Pre-supplementary Motor Cortex Research Articles

The role of pre-supplementary motor cortex in action control with emotional stimuli: Arepetitive transcranial magnetic stimulationstudy.

Swiftly halting ongoing motor actions is essential to react to unforeseen and potentially perilous circumstances. However, the neural bases subtending the complex interplay between emotions and motor control have been scarcely investigated. Here, we used an emotional stop signal task (SST) to investigate whether specific neural circuits engaged by action suppression are differently modulated by emotional signals with respect to neutral ones. Participants performed an SST before and after the administration of one session of repetitive transcranial magnetic stimulation (rTMS) over the pre-supplementary motor cortex (pre-SMA), the right inferior frontal gyrus (rIFG), and the left primary motor cortex (lM1). Results show that rTMS over the pre-SMA improved the ability to inhibit prepotent action (i.e., better action control) when emotional stimuli were presented. In contrast, action control in a neutral context was fostered by rTMS over the rIFG. No changes were observed after lM1 stimulation. Intriguingly, individuals with higher impulsivity traits exhibited enhanced motor control when facing neutral stimuli following rIFG stimulation. These results further our understanding of the interplay between emotions and motor functions, shedding light on the selective modulation of neural pathways underpinning these processes.

Pre-supplementary Motor Cortex Mediates Learning Transfer from Perceptual to Motor Timing.

When we intensively train a timing skill, such as learning to play the piano, we not only produce brain changes associated with task-specific learning but also improve our performance in other temporal behaviors that depend on these tuned neural resources. Since the neural basis of time learning and generalization is still unknown, we measured the changes in neural activity associated with the transfer of learning from perceptual to motor timing in a large sample of subjects (n = 65; 39 women). We found that intense training in an interval discrimination task increased the acuity of time perception in a group of subjects that also exhibited learning transfer, expressed as a reduction in inter-tap interval variability during an internally driven periodic motor task. In addition, we found subjects with no learning and/or generalization effects. Notably, functional imaging showed an increase in pre-supplementary motor area and caudate-putamen activity between the post- and pre-training sessions of the tapping task. This increase was specific to the subjects that generalized their timing acuity from the perceptual to the motor context. These results emphasize the central role of the cortico-basal ganglia circuit in the generalization of timing abilities between tasks.

Neural correlates underlying preference changes induced by food Go/No-Go training

Consistently not responding to appetitive foods during food go/no-go training could change individuals' food choices and sometimes even body weight, however, fewer studies have explored the neural pathways underlying the effects of food go/no-go training. In this study, we scanned eighty-six female participants using functional magnetic resonance imaging and investigated the neural bases of preference changes in a binary food choice task following action (e.g., go) or inaction (e.g., no-go) toward distinct foods within a food go/no-go training paradigm. In line with prior behavioral work, we found that participants' food preferences changed as a function of food go/no-go training, with participants choosing more “go” over “no-go” foods for consumption following training. At a neural level, preference changes were inversely associated with frontoparietal and salience network activity when choosing go (vs. no-go) foods. Additionally, task-related functional connectivities from the inferior parietal lobule to the pre-supplementary motor cortex, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex were related to these preference changes. Together, current work supports that food go/no-go training reliably changes people's preferences. More importantly, our findings suggest that a neural pathway centered on areas traditionally associated with selective attention may interface with prefrontal regions to guide preference changes induced by food go/no-go training, though future studies using other tasks (e.g., passive viewing tasks) are still needed to test this potential neural mechanism.

Cortical oscillatory dysfunction in Parkinson disease during movement activation and inhibition.

Response activation and inhibition are functions fundamental to executive control that are disrupted in Parkinson disease (PD). We used magnetoencephalography to examine event related changes in oscillatory power amplitude, peak latency and frequency in cortical networks subserving these functions and identified abnormalities associated with PD. Participants (N = 18 PD, 18 control) performed a cue/target task that required initiation of an un-cued movement (activation) or inhibition of a cued movement. Reaction times were variable but similar across groups. Task related responses in gamma, alpha, and beta power were found across cortical networks including motor cortex, supplementary and pre- supplementary motor cortex, posterior parietal cortex, prefrontal cortex and anterior cingulate. PD-related changes in power and latency were noted most frequently in the beta band, however, abnormal power and delayed peak latency in the alpha band in the pre-supplementary motor area was suggestive of a compensatory mechanism. PD peak power was delayed in pre-supplementary motor area, motor cortex, and medial frontal gyrus only for activation, which is consistent with deficits in un-cued (as opposed to cued) movement initiation characteristic of PD.

Two Neural Networks for Laughter: A Tractography Study

Laughter is a complex motor behavior occurring in both emotional and nonemotional contexts. Here, we investigated whether the different functions of laughter are mediated by distinct networks and, if this is the case, which are the white matter tracts sustaining them. We performed a multifiber tractography investigation placing seeds in regions involved in laughter production, as identified by previous intracerebral electrical stimulation studies in humans: the pregenual anterior cingulate (pACC), ventral temporal pole (TPv), frontal operculum (FO), presupplementary motor cortex, and ventral striatum/nucleus accumbens (VS/NAcc). The primary motor cortex (M1) and two subcortical territories were also studied to trace the descending projections. Results provided evidence for the existence of two relatively distinct networks. A first network, including pACC, TPv, and VS/NAcc, is interconnected through the anterior cingulate bundle, the accumbofrontal tract, and the uncinate fasciculus, reaching the brainstem throughout the mamillo-tegmental tract. This network is likely involved in the production of emotional laughter. A second network, anchored to FO and M1, projects to the brainstem motor nuclei through the internal capsule. It is most likely the neural basis of nonemotional and conversational laughter. The two networks interact throughout the pre-SMA that is connected to both pACC and FO.

Checking and washing rituals are reflected in altered cortical thickness in obsessive-compulsive disorder

There is growing evidence for structural brain alterations in obsessive-compulsive disorder (OCD). The overall picture is however rather heterogeneous. To detect meaningful associations between clinical symptom profiles and structural alterations, we applied a classification approach, the k-means cluster analysis on clinical data, i.e., the Obsessive Compulsive Inventory-Revised (OCI-R) questionnaire. 73 OCD patients were assigned to three distinct symptom profiles. Using structural MRI and surface-based morphometric analysis (SBM), we compared cortical thickness between all OCD patients and 69 matched healthy subjects as well as among patients according to three symptom profiles. The total sample of OCD patients exhibited a thicker cortex in the pre-supplementary motor cortex (pre-SMA), dorsomedial prefrontal (DMPFC), anterior cingulate cortex and in the right anterior insula. Comparing patients of the three symptom clusters, a subgroup of OCD patients with a specific symptom profile was identified, which showed a thicker cortex in pre-SMA/DMPFC and in the contralateral primary motor cortex. In contrast to both other subgroups, patients in this group were mainly characterized by the predominance of a combination of checking and washing rituals. The other two OCD symptom subgroups showed comparable cortical thickness to healthy controls. Higher cortical thickness in regions of the motor circuitry seems to be related to motor activity-induced neuroplasticity in a specific group of OCD patients. Thicker anterior insular cortex in the total sample of patients points toward a more general pathophysiological process in OCD and potentially indicates abnormal interoceptive processing in OCD.

Modulation of working memory load distinguishes individuals with and without balance impairments following mild traumatic brain injury

ABSTRACTObjectives: Balance and gait deficits can persist after mild traumatic brain injury (TBI), yet an understanding of the underlying neural mechanism remains limited. The purpose of this study was to investigate differences in attention network modulation in patients with and without balance impairments 2–8 weeks following mild TBI.Methods: Using functional magnetic resonance imaging, we compared activity and functional connectivity of cognitive brain regions of the default mode, central-executive and salience networks during a 2-back working memory task in participants with mild TBI and balance impairments (n = 7, age 47 ± 15 years) or no balance impairments (n = 7, age 47 ± 15 years).Results: We first identified greater activation in the lateral occipital cortex in the balance impaired group. Second, we observed stronger connectivity of left pre-supplementary motor cortex in the balance impaired group during the working memory task, which was related to decreased activation of regions within the salience and central executive networks and greater suppression of the default mode network.Conclusions: Results suggest a link between impaired balance and modulation of cognitive resources in patients in mTBI. Findings also highlight the potential importance of moving beyond traditional balance assessments towards an integrative assessment of cognition and balance in this population.

Atomoxetine restores the response inhibition network in Parkinson's disease.

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson's disease.

Recording extracellular neural activity in the behaving monkey using a semichronic and high-density electrode system.

We describe a technique to semichronically record the cortical extracellular neural activity in the behaving monkey employing commercial high-density electrodes. After the design and construction of low cost microdrives that allow varying the depth of the recording locations after the implantation surgery, we recorded the extracellular unit activity from pools of neurons at different depths in the presupplementary motor cortex (pre-SMA) of a rhesus monkey trained in a tapping task. The collected data were processed to classify cells as putative pyramidal cells or interneurons on the basis of their waveform features. We also demonstrate that short time cross-correlogram occasionally yields unit pairs with high short latency (<5 ms), narrow bin (<3 ms) peaks, indicative of monosynaptic spike transmission from pre- to postsynaptic neurons. These methods have been verified extensively in rodents. Finally, we observed that the pattern of population activity was repetitive over distinct trials of the tapping task. These results show that the semichronic technique is a viable option for the large-scale parallel recording of local circuit activity at different depths in the cortex of the macaque monkey and other large species.

Decoding Internally and Externally Driven Movement Plans.

The way the human brain prepares the body for action constitutes an essential part of our ability to interact with our environment. Previous studies demonstrated that patterns of neuronal activity encode upcoming movements. Here we used multivariate pattern analysis of human fMRI data to distinguish between brain regions containing movement plans for instructed (externally driven) movements, areas involved in movement selection (internally driven), and areas containing abstract movement plans that are invariant to the way these were generated (i.e., that generalize across externally and internally driven movement plans). Our findings extend our understanding of the neural basis of movement planning and have the potential to contribute to the development of brain-controlled neural prosthetic devices.

Task switching and shifting between stopping and going: Developmental change in between-trial control adjustments

This study set out to investigate developmental differences in the ability to switch between choice tasks and to shift between Go/NoGo and choice tasks. Three age groups (7-year-olds, 11-year-olds, and young adults) were asked to consider the shape or color of a bivalued target stimulus. The participants performed a switch task in which a cue signaled the task to be performed (i.e., respond to shape vs. respond to color) and a shift task in which a cue instructed them to make a choice reaction to the shape of the stimulus or to respond (Go) versus inhibit (NoGo) to the color of the stimulus. The ability to switch was examined by considering choice–choice switches versus choice–choice repeats. The ability to shift was examined by considering NoGo-to-choice shifts versus choice–choice repeats and NoGo-to-Go shifts versus Go–Go repeats. The results showed that responding on Go trials was delayed following response inhibition on a NoGo trial. This delay did not discriminate between age groups. Responding on choice trials was considerably slowed when following response inhibition on NoGo trials. This slowing decreased with advancing age. Finally, responses on switch trials were slower compared with repeat trials, and this slowing was disproportionately large in young children compared with the other two age groups. This pattern of findings was interpreted in terms of a generic mechanism involving between-trial control adjustments in the setting of response thresholds that are likely to be mediated by a complex neural network implicating the dorsolateral prefrontal cortex and the presupplementary motor cortex.

Response inhibition is associated with white matter microstructure in children

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor cortex (preSMA), and subthalamic nucleus. Though the brain's fibre tracts are known to develop during childhood, little is known about how fibre tract development within this network relates to developing behavioural control. Here we examined the relationship between response inhibition, as measured with the stop-signal task, and indices of regional white matter microstructure in typically-developing children. We hypothesized that better response inhibition performance would be associated with higher fractional anisotropy (FA) in fibre tracts within right IFG and preSMA after controlling for age. Mean FA and diffusivity values were extracted from right and left IFG and preSMA. As hypothesized, faster response inhibition was significantly associated with higher FA and lower perpendicular diffusivity in both the right IFG and the right preSMA, possibly reflecting faster speed of neural conduction within more densely packed or better myelinated fibre tracts. Moreover, both of these effects remained significant after controlling for age and whole brain estimates of these DTI parameters. Interestingly, right IFG and preSMA FA contributed additively to the prediction of performance variability. Observed associations may be related to variation in phase of maturation, to activity-dependent alterations in the network subserving response inhibition, or to stable individual differences in underlying neural system connectivity.

Impaired implicit learning and reduced pre-supplementary motor cortex size in early-onset major depression with melancholic features

Background:Major depression is a heterogeneous disorder. Biological markers and cognitive tasks have been employed to distinguish clinical subtypes but results have been inconclusive. Methods:The current study assessed implicit learning with the Serial Reaction Time Task (SRTT) known to be sensitive to frontostriatal dysfunctions and regional brain volumes of the anterior supplementary motor area (pre-SMA) in participants with early-onset major depression (MD) of either melancholic (n=26) or non-melancholic (n=9) subtype, and 26 matched controls. Results:Depressive subjects with melancholic features but not those with non-melancholic depression showed implicit learning deficits. This deficit could not be explained in terms of more severe depression or psychomotor retardation. Regional volumes of the right pre-SMA were reduced in depressive subjects with melancholic features. Limitations:Medication effects in depressive subjects and the small size of the non-melancholic sample should be taken into consideration when reviewing the implications of these results. Conclusions:Deficits in implicit motor sequence learning seem to be an additional characteristic of the melancholic subtype of depression. It might be linked to dysfunction within structural or functionally altered frontostriatal circuits. Use of implicit sequence learning tasks could offer useful diagnostic and aetiological cues for future research.

The influence of complex action knowledge on representations of novel graspable objects: Evidence from functional magnetic resonance imaging

The influence of action knowledge associated with novel objects was investigated using functional magnetic resonance imaging. Participants were trained on complex actions associated with novel objects ("tools") and had experience manipulating other visually similar novel objects ("shapes"). During scanning, participants viewed, imagined grasping, and imagined using the objects. Based on previous neuroimaging and neuropsychological findings, our primary goal was to examine frontal and parietal regions subserving action representations associated with visual objects, namely the left inferior parietal lobule (IPL), the left ventral premotor cortex (VPM) and the presupplementary motor cortex (pre-SMA). We predicted differences between the tool and shape stimuli, modulated also by task demands. In viewing, we found greater effect sizes in the left VPM and IPL for tools versus shapes. In grasping, there was similar activation with both object types. The largest differences existed in using, in which greater effect sizes were found for tools versus shapes in left IPL and pre-SMA, and marginally in the left VPM. We suggest that representations of tools extend beyond classically defined affordances and recruit processing about both graspability and known action plans in tasks involving visual memory, motor imagery, and motor execution.

A network for audio–motor coordination in skilled pianists and non-musicians

Playing a musical instrument requires efficient auditory and motor processing. Fast feed forward and feedback connections that link the acoustic target to the corresponding motor programs need to be established during years of practice. The aim of our study is to provide a detailed description of cortical structures that participate in this audio–motor coordination network in professional pianists and non-musicians. In order to map these interacting areas using functional magnetic resonance imaging (fMRI), we considered cortical areas that are concurrently activated during silent piano performance and motionless listening to piano sound. Furthermore we investigated to what extent interactions between the auditory and the motor modality happen involuntarily. We observed a network of predominantly secondary and higher order areas belonging to the auditory and motor modality. The extent of activity was clearly increased by imagination of the absent modality. However, this network did neither comprise primary auditory nor primary motor areas in any condition. Activity in the lateral dorsal premotor cortex (PMd) and the pre-supplementary motor cortex (preSMA) was significantly increased for pianists. Our data imply an intermodal transformation network of auditory and motor areas which is subject to a certain degree of plasticity by means of intensive training.

Differentiation between external and internal cuing: An fMRI study comparing tracing with drawing

Externally cued movement is thought to preferentially involve cerebellar and premotor circuits whereas internally generated movement recruits basal ganglia, pre-supplementary motor cortex (pre-SMA) and dorsolateral prefrontal cortex (DLPFC). Tracing and drawing are exemplar externally and internally guided actions and Parkinson's patients and cerebellar patients show deficits in tracking and drawing, respectively. In this study we aimed to examine this external/internal distinction in healthy subjects using functional imaging. Ten healthy subjects performed tracing and drawing of simple geometric shapes using pencil and paper while in a 3-T fMRI scanner. Results indicated that compared to tracing, drawing generated greater activation in the right cerebellar crus I, bilateral pre-SMA, right dorsal premotor cortex and right frontal eye field. Tracing did not recruit any additional activation compared to drawing except in striate and extrastriate visual areas. Therefore, drawing recruited areas more frequently associated with cognitively challenging tasks, attention and memory, but basal ganglia and cerebellar activity did not differentiate tracing from drawing in the hypothesised manner. As our paradigm was of a simple, repetitive and static design, these results suggest that the task familiarity and the temporal nature of visual feedback in tracking tasks, compared to tracing, may be important contributing factors towards the degree of cerebellar involvement. Future studies comparing dynamic with static external cues and visual feedback may clarify the role of the cerebellum and basal ganglia in the visual guidance of drawing actions.

Reduced size of the pre-supplementary motor cortex and impaired motor sequence learning in first-episode schizophrenia

Increasing evidence suggests that schizophrenia is associated with various morphological and functional abnormalities of the frontal cortex. So far research has concentrated on the dorsolateral and orbitofrontal cortex. Behavioral evidence suggests however that regions responsible for higher motor control are compromised in schizophrenia as well. The current study assessed volumes of the anterior supplementary motor area (pre-SMA) and implicit motor sequence learning in 15 subjects with first-episode schizophrenia and 15 healthy matched controls. Pre-SMA volumes were assessed by three-dimensional structural magnetic resonance imaging (3D-MRI) and manual parcellation according to an established protocol. Implicit motor sequence learning was assessed using the Serial Reaction-Time Task (SRTT). Compared with control subjects, schizophrenia subjects had significantly smaller volumes of the left pre-SMA (16%). Subjects with schizophrenia were severely impaired on sequence-specific implicit motor learning. Size of the left pre-SMA of schizophrenia subjects was significantly related to impaired implicit learning. We conclude that subjects with first-episode schizophrenia have a morphological abnormality of the left pre-SMA that might predispose them to develop disturbances of higher motor control during acute episodes of psychosis. These structural and behavioral abnormalities might be conceptualized within a broader model that views schizophrenia as a disorder of disturbed coordination of thought and action.

Cerebral cortical control of orbicularis oculi motoneurons

Cerebral cortical neural networks associated with eyelid movement play a critical role in facial animation, contribute to the regulation of blink frequency, and help prevent ocular injury. Eyelid closure depends, in part, on motoneurons that innervate the orbicularis oculi (OO) muscles. In this study, OO motoneuron cortical afferents were identified in rhesus monkeys with rabies virus, a retrograde transneuronal tracer. Virus was injected into the right OO muscle and immunohistochemically localized after 4–6 day transport intervals. Labeled motoneurons were limited to dorsal portions of the ipsilateral facial motor nucleus. After 4- and 4.5-day transport intervals, most labeled cortical neurons were localized to ventrolateral premotor (LPMCv), dorsolateral premotor (LPMCd), and motor (M1) cortices. Labeled neurons were more sparsely distributed in supplementary (M2), caudal (M4), and rostral (M3) cingulate motor cortices; the frontal eye fields (FEF); pre-supplementary motor cortex (pre-SMA); somatosensory cortices (areas 3a, 3b, and 1); and prefrontal cortex. At longer transport intervals (5–6 days), labeled neurons increased substantially in LPMCv, LPMCd, M2, M3, M4, pre-SMA, and FEF. Concentrations of labeled neurons also appeared in cortices along the lateral fissure and intraparietal sulcus. Overall, the densest collection of labeled neurons was localized to the caudal junction of LPMCd and LPMCv with M1. Rostral M3 was another focus of OO premotor neurons. Labeled neurons were distributed bilaterally in all motor cortical areas with a modest contralateral predominance for M2, LPMC, and M1. Thus, the cortical control of OO motor activity is distributed bilaterally among multiple motor areas.

Brain activity correlates differentially with increasing temporal complexity of rhythms during initialisation, synchronisation, and continuation phases of paced finger tapping

Activity in parts of the human motor system has been shown to correlate with the complexity of performed motor sequences in terms of the number of limbs moved, number of movements, and number of trajectories. Here, we searched for activity correlating with temporal complexity, in terms of the number of different intervals produced in the sequence, using an overlearned tapping task. Our task was divided into three phases: movement selection and initiation ( initiate), synchronisation of finger tapping with an external auditory cue ( synchronise), and continued tapping in absence of the auditory pacer ( continue). Comparisons between synchronisation and continuation showed a pattern in keeping with prior neuroimaging studies of paced finger tapping. Thus, activation of bilateral SMA and basal ganglia was greater in continuation tapping than in synchronisation tapping. Parametric analysis revealed activity correlating with temporal complexity during initiate in bilateral supplementary and pre-supplementary motor cortex (SMA and preSMA), rostral dorsal premotor cortex (PMC), basal ganglia, and dorsolateral prefrontal cortex (DLPFC), among other areas. During synchronise, correlated activity was observed in bilateral SMA, more caudal dorsal and ventral PMC, right DLPFC and right primary motor cortex. No correlated activity was observed during continue at P<0.01 (corrected, cluster level), though left angular gyrus was active at P<0.05. We suggest that the preSMA and rostral dorsal PMC activities during initiate may be associated with selection of timing parameters, while activation in centromedial prefrontal cortex during both initiate and synchronise may be associated with temporal error monitoring or correction. The absence of activity significantly correlated with temporal complexity during continue suggests that, once an overlearned timed movement sequence has been selected and initiated, there is no further adjustment of the timing control processes related to its continued production in absence of external cues.

The functional anatomy of parkinsonian bradykinesia

To investigate the difficulty that patients with Parkinson’s disease (PD) have in performing fast movements, we used H 2 15O PET to study regional cerebral blood flow (rCBF) associated with performance of a simple predictive visuomanual tracking task at three different velocities. Tracking movements in PD patients (versus tracking with the eyes alone) were associated with a general underactivation of the areas normally activated by the task (sensorimotor cortex contralateral to the moving arm, bilateral dorsal premotor cortices, and ipsilateral cerebellum). Presupplementary motor cortex (pre-SMA) ipsilateral to the moving arm had greater than normal movement-related activations. Increasing movement velocity led to increased rCBF in multiple premotor and parietal cortical areas and basal ganglia in the patients as opposed to the few cerebral locations that are normally velocity-related. The functional correlates of PD bradykinesia are: (1) impaired recruitment of cortical and subcortical systems that normally regulate kinematic parameters of movement such as velocity; and (2) increased recruitment of multiple premotor areas including both regions specialized for visuomotor control (ventral premotor and parietal cortices) and some that are not (pre-SMA). The overactivation of cortical regions observed in patients may be functional correlates of compensatory mechanisms and/or impaired suppression as a facet of the primary pathophysiology of PD.