Evaluating the Acute Contributions of Dopaminergic Replacement to Gait With Obstacles in Parkinson's Disease

The influence of dopaminergic replacement (DR) on gait in people with Parkinson's disease (PD) is well documented. However, little is known about the acute effects of dopamine on more complex locomotor tasks that require visual guidance to avoid obstacles during gait. The authors investigated the influence of DR on locomotor behavior in a task where movement planning and control might be challenged by the height of the obstacle. The PD group included patients diagnosed with idiopathic PD (n = 12), as well as healthy controls (n = 12). Patients walked and stepped over obstacles of different heights before (OFF) and after (ON) levodopa intake. Spatial adjustments were not modulated by DR, but the step time to perform these anticipatory gait adjustments was longer only in PD-OFF (compared with healthy controls) when approaching the highest obstacle, but not PD-ON. During the crossing phase, trail limb toe clearance of PD patients was shorter than healthy controls only during the OFF state. ON-OFF comparisons were significantly different only for the time to reach the lead foot clearance over the highest obstacle. In summary, DR partially improved movement slowness but did not directly affect movement amplitude of lower limb regulation in this gait task.     

Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson’s disease

The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson’s disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n = 8) and bilateral group (n = 11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups × medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups × medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior–posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior–posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks.     

Intensity effects of the auditory evoked brain response to stimulus onset and cessation

Average evoked brain responses (EBR) to the onset (ON) and cessation (OFF) of 1-kHz pure-tone stimuli were computed from human scalp recordings. Stimuli of 2,000 msec duration were presented binaurally at 10 intensity levels. The waveform of the OFF EBR is similar to the ON EBR. The ON response is in general larger than the OFF response. Comparable ON and OFF amplitude response measures are both sensitive to changes in stimulus intensity which may be fit by a linear function. Significant differences in slope between ON and OFF amplitude intensity functions were demonstrated, which suggests different physiological systems for these responses.     

The effect of dopaminergic medication on conflict adaptation in Parkinson's disease

Parkinson's disease (PD) is a neurological disorder associated primarily with motor symptoms such as tremor, slowness of movement, and difficulties with gait and balance. Most patients take dopaminergic medication to improve their motor functions. Previous studies reported indications that such medication can impair higher cognitive functions (cf. dopamine overdose hypothesis). In the present study, we examined the effect of medication status on conflict adaptation. PD patients performed a Stroop task in which we manipulated the proportion of congruent and incongruent items, thereby allowing us to explore conflict adaptation. The use of mouse movements allowed us to examine the action dynamics of conflict adaptation in PD, and their sensitivity to dopaminergic medication. Each patient performed the same task twice: once without making changes to their regular medication regime, and once after overnight withdrawal from their medication. Results showed that medication improved mouse movements and alleviated motor symptoms. Moreover, patients' mouse movements were modulated as a function of the proportion congruency manipulation, revealing conflict adaptation in PD, which was unaffected by medication status. The present study extends earlier work on conflict adaptation in PD where reduced transient (trial-by-trial) conflict adaptation was observed ON compared to OFF medication (Duthoo et al., 2013, Neuropsychology, 27, 556). Our findings suggest that more sustained cognitive control processes may not be sensitive to dopamine overdose effects.     

Emotional state affects gait initiation in individuals with Parkinson’s disease

The purpose of the present study was to determine the impact of manipulating emotional state on gait initiation in persons with Parkinson’s disease (PD) and healthy older adults. Following the presentation of pictures that are known to elicit specific emotional responses, participants initiated gait and continued to walk for several steps at their normal pace. Reaction time, the displacement and velocity of the center of pressure (COP) trajectory during the preparatory postural adjustments, and length and velocity of the first two steps were measured. Analysis of the gait initiation measures revealed that exposure to (1) threatening pictures, relative to all other pictures, speeded the initiation of gait for PD patients and healthy older adults; (2) approach-oriented emotional pictures (erotic and happy people), relative to withdrawal-oriented pictures, facilitated the anticipatory postural adjustments of gait initiation for PD patients and healthy older adults, as evidenced by greater displacement and velocity of the COP movement; and (3) emotional pictures modulated gait initiation parameters in PD patients to the same degree as in healthy older adults. Collectively, these findings hold significant implications for understanding the circuitry underlying the manner by which emotions modulate movement and for the development of emotion-based interventions designed to maximize improvements in gait initiation for individuals with PD.     

Pigeons respond to produce periods in which rewards are independent of responding

Pecks by pigeons on a response key produced an ON state during which intermittent rewards were freely available, i.e., independently of responding. Pecks during the ON state caused it to remain ON. If no pecks occurred, the state changed to OFF—the key color changed—and rewards were not presented. The state remained OFF until the next response. Thus, responses controlled the state in the chamber but did not cause immediate reinforcement. Four dimensions of the schedule were varied: the rates of response-independent rewards during ON; the duration of ON produced by each peck; the pattern of rewards during ON; and the presence vs absence of exteroceptive cues during ON and OFF. The results showed that rates of responding were primarily controlled by the duration of ON produced by each response. When each response caused a long period of ON, pecks occurred infrequently; when each response caused a brief period of ON, pecks were frequent.     

A Note on Motor Learning Without Post-Response Knowledge of Results

The authors studied the adjustment of the 2 distinct known expressions of gait velocity, the velocity of the center of gravity (CG) and the velocity of the center of foot pressure (CP) at the end of the 1st step in 2 experimental situations: natural gait initiation (the control situation, CS) and heel-off gait initiation (the test situation, TS). Gait was initiated by 7 healthy participants, from an erect spontaneous posture in the CS and from a posture with heels raised in the TS, on a force platform at 3 self-selected speed conditions. Biomechanical data from the force platform were collected in both experimental situations, and the authors used a particular gait analysis based on the differential method of Y. Brenière (2003) in order to approach velocity modulation by means of step length and frequency. Results showed that CG and CP velocities were adjusted differently during heel-off gait initiation than during natural gait initiation. CP velocity, as compared with CG velocity, was overestimated in TS. Results also established the relevance of the expression of step velocity by means of step length and frequency: The central nervous system, taking into account the specific postural constraints of each experimental situation, uses a reference value and a regulating parameter to modulate step velocity. Moreover, the contributions of 1st step length and frequency to the expression of step velocity in TS and CS were different. Thus, a specific locomotor behavior corresponds to a given experimental situation that is characterized by its own initial biomechanical constraints.     

How does the heel-off posture modify gait initiation parameter programming?

The authors studied the adjustment of the 2 distinct known expressions of gait velocity, the velocity of the center of gravity (CG) and the velocity of the center of foot pressure (CP) at the end of the 1st step in 2 experimental situations: natural gait initiation (the control situation, CS) and heel-off gait initiation (the test situation, TS). Gait was initiated by 7 healthy participants, from an erect spontaneous posture in the CS and from a posture with heels raised in the TS, on a force platform at 3 self-selected speed conditions. Biomechanical data from the force platform were collected in both experimental situations, and the authors used a particular gait analysis based on the differential method of Y. Brenière (2003) in order to approach velocity modulation by means of step length and frequency. Results showed that CG and CP velocities were adjusted differently during heel-off gait initiation than during natural gait initiation. CP velocity, as compared with CG velocity, was overestimated in TS. Results also established the relevance of the expression of step velocity by means of step length and frequency: The central nervous system, taking into account the specific postural constraints of each experimental situation, uses a reference value and a regulating parameter to modulate step velocity. Moreover, the contributions of 1st step length and frequency to the expression of step velocity in TS and CS were different. Thus, a specific locomotor behavior corresponds to a given experimental situation that is characterized by its own initial biomechanical constraints.     

An accurate repeat cycle timer.

This timer was designed to provide a compact and quiet unit to control the presentation of visual stimuli by means of a slide projector, but it is not limited to this use. It is a solid state device, ready for use as soon as switched on, and is made largely from commercial logic units. The output is in the form of contact closures: the ON relay and the OFF relay give short pulse closures at the beginning of their respective cycles. With circuit values as shown in Fig. 1, times, from 0.5 to 10 sec in increments of 0.5 sec with an accuracy of ±1%, are selected by separate switches on the ON and the OFF cycles. Single interval solid state timers have been described by Saslow and Markowitz (1964) and by Tapp and Clark (1964).     

Auditory evoked brain responses: Comparison of ON and OFF responses at long and short durations

Average evoked brain responses (EBRs) to three durations of one kilohertz pure-tone stimuli were computed from human scalp recordings. Stimuli of 25, 75, and 2,000 msec duration were each presented binaurally at each of eight equally spaced intensity levels, ranging from 58 to 86 dB SPL. EBRs computed immediately following presentation, and immediately following removal of the 2,000-msec-duration stimulus result in ON and OFF responses, respectively. EBRs computed immediately following presentation of the 25- and 75-msec-duration stimuli appear to be the result of the sum of separate responses to stimulus onset and offset. Computer-dissected ON and OFF EBRs to short-duration stimuli are very similar in waveform and amplitude to the responses evoked by the onset and offset, respectively, of the 2,000-msec duration stimulus. Dissected ON and OFF responses demonstrate linear amplitude-intensity functions in amplitude ranges similar to respective ON and OFF responses to 2,000-msec stimulation. The data suggest that ON and OFF responses are mediated by independent physiological mechanisms.     

Auditory streaming: Competition among alternative organizations

It has been suggested that the ON and OFF components of the auditory evoked potential (AEP) may be mediated by independent physiological mechanisms and that the response to a brief tone consists of overlapping ON and OFF responses. Two experiments were performed to evaluate these proposals. First, AEPs were recorded to tonebursts of various durations presented at a fixed rate. As the tonebursts were made longer, they evoked smaller ON responses and larger OFF responses, particularly when either response followed the other by less than 5 sec. This indicates that ON and OFF responses are not physiologically independent. Second, the AEP to a 25-msec tone was compared with the ON response to a 2,000-msec tone. At an interstimulus interval of 4 sec, the difference wave formed by subtracting the latter AEP from the former contained clear N₁ (ca. 100 msec) and P₂ (ca. 180 msec) components, which have been interpreted as an OFF response by some authors. These components in the difference wave were greatly reduced or even inverted at 10-sec interstimulus intervals, however, where interactions between ON and OFF responses to successive stimuli were minimized. This result indicates that any residual OFF response in the AEP to a brief tone is very small in amplitude, if present at all.     

Postural control after unexpected external perturbation: Effects of Parkinson’s disease subtype

Different clinical subtypes of Parkinson’s disease (PD) have long been recognized. Recent studies have focused on two PD subtypes: Postural Instability and Gait Difficulty (PIGD) and Tremor Dominant (TD). PIGD patients have greater difficulties in postural control in relation to TD. However, knowledge about the differences in reactive adjustment mechanisms following a perturbation in TD and PIGD is limited. This study aimed to compare reactive postural adjustments under unexpected external perturbation in TD, PIGD, and control group (CG) subjects. Forty-five individuals (15 TD, 15 PIGD, and 15 CG) participated in this study. Postural perturbation was applied by the posterior displacement of the support surface in an unexpected condition. The velocity (15 cm/s) and displacement (5 cm/s) of perturbation were the same for all participants. Center of pressure (CoP) and center of mass (CoM) were analyzed for two reactive windows after the perturbation (0–200 ms and 200–700 ms). The Bonferroni post hoc test indicated a higher range of CoP in the PIGD when compared to the CG (p = 0.021). The PIGD demonstrated greater time to recover the stable posture compared to the TD (p = 0.017) and CG (p = 0.003). Furthermore, the TD showed higher AP-acceleration peak of CoM when compared to the PIGD (p = 0.048) and CG (p = 0.013), and greater AP-acceleration range of CoM in relation to the CG (p = 0.022). These findings suggest that PD patients present worse reactive postural control after perturbation compared to healthy older individuals. CoP and CoM parameters are sensitive to understand and detect the differences in reactive postural mechanisms in PD subtypes.     

Neuropharmacological treatment of mental dysfunction in Parkinson's disease

Many patients with Parkinson's Disease (PD) experience significant cognitive and mood impairment -even early in the course of the disease. These mental impairments are only partially responsive to levodopa treatment and are often as disabling as the motor impairment, particularly in mid and late stages of the disease. Investigators have recently begun a search for new agents that can effectively treat mental dysfunction of PD. Although there have been only a handful of properly controlled clinical trials of interventions targeted at amelioration of mental dysfunction in PD, progress has been made. Based on the available evidence, targeting catecholaminergic and cholinergic function may be an effective strategy for amelioration of cognitve, mood and psychiatric disturbances in PD.     

Quantitative measurement of handwriting in the assessment of drug-induced parkinsonism

Monitoring drug-induced side effects is especially important for patients who undergo treatment with antipsychotic medications, as these drugs often produce extrapyramidal side effects (EPS) resulting in movement abnormalities similar to parkinsonism. Scientists have developed several objective laboratory tests to measure and research drug-induced movement disorders, but equipment and tests are complex and costly and have not become accepted in large-scale, multi-site clinical trials. The goals of this study were to test whether a simple handwriting measure can discriminate between individuals with psychotropic-induced parkinsonism, Parkinson's disease, and healthy individuals, and to examine some of the psychometric properties of the measure. We examined pen movement kinematics during cursive writing of a standard word in 13 patients with idiopathic Parkinson's disease (PD), 10 schizophrenia patients with drug-induced parkinsonism (SZ), and 12 normal healthy control participants (NC). Participants were instructed to write the word "hello" in cursive twice, at three vertical height scales. Software was used for data acquisition and analysis of vertical stroke velocities, velocity scaling, and smoothness. There were four important results from this study: (1) both SZ patients with drug-induced EPS and PD participants exhibited impaired movement velocities and velocity scaling; (2) performance on the velocity scaling measure distinguished drug-induced EPS from normal with 90% accuracy; (3) SZ, but not PD participants displayed abnormalities in movement smoothness; and (4) there was a positive correlation between age and magnitude of the velocity scaling deficit in PD participants. This study demonstrates that kinematic analyses of pen movements during handwriting may be useful in detecting and monitoring subtle changes in motor control related to the adverse effects of psychotropic medications.     

Motor planning in Parkinson’s disease patients experiencing freezing of gait: The influence of cognitive load when approaching obstacles

Freezing of gait (FOG) in Parkinson’s disease (PD) is typically assumed to be a pure motor deficit, although it is important to consider how an abrupt loss of gait automaticity might be associated with an overloaded central resource capacity. If resource capacity limits are a factor underlying FOG, then obstacle crossing may be particularly sensitive to dual task effects in eliciting FOG. Participants performed a dual task (auditory digit monitoring) in order to increase cognitive load during obstacle crossing. Forty-two non-demented participants (14 PD patients with FOG, 13 PD who do not freeze, and 14 age-matched healthy control participants) were required to walk and step over a horizontal obstacle set at 15% of the participants’ height. Kinematic data were split into two phases of their approach: early (farthest away from the obstacle), and late (just prior to the obstacle). Interestingly, step length variability and step time variability increased when PD patients with FOG performed the dual task, but only in the late phase prior to the obstacle (i.e. when closest to the obstacle). Additionally, immediately after crossing, freezers landed the lead foot abnormally close to the obstacle regardless of dual task condition, and also contacted the obstacle more frequently (planning errors). Strength of the dual task effect was associated with low general cognitive status, declined executive function, and inappropriate spatial planning, but only in the PD-FOG group. This study is the first to demonstrate that cognitive load differentially impacts planning of the final steps needed to avoid an obstacle in PD patients with freezing, but not non-freezers or healthy controls, suggesting specific neural networks associated with FOG behaviours.     

Shrinkage of perceived tonal duration produced by extra sounds: effects of spectral density, temporal position, and transition direction

To investigate the mental mechanism that estimates the duration of sounds, the subjective duration of a tone was measured. In the first experiment a portion of the target sound was replaced with another sound. In the second and third experiments another sound either started or ended in the middle of the target sound. Ten or eleven undergraduates participated as listeners in each of the experiments. In the first experiment, effects of spectral spacing and those of temporal position of the replacing sound were tested. Compared with the intact case, the subjective duration of the replaced target shrunk, and the degree of shrinkage increased as the spectral spacing became wider. The temporal position of the replacing sound did not affect the degree of shrinkage. In the second experiment, effects produced by the start (ON) of the concurrent sound and those by the end (OFF) were compared. The ON case was more effective than the OFF case. In the third experiment, effects of the rise time and fall time of the concurrent sound were tested. A long rise and fall time reduced the difference between the ON and OFF cases. These results are discussed from two viewpoints, one assuming an interaction between the time markers, the other assuming continuous gate control in a neural-counting model for duration.     

Dynamic balance assessment during gait in children with Down and Prader-Willi syndromes using inertial sensors

Down (DS) and Prader-Willi (PWS) syndromes are chromosomal disorders both characterized by obesity, ligament laxity, and hypotonia, the latter associated with gait instability. Although these shared features may justify a common rehabilitation approach, evidence exists that adults with DS and PWS adopt different postural and walking strategies. The development of an instrumented protocol able to describe these strategies and quantify patients’ gait stability in the current clinical routine would be of great benefit for health professionals, allowing them to design personalized rehabilitation programs. This is particularly true for children with DS and PWS, where motor development is dramatically constrained by severe hypotonia and muscle weakness. The aim of this study was, thus, to propose an instrumented protocol, integrated with the clinical routine and based on the use of wearable inertial sensors, to assess gait stability in DS and PWS children.Fifteen children with DS, 11 children with PWS, and 12 typically developing children (CG) were involved in the study. Participants performed a 10-meter walking test while wearing four inertial sensors located at pelvis, sternum, and both distal tibiae levels. Spatiotemporal parameters (walking speed, stride frequency, and stride length) and a set of indices related to gait symmetry and upper-body stability (Root Mean Square, Attenuation Coefficient and Improved Harmonic Ratio) were estimated from pelvis and sternum accelerations. The Gross Motor Functional Measures (GMFM-88) and Intelligence Quotient (IQ Wechsler) were also assessed for each patient. A correlation analysis among the GMFM-88 and IQ scales and the estimated parameters was then performed.Children with DS and PWS exhibit reduced gait symmetry and higher accelerations at pelvis level than CG. While these accelerations are attenuated by about 40% at sternum level in CG and DS, PWS children display significant smaller attenuations, thus reporting reduced gait stability, most likely due to their typical “Trendelenburg gait”. Significant correlations were found between the estimated parameters and the GMFM-88 scale when considering the whole PWS and DS group and the PWS group alone.These results promote the adoption of wearable technology in clinical routines to monitor gait patterns in children with DS and PWS: the proposed protocol allows to markedly characterize patient-specific motor limitations even when clinical assessment scores provide similar results in terms of pathology severity. This protocol could be adopted to support health professionals in designing personalized treatments that, in turn, could help improving patients’ quality of life in terms of both physical and social perspectives.     

Divergent and Convergent Validation of the Complicated Grief Prototype Narrative

Although there is a prototype narrative for complicated grief (CG), there are neither divergent nor convergent validity studies of its clinical value. We evaluated the CG prototype narrative using a sociodemographic questionnaire and the Clinical Interview for Complicated Grief Diagnosis. We first conducted a convergent validation analysis followed by a divergent validation analysis. Results showed that participants with CG identified significantly more with the complicated grief prototype narrative than participants without CG.     

Dopamine modulation affects the performance of parkinsonian patients in a precision motor task measured by an antropomorphic device

Several parameters related to the timing, grip force and load force involved in a precision grasping task were studied in patients with Parkinson's disease (PD) at different moments of medication and healthy controls, using a sensorized anthropomorphic device which was totally adapted to the human hand. The aim of this work was to carry out an accurate study of the reach-load-grip-hold-place-release subtasks to identify any physical motor impairment, its relation to medication and Parkinsonian strategies. Twenty seven patients in ON and OFF-like medication moments, and twenty seven age-matched controls took part in the experiment, which consisted of using the index finger and the thumb to perform a precision motor task involving different experimental objects. Visual cues were used as distracting elements. Results showed several motor parameters impaired in OFF-like medication moment but attenuated in ON state, suggesting a medication effect on the performance of the task.     

Five-factor model prototypes for personality disorders: the utility of self-reports and observer ratings

The current study examined the prototype-matching technique for using the five-factor model (FFM) of personality to assess personality disorders (PDs) and their correlates. The sample was composed of 69 psychiatric patients, most of whom suffered from affective or anxiety disorders. The participants were predominantly outpatients (78%), Caucasian (94%), and women (58%). NEO Personality Inventory (NEO-PI) data from these patients and informants were available for deriving PD prototype scores. The results supported four conclusions. First, the FFM prototype-matching method is useful for clinical samples. Second, agreement between self-reports and information from significant others (SOs) using this method is good compared to previous results. Third, this agreement varies systematically with the observability of the PD criteria. Fourth, the value of self- and other-reported personality information depends on the rating source of the outcome variables. Other-reported information provides incremental utility in predicting impairment and interpersonal distress rated by clinicians and significant others.