Description of the PD patient's group (N = 12).

<p>Mean ± SD and variance range is reported for each parameter. MMSE – Mini Mental State Examination. The UPDRS-III was assessed in OFF condition (medication OFF in session 1; medication OFF and STN DBS OFF in sessions 2 and 3) and in mON condition (after administration of 250 mg of levodopa/carbidopa) in session 1 and in sON condition (medication OFF and bilateral STN DBS ON) in sessions 2, 3, 4. DBS parameters – mean amplitude, variance in pulse duration, frequency and mode of stimulation in both hemispheres. Medtronic electrode (type 3389) positions were measured in native space according to methodology <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049056#pone.0049056-Ruzicka1" target="_blank">[37]</a> on T1-MRI obtained one year after surgery: The x-coordinate of each contact 0 and 3 was measured from the wall of the third ventricle (+ towards right; − towards left), whereas the y-coordinate (+ towards anterior; − towards posterior) and z-coordinate (+ towards vertex; − towards brainstem) were measured from the mid-commissural point.</p

The Subthalamic Microlesion Story in Parkinson's Disease: Electrode Insertion-Related Motor Improvement with Relative Cortico-Subcortical Hypoactivation in fMRI

<div><p>Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9–15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (<em>p</em><0.001), correlating with the postoperative oedema score (<em>p</em><0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (<em>p</em><0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (<em>p</em><0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, <em>p</em> = 0.4).</p> <p>In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.</p> </div

Native <i>T2</i>-weighted images of collateral oedema surrounding implanted electrode 3 days after surgery in PD patients.

<p>Left – Example of bilateral oedema (score 2) involving frontal cortical regions in patient 4. Right – subcortical oedema (score 2) around contacts of the right electrode involving subthalamus and globus pallidus in patient 3. While the susceptibility artifacts from the electrodes are hypointense, the oedema appears hyperintense (white arrows).</p

UPDRS-III in ON condition in PD patients (N = 12) during the study.

<p>The UPDRS-III score before implantation (mON) in session 1 after administration of 250 mg levodopa/carbidopa; in session 2 within 1–3 days after implantation of the electrode bilaterally to STN; in session 3 one month after implantation; and in session 4 one year after implantation examined each time with STN DBS ON (sON state) always with antiparkinsonian medication withdrawn; UPDRS-III – error bars (mean and SD); * (<i>p</i><0.05), *** (<i>p</i><0.001).</p

fMRI group analysis of the tapping test performed by PD patients (N = 12) before and after implantation of the electrodes bilaterally to the STN in absence of DBS.

<p>a) Contrast showing decrease of the BOLD signal after implantation (OFF state) as compared to situation before implantation (OFF state) with the UPDRS-III or the oedema score as covariates; x, y, z – local maxima of clusters in MNI coordinates derived from the contrast <i>before vs. after implantation</i> with the UPDRS-III covariate; k – size of the cluster in voxels;</p>‡<p>- regions belonging to the same cluster; T – T-score; <i>p</i> – uncorrected level of significance;</p>*<p>(<i>p</i><0.05),</p>**<p>(<i>p</i><0.01),</p>***<p>(<i>p</i><0.001) – significance with FWE correction at cluster-level;</p>†<p>– values derived from the contrast <i>before vs. after implantation</i> with the UPDRS-III covariate;</p>#<p>– values derived from the contrast <i>before vs. after implantation</i> with the oedema covariate.</p><p>b), c), d), e) – Impact of the UPDRS-III sub-scores on size of the BOLD response expressed as inverse effects of rigidity and axial covariates.</p