Parkinson's Disease Off Research Articles

Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson's disease

Repetitive finger tapping is commonly used to assess bradykinesia in Parkinson's disease. The Queen Square Brain Bank diagnostic criterion of Parkinson's disease defines bradykinesia as 'slowness of initiation with progressive reduction in speed and amplitude of repetitive action'. Although progressive supranuclear palsy is considered an atypical parkinsonian syndrome, it is not known whether patients with progressive supranuclear palsy have criteria-defined bradykinesia. This study objectively assessed repetitive finger tap performance and handwriting in patients with Parkinson's disease (n = 15), progressive supranuclear palsy (n = 9) and healthy age- and gender-matched controls (n = 16). The motion of the hand and digits was recorded in 3D during 15-s repetitive index finger-to-thumb tapping trials. The main finding was hypokinesia without decrement in patients with progressive supranuclear palsy, which differed from the finger tap pattern in Parkinson's disease. Average finger separation amplitude in progressive supranuclear palsy was less than half of that in controls and Parkinson's disease (P < 0.001 in both cases). Change in tap amplitude over consecutive taps was computed by linear regression. The average amplitude slope in progressive supranuclear palsy was nearly zero (0.01°/cycle) indicating a lack of decrement, which differed from the negative slope in patients with Parkinson's disease OFF levodopa (-0.20°/cycle, P = 0.002). 'Hypokinesia', defined as <50% of control group's mean amplitude, combined with 'absence of decrement', defined as mean positive amplitude slope, were identified in 87% of finger tap trials in the progressive supranuclear palsy group and only 12% in the Parkinson's disease OFF levodopa group. In progressive supranuclear palsy, the mean amplitude was not correlated with disease duration or other clinimetric scores. In Parkinson's disease, finger tap pattern was compatible with criteria-defined bradykinesia, characterized by slowness with progressive reduction in amplitude and speed and increased variability in speed throughout the tap trial. In Parkinson's disease, smaller amplitude, slower speed and greater speed variability were all associated with a more severe Unified Parkinson's Disease Rating Scale motor score. Analyses of handwriting showed that micrographia, defined as smaller than 50% of the control group's mean script size, was present in 75% of patients with progressive supranuclear palsy and 15% of patients with Parkinson's disease (P = 0.022). Most scripts performed by patients with progressive supranuclear palsy did not exhibit decrements in script size. In conclusion, patients with progressive supranuclear palsy have a specific finger tap pattern of 'hypokinesia without decrement' and they do not have criteria-defined limb bradykinesia. Similarly, 'micrographia' and 'lack of decrement in script size' are also more common in progressive supranuclear palsy than in Parkinson's disease.

Magnetization transfer and adiabatic R1ρ MRI in the brainstem of Parkinson’s disease

BackgroundIn addition to classic midbrain pathology, Parkinson’s disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. Methods: Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R1ρ (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. Results: We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. Conclusions: These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD.

Dopamine Alters Tactile Perception in Parkinson's Disease

Abnormal somatosensory processing may contribute to motor impairments observed in Parkinson's disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception. Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinson's disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli. Temporal order judgment in PD patients of and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactical acuity in controls and in PD patients off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications. These findings suggest that dopamine in PD reduces cortico-cortical connectivity with SI and this leads to changes in tactical sensitivity.

Effects of theta burst stimulation on motor cortex excitability in Parkinson’s disease

ObjectiveLong-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson’s disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD. MethodsiTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS. ResultsAfter iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60min. Changes in intracortical circuits induced by iTBS were also similar for the different groups. ConclusionsiTBS produced similar effects on cortical excitability for PD patients and controls. SignificanceSpike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS.

Differential role of dopamine in emotional attention and memory: Evidence from Parkinson's disease

Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinson's disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinson's disease, we assessed 15 nondemented patients with Parkinson's disease while on and off dopaminergic medication and 15 age-matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinson's disease tested off medication had significantly better memory for negative than positive items. This negativity bias was lost when they were tested while on dopaminergic medication. Reaction times in patients with Parkinson's disease off medication were longer than in healthy controls and, paradoxically, were even longer when on medication. Further, although both healthy controls and patients with Parkinson's disease in the "off" state had arousal-induced prolongation of reaction time, this effect was not seen in patients with Parkinson's disease on medication. These data indicate that dopaminergic neurotransmission is implicated in emotional memory and attention and suggest that dopamine mediates emotional memory via the valence dimension and emotional attention via arousal. Furthermore, our findings suggest that emotional changes in Parkinson's disease result from the effects of both the disease process and dopaminergic treatment.

Postural preparation prior to stepping in patients with Parkinson's disease

People with Parkinson's disease (PD) frequently have difficulties with generating anticipatory postural adjustments (APAs) for forward propulsion and lateral weight transfer when initiating gait. This impairment has been attributed to deficits in motor planning and preparation. This study examined the preparation of APAs prior to an imperative cue to initiate forward stepping. A startling acoustic stimulus (SAS) was used to probe the state of preparation of the APA in eight PD (off medication) and seven matched control subjects. Subjects performed visually cued trials involving a pre-cue light instructing them to prepare to step, followed 3.5 s later by a go-cue light to rapidly initiate stepping. In random trials, a SAS (124 dB) was presented at -1,500, -1,000, -500, -250, -100, or 0 ms before the go-cue. Subjects also performed self-initiated steps. Ground reaction forces (GRFs), center of pressure (CoP) changes, and electromyographic (EMG) signals were recorded. The SAS triggered APAs in 94 ± 11% (PD) and 96 ± 8% (control) of trials at latencies 89 ± 4 ms (PD) and 97 ± 3 ms (control) earlier than Control trials. The temporal profile of APA preparation was similar between groups. However, peak EMG, GRF, and mediolateral CoP amplitudes were reduced in PD. SAS-evoked APAs at 0 ms matched Control trial APAs and were enhanced compared with self-initiated stepping. These results demonstrate that people with mild to moderate PD can plan and prepare the appropriate APA sequence prior to the expected cue to initiate gait; however, the prepared APAs are underscaled in magnitude.

The Effects of Medication on Turning in People with Parkinson Disease with and without Freezing of Gait

Turning difficulty is prevalent in Parkinson disease (PD) and may lead to falls or freezing. Medication improves motor symptoms of PD, but its effects on turning in people with PD with (PD+FOG) and without (PD-FOG) freezing of gait are unclear. This study evaluated the effects of medication on turning in PD compared to healthy older adults (controls), and in PD+FOG compared to PD-FOG. We assessed timed-up-and-go (TUG), and in-place turns in 16 controls and 20 people with PD (10 PD+FOG, 10 PD-FOG) OFF and ON medication. PD+FOG performed worse than PD-FOG (p < 0.05) in TUG, turn duration, step count, and had earlier head rotation onset (HTO). These measures improved ON medication in PD+FOG and PD-FOG (p < 0.05). Turn duration and step count improved more with medication in PD+FOG than PD-FOG (p < 0.005). There were subtle differences in gastrocnemius and sternocleidomastoid onsets, with PD OFF or ON activating muscles earlier than controls. Tibialis anterior, gastrocnemius, and sternocleidomastoid initial onset times were similar between PD+FOG and PD-FOG. Though medication improved turning, turn duration and step count impairments still existed in PD ON, compared to controls. Relative to PD-FOG, PD+FOG turned worse, but improved more with medication, potentially because PD+FOG were initially more impaired than PD-FOG or were taking higher medication dosages. Further treatment options may be needed to address ON medication turning deficits.

Saccadic Eye Movements are Related to Turning Performance in Parkinson Disease

Persons with Parkinson disease (PD) experience difficulty turning, leading to freezing of gait and falls. We hypothesized that saccade dysfunction may relate to turning impairments, as turns are normally initiated with a saccade. Determine whether saccades are impaired during turns in PD and if characteristics of the turn-initiating saccade are predictive of ensuing turn performance. 23 persons with PD off medication and 19 controls performed 90 and 180 degree in-place turns to the right and left. Body segment rotations were measured using 3-D motion capture and oculomotor data were captured using a head-mounted eye tracking system and electrooculography. Total number of saccades and the amplitude, velocity, and timing of the first saccade were determined. Turn performance (turn duration, number of steps to turn) was impaired in PD (p<0.05). PD performed more saccades, and the velocity and timing of the first saccade was impaired for both turn amplitudes (p<0.05). Amplitude of the first saccade was decreased in PD during 180 degree turns. Turn duration correlated with oculomotor function. Characteristics of the first saccade explained 48% and 58% of the variance in turn duration for 90 and 180 degree turns, respectively. Turning performance is impaired in PD and may be influenced by saccade dysfunction. An association between saccade function and turning performance may be indicative of the key role of saccades in initiating proper turning kinematics. Future work should focus on improving saccade performance during functional tasks and testing the effects of therapeutic interventions on related outcomes.

Rate-dependent impairments in repetitive finger movements in patients with Parkinson's disease are not due to peripheral fatigue

Performance of repetitive finger movements is an important clinical measure of disease severity in patients with Parkinson's disease (PD) and is associated with a dramatic deterioration in performance at movement rates near 2 Hz and above. The mechanisms contributing to this rate-dependent movement impairment are poorly understood. Since clinical and experimental testing of these movements involve prolonged repetition of movement, a loss of force-generating capacity due to peripheral fatigue may contribute to performance deterioration. This study examined the contribution of peripheral fatigue to the performance of unconstrained index finger flexion movements by measuring maximum voluntary contractions (MVC) immediately before and after repetitive finger movements in patients with PD (both off- and on-medication) and matched control subjects. Movement performance was quantified using finger kinematics, maximum force production, and electromyography (EMG). The principal finding was that peak force and EMG activity during the MVC did not significantly change from the pre- to post-movement task in patients with PD despite the marked deterioration in movement performance of repetitive finger movements. These findings show that the rate-dependent deterioration of repetitive finger movements in PD cannot be explained by a loss of force-generating capacity due to peripheral fatigue, and further suggest that mechanisms contributing to impaired isometric force production in PD are different from those that mediate impaired performance of high-rate repetitive movements.

Excitability of the lower-limb area of the motor cortex in Parkinson's disease

The excitability of the lower-limb area of the motor cortex was investigated in patients with Parkinson's disease (PD) and in control subjects. Our results were compared to literature data assessing upper-limb cortical area. We analysed the effect of dopaminergic substitution therapy (DST). Motor evoked potential (MEP) were assessed with transcranial magnetic stimulation (TMS) in 24 PD patients with (ON) and without (OFF) DST, and nine age-matched controls. Resting motor threshold (RMT), active motor threshold (AMT), cortical silent period (CSP), MEP amplitude and area did not differ significantly between groups and medication states. A paired-pulse TMS study revealed normal short-interval intracortical inhibition (SICI) but impaired intracortical facilitation (ICF) in PD OFF, partially normalized under DST. Post-hoc analysis uncovered two opposite effects of DST on MEP amplitude, separating the population in two groups. The paired-pulse study confirmed this division, showing that both groups exhibited distinct intracortical functioning, which was differently influenced by DST. The lower-limb motor cortical areas of PD patients essentially exhibited an ICF reduction whereas in upper-limb areas, literature data demonstrated impairment of both SICI and ICF. Our data revealed two groups of patients showing different excitability states and opposite responses to DST. The defective ICF in lower-limb areas could play a key role in the pathophysiology of gait disorders in PD. The fact that two cortical excitability states are inversely influenced by DST may reflect different conditions of denervation and compensatory mechanisms progression.

Altered Resting State Cortico-Striatal Connectivity in Mild to Moderate Stage Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI in mild to moderate stage Parkinson's patients on and off l-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off l-DOPA compared to controls. This enhanced connectivity was down-regulated by l-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off l-DOPA exhibited increased power in the frequency band 0.02–0.05 Hz compared to controls and to PD on l-DOPA. The l-DOPA associated decrease in the power of this frequency range modulated the l-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the l-DOPA associated decrease in power in this frequency band correlated with the l-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and l-DOPA modulate striatal resting state BOLD signal oscillations and cortico-striatal network coherence.

Effect of Dopaminergic Medications on the Time Course of Explicit Motor Sequence Learning in Parkinson's Disease

The capacity to learn new motor sequences is fundamental to adaptive motor behavior. The early phase of motor sequence learning relies on the ventral and anterior striatal circuitry, whereas the late phase relies on the dorsal and posterior striatal circuitry. Early Parkinson's disease (PD) is mainly characterized by dopaminergic denervation of the dorsal and posterior striatum while sparing anterior and ventral regions. Dopaminergic medication improves dorsal and posterior striatum function by compensating for the loss of dopamine. However, previous work has shown that dopaminergic medication interferes with the ventral and anterior striatum function by overdosing this relatively intact structure in early-state PD. Here we test whether these effects are also observed over the time course of motor sequence learning. Fourteen PD patients ON and OFF dopaminergic medications and 11 healthy age-matched control participants performed an explicit motor sequence learning task. When sequence learning was compared across different learning phases in patients ON and OFF medication, a significant impairment associated with medication was observed in the early relative to later phases of learning. The rate of learning in the early phase measured trial by trial in patients ON medication was significantly slower than that in controls and when patients were OFF medication. No significant impairment was found in the later learning phases. These results demonstrate that dopaminergic medications may selectively impair early-phase motor sequence learning. These results extend and generalize the dopamine overdose effects previously reported for (antero)ventral striatum-mediated cognitive tasks to motor sequence learning.

Dopamine-dependent high-frequency oscillatory activity in thalamus and subthalamic nucleus of patients with Parkinson's disease

In recent years there has been great interest in oscillatory activity in the brain and in the role of pathological oscillations in the basal ganglia in mediating some of the symptoms of Parkinson's disease (PD). In this study, thalamic and subthalamic nucleus local field potentials were intraoperatively recorded from pairs of closely separated microelectrodes in six PD patients ON and OFF dopaminergic medication. Using correlation and coherence analyses, we found high-frequency oscillatory activity in the 110-170 Hz band in thalamus in patients OFF dopamine. These oscillations were significantly reduced after administration of dopamine-replacement therapy. In contrast, activity in the lower frequencies (the theta and beta ranges) was increased. However, in subthalamic nucleus, we observed an increase in high-frequency oscillatory activity (150-200 Hz), and a reduction of the activity in the low-frequency range after levodopa administration. These findings confirm and extend earlier findings suggesting that in PD there are marked changes in basal ganglia oscillatory activity and that these can be reversed after dopaminergic therapy.

Gait Analysis in Patients With Parkinson's Disease Off Dopaminergic Therapy

Švehlík M, Zwick EB, Steinwender G, Linhart WE, Schwingenschuh P, Katschnig P, Ott E, Enzinger C. Gait analysis in patients with Parkinson's disease off dopaminergic therapy. Objective To compare time-distance, kinematic, and kinetic gait parameters in patients with idiopathic Parkinson's disease (PD) off dopaminergic therapy with a group of healthy control subjects. Design A group-comparison study. Setting Gait analysis laboratory. Participants Patients with PD (n=20) and healthy age-matched controls (n=20). Interventions Not applicable. Main Outcome Measures Time-distance, kinematic, and kinetic gait variables. Results PD patients walked slower with shorter stride-length, comparable cadence, and longer double support times. Kinematics showed a reduction of the range of motion in the hip, knee, and ankle joints. Maximum hip extension and the ankle plantar flexion were significantly reduced. Kinetic gait parameters showed reduced push-off ankle power and lift-off hip power generation. Strong correlations between these important body advancement mechanisms and the walking velocity were observed. Conclusions In addition to previously described dysfunctional kinematics, abnormal kinetic parameters play an important role in the characterization of gait in PD patients off therapy. Hence, these parameters could be used to document treatment effects of parkinsonian gait disorders.

Impaired presynaptic inhibition in the motor cortex in Parkinson disease

Intracortical inhibition in the motor cortex may be measured with short interval intracortical inhibition (SICI), likely mediated by GABA(A) receptors, and long interval intracortical inhibition (LICI), likely mediated by GABA(B) receptors. Separate neuronal populations mediate SICI and LICI, and LICI inhibits SICI, likely through GABA(B) mediated presynaptic inhibition. The purpose of this study was to test the hypothesis that cortical presynaptic inhibition in Parkinson disease (PD) is impaired. Eleven patients with PD were studied at rest both OFF and ON dopaminergic medications and the results were compared to nine healthy, age-matched controls. Motor evoked potentials were recorded from the first dorsal interosseous muscle and a triple-stimulus transcranial magnetic stimulation paradigm was used to evaluate SICI in the presence of LICI. The interstimulus interval (ISI) for SICI was 2 msec and LICI was studied at 100 (LICI(100)) and 150 msec (LICI(150)) ISIs. There was no difference in SICI between the controls and PD ON and PD OFF groups. LICI(100) was stronger than LICI(150) and both were reduced in the PD ON and OFF groups. LICI(100) led to a much greater reduction in SICI in the control group compared to both the PD OFF and ON groups. LICI(150) caused no significant change in SICI with no significant difference between the controls and PD OFF and PD ON groups. The inhibitory effect of long interval intracortical inhibition on short interval intracortical inhibition, likely representing presynpatic inhibition in the motor cortex, is decreased in Parkinson disease and may be a nondopaminergic feature of the disease.

Deep Brain Stimulation of the Subthalamic Nucleus Facilitates Coordination of Hand Preshaping in Parkinson's Disease

Several studies have found that Parkinson's disease (PD) disrupts the organization of complex motor sequences regardless of the influence of parkinsonian medications. A clear candidate for the neural bases of such deficits, which we term “coordinative,” is the failure to integrate propioceptive and visual information by cortico-striatal circuits in a timed fashion. Recent reports, however, have indicated that deep-brain stimulation of the subthalamic nucleus (STN DBS) may result in an improvement in coordinative deficits beyond the amelioration of “intensive deficits” such as bradykinesia and scaling errors. The present study examined the spatio-temporal organization underlying the shaping of the hand during reaching to grasp objects differing in shape. Six PD patients ON and OFF their STN DBS when OFF their concomitant medications and six age-matched controls participated in this study. STN DBS improved the coordination involved in preshaping the hand while grasping. We discuss these results in light of our earlier work with PD patients on and off dopamine replacement therapy.

Lateral Stepping for Postural Correction in Parkinson’s Disease

King LA, Horak FB. Lateral stepping for postural correction in Parkinson’s disease. Objective To characterize the lateral stepping strategies for postural correction in patients with Parkinson’s disease (PD) and the effect of their anti-parkinson medication. Design Observational study. Setting Outpatient neuroscience laboratory. Participants Thirteen participants with idiopathic PD in their on (PD on) and off (PD off) levodopa state and 14 healthy elderly controls. Interventions Movable platform with lateral translations of 12cm at 14.6cm/s ramp velocity. Main Outcome Measures The incidence and characteristics of 3 postural strategies were observed: lateral side-step, crossover step, or no step. Corrective stepping was characterized by latency to step after perturbation onset, step velocity, and step length and presence of an anticipatory postural adjustment (APA). Additionally, percentages of trials resulting in falls were identified for each group. Results Whereas elderly control participants never fell, PD participants fell in 24% and 35% of trials in the on and off medication states, respectively. Both PD and control participants most often used a lateral side-step strategy; 70% (control), 67% (PD off), and 73% (PD on) of all trials, respectively. PD participants fell most often when using a crossover strategy (75% of all crossover trials) or no-step strategy (100% of all no-step trials). In the off medication state, PD participants’ lateral stepping strategies were initiated later than controls (370±37ms vs 280±10ms, P<.01), and steps were smaller (254±20mm vs 357±17mm, P<.01) and slower (0.99±0.08m/s vs 1.20±0.07m/s, P<.05). No differences were found between the PD off versus PD on state in the corrective stepping characteristics. Unlike control participants, PD participants often (56% of side-step strategy trials) failed to activate an APA before stepping, although their APAs, when present, were of similar latency and magnitude as for control participants. Levodopa on or off state did not significantly affect falls, APAs, or lateral step latency, velocity, or amplitude ( P>.05). Conclusions PD participants showed significantly more postural instability and falls than age-matched controls when stepping was required for postural correction in response to lateral disequilibrium. Although PD participants usually used a similar lateral stepping strategy as controls in response to lateral translations, lack of an anticipatory lateral weight shift, and bradykinetic characteristics of the stepping responses help explain the greater rate of falls in participants with PD. Differences were not found between the levodopa on and off states. The results suggest that rehabilitation aimed at improving lateral stability in PD should include facilitating APAs before a lateral side-stepping strategy with faster and larger steps to recover equilibrium.

Role of dopamine in cognitive control: Insights from pharmacological neuroimaging

Event Abstract Back to Event Role of dopamine in cognitive control: Insights from pharmacological neuroimaging Roshan Cools1* 1 Radboud University Nijmegen, Netherlands Our constantly changing environment requires a dynamic balance between cognitive flexibility and cognitive stability. How do we regulate this balance? We tested the hypothesis that changes in dopamine may shift the balance between cognitive flexibility and stability by modulating striatal and frontal activity respectively. To this end, we assessed the neural effects of dopamine receptor stimulation in young healthy volunteers with fMRI and the behavioral effects of common anti-parkinson medication in patients with Parkinson's disease. A paradigm was employed that allowed the separate investigation of cognitive flexibility (switching) and cognitive stability (distractor-resistence in working memory). Results revealed that dopamine receptor stimulation modulated striatal activity during switching, but frontal activity during distraction. Furthermore, striatal dopamine depletion in patients with Parkinson's disease off their normal medication was associated with numerically larger switch-costs, and significantly smaller distractor-costs. The abnormal distractor-resistence in patients off their medication may reflect over-focusing on currently relevant information. Based on the above-mentioned fMRI study, we hypothesize that this effect reflects up-regulation of frontal dopamine. Dopaminergic medication restored performance, probably by normalizing the balance between striatal and frontal dopamine. These data suggest that the balance between cognitive flexibility and stability might be subserved by a dynamic and reciprocal relationship between dopamine in the striatum and dopamine in the frontal cortex. Conference: 10th International Conference on Cognitive Neuroscience, Bodrum, Turkey, 1 Sep - 5 Sep, 2008. Presentation Type: Oral Presentation Topic: Symposium 8: Dopaminergic modulation of memory and cognitive control Citation: Cools R (2008). Role of dopamine in cognitive control: Insights from pharmacological neuroimaging. Conference Abstract: 10th International Conference on Cognitive Neuroscience. doi: 10.3389/conf.neuro.09.2009.01.039 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Nov 2008; Published Online: 27 Nov 2008. * Correspondence: Roshan Cools, Radboud University Nijmegen, Nijmegen, Netherlands, roshan.cools@fcdonders.ru.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Roshan Cools Google Roshan Cools Google Scholar Roshan Cools PubMed Roshan Cools Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Enhancement of rigidity in Parkinson's disease with activation

Rigidity, a cardinal symptom of Parkinson's disease (PD), increases with movement of a contralateral limb. It is unclear whether this effect is specific for movement of a contralateral limb. The goal of this study was to test the hypothesis that ipsilateral or contralateral movement would enhance rigidity but that bilateral limb movements would maximally increase rigidity in people with PD. We assessed rigidity in 12 people with PD off meds, 12 matched controls, and 10 young controls, using a Rigidity Analyzer (Neurokinetics, Alberta, Canada). The elbow was passively moved repetitively into flexion and extension by the examiner, while the subjects engaged in different toe tapping conditions: no tapping, ipsilateral tapping, contralateral tapping, and bilateral tapping. Three 50-second trials were done for each condition and the order of the trials was randomized. A 2-way repeated measures ANOVA and Holm-Sidak post hoc tests were used to determine differences across conditions and groups. There was a significant effect of group, tapping conditions and an interaction of the two. Post hoc tests revealed that for the PD group, all tapping conditions were significantly different from the no tapping condition but not different from each other. There were no differences across conditions for the controls. We conclude that movement of either the contralateral or ipsilateral lower extremity can increase arm rigidity in people with PD but the effects from left and right are apparently not additive. Further, activation did not enhance muscle tone in controls suggesting that this procedure may help distinguish people with PD from controls.

Motor function in Parkinson's disease and supranuclear palsy: simultaneous factor analysis of a clinical scale in several populations

BackgroundIn order to better understand the similarities and differences in the motor behaviour of different groups of patients, their scores on the Motor Examination section of the Unified Parkinson's Disease Rating Scale (UPDRS) were analysed simultaneously. The three groups consisted, respectively, of patients with Parkinson's disease (PD) on medication, patients with Parkinson's disease withdrawn from anti-parkinsonian medication for at least 12 hours, and patients diagnosed with a specific Parkinsonism syndrome: Progressive Supranuclear Palsy (PSP).MethodsA total of 669 consecutively sampled patients from three separate hospital-based clinics participated (294 PD on medication; 200 PD off medication: 175 PSP). The Motor Examination section of the UPDRS was administered by neurologists at the three participating clinics. The patient scores on each item were recorded. To assess similarities and differences among the components of the UPDRS in these samples, we performed simultaneous or multigroup factor analysis on the covariance matrices of the three groups. In addition, it was investigated whether a single model for the Motor Examination section of the UPDRS could be developed which would be valid for all three groups at the same time.ResultsA single six-dimensional factor solution was found that fitted all groups, although this was not straightforward due to differences between the tremor-at-rest variables. The factors were identified as Tremor-at-rest, Postural Tremor, Axial Dysfunctioning, Rigidity, Left Bradykinesia and Right Bradykinesia. The analysis also pointed to a somewhat lower lateralization in bradykinesia for PSP patients. The groups differed in intensity of motor impairment, especially with respect to Tremor-at-Rest, but the overall relationships between the variables were shared by the three groups. In addition, apart from the common factor structure evidence of differences in body part-specific and motor-specific variances was found.ConclusionFrom a clinical point of view, the analyses showed that using the Motor Examination section of the UPDRS is also appropriate for patients with PSP, because the correlational structure of the items is directly comparable to that of Parkinson's patients. Methodologically, the analysis of all groups together showed that it is possible to evaluate similarities and differences between factor structures in great detail.