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The mechanism and time course of emotional side effects of subthalamic deep brain stimulation in Parkinson's disease are a matter for discussion. We report a 53-month follow-up of a patient with affective lability. Postoperative lesion plus bilateral stimulation strongly influenced mood in the first week in terms of laughing behavior, while voltage changes had only minor long-term impact up to 37 months on negative emotion, possibly caused by the right electrode stimulating the subthalamic nucleus and adjacent fiber tracts involving the internal capsule. Thus we conclude that affective lability can occur with different temporal dynamics of microlesion, and early and chronic stimulation. [ABSTRACT FROM AUTHOR]

During the last 15 years deep brain stimulation (DBS) has been established as a highly-effective therapy for advanced Parkinson’s disease (PD). Patient selection, stereotactic implantation, postoperative stimulator programming and patient care requires a multi-disciplinary team including movement disorders specialists in neurology and functional neurosurgery. To treat medically refractory levodopa-induced motor complications or resistant tremor the preferred target for high-frequency DBS is the subthalamic nucleus (STN). STN-DBS results in significant reduction of dyskinesias and dopaminergic medication, improvement of all cardinal motor symptoms with sustained long-term benefits, and significant improvement of quality of life when compared with best medical treatment. These benefits have to be weighed against potential surgery-related adverse events, device-related complications, and stimulus-induced side effects. The mean disease duration before initiating DBS in PD is currently about 13 years. It is presently investigated whether the optimal timing for implantation may be at an earlier disease-stage to prevent psychosocial decline and to maintain quality of life for a longer period of time. [ABSTRACT FROM PUBLISHER]

Abstract: This report describes a case of sudden onset of hyperglycaemic hemichorea–hemiballism as first manifestation of diabetes mellitus in a patient with previous history of Whipple’s surgery. Initial cranial computed tomography scanning and magnetic resonance imaging showed characteristic striatal lesions contralateral to the affected body side. A treatment with insulin led to an improvement of diabetic laboratory parameters but hyperkinesia still persisted and follow-up imaging revealed an enduring lesion in the posterior part of the caudate nucleus head. [Copyright &y& Elsevier]

Decisions about how to respond optimally in daily life are often guided by learning from consequences of chosen actions. Response-outcome associations can be learned by active responding to a stimulus or by observing responses and associated consequences in others. There is evidence that, depending on medication status, patients with Parkinson’s disease (PD) are relatively impaired in tasks requiring active learning from feedback. Regarding subthalamic nucleus (STN) deep brain stimulation (DBS), an increasingly utilized and highly effective treatment option for PD-symptoms, effects on learning are less clear. There are first indications of enhanced active feedback learning with STN stimulation due to a suggested modulatory effect of STN-DBS on the dorsal striatum, which is involved in linking own actions and outcomes. The aim of the present investigation was to compare the effect of DBS on active and observational feedback learning in patients with PD. Since learning by observation may depend less on the dorsal striatum, we hypothesized that STN stimulation affects learning of associations during active but not observational feedback learning. Twenty PD patients with STN-DBS and 20 age-matched controls performed active and observational feedback learning tasks. PD patients, remaining on their regular dopaminergic medication, completed both tasks ON and OFF-stimulation. During the active learning task, subjects had to respond to abstract visual stimuli with either the left or the right hand by button press. After each response, they received positive or negative feedback. During the observational learning task, subjects observed responses and accompanying outcomes of another person. Test phases consisting of trials without feedback served to assess learning of stimulus–response-outcome associations. We will present preliminary results regarding the effects of STN-DBS on observational and active feedback learning in PD patients. The findings will be discussed in light of the need to further understand not only motor but also cognitive effects of DBS in PD patients. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to better understand the development of clinical efficacy and impedance levels in the long-term course of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD).Methods: In this retrospective study of twenty PD patients, the motor part of the Unified Parkinson's Disease Rating Scale was periodically assessed i) after withdrawal of medication and inactivated stimulation, ii) after withdrawal of medication with activated stimulation and iii) after challenge with l-Dopa during activated stimulation up to 13 years after surgery.Results: STN-DBS with or without medication significantly improved motor function up to 13 years after surgery. The contribution of axial symptoms increased over time. While the stimulation parameters were kept constant, the therapeutic impedances progressively declined.Conclusion: STN-DBS in PD remains effective in the long-term course of the disease. Constant current stimulation might be preferable over voltage-controlled stimulation, as it would alleviate the impact of impedance changes on the volume of tissue activated. [ABSTRACT FROM AUTHOR]

Introduction One of the key symptoms of Parkinson’s disease (PD) is the impairment of spontaneous movement also known as akinesia ( Berardelli et al., 2001 ). Correspondingly, patients performing motor tasks feature abnormal activation in regions such as posterior medial frontal cortex (pMFC) and putamen ( Herz et al., 2013 ). These areas play crucial roles in the internal timing of volitional movements in healthy individuals ( Hoffstaedter et al., 2013 ). Yet, little is known about these regions’ functional connectivity (FC) in PD and its relationship with akinesia. The present study investigated FC alterations of the ’motor initiation network’ in PD, using a seed-based resting-state (RS) analysis. Methods RS fMRI data of 60 patients diagnosed with idiopathic PD (mean age 61.6 ± 10.2; mean disease duration 6.5 ± 5.5 years) and 72 healthy volunteers (mean age 60.1 ± 8.8, matched for age, gender and within-scanner movement) was acquired at two sites. After spatial preprocessing (realignment, normalization, smoothing), temporal filtering was conducted including motion confound removal and band-pass filtering. Seeds in bilateral putamen and pMFC were derived from a meta-analysis on volitional movements ( Hoffstaedter et al., 2014 ). Two more seeds were selected in bilateral primary motor cortex (M1). For each seed, (i) whole-brain FC and (ii) its interaction with akinesia (UPDRS item 3.14) were assessed. RS networks for the aforementioned regions were first mapped in healthy controls only: Contrasting each region’s FC to the FC of all respective other seeds yielded maps of specific connectivity with either seed. These networks were then used to map whole-brain corrected changes of FC in PD. Results were cluster-level corrected for multiple comparisons ( p < 0.05). Results In healthy participants, RS analysis differentiated three networks, specifically (more than all other seeds) connected to bilateral putamen, bilateral M1, and pMFC. In PD, all seeds consistently featured decreased FC with regions in their most related network. That is, M1 mainly showed FC decrease within the M1-related network, pMFC lost FC with anterior insulae and left dorsolateral prefrontal cortex (DLPFC; pMFC-related network), and putamen lost FC with caudate nucleus, pallidum and thalamus (Putamen-related network). Additionally, putamen FC decreased extensively also in those regions more related to M1 and pMFC, including visual, superior parietal, primary somatosensory, M1, pMFC and DLPFC. Testing for each seed’s interaction with akinesia, pMFC showed a decreased FC with inferior parietal lobe (IPL) in the pMFC-related network. In turn, FC of the other seeds did not significantly relate to akinesia. Conclusions The present study examined RS FC changes of bilateral putamen, M1 and pMFC in PD. In patients, putamen FC suggests a marked cortico-striatal decoupling, in line with pathophysiological models of the disease ( Braak et al., 2004 ). In contrast, pMFC featured more selective FC decreases, predominantly in regions involved in motor control ( Hoffstaedter et al., 2013; Hoffstaedter et al., 2014 ). Notably, akinesia was exclusively related to pMFC-connectivity. With increasing impairment, pMFC decoupled from the right IPL. In sum, the present study demonstrates a disruption of cortico-striatal FC and specifies the role of pMFC - IPL connectivity for movement initiation in PD. [ABSTRACT FROM AUTHOR]

Alpha-band activity (8–12 Hz) is a prominent electrophysiological signal in the human brain. Alpha power is known to be modulated by visuospatial attention in healthy humans( Thut et al., 2006; Klimesch, 2012 ). Patients with Parkinson’s disease (PD) show a decrease in attentional control and deficits in switching of attention ( Aarsland et al., 2010 ). Here, we studied the role of alpha power in switching of visuospatial attention in PD. In PD, motor symptoms improve with dopamine replacement medication. We additionally studied whether dopaminergic medication alters the network activity in the alpha band during visuospatial attention. 20 subjects with diagnosed PD (15 male, 55 ± 10 y) performed the task in which they had to attend either to the left or right visual hemifield, indicated by a central cue. After a delay (1200 ms) a visual stimulus was presented in each hemifield. After another randomly chosen time, one of the two stimuli changed its color. A button press was required when the color change appeared on the cued side. We measured reaction times, and brain activity with magnetoencephalography. To analyze frequency bands of brain activity, we applied fast Fourier transform on the neural data. Subjects performed the task after 12 h withdrawal from dopamine replacement medication (“OFF”) and after receiving L-DOPA (“ON”). Before and after receiving L-DOPA, we performed the Unified Parkinson’s Disease Rating Scale (UPDRS) to assess efficiency of L-DOPA. We compared switching with not-switching trials, with “switching” meaning two successive trials required attention to opposite hemifields, “not-switching” meaning two successive trials required attention to the same hemifield. Comparison was done between and within medication factor (ON/OFF).UPDRS scores showed significant improvement of motor symptoms after receiving L-DOPA. During OFF, subjects responded faster in not-switching than in switching, whereas during ON there was no difference in reaction times. During OFF, we found a decrease of alpha power for switching relative to not-switching in right parietal (5–15 Hz) and right frontal areas (10–17 Hz) during the delay period. During ON, we found a decrease of alpha power for switching relative to not-switching in right occipital regions (2.5–15 Hz) during the cue period. Finally, we found a positive correlation between alpha power (8–12 Hz) and reaction times during OFF for switching, but not for not-switching. Faster reaction times for not-switching during OFF might reflect a strong focus on the previously attended side. Switching attention during OFF is therefore more difficult, which is reflected in less relative alpha power for switching, and thus more activity, in the fronto-parietal network. L-DOPA, therefore, increases flexibility for switching by lessening suppressing alpha-band activity in the fronto-parietal network. This could be achieved by better visual processing of the cue, as reflected in less alpha power during the cue period in visual areas. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that action perception is linked to action execution. For example, it has been shown that perception of an action is altered by simultaneous performance of the same action ( Jacons and Shiffrar, 2005 ). Parkinson‘s disease (PD) is typically characterized by impaired motor execution. In the present study, we investigated whether PD also adversely affects biological (i.e. human) motion perception. 17 PD patients and 17 matched neurologically healthy controls participated in the study. The participants watched point-light displays of human, animal and object motion and were asked to differentiate between biomechanically plausible point-light motions and distorted versions of these motions. All participants completed two identical testing sessions. The PD patients completed the first testing session in an “OFF”-state, that is 12 hours after last taking dopaminergic medication. The second testing session was completed after the ingestion of levodopa (“ON”). Control subjects completed two identical session with a break of ∼30–60 min in between. The Unified Parkinson’s Disease Rating Score (UPDRS) was measured in OFF and ON for the PD group to ensure an effect of medication. We analyzed participants‘ sensitivity for plausible vs. distorted motion. In the OFF state, PD patients showed significantly lower sensitivity for human and animal motion than controls. Post hoc analysis revealed that the difference between PD patients and controls was significantly stronger for transitive than for intransitive human motions. Sensitivity for object motion did not differ between both groups. In the second testing session, controls showed a slight improvement of performance compared to the first session, probably due to learning effects. PD patients, however, showed no improvement of performance in the ON state (i.e., second session) compared to the OFF state. This might be due to adverse side-effects of the medication, e.g., fatigue. Our results confirm the hypothesis that PD patients who are impaired in motor execution are also impaired in the perception of human and animal motion. It has been argued that perception of actions and action execution interact in the human mirror neuron system. Mirror neurons are cells that respond to both the execution and observation of motion ( Rizzolatti and Craighero, 2004 ). We propose that human and animal motion perception deficits in patients with Parkinson‘s disease might be caused by mirror neuron system dysfunction. [ABSTRACT FROM AUTHOR]

Question Deep Brain stimulation (DBS) is a widely established, effective and well-tolerated treatment for Parkinson’s disease (PD). The patients’ way to receive this treatment usually consists of two steps: first, general neurologists refer them to a specialized DBS center where they undergo further diagnostic assessment and the final decision for or against this treatment is made. Electronic tools are available to support general neurologists in the selection of DBS candidates. Nevertheless, even after being preselected as an appropriate candidate, the majority of patients refused to be referred to a DBS center (Wächter et al., J Neurol 2011;258:641–646). Patients and methods Two projects were initiated to increase the treatment acceptance of DBS for PD: (A) A collaboration of 20 general neurologists and two movement disorder specialists at the University Hospital Düsseldorf was established. (B) 51 general neurologists located all over Germany were trained to use the electronic preselection tool STIMULUS and were handed out newly developed information materials. In both projects, appropriate DBS candidates were preselected. Their acceptance or refusal to undergo further diagnostic assessment at a DBS center was documented within a 16 months follow-up period. Further, several clinical characteristics and details of the patient briefing were collected and analyzed to identify factors which were predictive for patients’ decisions. Results (A) 912 PD patients were examined by the movement disorder specialist together with the general neurologist. In 92 cases (10.1%), a referral to undergo further diagnostic assessment at the University Hospital Düsseldorf was recommended. Within 16 months, 69 (70.4%) of those patients showed up in the specialized DBS center. (B) 264 patients were identified as appropriate candidates for DBS, using the electronic preselection tool STIMULUS and 114 (43.2%) had accepted to be referred to a DBS center within a 16 month follow-up period. The patients’ decisions were significantly influenced by their age, their classification as an akinetic-rigid type and when mentioning a potential reduction of dopaminergic side effects as well as the optimal time frame for DBS during the clarification talk. Conclusion Consultation visits by movement disorder specialists in collaboration with general neurologists substantially improved the treatment acceptance of PD patients for DBS. A training of general neurologists in combination with adequate information material might be a low-cost and effective alternative option. Both findings indicate the importance of a clarification talk to be crucial in order to increase the treatment acceptance for DBS. This assumption is supported by the talks’ topics side effects of dopaminergic medication and optimal time frame which were significantly related to a higher rate of acceptance if mentioned. [ABSTRACT FROM AUTHOR]

When a brief single visual stimulus is presented interposed between two brief tactile stimuli in a time window (SOA; Stimulus Onset Asynchrony) of 70–100 ms healthy subjects frequently perceive an illusory second visual stimulus. This phenomenon is known as “Double-Flash-Illusion” (DFI) ( Shams et al., 2000 ). Hypothesis Studies have shown that patients with Parkinson’s disease (PD) need a longer time interval to perceive two unimodal stimuli correctly as two ( Artieda et al., 1992 ). Here we investigated whether in PD patients the time window to perceive the DFI is also prolonged compared to healthy controls. We hypothesized that the SOA to perceive the DFI is prolonged in PD patients and that dopamine medication (ON) shortens the SOA to perceive the DFI relative to medication withdrawal (OFF). Methods Up to now 20 PD patients (6 female; mean age 58, 5 y) and 16 matched controls took part. Only patients with a hypokinetc-rigid subtype in state I–III by Hoehn & Yahr, who received medical treatment only and did not have any other neurological disorders took part. Participants received visuo-electrotactile stimulation to the left index finger. Either one or two visual stimuli were presented with either one or two electrotactile stimuli (combinations: v, vv, tv, tvt, tvtv, vtv; with v standing for the visual and t for the tactile stimulus). The stimuli in each combination were separated by the following SOAs: 67, 84, 100, 135, 170, 200, 270, 300, 400, 500 and 600 ms. The condition with two electrotactile stimuli interposed with one visual stimulus (tvt) was supposed to induce the DFI. Participants reported the number of perceived visual stimuli. The experiment was first done without medication (OFF) and than repeated with dopamine medication (ON) with PD patients. The control subjects performed the experiment twice without any medication. The UPDRS (Unified Parkinson’s Disease Rating Score) was measured in OFF and ON for the PD group. Findings Among the PD patients, we found two groups: one group (9 subjects) who did not report the DFI (NOSEEer; one female), while the other group (11 subjects) frequently reported the DFI (SEEer; 5 female). The SEEer-Group shows significantly increased DFI perception in the ON condition compared to OFF for the SOAs 64, 100 and 135 ms. Additionally, we found that the SOA for which we observed maximum illusory perception shifted from 270 ms to 200 ms from OFF to ON. In the control group we found 12 SEEer and 4 NOSEEer. There was no significant difference between first measurements in PD patients (OFF) and controls with respect to perception of illusion. When patients’ ON condition was compared to the controls’ second measurement the patients perceived the stimulation significantly more often as two visual stimuli for the SOAs 64 and 84 ms. Conclusion In summary, we find a modulation of DFI perception by dopamine: With medication, patients perceived the illusion more often for short SOAs than without medication. Interestingly, we did not find a significant difference between patients in the OFF state and healthy controls’ first measurement. This finding indicates that other factors than disease or dopamine may additionally influence the perception of the DFI. Future studies analysing brain activity of both groups might help to understand the present findings as well as the differences between SEEer group and NOSEEer group. [ABSTRACT FROM AUTHOR]