Execution Of Motor Tasks Research Articles

Multivariate analysis: Applications to the study of hereditary movement disorders

Idiopathic torsion dystonia and Huntington’s disease represent autosomal dominant inherited hyperkinetic disorders that vary considerably with regard to pathologic mechanisms and clinical penetrance. To study these mechanisms, non-manifesting DYT1 mutation carriers (nmDYT1) and presymptomatic HD gene carriers (p-HD), as well as age-matched controls were scanned with (i) FDG PET in the resting state, and (ii) 15O-labeled water PET while performing a motor sequence learning task and motor execution task. We used voxel-based principal components analysis (PCA) to isolate the effects of genotype on regional metabolism in the resting state and on patterns of activation during motor performance. We detected two specific genotype-related metabolic patterns in the resting state. The torsion dystonia-related pattern was characterized by hypermetabolism of the basal ganglia, cerebellum and the supplementary motor area (SMA). By contrast, the voxel-based HD-related pattern displayed reductions in caudate and putamen metabolic activity associated with relative increases in the thalamus, the calcarine cortex, and primary motor cortex. Both mutations were associated with sequence learning deficits compared to controls. Carriers of each genotype activated different networks while performing the sequence learning task. In nmDYT1, learning was associated with activation of a specific network involving the cerebellar hemispheres, the left pre-SMA and anterior cingulate region, as well as inferior prefrontal and occipital association cortices. In p-HD, the learning network involved activation of the orbitofrontal and occipital association regions bilaterally, the left mediodorsal thalamus, and the right cerebellar hemisphere. These topographies illustrate the utility of PCA in identifying functional abnormalities in fronto-striatal loops and related pathways.

How do the elderly negotiate a step? A biomechanical assessment

Tripping over a raised surface is considered to be the most common cause of falls in the elderly. The aim of this study was to detect alterations of the motor pattern of elderly subjects while climbing a single step ("one step negotiation") which may account for tripping and risk of falling. We tested a sample of 32 "healthy" elderly subjects with a mean age of 72.4 years (SD 4.81; range 65-86). The control group consisted of 18 young subjects with a mean age of 26.5 years (SD 2.12; range 24-33). An experimental set-up for kinematic assessment while climbing a single step was provided. The elderly population was characterized clinically and functionally by a comprehensive geriatric assessment including information about comorbidity, disability, depression, motor, and muscular function. Despite the high level of motor ability measured clinically, biomechanical analysis enabled us to demonstrate precise changes in step-climbing strategy in the elderly. A prolonged double stance phase duration, a greater anterior flexion of the trunk, a greater flexion of the hip, and a reduced dorsiflexion of the ankle were detected with respect to controls. All these factors and especially the latter could be determinants in the possible risk of tripping. The biomechanical analysis performed on a population of healthy elderly subject has shown precise abnormalities of the trunk, hip and ankle kinematic during the motor task execution. This information can be of relevance in planning physical activity programs adapted for elderly and aimed at reducing the risk of tripping and falling.

Compensatory cortical mechanisms in Parkinson's disease evidenced with fMRI during the performance of pre-learned sequential movements

We used fMRI to study brain activity associated with the performance of a pre-learned sequence of complex movements of the hand-made unimanually in a group of 13 Parkinson's disease patients and a group of 11 control volunteers. Patients were scanned “off” medication. In controls, sequential movements led to the activation of bilateral sensorimotor and premotor cortex, bilateral inferior parietal cortex, supplementary motor area, bilateral putamen and globus pallidus, and the left ventral lateral nucleus of the thalamus. Sequential movements in the Parkinson's disease group were associated with a similar pattern of activation, although relative decrease of activation in striatum and thalamic areas was observed. Patients in comparison with controls showed a hyperactivation in ipsilateral premotor areas and a hypoactivation in structures of the frontostriatal motor loop. Furthermore, patient scores in the motor scale of the UPDRS correlated positively with the activation thalamus and motor cortical areas during the sequential motor task. We concluded that in Parkinson's disease there is a compensatory mechanism of the dopamine deficit in frontostriatal motor circuits that increases participation in the execution of motor tasks of parietal–lateral premotor circuits.

The Linear Computational Algorithm of Cerebellar Purkinje Cells

The orchestration of simple motor tasks by the cerebellum results in coordinated movement and the maintenance of balance. The cerebellum integrates sensory and cortical information to generate the signals required for the coordinated execution of simple motor tasks. These signals originate in the firing rate of Purkinje cells, each of which integrates sensory and cortical information conveyed by granule cell synaptic inputs. Given the importance of the granule cell input-Purkinje cell output function for cerebellar computation, this algorithm was determined. Using several stimulation paradigms, including those that mimicked patterns of granule cell activity similar to those observed in vivo, we quantified the poststimulus maximum firing rate and number of extra spikes in response to granule cell synaptic input. Both of these parameters linearly encoded the strength of synaptic input when inhibitory synaptic transmission was blocked. This linear algorithm was independent of the location or temporal pattern of synaptic input. With inhibitory synaptic transmission intact, the maximum firing rate, but not the number of extra spikes, encoded the strength of granule cell synaptic input. Furthermore, the maximum firing rate of Purkinje cells linearly encoded the strength of synaptic input whether or not the activation of granule cells resulted in a pause in Purkinje cell firing. On the basis of the data presented, we propose that Purkinje cells encode the strength of granule cell synaptic input in their maximum firing rate with a linear algorithm.

Estimation of the cortical connectivity patterns during the intention of limb movements

The problem of the definition and evaluation of brain connectivity has become a central one in neuroscience during recent years as a way to understand the organization and interaction of cortical areas during the execution of cognitive or motor tasks. In this article, we propose the use of the directed transfer function (DTF) method on cortical signals estimated from high-resolution electroencephalography (EEG) recordings. An application of the proposed technique to the estimation of the cortical connectivity pattern in normal subjects and in one spinal-cord-injured patient is also provided

Mental chronometry of target detection: human thalamus leads cortex

Attentive monitoring of environmental stimuli is most fundamental for rapid target detection. The aim of this study was to assess the timing of thalamic versus cortical processes involved in this cognitive operation. To this end, simultaneous depth and scalp EEG was recorded in eight patients with essential tremor, undergoing thalamic deep brain stimulation (DBS), when the DBS electrodes could be accessed via their temporarily externalized leads. The patients performed an oddball task consisting of 300 presentations of one frequent and two rare visual cues, appearing in randomized order. One of the rare cues was defined as a target, the occurrences of which had to be indicated by a button press (motor condition) or silently counted (non-motor condition). At the scalp and the thalamus, event-related potentials (ERP) were largest upon target presentation, with peak latencies in the time domain of classical P300 responses. Remarkably, target-specific thalamic ERP emerged significantly prior to scalp P300. Furthermore, whereas scalp ERP had a higher amplitude upon rare than upon frequent non-target signals, thalamic ERP were independent of stimulus probability. This pattern was identified during motor and non-motor task execution. We conclude that the human thalamus specifically supports the early recognition of target events and can widely distribute this label through its divergent cortical projections.

Preclinical Huntington's disease: Compensatory brain responses during learning

Motor sequence learning is abnormal in presymptomatic Huntington's disease (p-HD). The neural substrates underlying this early manifestation of HD are poorly understood. To study the mechanism of this cognitive abnormality in p-HD, we used positron emission tomography to record brain activity during motor sequence learning in these subjects. Eleven p-HD subjects (age, 45.8 +/- 11.0 years; CAG repeat length, 41.6 +/- 1.8) and 11 age-matched control subjects (age, 45.3 +/- 13.4 years) underwent H(2) (15)O positron emission tomography while performing a set of kinematically controlled motor sequence learning and execution tasks. Differences in regional brain activation responses between groups and conditions were assessed. In addition, we identified discrete regions in which learning-related activity correlated with performance. We found that sequence learning was impaired in p-HD subjects despite normal motor performance. In p-HD, activation responses during learning were abnormally increased in the left mediodorsal thalamus and orbitofrontal cortex (OFC; BA 11/47). Impaired learning performance in these subjects was associated with increased activation responses in the precuneus (BA 18/31). These data suggest that enhanced activation of thalamocortical pathways during motor learning can compensate for caudate degeneration in p-HD. Nonetheless, this mechanism may not be sufficient to sustain a normal level of task performance, even during the presymptomatic stage of the disease.

INFLUENCE OF MOTOR-IMAGERY ABILITY ON SMA and PSMA CORTICAL ACTIVATION.

Purpose/Hypothesis: The supplementary motor area (SMA) and pre-sup-plementary motor area (PSMA) are considered to be vital in the planning, initiation, and execution of motor tasks. Several studies have investigated the role of SMA in mental imagery, but little is known about how the ability to imagine influences brain activation. The purpose of this study was to investigate the role of SMA and PSMA during mental imagery in both healthy subjects and subjects with stroke and how the ability to imagine influences brain activation. Number of Subjects: Six subjects with severe hemiparesis (Fugl Meyer UE score: 9–14, range: 8–113 months post stroke, mean: 64.3 months) and six age and gender matched healthy subjects. Materials/Methods: Whole-brain 3-Tesla fMRI was performed in subjects with stroke during alternating phases of active wrist-tracking with the less affected hand and imagined wrist-tracking with the hemiparetic side and resting. Control subjects were assigned a side to imagine and a side to track. At the end of the session, subjects were asked to rate the ability to imagine the movements, on a scale of 0–5 with zero being inability to imagine and five being perfect imagining of the task. Cortical activation intensity within each region was determined and the percent change in signal intensity from baseline was calculated. Subjects with stroke and healthy subjects were divided into two groups: high imagery ability (self-rating: 3–5) and low imagery ability (self-rating: 0–2). Statistical analysis of fMRI data was done with two-tailed T-tests using percent signal intensity change. Results: During the motor imagery task, subjects with stroke displayed significantly greater percent increase in activation in contralateral SMA as compared to healthy subjects [SMA: healthy: 0.88 ± 0.14, stroke: 1.39 ± 0.52, P = 0.03]. Pre SMA also showed a greater percent increase in the stroke group, but this was not significant [PSMA: healthy: 0.48 ± 0.71, stroke: 1.10 ± 1.24]. For the imagined wrist-tracking task, there was no significant difference in the percent signal-intensity change between the high and low imagining ability groups. This finding of no difference is supported by adequate power [effect size: 1.1, N=12, power .80]. Conclusions: This study provides evidence that mental imagery of a motor task in patients with stroke promotes cortical activity, which is consistent with previous research. Additionally, self-reported ability to imagine does not influence the signal intensity of SMA and PSMA activation. Clinical Relevance: Studies have shown that mental imagery may have beneficial effects when combined with rehabilitation. Our findings show that motor imagery facilitates cortical activity that is functionally relevant. The data also support that the strength of motor imagery ability does not influence the amount of cortical activation. Thus, it is plausible that even patients that have difficulty performing motor imagery will exhibit increases in cortical activation which may be an important adjunct to rehabilitation.

INVERSE DYNAMICS MODELING IN GAIT ANALYSIS: AN APPLICATION

A method based on inverse dynamics modeling for the subject specific in vivo evaluation of muscle activity in one subject during the execution of chair rising is being described in this article. The calculation of net joint loads and moments is performed through the solution of Newton–Euler mechanics applied to each body segment. Accuracy in the calculation of these quantities is a prerequisite for the reliability of the final results. This accuracy depends on several modeling factors: the choice of the inertial parameters data-set was specifically investigated here. This choice did not result in relevantly affecting the accuracy of the calculated net joint loads for stair ascending and descending, thus even more for a slow motor task like chair rising. Thus, the choice of an inertial parameter data set from the literature was acceptable for the specific application. In order to solve the undetermined problem, the method for the estimation of the contribution of each muscle from internal joint loads and moments was based on static optimization. The static optimization allowed for the estimation of the time histories of the force exerted by each muscolo-tendineous modeled actuator. Among these, the Rectus Femoris exerted the maximum force. In conclusion, the preliminary results obtained with the proposed method allowed for obtaining a realistic estimate of the force exerted in vivo by each muscle during the execution of chair rising-sitting motor task. This is promising in gaining a better understanding on the biomechanical role of muscles during every day living motor tasks, and for the planning and evaluation of surgical and/or rehabilitative procedures.

Movement-related parameters modulate cortical activity during imaginary isometric plantar-flexions

A multitude of studies have demonstrated a clear activation of the motor cortex during imagination of various motor tasks; however, it is still unclear if movement-related parameters (movement direction, range of motion, speed, force level and rate of force development) specifically modulate cortical activation as they do during the execution of actual motor tasks. Accordingly, this study examined whether the rate of torque development (RTD) and/or the torque amplitude modulates cortical potentials generated during imaginary motor tasks. Fifteen subjects imagined four different left-sided isometric plantar-flexion tasks, while EEG and EMG recordings were being performed. The averaged EEG activity was analyzed in terms of movement-related potentials (MRPs), consisting of readiness potential (RP), motor potential (MP) and movement-monitoring potential (MMP). It was demonstrated that RTD and torque amplitude indeed modulate cortical activity during imaginary motor tasks. Information concerning movement-related parameters for imaginary plantar-flexion tasks seems to be encoded in the supplementary motor area (SMA) and the primary motor cortex (M1). A comparison between MRPs of imaginary and actual motor tasks revealed that early MRPs were morphologically similar, but differed significantly in amplitude. One of the possible suggestions to explain such a difference may be an "abortion" of ongoing motor programs.

Behavioral motor dysfunction in Kv3‐type potassium channel‐deficient mice

The voltage-gated potassium channels Kv3.1 and Kv3.3 are expressed in several distinct neuronal subpopulations in brain areas known to be involved in motor control such as cortex, basal ganglia and cerebellum. Depending on the lack of Kv3.1 or Kv3.3 channel subunits, mutant mice show different Kv3-null allele-dependent behavioral alterations that include constitutive hyperactivity, sleep loss, impaired motor performance and, in the case of the Kv3.1/Kv3.3 double mutant, also severe ataxia, tremor and myoclonus (Espinosa et al. 2001, J Neurosci 21, 6657-6665, Genes, Brain Behav 3, 90-100). The lack of Kv3.1 channel subunits is mainly responsible for the constitutively increased locomotor activity and for sleep loss, whereas the absence of Kv3.3 subunits affects cerebellar function, in particular Purkinje cell discharges and olivocerebellar system properties (McMahon et al. 2004, Eur J Neurosci 19, 3317-3327). Here, we describe two sensitive and non-invasive tests to reliably quantify normal and abnormal motor functions, and we apply these tests to characterize motor dysfunction in Kv3-mutant mice. In contrast to wildtype and Kv3.1-single mutants, Kv3.3-single mutants and Kv3 mutants lacking three and four Kv3 alleles display Kv3-null allele-dependent gait alterations. Although the Kv3-null allele-dependent gait changes correlate with reduced motor performance, they appear to not affect the training-induced improvement of motor performance. These findings suggest that altered cerebellar physiology in the absence of Kv3.3 channels is responsible for impaired motor task execution but not motor task learning.

Motor-related cortical dynamics to intact movements in tetraplegics as revealed by high-resolution EEG.

We explored the cortical dynamics during movements of an unaffected body part in tetraplegic subjects with chronic spinal cord injury (SCI). The aims were to find out whether the intact movements were associated with a physiological time-varying pattern of activity in the motor-related cortical areas and whether the primary motor area (MI) activation followed a somatotopic distribution. Event-related potentials to self-initiated lip movements were analyzed by means of cortical source imaging of EEG recorded from seven tetraplegic subjects and seven control subjects. Regions of interest (ROIs) were selected on individual MRI and the time-varying electrophysiologic activity (cortical current density, CCD) was estimated on these ROIs and subjected to across-subject analysis. A significant, bilateral movement-related pattern of MI activation was detected during motor task execution in SCI patients as well as in controls. The site of local maxima activation displayed a symmetrical discrete distribution within MI, consistently with a putative somatotopic lip representation, in all the subjects. The supplementary motor area proper (SMAp) was always coactivated with MI and coactivation was characterized by a time course with typical premotion and motion phases over both motor areas. A clear-cut temporal delay between the SMAp and MI activation did not occur either in SCI patients or in controls. These findings obtained with noninvasive neuroelectrical source imaging document that in chronic SCI subjects "executive" motor areas are engaged with a preserved temporal and spatial pattern during preparation and execution of intact movements.

The cerebral oscillatory network associated with auditorily paced finger movements

Motor tasks involve neural activity in a spatially distributed network. It is assumed that coherent activity between these brain structures reflects functional connectivity. The aim of the present study was to investigate brain areas associated with a unimanual auditorily paced finger-tapping task and to characterize their dynamic interplay. We examined cerebromuscular and cerebrocerebral coupling in 10 right-handed subjects using recordings of continuous brain activity with a 122-channel whole-head neuromagnetometer while subjects performed the task with both hands consecutively. Additionally, surface EMG of the first dorsal interosseus was measured. Our data demonstrate that an oscillatory network composed of primary sensorimotor cortex, lateral as well as mesial premotor areas, the posterior parietal cortex and thalamus contralateral, and cerebellum and primary auditory cortex ipsilateral to the tapping hand subserves task execution. Connectivity between these areas and direction of coupling agree well with anatomical findings. During the right-hand condition, additional oscillatory activity in the primary sensorimotor cortex ipsilateral to the tapping hand was evident. This result suggests an asymmetric motor control in right-handers. Cerebrocerebral coupling predominantly occurs at 8–12 Hz. Therefore, our data support the hypothesis that coupling at 8–12 Hz in a cerebello-thalamic-cortical network represents a fundamental characteristic of the motor system and provides evidence for the significance of 8–12 Hz oscillations in a large scale network during the execution of simple motor tasks.

January 13 Highlight and Commentary

Lange et al. described a new filamin A mutation in a patient with periventricular nodular heterotopia. Their fMRI data indicated that ectopic neurons were functionally required in motor execution tasks. see page 151 Commentary by Renzo Guerrini, MD Heterotopia agglomerates of morphologically normal neurons in an abnormal site is the most common neuronal migration disorder observed in the human brain. Heterotopia can be unilateral or bilateral, diffuse or localized, subependymal or subcortical, or may extend from the subependymal region to the subcortex. Heterotopia can readily be diagnosed with MRI, showing the same …

Task-specific plasticity of somatosensory cortex in patients with writer's cramp

Focal dystonias such as writer's cramp are characterized by muscular cramps that accompany the execution of specific motor tasks. Until now, the pathophysiology of focal dystonia remains incompletely understood. Recent studies suggest that the development of writer's cramp is related to abnormal organization of primary somatosensory cortex (SI), which in turn leads to impaired motor function. To explore contributions of SI on mechanisms of task specificity in focal dystonia, we investigated dynamic alterations in the functional organization of SI as well as sensory-motor gating for rest, left- and right-handed writing and brushing in writer's cramp patients and healthy controls. The functional organization of somatosensory cortex was assessed by neuromagnetic source imaging (151 channel whole-head MEG). In accordance with previous reports, distances between cortical representations of thumb and little finger of the affected hand were smaller in patients compared to healthy subjects. However, similar to healthy controls, patients showed normal modulation of the functional organization of SI as induced by the execution of different motor tasks. Both in the control subjects and patients, cortical distances between representations of thumb and little finger increased when writing and brushing compared to the resting condition. Although, cramps only occured during writing, no differences in the organization of SI were seen among motor tasks. Our data suggest that despite alterations in the organization of primary somatosensory cortex in writer's cramp, the capability of SI to adapt dynamically to different tasks is not impaired.

Effect of strength training on human patella tendon mechanical properties of older individuals

This study investigated the effect of strength training on the mechanical properties of the human patella tendon of older individuals. Subjects were assigned to training (n = 9; age 74.3 +/- 3.5 years, body mass 69.7 +/- 14.8 kg and height 163.4 +/- 9.1 cm, mean +/- S.D.) and control (n = 9; age 67.1 +/- 2 years, body mass 73.5 +/- 14.9 kg and height 168.3 +/- 11.5 cm) groups. Strength training (two series of 10 repetitions at 80 % of five-repetition maximum) was performed three times per week for 14 weeks using leg extension and leg press exercises. Measurements of tendon elongation during a ramp isometric knee extension were performed before and after training and control periods in vivo using ultrasonography. Training caused a decreased tendon elongation and strain at all levels of force and stress (P 0.05). This study shows for the first time that strength training in old age increases the stiffness and Young's modulus of human tendons. This may reduce the risk of tendon injury in old age and has implications for contractile force production and the rapid execution of motor tasks.

Effect of strength training on human patella tendon mechanical properties of older individuals.

This study investigated the effect of strength training on the mechanical properties of the human patella tendon of older individuals. Subjects were assigned to training (n = 9; age 74.3 +/- 3.5 years, body mass 69.7 +/- 14.8 kg and height 163.4 +/- 9.1 cm, mean +/- S.D.) and control (n = 9; age 67.1 +/- 2 years, body mass 73.5 +/- 14.9 kg and height 168.3 +/- 11.5 cm) groups. Strength training (two series of 10 repetitions at 80 % of five-repetition maximum) was performed three times per week for 14 weeks using leg extension and leg press exercises. Measurements of tendon elongation during a ramp isometric knee extension were performed before and after training and control periods in vivo using ultrasonography. Training caused a decreased tendon elongation and strain at all levels of force and stress (P < 0.01). Baseline tendon elongation and strain at maximal tendon load were 4.7 +/- 1.1 mm and 9.9 +/- 2.2 %, respectively (maximum force: 3346 +/- 1168 N; maximum stress: 40 +/- 11 MPa). After training, these values decreased to 2.9 +/- 1.2 mm and 5.9 +/- 2.4 % (P < 0.01), respectively (maximum force: 3555 +/- 1257 N; maximum stress: 42 +/- 11 MPa). Tendon stiffness increased by 65 % (2187 +/- 713 to 3609 +/- 1220 N mm-1; P < 0.05) and Young's modulus increased by 69 % (1.3 +/- 0.3 to 2.2 +/- 0.8 GPa; P < 0.01). As a result of these changes, the rate of torque development increased by 27 % (482.8 +/- 302.5 to 612.6 +/- 401 N m s-1; P < 0.01) following training. No significant changes occurred in any measured variables in the control group (P > 0.05). This study shows for the first time that strength training in old age increases the stiffness and Young's modulus of human tendons. This may reduce the risk of tendon injury in old age and has implications for contractile force production and the rapid execution of motor tasks.

Artificial neural network model of the mapping between electromyographic activation and trajectory patterns in free-arm movements.

Artificial neural networks (ANNs) have been used to identify the relationship between electromyographic (EMG) activity and arm kinematics during the execution of motor tasks. Although considerable work has been devoted to showing that ANNs perform this mapping, there has been little work to explore any relationship with physiological properties of the neuromuscular systems. A back-propagation through time (BPTT) ANN was used to map the EMG of five selected muscles (pectoralis major (PM), anterior deltoid (AD), posterior deltoid (PD), biceps brachii (BB) and triceps brachii (TB)) on arm kinematics in seven normal subjects performing three-dimensional unrestrained grasping movements. To investigate the physiological validity of the BPTT-ANN, inputs were artificially altered, and the predicted outputs were analysed. Results show that the BPTT-ANN performed the mapping correctly (root mean square (RMS) error between target and predicted outputs averaged across subject test sets was 0.092 +/- 0.015). Moreover, it provided insights into the roles of muscles in performing the movement (average indexes measuring the output alteration with respect to the target were 0.070 +/- 0.027, 0.356 +/- 0.172, 0.568 +/- 0.413, 0.510 +/- 0.268, 0.681 +/- 0.430 for PM, AD, PD, BB, TB, respectively, in the movement forward phase, and 0.077 +/- 0.015, 0.179 +/- 0.147, 0.291 +/- 0.247, 0.671 +/- 0.054, 0.232 +/- 0.097 in the return phase).

Sensory motor organization and re-organization in normals and patients using a combined MEG and fMRI approach

A review of the research activity on the organization and re-organization of the sensory motor cortex carried out at the Institute of Advanced Biomedical Technology of the University of Chieti, Italy, is presented. These studies were performed by means of magnetoencephalography (MEG) and functional magnetic resonance (fMRI), that were used either independently or, when possible, in combination, to take maximum advantage of the high temporal resolution of the former technique and of the high spatial resolution of the latter. The most interesting results obtained both in basic research and in the clinical field will be illustrated. In particular, we will deal with: (i) the organization of the primary and secondary sensory areas with respect to different stimulus intensities and different district stimulations, (ii) the area activated during execution of complex motor tasks, such as handwriting, versus simple movements, (iii) the possibility of identifying the epileptogenic area with respect to functional landmarks from the interictal activity of patients with or without a lesion, as well as the localization of functional reference points in pre-surgical mapping and, finally, (iv) monitoring of plasticity phenomena in patients affected by vascular lesions during the recovery phase.

Functional brain networks in Parkinson's disease

With the advent of new methods of network analysis, we have utilized metabolic data acquired through positron emission tomography (PET) to identify disease-related patterns of functional pathology in the movement disorders. In Parkinson's disease (PD), we have used [ 18F]-fluorodeoxyglucose (FDG)/PET to identify a disease-related regional metabolic covariance pattern characterized by lentiform and thalamic hypermetabolism associated with regional metabolic decrements in the lateral premotor cortex, the supplementary motor area, the dorsolateral prefrontal cortex, and the parieto-occipital association regions. The expression of this network is modulated in a predictable fashion by levodopa therapy and by stereotaxic interventions for PD. We have extended this network analytical approach from studies of glucose metabolism in the resting state to dynamic studies of brain activation during motor performance. These PET studies utilized [ 15O]–water (H 2 15O) to measure cerebral blood flow activation responses during the execution of simple and complex motor tasks. In addition to the modulation of abnormal resting metabolic networks, effective PD therapy can enhance brain activation responses during motor execution, with specific regional associations with improvements in timing and spatial accuracy. This approach is also useful in identifying specific brain networks mediating the learning of sequential information. We have found that the normal relationship between brain networks and learning performance are altered in the earliest stages of PD with a functional shift from striatal to cortical processing. Brain activation PET studies during therapeutic interventions for PD demonstrate how normal brain-behavior relationships can be restored with successful therapy. Thus, functional brain imaging with network analysis can provide insights into the mechanistic basis of basal ganglia disorders and their treatment.