Long‐range temporal correlations in the subthalamic nucleus of patients with Parkinson’s disease

Abstract

Neuronal activity in the subthalamic nucleus (STN) of patients with Parkinson's disease (PD) is characterised by excessive neuronal synchronization, particularly in the beta frequency range. However, less is known about the temporal dynamics of neuronal oscillations in PD. In this respect long-range temporal correlations (LRTC) are of special interest as they quantify the neuronal dynamics on different timescales and have been shown to be relevant for optimal information processing in the brain. While the presence of LRTC has been demonstrated in cortical data, their existence in deep brain structures remains an open question. We investigated (i) whether LRTC are present in local field potentials (LFP) recorded bilaterally from the STN at wakeful rest in ten patients with PD after overnight withdrawal of levodopa (OFF) and (ii) whether LRTC can be modulated by levodopa treatment (ON). Detrended fluctuation analysis was utilised in order to quantify the temporal dynamics in the amplitude fluctuations of LFP oscillations. We demonstrated for the first time the presence of LRTC (extending up to 50 s) in the STN. Importantly, the ON state was characterised by significantly stronger LRTC than the OFF state, both in beta (13-35 Hz) and high-frequency (> 200 Hz) oscillations. The existence of LRTC in subcortical structures such as STN provides further evidence for their ubiquitous nature in the brain. The weaker LRTC in the OFF state might indicate limited information processing in the dopamine-depleted basal ganglia. The present results implicate LRTC as a potential biomarker of pathological neuronal processes in PD.

Functional and effective connectivity in subthalamic local field potential recordings of patients with Parkinson’s disease

“…For the analysis of connectivity, the bipolar channels were grouped into pairs, with three channel pairs for the connections in each STN (left STN: L01-12, L12-23, and L01-23; right STN: R01-12, R12-23, and R01-23). Notably, in comparison to other studies of connectivity involving STN (e.g., Klostermann et al, 2007;de Solages et al, 2010;Hirschmann et al, 2011;Litvak et al, 2011) an advantage of the present study is that we used an anatomical reconstruction of the electrode trajectory (Scho¨necker et al, 2009) for analyzing only those bipolar channels with at least one contact in STN (see Hohlefeld et al, 2012, for details and for the justification of including contact pairs in the analysis). The present selection approach ensures that if in a given bipolar channel (e.g., channel 23) both contacts were outside of STN (for channel 23 this would mean that the dorsal end of the electrode track being out of STN), then this channel was excluded and no coherence was calculated between this channel and others.…”

“…Ten patients (six males; mean age 61 years, range 47-71 years) diagnosed with idiopathic PD (mean disease duration 10 years, range 5-20 years) participated in the study, as described in our previous study (Hohlefeld et al, 2012), where further details about the patients were reported (see Table 1 therein). This data set was reanalyzed for the purposes of the present study.…”

“…For all patients informed consent was obtained and the experimental procedures were approved by the local ethics committee in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki, 1964). The pre-surgery motor Unified Parkinson's Disease Rating Scale (UPDRS) scores were assessed by an experienced clinician (see Table 1 in Hohlefeld et al, 2012) for OFF and ON levodopa (scores available in nine patients). Additionally, the body side being more strongly affected was also evaluated by the clinician, and was furthermore confirmed by the presurgery UPDRS hemibody scores OFF levodopa (in seven out of 10 patients, in which the hemibody scores were available).…”

“…13-35 Hz: Priori et al, 2004;Ku¨hn et al, 2005;Lo´pez-Azca´rate et al, 2010;Marceglia et al, 2011): The abnormally elevated power of beta oscillations decreased after single-dose levodopa administration (Brown et al, 2001;Priori et al, 2004;Brown and Williams, 2005;Ku¨hn et al, 2009) and the temporal dependency (or ''memory'') in the beta oscillations increased, as indicated by stronger longrange temporal correlations up to 50 s in the ON medication condition (Hohlefeld et al, 2012). Potential underlying mechanisms contributing to these findings are manifold, for instance levodopa-induced altered connectivity within the cortex-basal ganglia loop (Brown et al, 2001;Williams et al, 2002;Lalo et al, 2008) and, possibly, also altered neuronal synchronization between different regions within the STN, as addressed by the present study.…”

The Neuronal Network Oscillation as a Critical Phenomenon

“…Invasive recordings in nonhuman primates, however, have reported 1/f spectra for the amplitude modulation in both low and high gamma bands [53]. Recordings from the subthalamic nucleus in Parkinson patients even show prominent LRTC in the very high-frequency gamma range (>200 Hz), especially when treated with the dopamine-precursor drug Levodopa [54].…”