Bilateral STN-DBS active contact positions of 20 patients with Parkinson's disease plotted in the coronal plane with respect to weight gain.

<p>Patients (N = 11) with at least one active contact (a) placed within 9.3-mm of the wall of the third ventricle gained significantly more weight than patients (N = 9) with both contacts (b) located more laterally (p<0.001).</p

Mean changes in weight after implantation in 20 patients with Parkinson's disease.

<p>Body weight gradually increased during the study period. Weight gain represents the difference in weight (±SD) compared to the preoperative state.</p

Weight gain in 20 patients with Parkinson's disease in relation to the mediolateral position of the active contact with bilateral STN-DBS (r = −0.55, p<0.01).

<p>Only one active contact (more medial contact from both hemispheres) was used in each patient. The x-coordinate represents the distance of the active contact from the wall of the third ventricle. Each millimeter in the medial direction was associated on average with a 1.6-kg increase in body weight. Dotted lines denote the 95% confidence interval of the regression line.</p

Hemi-body UPDRS-III subscores in the sON condition after overnight withdrawal of dopaminergic therapy in relation to the mediolateral position of the contralateral active contact.

<p>After initiation of STN-DBS, the hemi-body side with the lowest motor score (best motor condition) had the contralateral contacts located more laterally from the wall of the third ventricle (r = −0.42, p<0.01). Dotted lines denote the 95% confidence interval of the regression line.</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

Description of patients with Parkinson’s disease.

<p>Age – age on the day of surgery; STN – subthalamic nucleus; GPi – globus pallidus interna; DD – Parkinsońs disease duration; Levodopa – dose/day in mg including levodopa equivalent dosage of dopamine agonist; patient 4 was also treated with mianserin; patients 6, 7, 8, 9, 10 with citalopram and 16 with bupropion; UPDRS III – motor score of the Unified Parkinsońs Disease Rating Scale in OFF medication condition; H-Y – Hoehn and Yahr stage in OFF medication condition; DBS target – nucleus chosen for bilateral deep brain stimulation; SEM – scanning eye movement task; VGS – visually guided saccade task; neurons – number of neurons identified in the basal ganglia.</p

Eye movement (EM) tasks employed in the study.

<p><b>A - The scanning EM task</b>. After the presentation of the black screen with a central cross, a photograph chosen from the International Affective Picture System was presented for 2 s. Patients were asked to initially fix their eyes on the cross (left picture) and then simply watch the photograph (right picture). In total, 24 pictures were consecutively used during the task. The blue line highlights a possible eye scanpath. <b>B - The visually guided saccade task</b> consisted of a presentation of 10 pairs of indifferent central (left picture) and lateral GO (right picture) targets positioned pseudorandomly on the left/right side of the screen. Patients were instructed to initially fixate the central cross and then track to the lateral targets as fast as possible.</p

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

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

Eye movement-related neurons detected in the scanning eye movement task and/or visual guided saccade tasks.

<p>EM-related neurons – the number of eye movement-related neurons associated with at least one kinematic parameter (^†Bonferroni-corrected number of neurons for three kinematic parameters) identified from patients 16-19 which performed both the scanning eye movement task (SEM) and visual guided saccade task (VGS) in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr). Neurons functionally associated with one or more kinematic parameters (POS – eye position; VELOC – eye velocity; ACCEL – eye acceleration) are reported for each nucleus separately.</p