Associations of Later-Life Education, the BDNF Val66Met Polymorphism and Cognitive Change in Older Adults.

In 358 participants of the Tasmanian Healthy Brain Project, we quantified the cognitive consequences of engaging in varying loads of university-level education in later life, and investigated whether or not BDNF Val66Met affected outcomes. Assessment of neuropsychological, health, and psychosocial function was undertaken at baseline, 12-month, and 24-month follow-up. Education load was positively associated with change in language processing performance, but this effect did not reach statistical significance (P = 0.064). The BDNF Val66Met polymorphism significantly moderated the extent to which education load was associated with improved language processing (P = 0.026), with education load having a significant positive relationship with cognitive change in BDNF Met carriers but not in BDNF Val homozygotes. In older adults who carry BDNF Met, engaging in university-level education improves language processing performance in a load-dependent manner.

The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function.

The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR.

Reducing false positive diagnoses in mild cognitive impairment: the importance of comprehensive neuropsychological assessment.

BACKGROUND AND PURPOSE: Longitudinal studies of mild cognitive impairment (MCI) report that a sizeable proportion of MCI cases revert to normal levels of functioning over time. The rate of recovery from MCI indicates that existing MCI diagnostic criteria result in an unacceptably high rate of false positive diagnoses and lack adequate sensitivity and specificity. METHODS: The aim of the present study was to identify a set of neuropsychological measures able to differentiate between true positive cases of MCI from those who were unimpaired at 11 months' follow-up. RESULTS: A discriminant function analysis identified that a combination of measures of complex sustained attention, semantic memory, working memory, episodic memory and selective attention correctly classified outcome in more than 80% of cases. The rate of false positive diagnoses (5.93%) was considerably lower than is evident in previously published MCI studies. CONCLUSIONS: The results of the present study indicate that the rate of false positive MCI diagnoses can be significantly reduced through the use of sensitive and specific neuropsychological measures of memory and non-memory functions.

The effect of occupational exposure to manganese dust and fume on neuropsychological functioning in Australian smelter workers.

Chronic low-level occupational exposure to manganese (Mn) is reportedly associated with the development of Parkinsonian-like symptoms. In a study of 143 manganese smelter workers, inhalable Mn exposure was associated with lower performances on the Digit Symbol Coding and Stroop tests; respirable Mn exposure was associated with improved Digit Symbol Coding test performance and reduced performance on the Trail Making (Part A), Matrix Reasoning, and Stroop tests. While these relationships reached statistical significance, the magnitude of these effects was significantly smaller than the standard error of measurement of the neuropsychological tests, indicating that these differences are not of clinical significance.

Cortical activation during temporal preparation assessed by transcranial magnetic stimulation.

Preparatory modulations relative to the timing of upcoming stimuli may involve activation or suppression mechanisms. Here, we assessed the interplay between these mechanisms with transcranial magnetic stimulation (TMS) of the motor cortex. Single- or paired-pulse TMS with 3- or 15-ms interstimulus intervals was delivered during the interval between the warning and the imperative stimuli (i.e., the foreperiod) of a choice reaction time task. Temporal uncertainty was manipulated through between-block variation of the foreperiod duration (500 or 2500ms). The shortening of reaction time for the short foreperiod was accompanied with a decrease in amplitude of the single-pulse motor evoked potential (MEP), indicating corticospinal suppression. The co-occurring increase in amplitude of both paired-pulse MEPs (3 and 15ms) expressed relative to single-pulse MEPs reveals released short intracortical inhibition (SICI) and enhanced intracortical facilitation (ICF). These results suggest that temporal preparation is associated with both corticospinal suppression and cortical activation.

The behavioural and electrophysiological effects of visual task difficulty and bimanual coordination mode during dual-task performance.

The difficulty of a visual three stimulus and a bimanual coordination task was manipulated by varying discrimination difficulty (easy, hard) and coordination mode (in-phase, anti-phase) respectively. Electroencephalographic activity was recorded from 32 sites whilst participants (n = 16) completed four dual-task conditions in counterbalanced order. Longer reaction time and lower accuracy were found for the hard relative to the easy visual task and, for the hard visual task, accuracy was lower under anti-phase relative to in-phase conditions. Amplitude and latency of event-related potential components P3a and P3b were recorded and measured. There was a reduction in P3b amplitude and increase in P3a amplitude for the hard visual task overall and a further reduction in frontal P3b amplitude under the more demanding anti-phase condition. For the easy visual task, however, P3b and P3a amplitude were greater under the anti-phase relative to in-phase coordination condition at left hemisphere frontal sites. These findings suggest that the attentional cost of stabilising anti-phase bimanual coordination is largely associated with top-down automatic processes subserved by the frontal attentional network.

Neuromuscular and spatial constraints on bimanual hand-held pendulum oscillations: dissociation or combination?

The present work investigated the effects of spatial and neuromuscular constraints on the mean states and variability of interlimb coordination patterns performed in the para-sagittal plane of motion in a hand-held pendulum oscillation task. Nine right-handed students had to oscillate two pendulums through wrist adduction-abduction movements. Relative movement direction was manipulated by asking participants to perform both isodirectional and non-isodirectional movements. Participants were required to grab the pendulums either with both forearms in the same neutral or supine posture or with one forearm in neutral while the other one was in prone-inversed position. When both forearms were in a similar posture, isodirectional movements were generated predominantly by simultaneous activation of homologous muscle groups whereas non-isodirectional movements mainly resulted from simultaneous activation of non-homologous muscle groups. When forearms were in dissimilar posture, isodirectional movements were generated predominantly by the simultaneous activation of non-homologous muscle groups whereas non-isodirectional movements mainly resulted from simultaneous activation of homologous muscle groups. Standard deviation of relative phase and absolute error of relative phase were analyzed for each forearm posture condition. We hypothesized that neuromuscular and spatial constraints would affect two different aspects of coordination performance, i.e., pattern stability and accuracy, respectively. Comparison of the results obtained for similar and dissimilar postures suggested that changes of pattern stability were mediated by changes in the nature of the muscle activation patterns that gave rise to wrist movement in each condition. On the other hand, the results also showed that movement direction exclusively affected phase shift. The findings are consistent with the conclusion of Park et al. [Park, H., Collins, D. R., & Turvey, M. T. (2001). Dissociation of muscular and spatial constraints on patterns of interlimb coordination. Journal of Experimental Psychology: Human Perception and Performance, 27, 32-47.] that neuromuscular constraints affect variability of relative phase (attractor strength) and spatial constraints affect the shift of relative phase (attractor location).

The coalition of constraints during coordination of the ipsilateral and heterolateral limbs.

Previous work on the coordination between the upper and lower limbs has invariably shown that its accuracy/stability is primarily determined by the mutual direction between limbs in extrinsic space and not by muscle relationships. Here we show that muscle grouping does play a critical role in coordination of the arm and leg, in addition to direction. More specifically, the simultaneous activation of isofunctional muscles and/or limb movements proceeding in the same direction, results in more successful performance than the alternated activation of isofunctional muscles and/or movements occurring in different directions. In the absence of isofunctional muscle coupling, the mutual direction between the limbs plays a more prominent role in determining coordinative accuracy. These coordination constraints can largely account for the observed differences between ipsilateral and heterolateral limb coordination. The findings are discussed in view of the coalition of coordination constraints.

Effects of attentional prioritisation on the temporal and spatial components of an interlimb circle-drawing task.

This study aimed to examine the effects of directing attention to the spatial dimension of the circle-drawing task on interlimb coordination patterns across limbs. Eighteen participants performed a circle-drawing task involving in-phase and antiphase coordination modes under upper limb, contralateral and ipsilateral limb combinations. Results indicated that (a) coordination pattern stability co-varied with central cost when attentional focus was directed to the spatial dimensions of the interlimb circle-drawing task; (b) attentional focus on the spatial components modified the inherent performance asymmetries between the limbs; (c) finally, attention to the spatial components of the interlimb circle-drawing task modulated movement trajectories and at the same time the stability of temporal coordination.

Interlimb coordination following stroke.

Studies investigating whether simultaneous bilateral movements can facilitate performance of the impaired limb(s) of stroke patients have returned mixed results. In the present study we compared unilateral limb performance (amplitude, cycle duration) with performance during an interlimb coordination task involving both homologous (both arms, both legs) and non-homologous (one arm, one leg) limbs in stroke participants (n=7) and healthy age-matched controls (n=7). In addition, the effect of on-line augmented visual feedback on interlimb coordination was investigated. Participants performed cyclical flexion-extension movements of the arms and legs in the sagittal plane paced by an auditory metronome (1 Hz). Movement amplitudes were larger and cycle durations shorter during homologous limb coordination than non-homologous coordination. Compared with unilateral movements both groups had reduced movement amplitudes and the stroke group increased cycle duration when interlimb coordination tasks were performed. These effects were most evident during non-homologous (arm and leg) coordination. No evidence of facilitation of the impaired limb(s) was found in any of the interlimb coordination conditions. Augmented visual feedback had minimal effect on the movements of control participants but lead to an increase of cycle duration for stroke participants.

Mirror, mirror on the wall: viewing a mirror reflection of unilateral hand movements facilitates ipsilateral M1 excitability.

Primary motor cortex (M1) excitability is modulated by both ipsilateral limb movement and passive observation of movement of the contralateral limb. An interaction of these effects within M1 may account for recent research suggesting improved functional recovery of the impaired arm following stroke by viewing a mirror reflection of movements of the unimpaired arm superimposed over the (unseen) impaired arm. This hypothesis was tested in the present study using single-pulse transcranial magnetic stimulation (TMS) in eight neurologically healthy subjects. Excitability of M1 ipsilateral to a phasic, unilateral hand movement was measured while subjects performed paced (1 Hz), unilateral index finger-thumb opposition movements. Motor evoked potentials (MEPs) were obtained from the inactive first dorsal interosseous (FDI) in each of four viewing conditions: Active (viewing the active hand), Central (viewing a mark positioned between hands), Inactive (viewing the inactive hand) and Mirror (viewing a mirror-reflection of the active hand in a mirror oriented in the mid-sagittal plane) and with both hands at rest (Rest). MEPs were significantly enhanced during ipsilateral hand movement compared with the Rest condition (P<0.05). Largest MEPs were obtained in the Mirror condition, and this was significant compared with both the Inactive and Central viewing conditions (P<0.05). There was no difference between the dominant and non-dominant hand. Excitability of M1 ipsilateral to a unilateral hand movement is facilitated by viewing a mirror reflection of the moving hand. This finding provides neurophysiological evidence supporting the application of mirror therapy in stroke rehabilitation.

Attentional costs of coordinating homologous and non-homologous limbs.

This study aimed to examine the attentional demands of coordinating movement patterns across limbs. Eighteen participants performed a circle drawing task involving in-phase and anti-phase coordination modes under homologous, contralateral and ipsilateral limb combinations. Results indicated that: (a) attentional focus further stabilised coordination patterns with a cost at the central level; (b) there was an inverse relationship between stability and probe reaction time (RT) for all coordination patterns, that is the stronger the coupling between the limbs the lower the central cost. Overall, the results support previous research suggesting that attention plays an important role in sustaining coordination pattern stability and that the co-variation between coordination stability and central cost can also be extended to coordination across limbs.

Timing goals in bimanual coordination.

Phase coupling between movement trajectories has been proposed as the basic mechanism of hand coordination in the production of bimanual rhythmic movements with a 1:2 frequency ratio. Here a central temporal coupling view is proposed as an alternative. Extending previous models of two-handed synchronic and alternate-hand tapping, we hypothesized that 1:2 tapping is performed under the control of a single internal timekeeper set at the frequency required for the fast hand. The fast hand is assumed to use every signal and the slow hand every other signal of the timekeeper, to produce actions coordinated in time. The model's predictions for the variance-covariance pattern of tap timing within and across hands were tested in an experiment that required tapping with both hands with 1:1 or 1:2 frequency ratio. The finger contact on the response plate was to be short or long, according to instruction. Prolonged finger contact entailed profound modifications in the movement trajectories but failed to modify the variance-covariance pattern of the tap timing. This pattern proved to conform to predictions under both the short and the long contact conditions, thus supporting the central temporal coupling hypothesis.

The influence of task characteristics on the intermanual asymmetry of motor overflow.

The two studies reported here were designed to test the proposition that greater motor overflow occurs when movements are performed by the non-dominant hand. Unlike previous studies using normal adults, the task in these studies did not require force production. In the first study, a group of 19 right-handed participants performed unweighted finger lifting. That the frequency of motor overflow occurrence was the same regardless of which hand performed the task, did not support findings from other studies where tasks involving force production resulted in more overflow when performed by the non-dominant hand. To investigate further the influence of task characteristics on motor overflow occurrence, in the second study participants were required to remember and reproduce a prescribed sequence of four finger lifts. Left- and right-handed participants (N = 30) performed both single and sequenced finger lifting. The relative frequency of motor overflow (unintended lifts of fingers of the passive hand) was compared between hand preference groups, active hand and task type (single/sequenced). Contrary to the expectation that motor overflow would be greater for the sequenced finger lifting task, overflow was exhibited with a significantly greater frequency on single finger lifting. This finding indicates that task characteristics influence the pattern of overflow occurrence in normal adults. The task used in this study did not involve force production and did not result in an intermanual asymmetry of motor overflow. This contrasts with findings from other studies requiring adults to exert forces where greater overflow occurred when the non-dominant hand was active. However, this study confirms previous findings which show that left-handers produce greater overflow compared to right-handers regardless of the task being performed and the hand performing the task.

Simulating a neural cross-talk model for between-hand interference during bimanual circle drawing.

Studies on drawing circles with both hands in the horizontal plane have shown that this task is easy to perform across a wide range of movement frequencies under the symmetrical mode of coordination, whereas under the asymmetrical mode (both limbs moving clockwise or counterclockwise) increases in movement frequency have a disruptive effect on trajectory control and hand coordination. To account for these interference effects, we propose a simplified computer model for bimanual circle drawing based on the assumptions that (1) circular trajectories are generated from two orthogonal oscillations coupled with a phase delay, (2) the trajectories are organized on two levels, "intention" and "motor execution", and (3) the motor systems controlling each hand are prone to neural cross-talk. The neural cross-talk consists in dispatching some fraction of any force command sent to one limb as a mirror image to the other limb. Assuming predominating coupling influences from the dominant to the nondominant limb, the simulations successfully reproduced the main characteristics of performance during asymmetrical bimanual circle drawing with increasing movement frequencies, including disruption of the circular form drawn with the nondominant hand, increasing dephasing of the hand movements, increasing variability of the phase difference, and occasional reversals of the movement direction in the nondominant limb. The implications of these results for current theories of bimanual coordination are discussed.

Spontaneous and intentional pattern switching in a multisegmental bimanual coordination task.

Two experiments required right-handed subjects to trace circular trajectories while complying with either a symmetric or asymmetric pattern. In symmetric patterns, circles were traced in a mirror image either inward or outward. In asymmetric patterns, circles were traced in the same direction either clockwise or counterclockwise. Subjects were instructed to trace with spatial accuracy while maintaining a strict temporal relationship to a metronome that scaled movement rates from 1.25 to 3 Hz. The symmetric patterns were more stable than asymmetric patterns; the circularity of trajectories was greater for the dominant side; and there were spontaneous reversals in the direction of circling in the nondominant limb when performing asymmetric patterns. The second experiment examined the same subjects under the instruction of intentionally changing the pattern by reversing the left or right limb circling direction when cued to do so. The degree of interlimb interference was highly asymmetric and contingent on the direction of pattern change. Intentional direction reversals were more expedient and with less disruption to the contralateral limb when asymmetric to symmetric pattern changes were effected through a reversal in the direction of nondominant side. The results are interpreted with reference to evidence that the supplementary motor area mediates descending input to the upper limbs during disparate bimanual actions, but not during symmetric actions.

Athletic injury and minor life events: a prospective study.

Minor life events were examined in an attempt to determine their contribution to athletic injury risk. Male and female athletes (N = 98), from both team and individual sports (hockey, volleyball, and triathlon) were examined over the course of a competitive season. A high rate of injury was noted among these athletes (30%-46% of the members of each team sustained at least one injury during the season). The injured athletes were found to have a significant increase in minor life events for the week prior to injury. No significant changes in minor life events occurred for the non-injured athletes. The results of the present study provide substantial evidence for a link between minor life events and athletic injury.

Bimanual circle drawing during secondary task loading.

Seven right-handed participants performed bimanual circling movements in either a symmetrical or an asymmetrical coordination mode. Movements were paced with an auditory metronome at predetermined frequencies corresponding to transition frequency, where asymmetrical patterns became unstable, or at two-thirds transition frequency where both symmetrical and asymmetrical patterns were stable. The pacing tones were presented in either a high (1000 Hz) or low (500 Hz) pitch, and the percentage of high-pitched tones during a 20 s trial varied between 0% and 70%. Participants were instructed to count the number of high-pitched pacing tones that occurred during a trial of bimanual circling. Overall, the symmetrical pattern was more stable than the asymmetrical pattern at both frequencies. Errors on the tone-counting task were significantly higher during asymmetrical circling than symmetrical circling but only at the transition movement frequency. The results suggest that cognitive processes play a role in maintaining coordination patterns within regions of instability.

The dynamics of bimanual circle drawing.

A bimanual circle drawing task was employed to elucidate the dynamics of intralimb and interlimb coordination. Right-handed subjects were required to produce circles with both hands in either a symmetrical (mirror) mode (i.e. one hand moving clockwise, the other counter-clockwise) or in an asymmetrical mode (i.e. both hands moving clockwise or counter-clockwise). The frequency of movement was scaled by an auditory metronome from 1.50 Hz to 3.25 Hz in 8 (8-sec) steps. In the asymmetrical mode, distortions of the movement trajectories, transient departures from the target pattern of coordination, and phase wandering were evidence as movement frequency was increased. These features suggested loss of stability. Deviations from circular trajectories were most prominent for movements of the left hand. Transient departures from the required mode of coordination were also largely precipitated by the left hand. The results are discussed with reference to manual asymmetries and mechanisms of interlimb and intersegmental coordination.

Handedness and performance variability as factors influencing mirror movement occurrence.

A finger flexion task was used to investigate the effect of hand preference and performance variability on intensity of mirror movement. Right- and left-handed subjects were asked to maintain target forces, with either their index or small finger, that represented 25, 50, or 75% of their maximum strength capacity for the active finger. Greater mirror movement occurred when the small finger was active, and where there was greater variability in task performance, while mirror movement intensity was less when the dominant hand and the index finger were active. These findings were consistent with the cortical activation explanation of motor overflow (Todor & Lazarus, 1986a), and suggest that task variability is an important factor influencing motor overflow production. It was concluded that, if performance variability reflects the efficiency of cortical activation underlying control of a voluntary task, then refined cortical control decreases the potential for motor overflow to occur. However, it is necessary to clarify the relationship between hand preference, performance variability, and motor overflow, perhaps by examining the neural pathways involved in motor overflow production.