previous observations of thalamic gamma activity (Kempf et al., 2009) and are in line with findings of significant contralateral gamma increases observed in pallidal and subthalamic recordings from patients undergoing deep brain stimulation for various movement disorders (Androulidakis et

Conclusion

Our results lend further support to the idea that lateralized gamma band synchronization is a physiological feature of movement-related activity within subcortical motor circuits. The onset and degree of gamma synchronization may reflect processing of motor parameters such as force or vigor (Anzak et al., 2012, Mazzoni et al., 2007). In contrast, the observed fluctuations in pre-cue gamma activity that correlate with reaction time may relate to shifts in global arousal and attention. Low

Disclosure

A.A.K. received honoraries from Medtronic, St. Jude Medical, Novartis, Bayer AG, A.A.K. received support for travel to conferences by Ipsen Pharma.

C.B. received support for travel to conferences by UCB and Ipsen. C.B. and J.H. received a prize sponsored by Medtronic. JKK is a consultant to Medtronic; PB is a consultant to Medtronic and Sapiens Ltd.

Acknowledgments

The project was supported by the DFG grant KFO 247. Christof Brücke by a PhD-scholarship of the Charité — University Medicine Berlin and Antje Bock by a PhD grant from the Dr. Robert Leven and Dr. Maria Leven-Nievelstein-Stiftung. Peter Brown was supported by the Medical Research Council and the National Institute of Health Research Oxford Biomedical Research Centre.

Conflict of interest

We certify that there is no conflict of interest with any financial organization regarding the material

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