Limb and joint kinetics during walking in individuals with Mild-Moderate Parkinson's disease.

Given the known deficits in spatiotemporal aspects of gait for people with Parkinson's disease (PD), we sought to determine the underlying gait abnormalities in limb and joint kinetics, and examine how deficits in push-off and leg swing might contribute to the shortened step lengths for people with PD. Ten participants with PD and 11 age-matched control participants walked overground and on an instrumented treadmill. Participants with PD then walked on the treadmill with a posteriorly directed restraining force applied to 1) the pelvis to challenge push-off and 2) the ankles to challenge leg swing. Spatiotemporal, kinematic, and force data were collected and compared between groups and conditions. Despite group differences in spatiotemporal measures during overground walking, we did not observe these differences when the groups walked on a treadmill at comparable speeds. Nevertheless, the hip extension impulse appeared smaller in the PD group during their typical walking. When challenging limb propulsion, participants in the PD group maintained step lengths by increasing the propulsive impulse. Participants with PD were also able to maintain their typical step length against resistance intended to impede swing limb advancement, and even increased step lengths with cuing. The presence of reduced hip extension torque might be an early indicator of gait deterioration in this neurodegenerative disease. Our participants with PD were able to increase hip extension torque in response to needed demands. Additionally, participants with PD were able to increase limb propulsion and leg swing against resistance, suggesting a reserve in limb mechanics.

More than medications: a patient-centered assessment of Parkinson's disease care needs during hospitalization.

Background: Parkinson's disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step toward the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population. Objectives: This qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting. Methods: Focus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and the clinical team. The data were analyzed using inductive thematic analysis. Results: A total of 12 PwPs and 13 CPs participated in seven focus groups. Participants were 52% female and 28% non-white; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explored the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD. Conclusion: PD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility in ambulation protocols and an environment that accommodated their disability. These findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes.

Autonomic and Depression Symptoms in Parkinson's Disease: Clinical Evidence for Overlapping Physiology.

BACKGROUND: Autonomic dysfunction and depression are common non-motor symptoms of Parkinson's disease (PD) that confer poorer prognosis. These PD symptoms may have overlapping pathophysiologic underpinnings. OBJECTIVE: To investigate associations between autonomic and depression symptoms in early PD, and their evolution over time. METHODS: We obtained data from the Parkinson's Progression Markers Initiative, a prospective open-access database of early PD. Regression analyses were used to model effects of depression on autonomic symptoms in controls and in PD at baseline, visit 6 (24 months after baseline), and visit 12 (60 months after baseline), correcting for multiple comparisons. RESULTS: Data from 421 people with PD at baseline, 360 at visit 6, 300 at visit 12, and 193 controls were included. When controlling for age, depression, and anti-hypertensive medications, depression predicted autonomic symptoms in all groups. Accounting for motor symptoms did not alter these associations. When comparing groups, the influence of depression on autonomic symptoms was stronger in all PD groups compared to controls, and strongest in PD at visit 12. Depression predicted the presence of orthostatic hypotension only in the PD group at visit 12. CONCLUSION: We demonstrated the important impact of depression on autonomic symptoms in early and middle stages of PD, which are independent of motor symptoms. Though the physiologic basis of these two PD symptoms are not fully understood, our findings add to pathologic evidence of a shared mechanistic substrate, separate from that responsible for PD motor symptoms. These findings may influence clinical management and development of novel therapies.

Individuals With Parkinson's Disease Retain Spatiotemporal Gait Control With Music and Metronome Cues.

The purpose of this study was to determine the difference in spatiotemporal gait measures induced by stepping to the beat of a metronome and to music cues of various frequencies in individuals with Parkinson's disease. Twenty-one participants with Parkinson's disease were instructed to time their steps to a metronome and music cues (at 85%, 100%, and 115% of overground cadence). The authors calculated cadence, cadence accuracy, and step length during each cue condition and an uncued control condition. The music and metronome cues produced comparable results in cadence manipulation, with reduced cadence accuracy noted at slower intended frequencies. Nevertheless, the induced cadence elicited a concomitant alteration in step length. The music and metronome cues produced comparable changes to gait, but suggest that temporal control is more limited at slower frequencies, presumably by the challenge of increasing the step length.

Targeted Rhythmic Auditory Cueing During Treadmill and Overground Gait for Individuals With Parkinson Disease: A Case Series.

BACKGROUND AND PURPOSE: Rhythmic auditory cueing and treadmill walking can improve spatiotemporal gait parameters through entrainment of movement patterns. Careful selection of cue frequencies is necessary if treadmill walking is to be employed, because cadence and step length are differentially affected by walking on a treadmill and overground. The purpose of this study was to describe the treatment of gait impairments for individuals with Parkinson disease, using strategically selected rhythmic auditory cue frequencies on both a treadmill and overground. CASE DESCRIPTION: Three individuals with Hoehn & Yahr stage 2 Parkinson disease participated in this case series. INTERVENTION: All participants completed 6 weeks of gait training, in which each session employed rhythmic auditory cueing during treadmill-based gait training followed by overground gait training. We provided targeted rhythmic auditory cueing with a metronome set to 85% and 115% of their self-selected cadence for treadmill and overground training, respectively. We performed clinical tests of gait and balance prior to, midway, and following training, and at a 3-month follow-up. OUTCOMES: All participants improved overground gait speed (participant 1: +0.27 m/s; participant 2: +0.20 m/s; and participant 3: +0.18 m/s) and stride length (15.7 ± 4.17 cm) with small changes to cadence. Likewise, there were only small changes in balance. DISCUSSION: We hypothesize that the large improvements in gait speed are due to the concomitant increases in stride length. Further research is needed to test the effect of targeted rhythmic auditory cueing during treadmill and overground gait.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A309).

Recommendations for the Organization of Multidisciplinary Clinical Care Teams in Parkinson's Disease.

BACKGROUND: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. OBJECTIVE: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. METHODS: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. RESULTS: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. CONCLUSION: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care.

The effects of metronome frequency differentially affects gait on a treadmill and overground in people with Parkinson disease.

BACKGROUND: Treadmills and rhythmic auditory cueing can influence stepping rhythm for individuals with Parkinson disease (PD). Of concern, however, is that auditory cueing directly addresses the temporal features of gait, whereas adjusting step length may be more important for people with PD. Stepping to a faster cadence when walking overground may increase gait speed, but without requiring an increased step length. Furthermore, given the potentially valuable role of walking on a treadmill for individuals with PD, we are concerned that increasing cadence with rhythmic auditory cueing while walking at a constant treadmill speed will induce even shorter steps. RESEARCH QUESTION: What is the effect of different metronome cue frequencies on spatiotemporal gait parameters when walking overground compared to walking on a treadmill in people with PD? METHODS: Using a repeated-measures design, 21 people with PD (stage 1-3) walked overground and on a treadmill with and without metronome cues of 85 %, 100 %, and 115 % of their baseline cadence frequency for one minute each. We assessed step length, and cadence during all conditions. Gait speed was assessed during overground gait. RESULTS: An interaction effect between cue frequency and walking environment revealed that participants took longer steps during the 85 % condition on the treadmill only. When walking overground, metronome cues of 85 % and 115 % of baseline cadence yielded decreases and increases, respectively, in both cadence and gait speed with no associated change in step length. SIGNIFICANCE: These data suggest that people with PD are able to alter spatiotemporal gait parameters immediately when provided the appropriate metronome cue and walking environment. We propose to target shortened step lengths by stepping to the beat of slow frequency auditory cues while walking on a treadmill, whereas the use of fast frequency cues during overground walking can facilitate faster walking speeds.

Longitudinal change in autonomic symptoms predicts activities of daily living and depression in Parkinson's disease.

PURPOSE: The primary objective of this study was to examine the relationship of longitudinal changes in autonomic symptom burden and longitudinal changes in activities of daily living (ADLs); a secondary analysis examined the impact of depressive symptoms in this relationship. METHODS: Data were retrieved from the Parkinson's Progression Markers Initiative (PPMI), a dataset documenting the natural history of newly diagnosed Parkinson's disease (PD). The analysis focused on data from baseline, visit 6 (24 months after enrollment), and visit 12 (60 months after enrollment). The impact of longitudinal changes in autonomic symptom burden on longitudinal changes in ADLs function was examined. A secondary mediation analysis was performed to investigate whether longitudinal changes in depressive symptoms mediate the relationship between longitudinal changes in autonomic symptom burden and ADLs function. RESULTS: Changes in autonomic symptom burden, cognitive function, depressive symptoms, and motor function all correlated with ADLs. Only changes in ADLs and depression were found to be associated with changes in autonomic symptom burden. We found that longitudinal change in autonomic symptoms was a significant predictor of change in ADLs at 24 and 60 months after enrollment, with the cardiovascular subscore being a major driver of this association. Mediation analysis revealed that the association between autonomic symptoms and ADLs is partially mediated by depressive symptoms. CONCLUSIONS: Longitudinal changes in autonomic symptoms impact ADLs function in patients with early signs of PD, both directly and indirectly through their impact on depressive symptoms. Future investigation into the influence of treatment of these symptoms on outcomes in PD is warranted.

Physical activity mediates the association between striatal dopamine transporter availability and cognition in Parkinson's disease.

OBJECTIVE: Associations between cognition and nigrostriatal dopaminergic deficits in Parkinson's disease have been documented in the literature, but are incompletely understood. Here we studied the extent to which physical activity mediates the relationship between striatal dopamine transporter availability and global cognition among patients with Parkinson's disease. METHODS: Data from 174 patients from a multi-center study were analyzed using regression-based mediation analysis. Striatal dopamine transporter binding ratio (SBR), Physical Activity Scale for Elderly (PASE), and Montreal Cognitive Assessment (MoCA) were used to evaluate patients' dopamine transporter availability (DAT), physical activity, and global cognition respectively at the time of testing. Confidence intervals (CI) of 95% were established using a bootstrapping approach to test the statistical significance of the direct, indirect (i.e., mediation), and total effects of the mediation model. RESULTS: As hypothesized, the positive mediating effect of physical activity in the association between DAT and global cognition was significant, while adjusting for age (95% CI [0.0030, 0.3942]). Specifically, higher SBRs were positively associated with PASE scores, which in turn, were positively associated with MoCA scores. Secondary analyses revealed a similar positive mediation effect of physical activity for DAT in the caudate and putamen separately (95% CI [0.0377, 0.4231] and [0.0211, 1.1000], respectively). CONCLUSION: We report that the relationship of dopamine transporter availability with global cognition in Parkinson's disease is mediated by physical activity. Pending further research for specific recommendations, interventions to increase physical activity as tolerated should be considered in patients with Parkinson's disease.

Functional neuroimaging of the central autonomic network: recent developments and clinical implications.

PURPOSE: The central autonomic network (CAN) is an intricate system of brainstem, subcortical, and cortical structures that play key roles in the function of the autonomic nervous system. Prior to the advent of functional neuroimaging, in vivo studies of the human CAN were limited. The purpose of this review is to highlight the contribution of functional neuroimaging, specifically functional magnetic resonance imaging (fMRI), to the study of the CAN, and to discuss recent advances in this area. Additionally, we aim to emphasize exciting areas for future research. METHODS: We reviewed the existing literature in functional neuroimaging of the CAN. Here, we focus on fMRI research conducted in healthy human subjects, as well as research that has been done in disease states, to understand CAN function. To minimize confounding, papers examining CAN function in the context of cognition, emotion, pain, and affective disorders were excluded. RESULTS: fMRI has led to significant advances in the understanding of human CAN function. The CAN is composed of widespread brainstem and forebrain structures that are intricately connected and play key roles in reflexive and modulatory control of autonomic function. CONCLUSIONS: fMRI technology has contributed extensively to current knowledge of CAN function. It holds promise to serve as a biomarker in disease states. With ongoing advancements in fMRI technology, there is great opportunity and need for future research involving the CAN.

What predicts falls in Parkinson disease?: Observations from the Parkinson's Foundation registry.

BACKGROUND: We undertook this study to identify patients with Parkinson disease (PD) with no or rare falls who may progress to frequent falling by their next annual follow-up visit. METHODS: We analyzed data in the National Parkinson Foundation Quality Improvement Initiative database to identify factors predicting which patients with PD with no or rare falls at the baseline visit will report at least monthly falls at the annual follow-up visit. Multivariable models were constructed using logistic regression. Variables were introduced in 4 blocks: in the 1st block, variables present at or before the baseline visit were entered; in the 2nd, baseline visit assessments; in the 3rd, interventions implemented during baseline visit; and, in the 4th block, changes in comorbidities, living situation, and treatment between visits. RESULTS: Of 3,795 eligible participants, 3,276 (86.3%) reported no or rare falls at baseline visit, and of them, 382 (11.7%) reported at least monthly falls at follow-up visit. Predictors included female sex, <90% diagnostic certainty, motor fluctuations, levodopa treatment, antidepressant treatment, prior deep brain stimulation (DBS), worse quality of life, Hoehn & Yahr stage 2 or 3, worse semantic fluency, and, between visits, addition of amantadine, referral to occupational therapy, social services, or DBS, new diagnoses of cancer or osteoarthritis, and increased emergency visits. CONCLUSIONS: This large-scale analysis identified several predictors of progression to falling in PD. Such identifiers may help target patient subgroups for falls prevention intervention. Some factors are modifiable, offering opportunities for developing such interventions.

Disrupted hypothalamic functional connectivity in patients with PD and autonomic dysfunction.

OBJECTIVE: To test whether symptoms of autonomic dysfunction in Parkinson disease (PD) are associated with alterations in intrinsic hypothalamic functional connectivity, given the regulatory role of the hypothalamus (HTH) in the autonomic nervous system. METHODS: Resting-state fMRI scans from patients with PD were analyzed, comparing patients with the highest (n = 24) and lowest (n = 28) quartile scores in a questionnaire assessing autonomic dysfunction in PD (Scales for Outcomes in Parkinson's Disease-Autonomic [SCOPA-AUT]), obtained from a larger pool of patients (n = 93). Higher scores on the SCOPA-AUT indicate more severe symptoms. Seed-based functional connectivity maps, based on a seed region in the left and right HTH, were computed for each patient and compared by use of a general linear model, with false discovery rate correction for multiple comparisons. Partial correlation tests were additionally performed to test whether the associations between SCOPA-AUT scores and hypothalamic functional connectivity were independent of motor dysfunction, disease duration, cognitive function, and age. RESULTS: Relative to patients with PD with lower SCOPA-AUT scores, patients with higher scores displayed significantly reduced functional connectivity between the HTH and the striatum (caudate, putamen) and thalamus. The significant association between striato-thalamo-hypothalamic functional connectivity and SCOPA-AUT scores was retained after controlling for each patient's corresponding Movement Disorder Society Unified Parkinson's Disease Rating Scale scores, age, disease duration, and cognitive function. CONCLUSIONS: Patients with PD with symptoms of autonomic dysfunction show disrupted thalamo-striato-hypothalamic functional connectivity independently of overall motor dysfunction, disease duration, age and cognitive function. These findings suggest that symptoms of autonomic dysfunction in PD are accompanied by central deficits in the neural circuits that regulate autonomic function and their interaction with the basal ganglia.

Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson's disease.

Although the diagnosis of Parkinson's disease (PD) remains anchored around the cardinal motor symptoms of bradykinesia, rest tremor, rigidity and postural instability, it is becoming increasingly clear that the clinical phase of the disease is preceded by a long period of neurodegeneration, which is not readily evident in terms of motor dysfunction. The neurobiological mechanisms that underpin this prodromal phase of PD remain poorly understood. Based on converging evidence of basal ganglia (BG) dysfunction in early PD, we set out to establish whether the prodromal phase of the disease is characterized by alterations in functional communication within the input and output structures of the BG. We analyzed resting-state functional MRI data collected from patients with REM sleep behavior disorder (RBD) and/or hyposmia, two of the strongest markers of prodromal PD, in comparison to age-matched controls. Relative to controls, subjects in the prodromal group showed reduced intra- and interhemispheric functional connectivity in a striato-thalamo-pallidal network. Functional connectivity alterations were restricted to the BG and did not extend to functional connections with the cortex. The data suggest that local interactions between input and output BG structures may be disrupted already in the prodromal phase of PD.

The integrative care of Parkinson's disease: a systematic review.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, and it is characterized by a complex variety of both motor and neuropsychiatric issues. Effective treatment of PD symptoms requires a combination of pharmacotherapy and allied health therapies; however, treatment is generally monodisciplinary, with the neurologist referring out to varied therapists as needed. In order to more effectively manage PD as it progresses over time, clinics are beginning to implement and advocate the use of more integrative models of care for PD. In order to understand the effectiveness of these models, a comprehensive literature review was conducted through electronic searches of PubMed, Academic Search Premier, PsycINFO, Health Source: Nursing/Academic Edition, AgeLine, AMED (Alternative Medicine), Health and Psychosocial Instruments, Health Source - Consumer Edition, and Social Work Abstracts databases. The review identified only two published studies, both of which only evaluated the effectiveness of multidisciplinary care in outpatient settings. The results of the studies indicated that multidisciplinary treatment led to marked improvement in patient outcomes; however, these results are limited as they measured short term outcomes only. The limited available evidence on the efficacy of integrative healthcare delivery models in PD should serve as a call-to-action for clinicians to work to improve the care, and subsequently the quality of life, of PD patients through streamlining PD-specialized care with multiple complementary clinicians and incorporating patient preferences and goals into treatment.

What can we learn from freezing of gait in Parkinson's disease?

Freezing of gait (FOG) is defined as an episodic inability to generate effective stepping in the absence of any known cause, other than parkinsonism or high-level gait disorders. Substantial effort has been made to describe the clinical and kinematic characteristics of patients with FOG. In our review, we highlight the distinctive features of FOG in Parkinson's disease (PD) and apply the knowledge of its pathophysiology in PD to other clinical situations and conditions. It is possible that FOG in PD represents the ultimate break in the frontal lobe-basal ganglia-cerebellar-brainstem network that controls gait. Dysrhythmic and discoordinated gait with abnormal scaling of stride length, as well as gait festination, likely is the primary and continuous abnormality of "the gait network" in PD, and FOG represents its extreme and complete but transient disruption.

Botulinum toxin treatment of facial myoclonus in suspected Rasmussen encephalitis.

Patients with Rasmussen encephalitis (RE) may develop a variety of involuntary movements. We report a 26-year-old woman who presented with a 3-year history of progressive, continuous myoclonus of the left side of the face and left arm as well as left spastic hemiparesis. Magnetic resonance imaging of the brain showed right hemisphere and basal ganglia atrophy, and 24-hour electroencephalogram demonstrated diffuse slowing with random sharp waves in both hemispheres. An 18-fluoro-deoxy-glucose positron emission tomography scan indicated hypometabolism of the right cerebral hemisphere, including basal ganglia and thalamus. We successfully treated her myoclonus with injections of botulinum toxin A into the left zygomaticus muscle.

Effect of age on visuomotor functional MR imaging.

RATIONALE AND OBJECTIVES: We sought to determine the effect of age on functional MR imaging experiments performed with visual and motor stimulation. We hypothesized that there would be a diminution in the amplitude of fMRI activation with increasing subjects' age. MATERIALS AND METHODS: We used fixed effects models to study the amplitude of activation during a block design visuomotor task in three different age groups: old (mean: 75 years; standard deviation: 6 years), middle-aged (mean: 52 years; standard deviation: 9 years) and young (mean: 29 years; standard deviation: 5 years). Each group included 7 subjects. Regions of interest (ROI) were left primary motor area (LM1), supplementary motor area (SMA), and right and left occipital (RO, LO) visual areas. Individual subjects and group statistical parametric maps (SPMs) were generated for each ROI, and then the mean amplitude of activation was compared using the group analysis and t test. RESULTS: The young age group showed higher amplitude of activation than middle and old age groups in all ROI (P < 0.01 uncorrected). Unpaired two tailed t test results between the groups showed significant differences between middle and young, and old and young age groups in all ROIs (P < or = 0.05), with the exception of old and young age groups in RO region (P = 0.11). CONCLUSION: The group analysis, and unpaired t test results reveal higher amplitude of fMRI activation in the young versus the old and middle-aged groups.

Correlation between the amplitude of cortical activation and reaction time: a functional MRI study.

OBJECTIVE: We sought to examine the correlation between reaction time and the amplitude of cortical activation during the performance of a visuomotor response-time task in a functional MRI (fMRI) experiment. We hypothesized that the fMRI blood oxygenation level-dependent (BOLD) amplitude may have a negative correlation with a subject's reaction time: the lower the amplitude within the cortical areas along the visuomotor pathway, the slower the response. A larger amplitude of the fMRI signal would reflect faster response times. SUBJECTS AND METHODS: During a single-event fMRI experiment, the reaction times (in milliseconds) of 32 right-handed subjects responding to a visual cue were recorded. Analysis of the single-event paradigm using Statistical Parametric Mapping (SPM99) was performed, activation maps were produced for each subject, and then a random effects group analysis was performed. The maximum amplitudes of cortical activation (percent signal change) in four activated cortical regions were estimated and tabulated. The regions of interest included were the right and left occipital visual cortices, the supplementary motor area, and the left sensorimotor area. Simple and multiple regressions were performed between the mean reaction times of the subjects and the BOLD amplitudes in each region of interest and for the composite region of interest. RESULTS: The results showed significant negative associations between the reaction times and maximum amplitudes in the right occipital, left occipital, and left sensorimotor area cortical regions (p < 0.05). However, no significant association was found between reaction times and the amplitude within the supplementary motor area. When the effects of age and sex on these associations were analyzed, we found that age had an impact on the results for individual regions of interest in the left occipital and left sensorimotor areas, but the composite amplitude of activation remained significantly correlated with reaction times. CONCLUSION: The degree of signal change in BOLD fMRI response of the right occipital, left occipital, and left sensorimotor areas reflects the speed of performance during the visuomotor response time task by the subject. Thus, the amplitude of activation can be used as one parameter to assess change in function.

Timing of cortical activation: a latency-resolved event-related functional MR imaging study.

BACKGROUND AND PURPOSE: The time course of cortical activations of different anatomic areas has been demonstrated to reflect, to some degree, the temporal dynamics of the brain network. The purpose of this study was to determine the temporal sequence of the hemodynamic response in the visual, supplemental motor (SMA), and primary motor cortical areas by using a visuomotor reaction time task. METHODS: The reaction times (RTs) of 26 right-handed subjects were recorded in response to a visual cue during an event-related functional MR imaging (fMRI) experiment. Statistical parametric mapping (SPM99) was used, and activation maps were produced for each subject. This was followed by a random-effects group analysis. Using a weighted least-squares approach, we recorded the time at onset of the hemodynamic response of the fMRI activation in four regions of interest: the right occipital (RO) and left occipital (LO) visual cortices, the SMA, and the left sensorimotor area (LM1). Linear regression analysis was done between the RTs and the mean latencies for the four areas. RESULTS: Using the group analysis, the results showed that the first regions to activate were the visual occipital cortices (RO and LO) with mean latency +/- standard error of mean (SEM) of 1.74 +/- 0.05 s and 1.85 +/- 0.08 s, respectively. The visual occipital areas were followed by the SMA of 2.07 +/- 0.16 s and finally the LM1 with a mean latency of 2.1 +/- 0.15 s. There were significant differences in the mean onset of latencies between RO and LO, RO and SMA, and RO and LM1 (P <.05). On performing regression analysis between the RTs and the mean latencies by using the group analysis, there was no significant correlation with any of the four areas. By using an individual subject analysis, the results again showed that the first regions to activate were the visual occipital cortices (RO and LO) with mean latency +/- SEM of 1.75 +/- 0.06 s and 1.84 +/- 0.12 s, respectively, followed by the SMA with a mean latency of 2.19 +/- 0.25 s and finally the LM1 of 2.26 +/- 0.38 s. There was no significant difference between the mean onset latencies. CONCLUSION: The onset of the hemodynamic response started first in the visual cortex (input) followed by the SMA and primary motor cortical area (output). The onset of activation showed no direct correlation with the overall RTs of the subjects, leading one to suggest that the peripheral motor unit may have a greater impact on RT than the central contribution.