Impaired savings despite intact initial learning of motor adaptation in Parkinson’s disease

In motor adaptation, the occurrence of savings (faster relearning of a previously learned motor adaptation task) has been explained in terms of operant reinforcement learning (Huang et al. in Neuron 70(4):787–801, 2011), which is thought to associate an adapted motor command with outcome success during repeated execution of the adapted movement. There is some evidence for deficient savings in Parkinson’s Disease (PD), which might result from deficient operant reinforcement processes. However, this evidence is compromised by limited adaptation training during initial learning and by multi-target adaptation, which reduces the number of reinforced movement repetitions for each target. Here, we examined savings in PD patients and controls following overlearning with a single target. PD patients showed less savings than controls after successive adaptation and deadaptation blocks within the same test session, as well as less savings across test sessions separated by a 24-h delay. It is argued that impaired blunted dopaminergic signals in PD impairs the modulation of dopaminergic signals to the motor cortex in response to rewarding motor outcomes, thus impairing the association of the adapted motor command with rewarding motor outcomes. Consequently, the previously adapted motor command is not preferentially selected during relearning, and savings is impaired.     

Intraganglionic macrophages: a new population of cells in the enteric ganglia

The enteric nervous system shares embryological, morphological, neurochemical, and functional features with the central nervous system. In addition to neurons and glia, the CNS includes a third component, microglia, which are functionally and immunophenotypically similar to macrophages, but a similar cell type has not previously been identified in enteric ganglia. In this study we identify a population of macrophages in the enteric ganglia, intermingling with the neurons and glia. These intraganglionic macrophages (IMs) are highly ramified and express the hematopoietic marker CD45, major histocompatibility complex (MHC) class II antigen, and chB6, a marker specific for B cells and microglia in avians. These IMs do not express antigens typically associated with T cells or dendritic cells. The CD45⁺/ChB6⁺/MHCII⁺ signature supports a hematopoietic origin and this was confirmed using intestinal chimeras in GFP‐transgenic chick embryos. The presence of green fluorescent protein positive (GFP⁺⁾/CD45⁺ cells in the intestinal graft ENS confirms that IMs residing within enteric ganglia have a hematopoietic origin. IMs are also found in the ganglia of CSF1R^GFP chicken and CX3CR1^GFP mice. Based on the expression pattern and location of IMs in avians and rodents, we conclude that they represent a novel non‐neural crest‐derived microglia‐like cell population within the enteric ganglia.     

The effect of cerebellar cortical degeneration on adaptive plasticity and movement control

Clinical and neuroimaging studies provide converging evidence that the cerebellum plays an important role for sensorimotor adaptation by participating in the adaptive process per se, and/or by evaluating motor performance errors as a prerequisite for adaptation. Recent experimental evidence suggests that error signals pertinent to adaptation are related to sensory prediction rather than to online corrections (Tseng et al. in J Neurophysiol 98(1):54–62, 2007). To further elucidate the role of the cerebellum, the present study uses a multiple regression approach to separate out three independent determinants of adaptive success. Seventeen patients with cerebellar atrophy but without extra-cerebellar lesions, and 17 healthy, sex- and age-matched controls participated. Both subject groups performed center-out pointing movements before, during, and after exposure to 60° rotated visual feedback. From the registered data, we quantified four indicators of adaptive success (adaptive improvement, retention without feedback, intermanual transfer, and de-adaptation under normal feedback), as well as five measures of motor performance (reaction time, peak velocity, movement time, response variability, and ability for online error corrections). The variance of each adaptation indicator was then partitioned into three components, one related to subject group but not to motor performance, a second related to group and motor performance, and a third related to motor performance but not to group. In accordance with previous work, adaptation and motor performance were degraded in patients. The deficit was similar in magnitude for all four adaptation indicators, which suggests that adaptive recalibration rather than strategic control were affected in our patients. No adaptation indicator shared statistically significant variance with group alone; we therefore found no evidence for cerebellar circuitry dedicated to adaptation but not motor performance. Three indicators shared significant variance jointly with group and motor performance; this suggests that the cerebellar contribution to motor performance is related to adaptive success. All four indicators shared significant variance with motor performance alone; this indicates that extracerebellar contributions to motor performance are also related to adaptive success. In conclusion, our data support the view that neural structures inside and outside the cerebellum are processing motor performance-related signals as a prerequisite for adaptation, but provide no evidence for a cerebellar structure related exclusively to adaptation.

Strength training for 1h in humans: effect on the motor performance of normal upper extremities

It has been found that one session of intense muscle strength training decreases muscle strength temporarily and causes neuromuscular fatigue in the trained muscles, but little attention has been given to the effects of neuromuscular fatigue on the other components of motor performance. The purpose of this study was to examine in normal healthy volunteers the effects of a 1-h strength training session on the motor performance of the upper extremity, including reaction time, speed of movement, tapping speed and coordination. Group of 30 healthy female volunteers, aged 29–47 years, were randomly divided into sub-groups, (A and B, n?=?15 per group). Both groups first completed a set of motor performance tests on 3 consecutive days. On the 4th day, group A carried out a 1-h muscle strength training session of the upper extremities. Isometric muscle strengths and electromyogram (EMG) data were recorded before the training session. Immediately after the training session the same recordings were repeated, and additional motor performance tests were also performed. Group B carried out only the motor performance tests. The groups exchanged programmes the following week. The 1-h strength training session decreased the isometric muscle strength of wrist flexion by 18% (P?P?P?P?相似文献   

Saccadic-like visuomotor adaptation involves little if any perceptual effects

Studies on visuomotor adaptation provide crucial clues on the functional properties of the human motor system. The widely studied saccadic adaptation paradigm is a major example of such a fruitful field of investigation. Magescas and Prablanc (J Cogn Neurosci 18(1):75–83, 2006) proposed a transposition of this protocol to arm pointing behavior, by designing an experiment in which the informational context of the upper limb visuomotor system is comparable to that of the saccadic system. Subjects were given terminal only visual feedback in a hand pointing task, assumed to produce a purely terminal visual error signal. Importantly, this paradigm has been shown to induce no saccadic adaptation. Although the saccadic adaptation paradigm is known to induce a predominantly motor adaptation with minor sensory effects, the lack of sensory changes has not been tested in its transposition to pointing. The present study was a partial replication of Magescas and Prablanc’s (J Cogn Neurosci 18(1):75–83, 2006) study with additional control tests. A first experiment searched for a possible change in the static visual-to-proprioceptive congruency. A second experiment, based on an anti-pointing task, aimed at separating the sensory and motor effects of the adaptation in a dynamic condition. Consistent with most results on saccadic adaptation, we found a predominant adaptation of the motor components, with little if any involvement of the sensory components. Results are interpreted by proposing a causal relationship between the type of error signal and its adaptive effects.     

Influences of environmental-context changes on rehearsal effects in episodic memory]

Does rehearsal facilitate association between to-be-remembered items and environmental context (EC) as well as it strengthen the individual traces of items? The answer from the present experiment was affirmative. Subjects, 183 undergraduates, studied a list of 15 familiar nouns by rehearsing aloud with a subsidiary task, and then received a free recall test under one of three conditions: immediate recall (IM), same context (SC), and different context (DC). Subjects in IM were tested immediately after the study session, while the other subjects were tested 24 hours after the study session. The tests in IM and SC were conducted at the same place with the same experimenter after the same subsidiary task as the study session, whereas the test in DC were conducted at a different place with a different experimenter without the task. The magnitudes in DC of the effect of the number of rehearsals on free recall were about one-half of those in IM and SC, whereas the magnitudes in IM were nearly identical to those in SC. The results indicate that the rehearsal effect is one of EC-dependent phenomena.     

Movement chunking during sequence learning is a dopamine-dependant process: a study conducted in Parkinson’s disease

Chunking of single movements into integrated sequences has been described during motor learning, and we have recently demonstrated that this process involves a dopamine-dependant mechanism in animal (Levesque et al. in Exp Brain Res 182:499–508, 2007; Tremblay et al. in Behav Brain Res 198:231–239, 2009). However, there is no such evidence in human. The aim of the present study was to assess this question in Parkinson’s disease (PD), a neurological condition known for its dopamine depletion in the striatum. Eleven PD patients were tested under their usual levodopa medication (ON state), and following a 12-h levodopa withdrawal (OFF state). Patients were compared with 12 healthy participants on a motor learning sequencing task, requiring pressing fourteen buttons in the correct order, which was determined by visual stimuli presented on a computer screen. Learning was assessed from three blocks of 20 trials administered successively. Chunks of movements were intrinsically created by each participant during this learning period. Then, the sequence was shuffled according to the participant’s own chunks, generating two new sequences, with either preserved or broken chunks. Those new motor sequences had to be performed separately in a fourth and fifth blocks of 20 trials. Results showed that execution time improved in every group during the learning period (from blocks 1 to 3). However, while motor chunking occurred in healthy controls and ON-PD patients, it did not in OFF-PD patients. In the shuffling conditions, a significant difference was seen between the preserved and the broken chunks conditions for both healthy participants and ON-PD patients, but not for OFF-PD patients. These results suggest that movement chunking during motor sequence learning is a dopamine-dependent process in human.     

Induction of cortical plastic changes in wrist muscles by paired associative stimulation in healthy subjects and post-stroke patients

It has been shown on hand muscles in normal subjects that paired associative stimulation (PAS) combining peripheral nerve stimulation and transcranial magnetic stimulation (TMS) induces lasting changes in cortical motor excitability (Stefan et al., Brain 123 (Pt3):572–584, 2000). Because the motor recovery of distal upper limb and particularly wrist extension in post-stroke patients is one of the major rehabilitation challenge, we investigate here the effect of one session of paired associative stimulation on the excitability of the corticospinal projection to extensor carpi radialis (ECR) muscle (motor evoked potential size) before and after PAS in 17 healthy subjects and in two patients 5 months after stroke. The time course, the topographical specificity, changes in rest motor threshold (RMT), short intracortical inhibition and intracortical facilitation (SICI and ICF), the respective role of cutaneous and muscular afferents and the effect of a prolonged peripheral stimulation alone were also studied in normal subjects. Using a protocol derived from that of Ridding et al. J Physiol 537:623–631 (2001), PAS was able to induce lasting changes in the excitability of corticospinal projection to wrist muscles in healthy subjects and in the two post-stroke patients studied. Electrophysiological features of these plastic changes were similar to those previously observed in hand muscles: rapid evolution, 30–60 min duration, reversibility, relative topographical specificity and associative dependence suggesting an LTP-like mechanism. A contribution of cutaneous afferents in inducing PAS effects was also demonstrated. The decrease in ECR RMT after PAS observed in patients and in healthy subjects was an unexpected result because it has not been previously reported in the hand muscles of healthy subjects. However, it has been observed in dystonic patients (Quartarone et al., Brain 126:2586–2596, 2003). This suggests that other mechanisms like changes in membrane excitability could be involved in ECR facilitation after PAS. Further studies performed on patients using daily repeated PAS protocols and showing a functional improvement in hand motor function will be necessary to confirm that this technique could be relevant in motor rehabilitation, at least for some selected patients.     

Corticomotor facilitation associated with observation and imagery of hand actions is impaired in Parkinson’s disease

In the present report, we extend our previous observations on corticomotor facilitation associated with covert (action observed or imagined) and overt (action imitated) action execution in old adults (Leonard and Tremblay in Exp Brain Res 117:167–175, 2007) to investigate the impact of Parkinson’s disease (PD). Participants consisted of 22 older adults (age range 58–76 years) of whom 11 were medicated patients diagnosed with PD (patient group) and 11 were age-matched healthy controls (healthy group). Corticomotor facilitation was assessed by monitoring the changes in the amplitude of motor evoked potentials (MEP) in muscles of the right hand (first dorsal interosseous: FDI; and abductor digiti minimi: ADM) in response to transcranial magnetic stimulation of the left motor cortex. In each group, corticomotor facilitation was assessed with participants seated in front of a computer screen under four testing conditions: (1) REST: eyes closed and instructions to relax for 10 s, (2) OBS: observe action, (3) IMAG: imagine action and (4) IMIT: imitate action. The action depicted in the video displayed the hand of a male subject cutting a piece of material with scissors. Comparison of variations in MEP amplitude revealed a significant interaction between groups and conditions. In the healthy group, the OBS and IMAG conditions were both associated with significant facilitation in the FDI and ADM, whereas the same conditions failed to produce facilitation in the PD group. In both groups, the IMIT condition produced the largest facilitation in hand muscles. Further planned comparisons revealed a significant difference between groups in the FDI for the OBS condition. From these findings, we conclude that, even when properly medicated, old adults with PD may experience major difficulties in engaging the motor system for covert actions, particularly when asked to observe another person’s action. This failure of corticomotor facilitation for covert actions appears to be linked with the deficit in motor activation associated with basal ganglia dysfunction in PD and in line with the difficulty experienced in general by patients “to energize” the motor system in preparation for action.     

Depth perception in cerebellar and basal ganglia disease

There is increasing evidence that the cerebellum and the basal ganglia serve not only a role in motor control but also in visual perception. Patients with Parkinson’s disease (PD) as well as patients with cerebellar lesions exhibit impairments of vision that are not fully explained by ocular motor deficits. It is less clear to which extent these visual deficits contribute to an impaired control of visually guided movements. This study examined whether a dysfunction of the cerebellum or the basal ganglia induces impairments in depth perception, which affect action. We employed an illusionary display, the Ames trapezoidal window, to determine the ability of PD patients (n=10) and patients with spinocerebellar ataxia (SCA) (n=6) to process depth cues when estimating object slant. Participants either pointed to the edges of the window (motor judgement) or verbally indicated the perceived orientation of the display (verbal judgement). To control for ocular and limb motor deficits, participants judged the slant of a non-illusionary display in a second task. Slant estimation of the non-illusionary window was not impaired in either patient group when compared to control subjects (all P>0.2). In contrast, SCA as well as PD patients exhibited significantly greater slant estimation errors than controls when pointing to the illusionary window (P=0.005). In addition, both patient groups made larger errors than controls in their verbal judgements during binocular viewing of the illusion (P=0.005), but not during monocular viewing (P>0.2). In sum, the present findings point towards a role for both the basal ganglia and cerebellum for the processing of visual information about depth. Since the deficits were seen both in the context of action and perception and were only partially reconciled by the availability of binocular depth cues, we conclude that basal ganglia as well as cerebellar disease may affect the visual perception of depth.     

Immunohistochemistry and effect of vinblastine on intracisternal microtubules of the canine neurons

The immuno-histochemical and drug-binding properties of intracisternal microtubules (IMs) in the RER of canine neurons were studied with antitubulin IgG and vinblastine. Specific fluorescence against antitubulin IgG was not detected in the RER in which the IMs were aggregated but was observed in the cytoplasm outside the RER. Injection of vinblastine into the sympathetic ganglion did not change the size, shape or arrangement of IMs in the RER, although typical honeycomb crystals were formed near IM-containing RER. These findings show that the IM does not possess antigenicity to antitubulin IgG and has no vinblastine-binding site. Thus it is suggested that the IM may be a defective or modified microtubule.     

Basal ganglia circuits changes in Parkinson's disease patients

Functional changes in basal ganglia circuitry are responsible for the major clinical features of Parkinson's disease (PD). Current models of basal ganglia circuitry can only partially explain the cardinal symptoms in PD. We used functional MRI to investigate the causal connectivity of basal ganglia networks from the substantia nigra pars compacta (SNc) in PD in the movement and resting state. In controls, SNc activity predicted increased activity in the supplementary motor area, the default mode network, and dorsolateral prefrontal cortex, but, in patients, activity predicted decreases in the same structures. The SNc had decreased connectivity with the striatum, globus pallidus, subthalamic nucleus, thalamus, supplementary motor area, dorsolateral prefrontal cortex, insula, default mode network, temporal lobe, cerebellum, and pons in patients compared to controls. Levodopa administration partially normalized the pattern of connectivity. Our findings show how the dopaminergic system exerts influences on widespread brain networks, including motor and cognitive networks. The pattern of basal ganglia network connectivity is abnormal in PD secondary to dopamine depletion, and is more deviant in more severe disease. Use of functional MRI with network analysis appears to be a useful method to demonstrate basal ganglia pathways in vivo in human subjects.     

Procedural motor learning in Parkinson's disease

We have been investigating motor control and learning in parkinsonian subjects. In the current study, we sought to explore the existence of deficits in procedural motor learning, which is a form of implicit motor learning where skill improves over repetitive blocks of trials. We sought to determine, in particular, whether any such deficit is accentuated during specific types or phases of learning. We would expect that those specific learning tasks would require the greatest participation of the basal ganglia. Numerous studies have found that Parkinson's disease (PD) patients may show deficits in learning. Combined with information about basal ganglia neuronal connections and activity, this led some investigators to suggest that one of the key functions of the basal ganglia is to facilitate learning. To investigate these learning deficits, we used a robotic device to generate conservative force fields that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that subjects learned to manipulate. Movements were successively grouped into blocks comprising five different conditions: motor performance, early learning, late learning, negative transfer, and aftereffect motor performance. Our results with eight right-handed PD subjects and nine age-matched controls showed a relative decrease in the rate of learning for the PD patients in all blocks, but greater differences emerged between groups during novelty phases of learning. In particular, the difference in performance during the negative transfer condition reached statistical significance, suggesting that the basal ganglia might be a key center for "switching" motor patterns. Our results support the hypothesis that deficiencies in procedural motor learning are characteristic of PD. They add to existing evidence which has suggested a key role for the basal ganglia when new sensorimotor mappings are required by novel task environments. Better understanding of these deficits should facilitate the rehabilitation of PD patients.     

Lock-and-key mechanisms of cerebellar memory recall based on rebound currents

A basic question for theories of learning and memory is whether neuronal plasticity suffices to guide proper memory recall. Alternatively, information processing that is additional to readout of stored memories might occur during recall. We formulate a "lock-and-key" hypothesis regarding cerebellum-dependent motor memory in which successful learning shapes neural activity to match a temporal filter that prevents expression of stored but inappropriate motor responses. Thus, neuronal plasticity by itself is necessary but not sufficient to modify motor behavior. We explored this idea through computational studies of two cerebellar behaviors and examined whether deep cerebellar and vestibular nuclei neurons can filter signals from Purkinje cells that would otherwise drive inappropriate motor responses. In eyeblink conditioning, reflex acquisition requires the conditioned stimulus (CS) to precede the unconditioned stimulus (US) by >100 ms. In our biophysical models of cerebellar nuclei neurons this requirement arises through the phenomenon of postinhibitory rebound depolarization and matches longstanding behavioral data on conditioned reflex timing and reliability. Although CS–US intervals <100 ms may induce Purkinje cell plasticity, cerebellar nuclei neurons drive conditioned responses only if the CS–US training interval was >100 ms. This bound reflects the minimum time for deinactivation of rebound currents such as T-type Ca²⁺. In vestibulo-ocular reflex adaptation, hyperpolarization-activated currents in vestibular nuclei neurons may underlie analogous dependence of adaptation magnitude on the timing of visual and vestibular stimuli. Thus, the proposed lock-and-key mechanisms link channel kinetics to recall performance and yield specific predictions of how perturbations to rebound depolarization affect motor expression.     

The control of bimanual reach-to-grasp movements in hemiparkinsonian patients

The basal ganglia are thought to participate in the control and programming of a variety of motor behaviours. However, the precise nature of this participation still remains to be clarified. This paper examines the proposal that the basal ganglia may serve to scale the amplitude of limb movements, with basal-ganglia dysfunction leading to the inappropriate scaling of intended motor activity. Several authors have suggested that examining the loss of function in Parkinson's-disease (PD) patients offers perhaps the best way of learning about the role played by the basal ganglia in human motor function. While it has previously been reported that PD patients underscale the transport phase of their reach-to grasp movements, it has generally been assumed that the grasp component is normal. In this paper we demonstrate, using a group of hemiparkinson patients, that the scaling of the grasp component is also underscaled in PD patients.     

Bilateral basal ganglia activation associated with sensorimotor adaptation

Sensorimotor adaptation tasks can be classified into two types. When subjects adapt movements to visual feedback perturbations such as in prism lens adaptation, they perform kinematic adaptations. When subjects adapt movements to force field perturbations such as with robotic manipulanda, they perform kinetic adaptations. Neuroimaging studies have shown basal ganglia involvement in kinetic adaptations, but have found little evidence of basal ganglia involvement in kinematic adaptations, despite reports of deficits in patients with diseases of the basal ganglia, such as Parkinson’s and Huntington’s disease, in these. In an effort to resolve such apparent discrepancy, we used FMRI to focus on the first few minutes of practice during kinematic adaptation. Human subjects adapted to visuomotor rotations in the context of a joystick aiming task while lying supine in a 3.0 T MRI scanner. As demonstrated previously, early adaptive processes were associated with BOLD activation in the cerebellum and the sensory and motor cortical regions. A novel finding of this study was bilateral basal ganglia activation. This suggests that, at least for early learning, the neural correlates of kinematic adaptation parallel those of other types of skill learning. We observed activation in the right globus pallidus and putamen, along with the right prefrontal, premotor and parietal cortex, which may support spatial cognitive processes of adaptation. We also observed activation in the left globus pallidus and caudate nucleus, along with the left premotor and supplementary motor cortex, which may support the sensorimotor processes of adaptation. These results are the first to demonstrate a clear involvement of basal ganglia activation in this type of kinematic motor adaptation.     

Motor sequencing deficits in schizophrenia: a comparison with Parkinson's disease

Motor abnormalities occur in schizophrenia (SZ) and may arise from striatal dysfunction. This study examined whether the pattern of performance on simple and complex motor abilities in SZ was similar to that of patients with Parkinson's disease (PD). Quantitative tests of speeded movement and motor and cognitive sequencing were used to assess 25 SZ, 16 PD, and 84 normal controls (NCs). Sequencing performance was also examined with motor rigidity taken into account. Compared with the NC group, the SZ and PD groups were impaired on measures of motor rigidity and motor sequencing. With rigidity accounted for, the SZ group was significantly more impaired than the PD group on motor sequencing; cognitive and motor processes contributed to the motor deficit. Cognitive sequencing performance predicted motor sequencing performance in PD but not SZ. Although both SZ and PD resulted in significant motor and cognitive sequencing deficits, the pattern and correlates of these deficits differ, suggesting that the affected neural systems underlying motor deficits in SZ are different from those involved in PD.     

Visuomotor learning in immersive 3D virtual reality in Parkinson’s disease and in aging

Successful adaptation to novel sensorimotor contexts critically depends on efficient sensory processing and integration mechanisms, particularly those required to combine visual and proprioceptive inputs. If the basal ganglia are a critical part of specialized circuits that adapt motor behavior to new sensorimotor contexts, then patients who are suffering from basal ganglia dysfunction, as in Parkinson's disease should show sensorimotor learning impairments. However, this issue has been under-explored. We tested the ability of 8 patients with Parkinson's disease (PD), off medication, ten healthy elderly subjects and ten healthy young adults to reach to a remembered 3D location presented in an immersive virtual environment. A multi-phase learning paradigm was used having four conditions: baseline, initial learning, reversal learning and aftereffect. In initial learning, the computer altered the position of a simulated arm endpoint used for movement feedback by shifting its apparent location diagonally, requiring thereby both horizontal and vertical compensations. This visual distortion forced subjects to learn new coordinations between what they saw in the virtual environment and the actual position of their limbs, which they had to derive from proprioceptive information (or efference copy). In reversal learning, the sign of the distortion was reversed. Both elderly subjects and PD patients showed learning phase-dependent difficulties. First, elderly controls were slower than young subjects when learning both dimensions of the initial biaxial discordance. However, their performance improved during reversal learning and as a result elderly and young controls showed similar adaptation rates during reversal learning. Second, in striking contrast to healthy elderly subjects, PD patients were more profoundly impaired during the reversal phase of learning. PD patients were able to learn the initial biaxial discordance but were on average slower than age-matched controls in adapting to the horizontal component of the biaxial discordance. More importantly, when the biaxial discordance was reversed, PD patients were unable to make appropriate movement corrections. Therefore, they showed significantly degraded learning indices relative to age-matched controls for both dimensions of the biaxial discordance. Together, these results suggest that the ability to adapt to a sudden biaxial visuomotor discordance applied in three-dimensional space declines in normal aging and Parkinson disease. Furthermore, the presence of learning rate differences in the PD patients relative to age-matched controls supports an important contribution of basal ganglia-related circuits in learning novel visuomotor coordinations, particularly those in which subjects must learn to adapt to sensorimotor contingencies that were reversed from those just learned.     

Dynamic changes in cerebello-thalamo-cortical motor circuitry during progression of Parkinson's disease

Both the basal ganglia and cerebellum are known to influence cortical motor and motor-associated areas via the thalamus. Whereas striato-thalamo-cortical (STC) motor circuit dysfunction has been implicated clearly in Parkinson's disease (PD), the role of the cerebello-thalamo-cortical (CTC) motor circuit has not been well defined. Functional magnetic resonance imaging (fMRI) is a convenient tool for studying the role of the CTC in vivo in PD patients, but large inter-individual differences in fMRI activation patterns require very large numbers of subjects in order to interpret data from cross-sectional, case control studies. To understand the role of the CTC during PD progression, we obtained longitudinal fMRI 2 years apart from 5 PD (57±8 yr) and five Controls (57±9 yr) performing either externally- (EG) or internally-guided (IG) sequential finger movements. All PD subjects had unilateral motor symptoms at baseline, but developed bilateral symptoms at follow-up. Within-group analyses were performed by comparing fMRI activation patterns between baseline and follow-up scans. Between-group comparisons were made by contrasting fMRI activation patterns generated by the more-affected and less-affected hands of PD subjects with the mean of the dominant and non-dominant hands of Controls. Compared to baseline, Controls showed changes in CTC circuits, but PD subjects had increased recruitment of both cortical motor-associated and cerebellar areas. Compared to Controls, PD subjects demonstrated augmented recruitment of CTC circuits over time that was statistically significant when the IG task was performed by the hand that transitioned from non-symptomatic to symptomatic. This longitudinal fMRI study demonstrates increased recruitment of the CTC motor circuit concomitant with PD progression, suggesting a role of the CTC circuit in accommodation to, or pathophysiology of, PD.     

A Network Analysis of 15O-H2O PET Reveals Deep Brain Stimulation Effects on Brain Network of Parkinson's Disease

Purpose

As Parkinson''s disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies.

Materials and Methods

We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects.

Results

ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum.

Conclusion

Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.