Brain Advance Access originally published online on November 7, 2003
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Brain, Vol. 127, No. 2, 351-362, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh042
Sensorimotor slowing with ageing is mediated by a functional dysregulation of motor-generation processes: evidence from high-resolution event-related potentials
1 Institute of Occupational Physiology, Ardeystr. 67, D-44139 Dortmund, Germany and 2 Institute of Physiology, Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 23, 1113 Sofia, Bulgaria
Correspondence to: Dr Juliana Yordanova, MD, PhD, Institute of Physiology, Bulgarian Academy of Sciences, Acad. G. Bonchev str., bl. 23, 1113 Sofia, Bulgaria E-mail: jyord{at}iph.bio.bas.bg
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Summary |
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The objective of the present study was to identify the origin(s) of ageing-related behavioural slowing in sensorimotor tasks. For this aim, event-related potentials (ERPs) were analysed at 64 electrodes to evaluate the strength and timing of different stages of information processing in the brain. Electrophysiological indices of stimulus processing, sensorimotor integration/response selection and motor-related processing were used to compare the processing speed of young (n = 13, mean age = 22.5 years) and older adults (n = 14, mean age = 58.3 years) in simple- and choice-reaction tasks presented in two modalities, auditory and visual. The behavioural results showed significant ageing-related slowing, but only in the choice-reaction task. The quantification of separate central processing stages, in combination with advanced ERP methodology, helped to reveal that this slowing did not originate from the early processes of stimulus processing and response selection. Instead, it was produced by slower activation patterns over the contralateral motor cortex underlying response generation. It is concluded that ageing is accompanied by a functional dysregulation of motor cortex excitability during sensorimotor processing, with this deficit becoming progressively evident with greater task complexity.
Key Words: ageing; electroencephalography; event-related potentials; motor-related potentials; executive functions
Abbreviations: CRT= four-choice-reaction task; CSD = current source density; ERP = event-related potential; LRP = lateralized readiness potential; MRP = motor-related potential; r-ERP = response-related ERP; r-LRP = response-locked LRP; RT = reaction time; s-ERP = stimulus-related ERP; SR1, SR2, SR3, SR4 = stimulus–response types;s-LRP = stimulus-locked LRP; SRT = simple reaction task
Received June 26, 2003. Revised September 21, 2003. Accepted September 23, 2003.
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Introduction |
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It is well recognized that ageing is accompanied by changes in the speed and/or mode of information processing in the brain. Increased age is consistently associated with slower performance in a wide range of speeded tasks (Salthouse, 2000
). One robust finding, referred to as ‘the complexity effect’, is that behavioural slowing with age is not constant across tasks but increases with increasing task complexity (Kok, 2000; Salthouse, 2000).
Traditionally, cognitive capacity has received most attention as a major determinant of the task-related slowing in the elderly. Age-dependent deviations have been documented for a great variety of higher cognitive functions such as selective and divided attention, working memory and executive control (e.g. Kenemans et al., 1995; Cabeza et al., 1997, 2002; Chao and Knight, 1997; Grady, 1998; Pelosi and Blumhardt, 1999; Kok, 2000; Falkenstein et al., 2001; Reuter-Lorenz, 2002). It has also been suggested that higher cognitive processes are more affected by ageing than lower (sensory and motor) processes (Molenaar and van der Molen, 1994). Recent results have provided new evidence that the interdependence between higher cognitive and lower sensory/sensorimotor processes becomes stronger with advancing age (Li and Dinse, 2002; Li and Lindenberger, 2002). Yet, it remains to be determined whether specific processes (sensory, motor or cognitive) are selectively impaired with ageing or more general and unspecific alterations, such as neural loss, decline in inhibitory functioning or reduction of processing resources, produce behavioural decrements as a result of multiple distributed deteriorations (Kok, 2000; Salthouse, 2000; Li and Dinse, 2002). Further, it is not known precisely whether the age-related elevation of cognitive effort is due to a primary deterioration of sensory and/or motor input (Li and Dinse, 2002), or extra-activations of sensory and motor areas may occur to compensate for certain impairments of cognitive operations (Nyberg et al., 2002).
Concerning the contribution of lower sensorimotor processes to behavioural slowing in the elderly, previous research has documented the decline of the dopaminergic neurotransmitter system in the ageing human brain and, more specifically, the loss of dopamine receptors in the striatum and extrastriatal regions (Kaasinen et al., 2000), which has been associated with basic impairments in motor functions (Volkow et al., 1998). Animal studies have further found a reduction of inhibitory synapses in the sensorimotor cortex, suggesting an age-dependent deficit in the intrinsic inhibitory circuitry (Poe et al., 2001). In humans, intracortical inhibition and facilitation of primary motor areas have both been demonstrated to be reduced in aged individuals (Peinemann et al., 2001). Also, degenerative age-related changes in the primary somatosensory cortex of rats have been shown to exist in parallel with plastic-adaptive changes of neuronal cortical representations (Godde et al., 2002), as also established for elderly human subjects (Ghafouri and Lestienne, 2000). Such findings strongly imply that primarily the sensorimotor functions are altered in old age, and these changes would affect performance even in simple-task conditions.
Indeed, simple repetitive hand movements have produced a reduced activation in the contralateral sensorimotor and premotor cortices of old relative to young people (Hutchinson et al., 2002). However, in contrast to simple repetitive movements, movements paced or triggered by external stimulation have produced a greater activation in the contralateral sensorimotor, premotor and supplementary motor cortex of elderly subjects (Sailer et al., 2000; Mattay et al., 2002), implying that certain task-mediated interactions between sensory and motor mechanisms affect the process of response generation. In this line, Briggs et al. (1999; Raz et al., 1999) have concluded that ageing-related slowing in a variety of visuo-motor reaction-time tasks is associated with declines in working memory but not with a decrease of sensorimotor speed. However, results from a visuo-spatial attention (Simon) task, in which stimulus and response side did or did not correspond, have suggested that response delay in aged individuals originates from an impaired transmission of visuo-motor information from parietal to motor cortical areas (van der Lubbe and Verleger, 2002). By using a more complex mental rotation task, Band and Kok (2000) have assumed that the source of slowing with age may be in the motor-generation system, but this suggestion has not been confirmed by van der Lubbe and Verleger (2002). Thus, recent findings of the origins of sensorimotor delay with ageing remain inconclusive, and further studies are needed to clarify the question of why old subjects react slowly to external stimuli.
The aim of the present study was to analyse different stages of sensorimotor information processing in the brain in order to evaluate their contribution to ageing-related behavioural slowing. To describe precisely the timing of separate stages, event-related brain activity of young and older subjects was analysed. To enable a better distinction between fundamental aspects of stimulus processing, sensorimotor integration (response selection) and motor response production, sensorimotor tasks were used in which centrally presented stimuli required motor responses. A simple- and a choice-reaction task were employed to assess the effects of cognitive processing induced by a higher task complexity on response slowing with age. Yet, these tasks were designed to be relatively simple in order to avoid performance failures due to cognitive overload (Band and Kok, 2000). Also, the tasks were performed in two different modalities, auditory and visual, to separate modality-specific from supra-modal origins of delay. We also aimed to avoid confounding effects from differences in spatial information processing (Kenemans et al., 1995; Müller and Knight, 2002), multi-dimensional stimulus discrimination and search (for a review see Kok, 2000), orientation and novelty processing (Polich, 1997; Kok, 2000), and variations in long-term memory load (Cabeza et al., 1997), all of which have been shown to be affected by advancing age. Thus, bioelectrical indices of stimulus processing, sensorimotor integration and response generation were compared between young and older subjects, and further correlated with simple- and choice-response times.
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Methods |
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Subjects
A total of 25 subjects were studied. They were divided into two age groups: young (n = 13, six females, mean age 22.5 years, SE = ±1.5), and older (n = 14, six females, mean age 58.3 years, SE = ±2.1). All subjects were healthy, without history of neurological, psychiatric, chronic somatic or hearing problems. They were under no medication during the experimental sessions, with normal or corrected to normal vision. The study received prior approval by the Ethical Committee of the Institute of Occupational Physiology. Informed consent was obtained from each subject according to the Declaration of Helsinki.
Task and stimuli
(i) A visual and an auditory four-choice-reaction task (CRT) was used, in which four stimuli represented by the letters A, E, I and O were delivered randomly with equal probability of 25%. A total of 120 stimuli were presented in each experimental block, with n = 30 for each stimulus type. The letters A, E, I and O had to be responded to with the left middle, left index, right index and right middle fingers, respectively. They were designated as four stimulus–response types (SR1, SR2, SR3 and SR4). Response force was measured while subjects produced a flexion with each of the four fingers, which rested in force-measuring devices.
(ii) A visual and an auditory simple-reaction task (SRT) was also used, in which the same four letters served as stimuli with the instruction to respond as quickly as possible to each stimulus with the right middle finger. A total of 60 stimuli were presented in each experimental SRT block.
The auditory stimuli (duration 300 ms, intensity 67 dB sound pressure level) were delivered via headphones binaurally. The visual stimuli were presented in the middle of a monitor (duration 300 ms, intensity 50 cd/m2, visual angles 1° horizontal/1.5° vertical,) placed in front of the subject’s eyes. The interstimulus intervals varied randomly between 1440 and 2160 ms (mean 1800 ms). This was necessary to avoid time prediction effects on reaction times (RTs) in the SRT. When the response was slower than 700 ms, a feedback tone was delivered 1200 ms after stimulus onset. This tone had to be avoided by the subjects by keeping to the RT limit.
Data recording and analysis
Data were recorded on three consecutive experimental days. This enabled the assessment of practice effects. Sequences of auditory and visual, and SRT and CRT blocks were counterbalanced across subjects. To enable a comparison between SRT and CRT, data for only the SR4 type in the CRT were analysed.
Single RTs were measured at the instant when response force reached 5 N. Individual averages were computed for correct responses in each task, stimulus and modality condition. The number of errors in the CRT was computed for each individual in each experimental CRT block. An error was defined as a response to a wrong stimulus.
The EEG was recorded from 64 channels with Cz as a reference. In parallel, muscle activity (EMG) was recorded from the forearms. Before analyses, the EEG was scanned for gross EOG artefacts (larger than ±80 µV) and EMG artefacts. Contaminated trials were discarded along with records exceeding ±50 µV. Slight horizontal and vertical eye movements and blinks still present in the accepted epochs were corrected by means of a linear regression method for EOG correction (Gratton et al., 1983).
Individual averages for each stimulus–response type in each recording block were obtained, with the number of sweeps being between 25 and 30. For quantification and topography assessment, data were transformed to current source density (CSD) (Perrin et al., 1989). The CSD transform produces reference-free signals, which is important for a reliable topography analysis (Nunez, 1981). Another major advantage is that CSD leads to a spatial enhancement of the recorded EEG activity (Babiloni et al., 1996, 1998). Stimulus-locked and response-locked CSDs were computed in order to enable a better distinction of stimulus- and response-related ERP (s-ERP and r-ERP) components.
Evaluation of central processing stages
Figure 1 illustrates electrophysiological parameters analysed in this study to describe consecutive stages of central information processing.
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Stimulus processing
Perception. The first is the stage of stimulus processing (Fig. 1a, left). At that stage, stimulus characteristics are processed and stimulus recognition occurs. Early steps of stimulus processing are reflected by the P1 and N1 components of the s-ERP (e.g. Regan, 1989
; Gazzaniga et al., 1998). By measuring latencies and amplitudes of these components, it is possible to examine differences in the speed and intensity of early perceptual (or stimulus processing) mechanisms between young and old adults (e.g. Amenedo and Diaz, 1998). Peak amplitudes were measured with a baseline of 200 ms before stimulus onset at modality-specific sensory areas. For the auditory modality, P1 was identified as the most positive deflection within 40–100 ms, and N1 as the most negative deflection within 80–140 ms after stimulus onset at bilateral temporal locations (T7 and T8). For the visual modality, P1 was measured as the most positive deflection within 40–140 ms, and N1 as the most negative deflection within 120–200 ms after stimulus onset at bilateral occipital locations (O1 and O2).
Task-stimulus classification. To assess later stages of stimulus processing, the endogenous P300 component of s-ERPs was analysed. P300 (P3b) is a large positive wave with centro-parietal distribution that is elicited by task-relevant stimuli (for a review see Polich, 1998). P300 amplitude is assumed to reflect the attentional mechanisms engaged to ‘update’ the neural representations of the stimulus context after early stimulus evaluation, and P300 latency is considered to be a measure of the speed of task-related stimulus classification (Polich, 1998, 2003). It has been documented that P300 amplitude decreases and P300 latency increases with advancing age in adults (for a review see Polich, 1997). To compare stimulus classification speed of young and old subjects and its possible contribution to sensorimotor slowing with ageing, the P300 s-ERP component was analysed at the mid-line CPz electrode. P300 was identified as the most positive peak within 260–700 ms after stimulus occurrence, and its latency and amplitude were measured with a baseline of 200 ms before stimulus onset.
Sensorimotor integration/response selection
When a response to an external stimulus is demanded, response-related mechanisms at motor cortical areas are activated immediately after or even in parallel with stimulus identification. One s-ERP component that has been recognized to reflect the initiation of motor-related processes is the lateralized readiness potential, LRP (de Jong et al., 1988; Coles, 1989). As illustrated in Fig. 1b, motor response execution activates specific regions of the primary sensorimotor cortex contralateral to the responding effector (or hand), and such activation cannot be observed at the ipsilateral motor cortex. As shown in Fig. 1c (left), if the difference between contra- and ipsilateral s-ERPs [e.g. the stimulus-locked LRP (s-LRP)] is measured at motor cortical locations, the start of this difference would reflect the time when sensorimotor integration/response selection is finished and the effective movement is initiated. In the present study, the onset of the s-LRP was analysed to see if RT slowing might originate from slowing of central response initiation. To enable a comparison between s-LRPs in the SRT and the CRT, the s-LRP was not calculated in the classical way (Coles, 1989) but was computed as a C3–C4 difference for the right-hand responses in the SRT and the corresponding stimulus–response type (SR4) in the CRT. A possible problem with this computation can be a contamination with non-motor lateralizations. This is excluded here, because only centrally presented stimuli were used. s-LRP onset was measured as the time when s-LRP amplitude was 15% of its maximal value (Mordkoff and Gianaros, 2000). A low threshold (15%) was chosen to minimize artificial onset differences induced by differences in LRP slope (cf. Schwarzenau et al., 1998).
Motor processing
Motor processing can be evaluated by analysing motor-related potentials (MRPs) at contralateral motor cortical areas (Taniguchi et al. 2001). Figure 1b (left) shows that stimulus-locked averaging cannot extract MRPs reliably because of the varying response latencies. To analyse MRPs, it is necessary to calculate response-locked averages (r-ERPs). As demonstrated in Fig. 1b (right), this procedure emphasizes motor-related components by reducing response latency jitter. On the contrary, stimulus-locked components are smeared in the response-related ERP (Fig. 1A, right).
MRPs were analysed at C3 over the motor cortex contralateral to the responding right hand. The baseline was a 200 ms interval between 800 and 600 ms before the response. The baseline was chosen to subtract pre-stimulus activity, so that MRP measures were not affected by motor-related activations that could be induced shortly after stimulus appearance. Figure 1b (right) illustrates that: (i) peak latency and amplitude values of the most negative displacement of the MRP were measured; (ii) the onset latency of the MRP was also calculated with a threshold of 15% of MRP maximum; and (iii) the duration of the motor-related activation (MRP rise time) was measured as the difference between MRP peak latency and MRP onset latency.
Response-related ERPs at the ipsilateral motor cortex (C4) were also quantified (Taniguchi et al., 2001). Because no clear peaks or components were evident (Fig. 1b, right), ipsilateral r-ERPs were evaluated by measuring mean amplitude values within 200 ms before and after the response.
Finally, the response-locked LRP (r-LRP) was obtained by subtracting r-ERPs at C4 from those at C3, and r-LRP onset latency was calculated in the same way as for the s-LRP onset latency (Fig. 1c, right).
Statistical evaluation
The experimental data were assessed statistically by means of a repeated-measures analysis of variance (ANOVA).
RT data for SR4 in the CRT and in the SRT were subjected to ANOVA with a between-subjects factor age (young versus older), and within-subjects factors task (SRT versus CRT), modality (auditory versus visual) and practice (days 1–3). Error rate data for SR4 in the CRT were subjected to an age x modality x practice repeated-measures ANOVA.
Statistical analysis was performed separately for auditory and visual P1 and N1 s-ERP components. Peak amplitude and latency values of the P1 and N1 at the locations of their modality-specific maxima (T7/T8 for the auditory and O1/O2 for the visual modality) were subjected to a repeated-measures ANOVA with one between-subjects variable age, and within-subjects factors task, practice and electrode (left versus right). P300 measures at CPz were subjected to an age x task x modality x practice ANOVA.
The onset latencies of s-LRP and r-LRP were also subjected to an age x task x modality x practice ANOVA. Peak amplitude, peak latency and onset latency values of the MRP at the contralateral motor cortex, and mean amplitude measures at the ipsilateral cortex were analysed separately with the same design.
For repeated-measures variables with more than two levels, the Greenhouse–Geisser correction procedure was employed, with original degrees of freedom and corrected confidence probabilities (P) being reported. For most of the analysed parameters, main and interactive effects of practice were not significant. Therefore, practice effects and non-significant effects of other variables will not be described in the Results.
Correlations between various latency measures were obtained using Pearson correlation coefficients. To ascertain the determinants of the relationship between RT and the speed of preceding processing stages, stepwise multiple regression analyses were performed for young and older subjects separately. With respect to initial observations on correlational relationships among speeds of different stages, in the analysis design, RTs were the dependent variables in independent analyses for the SRT and CRT. The predictor variables included P1 latency, N1 latency, s-LRP onset latency, MRP onset latency, r-LRP onset latency and MRP rise time (the difference between MRP peak and onset latency). If one of these factors predicted significant variance of RT, the stepwise multiple regression analysis would select it as an independent predictor of RT.
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Results |
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Behavioural results
Table 1 shows group mean RT of young and older adults in SRT and CRT. RT was overall slower in the older (390 ms) than in the young (352 ms) adults [F(1/25) = 14.6, P < 0.001]. As expected, there was a strong main effect of task complexity due to significantly slower RT in the CRT (509 ms) relative to the SRT (233 ms) [F(1/25) = 1580.3, P < 0.0001]. However, RTs of older adults were delayed only in the choice [F(1/25) = 20.5, P < 0.001] but not in the simple-response condition [F(1/25) = 1.6, P > 0.2], as also indicated by a significant age x task interaction [F(1/25) = 12.5, P < 0.005]. In the SRT, RT was longer to visual than auditory stimuli, whereas in the CRT the opposite modality effect was observed [task x modality, F(1/25) = 37.1, P < 0.001]. RT decreased with practice [F(2/50) = 45.5, P < 0.001], but only in the CRT (task x practice, F(2/50) = 37.5, P < 0.001]. Error rate in the CRT was <5% and did not differ significantly between the two groups.
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Central processing mechanisms
Stimulus processing
Perception: P1–N1. Figure 2a (left) illustrates that the auditory P1 component manifested a topographical distribution at bilateral temporal locations. It is also shown that (i) the topography patterns were overall similar for the two age groups, with more posterior distribution of P1 for the young relative to the older subjects, and (ii) task complexity did not produce differences in the scalp distribution of auditory P1. Figure 2b (left) shows that the visual P1 component displayed a bilateral scalp distribution over the occipital cortex. These topography patterns were consistent across age groups and task conditions. Topography patterns of P1 in each modality were similar to those of N1, with vertex locations being additionally involved for the auditory N1.
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The right panels of Figure 2a and b illustrate that ageing effects on P1 amplitude in each modality depended on the task [age x task, F(1/25) = 2.8, P = 0.05 for the auditory, and F(1/25) = 8.62, P < 0.01 for the visual ERPs]: in the SRT, both auditory and visual P1 difference between young and older subjects was not significant [F(1/25) < 0.5, P > 0.85], whereas in the CRT, there was a trend for a larger P1 in older subjects [F(1/25) > 2.7, 0.05 < P < 0.1]. Older subjects had a significantly larger N1 amplitude than young adults in the SRT at O1 for the visual modality [age x task, F(1/25) = 5.2, P < 0.05; age x task x electrode, F(1/25) = 6.6, P < 0.01], whereas no significant age differences were found for the auditory N1 amplitude.
Latencies of the auditory P1 (mean 57 ms) and N1 (mean 120 ms) did not depend on age or task [F(1/25) < 1.5, P > 0.2]. In contrast, visual P1 latency was slightly, but significantly longer in the older (mean 89 ms) than in the young (mean 80 ms) subjects [age, F(1/25) = 3.56, P = 0.05]. Although visual N1 latency was longer in the older (154 ms) than young (147 ms) adults, this difference did not reach statistical significance.
Task-stimulus classification: P300. The classical P300 with centro-parietal distribution was reliably elicited only in the CRT, whereas in the SRT, P300 waveform was not expressed, nor did it manifest a centro-parietal dominance. P300 analysis was therefore performed only for the CRT. As expected, P300 amplitude was smaller [age, F(1/25) = 4.61, P < 0.05], and P300 latency was longer [age, F(1/25) = 4.21, P < 0.05] in the older (562 ms) than in the young (516 ms) subjects. As demonstrated in Table 1B, P300 latency was longer than RT (Table 1A). Therefore, P300 was not considered further as a predictor of response speed.
It is to be noted that in both the SRT and CRT conditions, a prominent occipito-parietal positive wave was elicited at 
230–280 ms after stimulus onset. This wave was consistently observed in the two age groups in the two modalities, and had a strong left hemisphere predominance for young adults. Because the latency and the scalp distribution of this wave did not meet P300 identification criteria, it was not analysed further in the present study.
Sensory–motor integration/response selection: s-LRP
Figure 3 depicts s-LRPs of the young and older subjects in the SRT and CRT conditions and shows that the s-LRP peak was substantially larger and later in the group of the older adults. The s-LRP onset strongly depended on task complexity and was significantly later in the CRT relative to the SRT [F(1/25) = 232.01, P < 0.0001, mean 237 versus 108 ms]. It is important to note, however, that no effects of ageing on s-LRP onset were found for either the SRT or the CRT condition, as shown in Fig. 3. S-LRP onset tended to be later for the visual than for the auditory tasks [modality, F(1/25) = 3.92, P = 0.059], which was due to delays only in the SRT (128 versus 88 ms) but not in the CRT (238 versus 238 ms) [task x modality, F(1/25) = 7.57, P < 0.01].
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Motor-related processes: MRP
Figure 4A demonstrates the topography maps calculated for the negative MRP peak shown in Fig. 4B. As illustrated in Fig. 4B, MRPs at the contralateral motor cortex were generally characterized by a large negative deflection. This negative deflection comprised a slow negative shift (pre-response MRP, pre-MRP), followed by a steeper negative deflection, peaking just prior to or at the time of response execution (MRP), and by a positive-going deflection after the movement (post-response MRP; Kristeva et al., 1991
; Gerloff et al., 1998; Luu and Tucker, 2001). It is also notable that a post-movement positivity was not clearly evident for the older adults in the CRT. Figure 4a shows that in the two age groups, there was a clear maximum of MRP at the contralateral motor cortex (C3). Particularly in young adults, a second medial focus of distribution was also seen due to a partial overlap with a midline negativity following the response. (The midline negativity was substantially suppressed in the older subjects, which reduced the second focus of activity, so that only a distribution over the contralateral motor cortex was evinced.) Figure 4c illustrates grand average r-ERPs at the ipsilateral motor cortices, which reveals clear positive waveshapes. Figure 4d shows that EMG activation patterns did not differ across age groups, tasks and modalities.
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Contralateral MRPs. As shown in Fig. 4b, overall MRP peak amplitude tended to be larger in older than in young adults [age, F(1/25) = 3.5, P = 0.07]. The CRT produced a significantly larger MRP relative to SRT [task, F(1/25) = 31.38, P < 0.0001]. Yet, an age x task interaction [F(1/25) = 6.45, P < 0.05] indicated that ageing was associated with a significant augmentation of peak MRP amplitude only in the CRT [F(1/25) = 5.38, P < 0.05] but not in the SRT [F(1/25) = 1.2, P > 0.3]. Also, the contralateral MRP peak was overall slightly but significantly larger for the auditory than for the visual modality [modality, F(1/25) = 6.95, P < 0.05]. MRP peak latency was shorter [F(1/25) = 15.98, P < 0.001] in the CRT (mean –43.6 ms) than in the SRT (mean –23 ms). This task effect was more pronounced for the visual modality [task x modality, F(1/25) = 8.2, P < 0.01] and for the group of young subjects [age x task x modality, F(1/25) = 6.6, P < 0.05].
MRP onset latency was longer in older (–262 ms) than in young subjects (–206 ms) [F(1/25) = 9.45, P < 0.005]. The MRP started earlier before the response in the CRT (–297 ms) than in the SRT (–171 ms). Importantly, as seen in Fig. 4b, age differences between MRP onset were present only in the CRT [F(1/25) = 8.6, P < 0.01] but not in the SRT condition [F(1/25) = 1.3, P > 0.2), as also revealed by the significant age x task interaction [F(1/25) = 3.8, P = 0.05]. MRP onset was earlier in the auditory than in the visual CRT [modality, F(1/25) = 10.2, P < 0.005; task x modality, F(1/25) = 4.5, P < 0.05].
Ipsilateral activity. Figure 4c demonstrates that response execution was accompanied by positive potential shifts at ipsilateral electrodes which were much larger for the CRT (mean 19.4 µV/m2) than for the SRT (mean 2.13 µV/m2) condition [task, F(1/25) = 67.7, P < 0.001]. Also, the ipsilateral activity was larger for older than for young subjects only in the SRT [F(1/25) = 6.65, P < 0.01], but not in the CRT [F(1/25) = 0.01, P > 0.9], as also indicated by the age x task interaction [F(1/25) = 5.07, P < 0.05]. This effect was more prominent for the visual modality [age x task x modality, F(1/25) = 4.44, P < 0.05].
Motor-related functional asymmetry: r-LRP
The r-LRP onset (illustrated in Fig. 1c) was significantly earlier in the older (–228 ms) than in the young adults (–173 ms) [age, F(1/25) = 9.92, P < 0.005]. Also, r-LRP began earlier in the CRT (–254 ms) than in the SRT (–147 ms) [task, F(1/25) = 99.27, P < 0.0001].
Correlational analyses
Multiple correlations were performed for various latency measures (RT, P1 and N1 latency, s-LRP onset latency, r-LRP onset latency, MRP onset and peak latency, and MRP rise time). With the exceptions of P1 and N1, all other variables were significantly correlated, with absolute Pearson coefficients ranging between 0.472 and 0.912, P < 0.01. To explore the determinants of associations of RT with the speed of preceding stages, multiple step-wise regression analyses were performed. Table 2 presents the results from these analyses and shows the following. (i) In the SRT condition, RT of each age group was predicted by N1 latency. (ii) In the CRT, RT of young subjects was independently predicted by several measures: r-LRP onset, s-LRP onset and MRP rise time. This indicates that in choice-reaction tasks, the RT is an integral outcome of various independent predictors, with those related to LRP onset and MRP duration (rise time) being of major relevance. (iii) In the CRT, the RT of the older adults was predicted by the MRP rise time, indicating the major contribution of MRP duration to response speed of older individuals in choice-reaction conditions.
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Discussion |
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The objective of the present study was to identify the origin(s) of ageing-related behavioural slowing in sensorimotor tasks. For this aim, an integrative approach based on advanced ERP methodology was originally employed to quantify separate central processing stages. High-resolution ERPs were analysed to evaluate the timing of stimulus processing, sensorimotor integration/response selection and motor-related processing, and electrophysiological indices were used to compare the speed of different processes of young and older adults in simple- and choice-reaction tasks.
Origins of sensorimotor response slowing with age
According to the present results: (i) behavioural responses were delayed with ageing in the choice- but not in the simple-reaction task; (ii) latencies of early ERP components (P1 and N1) were overall similar for the two age groups; (iii) no significant differences in s-LRP onset were detected between young and older adults for either task or modality; and (iv) there was a significant augmentation and prolongation of the activity over the motor cortex contralateral to the responding hand in older relative to young adults in the choice- but not in the simple-reaction task.
These results demonstrate that task complexity impairs the speed of sensorimotor information processing in aged individuals (Kok, 2000; Salthouse, 2000). Despite the subtle delay of visual perception in the older adults, behavioural slowing cannot be reliably explained with a decline of perceptual speed. As evinced by the lack of significant between-group differences in s-LRP onset, sensorimotor integration/response selection was not slower, nor did increasing task complexity interfere with the generally preserved ability of aged individuals to integrate sensory with motor information. Thus, in the currently used tasks, behavioural slowing is produced by stages later than response selection.
Indeed, the present results clearly show that the origin of age-related behavioural slowing in the choice-reaction task is localized primarily at the level of motor response generation. Specifically, the contralateral MRPs were substantially enhanced and prolonged in aged individuals in the CRT, whereas the ipsilateral motor activity did not differentiate the two age groups in the CRT. Finally, the duration of MRP progression at the contralateral motor cortex was the only predictor of the longer RTs of older individuals in the CRT. Thus, the age-related response slowing in choice-reaction tasks appears associated with the contralateral motor cortical activation triggering the responding effector.
Previous results from the visual modality have not presented unambiguous conclusions about the origin of sensorimotor slowing with ageing. When different dimensions of visual stimuli had to be selected, neither sensory discrimination, as indexed by ERP components, nor response initiation, as reflected by LRP onsets, were affected by ageing (Kenemans et al., 1995). In a visuo-spatial attention task, however, the transmission of information from posterior areas to the motor cortex has been proposed to deteriorate with ageing (van der Lubbe and Verleger, 2002). Thus, as implied by previous and present data, a delay with ageing may exist in the visual perception or in the transmission of visuo-motor information (e.g. Kok, 2000; Curran et al., 2001; van der Lubbe and Verleger, 2002). However, the current results indicate that (i) such a delay may not make a major contribution to ageing-related slowing of response speed in simple- and choice-reaction conditions, and (ii) an additional modality-independent slowing emerges in the motor cortex during response generation.
Excitability of the motor cortex and ageing
The critical question to be raised is whether this deficient motor activation in the older subjects is caused by a neurobiological alteration of the underlying substrate per se (Raz, 2001), or does it result from a functional dysregulation of the motor cortex (Sailer et al., 2000; Hutchinson et al., 2002; Mattay et al., 2002).
A negative MRP component with characteristics similar to those observed in the present study has been consistently correlated with functional activation of the primary motor area during voluntary movement (Kristeva et al., 1991). Movement-preceding negative shifts are suggested to reflect synaptic activation within the superficial cortical layers of the primary motor cortex (Kristeva et al., 1991), promoting movement execution via depolarization of cortical neurons (Rockstroh et al., 1989). In this view, a larger MRP reflects a more extensive depolarization of the contralateral motor cortex neurons and, therefore, a greater neuronal depolarization in older than in young subjects during a choice-reaction task.
One possible explanation of this finding is that the excitability of cortical motor neurons is reduced with age. Previous cellular studies on animals (Mednikova and Kopytova, 1994) and transcranial magnetic stimulation in humans (Rossini et al., 1992; Peinemann et al., 2001) have provided evidence that the excitability of the motor cortex neurons decreases with age. However, a basic reduction of motor cortex excitability should affect each type of response in the older adults, irrespective of whether the response is produced in a simple or in a complex task. The present results demonstrated that ageing was associated with significant MRP alterations only in the choice-reaction task. This observation indicates that age effects on MRP originate from functional rather than basic substrate deficiencies.
Effects of ageing on functional cortical regulation in sensorimotor tasks
From a functional point of view, neuronal excitability can vary according to the amount of ongoing subthreshold activation. Such variations result from higher top-down control mechanisms continuously adjusting the input state of task-relevant motor networks (Mesulam, 1998).
In sensorimotor tasks, a functional facilitation (depolarization) of the motor cortex may occur to promote a faster effective stage of response production (Rockstroh, 1989; Brunia, 1999; Brunia and van Boxtel, 2001). In the present study, such a facilitation is expected to be stronger in the SRT than in the CRT condition because the motor responses in the SRT are highly predictable (because always the same effector is active), in contrast to the low probability responses in the CRT preventing a reliable response-specific preparation (Brunia, 1999). Hence, in the SRT, there is already a facilitation, so that less extra-activation is needed to reach the response threshold. In the CRT, more extra-activation is required for response production due to insufficient functional facilitation. Given that the amplitude of the MRP peak virtually measures the difference between the electrical activity before and during the movement, the findings of smaller and shorter MRPs in the SRT relative to the CRT are consistent with this explanation. Another consequence is that the threshold of effective response production can be reached faster, as also found for the SRT.
Hence, these task effects on MRP magnitude and duration can be explained with a functional modulation of the reactivity of the contralateral motor cortex. Also, an insufficient pre-activation of cortical motor areas may be considered responsible for the larger and extended MRP of older adults observed here. Thus, in the choice-reaction task, a functional disfacilitation appears to affect the contralateral motor cortex of aged people, contributing to their slower reactions.
Notably, a functional dysregulation of the motor cortex in older subjects could be noticed even in the SRT, as demonstrated by differences in the functional involvement of ipsilateral motor regions in this condition. In contrast to the CRT, a deviant functional asymmetry in the SRT was produced by larger positive response-related ERPs at the ipsilateral motor cortex. These findings show that a functional dysregulation of the motor cortex activations is present in older subjects even in the absence of behavioural deficits. Yet, in the simple task, alterations in the ipsilateral activations do not seem to influence behaviour, whereas in the more complex task, the effective contralateral motor cortex is involved, which is accompanied by response delay.
The executive top-down mechanisms, however, modify multiple aspects of task-related processing. Thus, the input states of not only the motor, but also sensory and associative processing networks may be affected by ageing-related alterations in these mechanisms (Goldman-Rakic, 1995). Indeed, the present results additionally indicate that the functional dysregulation affecting the motor cortex in aged individuals appears to expand and affect other processing systems in the CRT. This is evinced by the results from the early P1 component. In the SRT, no differences were detected in the amplitudes of the P1 component between young and older adults. In contrast, in the CRT, P1 amplitudes of both auditory and visual ERPs tended to be larger in the group of older subjects. Age-related augmentation of early ERP components has been observed in many earlier reports (Allison, 1987; Yordanova et al., 1998, 2004; Kok, 2000; Kolev et al., 2002), which has been related to insufficient inhibitory control exerted by frontal lobe networks on sensory gating processes (Knight and Grabowecky, 1995; Alain and Woods, 1999; Kok, 2000). Alternatively, larger P1 and N1 amplitudes may reflect increased attention to external stimuli (Hillyard and Anllo-Vento, 1998). In this regard, it may be also suggested that when older adults perform a more complex sensorimotor task, their motor responses need to be guided by (or executed with a stronger reference to) external stimuli, so that more attention is focused on these stimuli to support movement execution. In view of these explanations, the present results show that the more complex task (CRT) may be accompanied by an impaired top-down regulation of both motor and sensory systems in older subjects.
Considering all these results together, several conclusions can be proposed about the functional origins of sensorimotor slowing with increasing age. (i) Age-related slowing of central motor mechanisms during sensorimotor tasks appears primarily due to a functional dysregulation from higher top-down control systems rather than to a modified neural substrate. (ii) Such a functional dysregulation with ageing involves a reduced preparatory facilitation of the contralateral motor cortex in a choice-reaction task. (iii) In a simple-reaction task, an age-related functional dysregulation is also present, but it is restricted to ipsilateral motor areas and has no significant impact on behaviour. (iv) With increasing task complexity, the motor dysregulation is accompanied by a dysregulation of sensory gating processes.
Conclusions
In contrast to previous EEG and neuroimageing studies, the currently employed advanced ERP methodology enhanced the spatial characteristics and quantified the timing of neural events from the millisecond scale. This approach helped to assess more precisely central stages of information processing and revealed that the behavioural ageing-related slowing in sensorimotor tasks originated at the stage of motor response generation. It was demonstrated that in addition to possible modality-specific perceptual delays, brain mechanisms supporting and controlling response execution in task conditions were primarily altered with age. As a result, a functional dysregulation of the contralateral motor cortex made a major contribution to delayed RTs in aged individuals.
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Acknowledgements |
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We wish to thank Jorg Hoormann, Ludger Blanke, Dagmar Winter and Christiane Westedt for help and technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft (DFG-Ho 965-5/3).
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