Reply to: Deep brain stimulation in Parkinson's disease can mimic the 300 Hz subthalamic rhythm Subthalamic high-frequency stimulation drives subthalamic oscillatory activity at stimulation frequency while firing rate is reduced

Neurophysique et Physiologie du Syste`me Moteur, Universite´ Paris V, Paris, FranceCorrespondence to: Dr Wassilios Meissner, CNRS UMR 5543, Universite´ Victor Se´galen, 146 rue Le´o Saignat,33076 Bordeaux Cedex, FranceE-mail: wassilios.meissner@umr5543.u-bordeaux2.frdoi:10.1093/brain/awl210We have read with interest the letter by Foffani and Priorithat will be published online alongside the same issue ofBrain. Foffani and Priori hypothesize that high-frequencystimulation (HFS) of the subthalamic nucleus (STN)might induce oscillatory activity around 250 Hz in thebasal ganglia network. To verify this assumption, we per-formed a new analysis of our entire data set, where wetried to be as close as possible to the analysis described inour recent publication (for details, see Meissner et al., 2005). Accordingly, single-cell oscillations and synchronized oscil-latory activity between pairs of neurons were assessed bycalculating auto-correlograms (AC) and cross-correlograms(CC), respectively (1000 ms offset with a bin width of 1 msinstead of 5 ms to enable the analysis of frequencies up to 350Hz). For each AC and CC the power spectrum was calculatedbetween3and350Hzandtheoscillatoryactivitywasassessedfor three distinct frequency bands: 3–30 Hz as in our recentpublication, 31–200Hz and 201–350Hz.A peak in the powerspectrumwasconsideredtobesignificantifitwashigherthanthe mean power of the entire spectrum [(3–350 Hz) + 5 SD]and if it had an oscillatory index >10%. The standard devia-tion was individually calculated for each frequency bandusing the two other frequency bands (i.e. for the 3–30 Hzband, the standard deviation was calculated in the 31–350 Hzrange). Differences of AC and CC between the experimentalstates were assessed by using z-tests.Total single oscillatory activity was 95.1% in the normalstate and 92.9% in the parkinsonian state (Fig. 1A, z = 0.1,P > 0.5) and was mainly related to oscillatory activity inthe 3–30 Hz frequency band (3–30 Hz: 90.2% versus 83.7%,z = 0.7, P > 0.05; 31–200 Hz: 4.9% versus 5.1%, z = 0.4,P > 0.5; 201–350 Hz: 2.4% versus 4.1%, z = 0.01, P > 0.5). The strong oscillatory activity in the normal state and theabsence of a significant increase in the parkinsonian stateare explained by the observation that the power spectrumin the 31–200 Hz and 201–350 Hz bands were generally flat,but contributed to the calculation of the mean and standarddeviation for the 3–30 Hz band, rendering the analysis verysensitive for that frequency band.Total synchronized oscillatory activity between pairs ofneurons was 40.4% in the normal and 50.0% in the parkin-sonian state (Fig. 1B, z = 1.1, P > 0.05). MPTP treatmentsignificantly increased synchronized oscillatory activity inthe 3–30 Hz frequency band (8.8% versus 23.3%, z = 2.2,P 0.5; 201–350 Hz: 24.6% versus 18.0%, z = 0.9,P > 0.05). STN–HFS in the parkinsonian state induced strong oscil-latory activity in the 31–200 Hz band at the stimulation fre-quency of 130 Hz (Fig. 1C and D, single neuron: 93.0%; pairsof neurons: 100.0%), while STN–HFS decreased the firingrate of subthalamic neurons to 48.9% of baseline values(Meissner et al., 2005). Only 7.3% of single neurons showedsignificant oscillatory activity in the 3–30 Hz band and 2.3%in the 201–350 Hz band. When comparing these values withthe MPTP-treated state, differences were significant for the3–30Hzandthe31–200Hzband(3–30Hz:z=8.4,P 0.5). Synchronizedoscillatoryactivityduring STN–HFSwasexclu-sively present in the 31–200 Hz frequency band. Differencesbetween MPTP and MPTP + HFS states were significant forall frequency bands (3–30 Hz: z = 3.4, P < 0.001; 31–200 Hz:z = 11.7, P < 0.001; 201–350 Hz: z = 2.9, P < 0.5). As shown in our previous paper, the recovery of themean firing probability of STN neurons between two elec-trical stimuli is represented by a sigmoid function: f(t) =F0/(1 + exp ( k(t t0))), where F0 is the baseline firingrate, t the time in seconds, k = 4.5 6 0.6 ms