Functional significance of age-related differences in motor activation patterns

Abstract

Recent functional MRI (fMRI) studies have revealed an increased task-related activation in older subjects during a variety of cognitive or perceptual tasks, which may signal beneficial compensatory activity to counteract structural and neurochemical changes associated with aging. Under the assumption that incremental movement rates are associated with an increased functional demand on the motor system, we used fMRI and acoustically paced movements of the right index finger at six different frequencies (2.0, 2.5, 3.0, 4.0, 5.0 and 6.0 Hz) to investigate the behavioral significance of additionally recruited brain regions in a group of healthy, older subjects (mean age 66 ± 8 years) compared with a group of young (mean age 23 ± 7 years) subjects. The actual tapping frequency (F(1,14) = 0.049, P = 0.829), the tapping interval (F(1,14) = 0.043, P = 0.847), and the error rates (F(1,14) = 0.058, P = 0.743) did not differ significantly between both groups, whereas there was a significant increase in reaction time in the older subjects (F(1,14) = 281.786, P ≤ 0.001). At all frequencies, the older subjects demonstrated significant overactivation within the ipsilateral sensorimotor and premotor cortex. However, we did not observe an increased age-related overactivation during higher movements rates in these or other motor regions. Moreover, the magnitude of the hemodynamic response in overactivated regions remained constant across all frequencies. In contrast to cognitive tasks, these findings indicate that an age-related overactivation within the motor system is not related to the functional demand and does not necessarily reflect reorganization to compensate for the neurobiological changes of aging.

Introduction

In the past few years, evidence has accumulated that aging is associated with anatomical, physiological, and metabolic changes in the human brain (Kuhl et al., 1982, Leenders et al., 1990, Marchal et al., 1992). Compared with younger adults, older adults for instance perform poorly on a variety of cognitive, perceptual or motor tasks (Cabeza et al., 1997, Cabeza et al., 2002, Grady and Craik, 2000, Heuninckx et al., 2005, Houx and Jolles, 1993, Kauranen and Vanharanta, 1996, Mattay et al., 2002, O'Sullivan et al., 2001, Reuter-Lorenz et al., 2000, Shimoyama et al., 1990, Smith et al., 1999).

Recently, functional magnetic resonance imaging (fMRI) has been used to clarify the impact of age-related structural and neurochemical changes on the physiological activity of these different neural systems. Most fMRI techniques are based on the blood oxygenation level-dependent (BOLD) contrast, using paramagnetic deoxyhemoglobin as an endogenous contrast agent (Ogawa et al., 1990). A number of these studies have investigated age effects on memory functions and have found greater activations in older subjects in several regions compared with younger subjects, even though performance levels were comparable in both groups (Grady and Craik, 2000, Hedden and Gabrieli, 2004, Rypma and D'Esposito, 2000). This pattern of findings has been conceptualized in the hemispheric asymmetry reduction in older adults (HAROLD) model, which proposes that prefrontal activity in both episodic memory and other cognitive tasks becomes less lateralized with increasing age (Cabeza et al., 1997, Cabeza et al., 2002). It has been suggested that these increased task-related activations in the aging brain reflect a compensatory recruitment of additional pathways with a positive effect on task performance (Buckner, 2004, Cabeza et al., 2004, Rajah and D'Esposito, 2005). In line with this hypothesis, Cabeza et al. found an increased prefrontal activation only in those older subjects that performed as well as young adults during recall and source memory of recently studied words (Cabeza et al., 2002). Also consistent with this hypothesis, older adults who recruited prefrontal cortical areas bilaterally were faster in a verbal memory task than those who did not in a PET study by Reuter-Lorenz et al. (2000). Thus, there is increasing evidence that age-related differences in brain activation during cognitive tasks may reflect a compensatory recruitment of cortical units required to produce the same performance. Although this compensation hypothesis is principally very attractive, it may not necessarily apply to other brain functions such as the motor system.

The aging brain is characterized by a degeneration of brain systems subserving motor function so that older adults have slower reaction times and increased error rates especially during complex movements (Houx and Jolles, 1993, Kauranen and Vanharanta, 1996, Mattay et al., 2002, Shimoyama et al., 1990, Smith et al., 1999). Comparable with the aforementioned studies using cognitive paradigms, several recent fMRI studies have demonstrated age-related increases in brain activation patterns during different motor tasks (Heuninckx et al., 2005, Hutchinson et al., 2002, Mattay et al., 2002, Ward and Frackowiak, 2003, Wu and Hallett, 2005). In line with the compensation hypothesis, one of these studies found a positive correlation between shorter reaction times during visually cued motor tasks (i.e., better performance) and the extent of activation within the motor system in older subjects (Mattay et al., 2002). In contrast, two other studies reported more extended activation patterns in the elderly during hand movements despite identical performance between young and old subjects (Hutchinson et al., 2002, Ward and Frackowiak, 2003). Notably, the age-related increases in cortical activation patterns were already observed during performance of rather simple motor tasks in the latter two studies, so that the behavioral significance of these findings is still unclear. In fact, it is well perceivable that only tasks of increasing complexity could shed light on the functional significance of age-related differences in movement representation (Catalan et al., 1998, Sadato et al., 1996, Smith et al., 1999, Verstynen et al., 2005). Under the assumption that incremental movement rates are associated with an increased functional demand on the motor system (Blinkenberg et al., 1996, Sabatini et al., 1993), we therefore used fMRI and acoustically paced movements of the right index finger at six different frequencies (2.0, 2.5, 3.0, 4.0, 5.0 and 6.0 Hz) to investigate the behavioral significance of additionally recruited brain regions in a group of healthy, older subjects compared with a group of young subjects. We hypothesized that age-related areas of overactivation should either increase during higher movement rates or should show a close coupling between the movement rate and the hemodynamic response. To exclude differences in activation due to task accuracy, we only included a selected group of healthy, older subjects who were able to perform the motor tasks as accurate as the young subjects.