The effects of aging on neural systems are typically investigated within a single specific behavioral domain. However, there is overwhelming evidence that aging is associated with decreases in language function including verbal working memory, word finding, and semantic fluency (Tomer & Levin, 1993; Harvey et al., 1997; Heinzel et al., 2013). In the visuospatial domain, there is increasing evidence that aging is associated with decreased spatial cognition rendering older adults less capable of navigating both novel and known environments (Hampstead et al. 2011, 2012). Within the motor system, aging has long been shown to affect muscle coordination, psychomotor speed, and fine dexterity (Salthouse, 1996).

The existence of deficits in behavioral abilities across these domains has long been known, however, the neural mechanisms leading to these losses in function have yet to be determined. However, we have recently found potential links between cognitive and motor losses using functional magnetic resonance imaging (fMRI) and trancranial magnetic stimulation (TMS). Specifically, we have reported (Zlatar et al., in press) that older individuals who have decreased ipsilateral silent periods in TMS (a measure of transcallosal inhibition) also show decreased asymmetry of activation of language areas during a semantic fluency task (verbally generating members of a semantic category). Additionally, fMRI has indicated that older adults appear to show an alteration in activity during spatial navigation tasks in the precuneus / retrosplenial cortex, where older persons show a decreased ability to suppress activity during semantic fluency. However, in spatial navigation, the change is in the opposite direction from that in semantic fluency: older persons fail to increase activity in this area during spatial navigation (Moffat et al., 2007). The motor and semantic fluency studies  indicate that aging may be associated with a loss of inhibitory neural function that has a detrimental outcome for behavior across multiple domains, but the spatial navigation study indicates that there may be other processes involved as well. We are aware of no studies that have attempted to assess aging related changes across all of these domains and, in particular, attempt to assess the relationship (or lack thereof) between the neural substrates of these domains. Hence, the overarching goal of the present study is to interpret the interrelationship between cortical network function (including TMS measure) and behavioral outcome using hierarchical modeling approach.

Effects of Aerobic Fitness Intervention on Neurological Markers of Aging

The objective of this research experience is to directly investigate the effects of an aerobic exercise regimen on motor performance in the upper extremity using modern neuroimaging techniques. The purpose of the proposed research project is to continue multimodality neurophysiological inquiry and investigate the effects of aerobic activity on interhemispheric communication during unimanual movement. Additionally, the present study will evaluate the effects of both short-term (12 weeks) and longer-term exercise (6 months) programs on motor performance level and interhemispheric communication. The study will employ functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS) to explore possible differences in interhemispheric communication after behavioral and exercise interventions. We expect that increased levels of aerobic fitness will result in improved upper extremity motor performance and decreased loss of interhemispheric inhibition typical of sedentary aging adults.

Effects of Aerobic Fitness on Neurological Markers of Aging:

My research program has indicated that physical fitness level may be associated with mitigating age-related changes in interhemispheric communication. However, like most aging-related cross-sectional studies, the research has focused on age extremes. For my VA CDA1 award, we approached the effects of physical fitness on aging-related changes in interhemispheric communication in middle age (40-60). Pilot results from my dissertation project led us to hypothesize that middle age adults would evidence patterns of interhemispheric communication similar to those in the elderly age group. We also are enrolling younger (18-30) of differing physical activity levels. For the CDA1 project, with the assistance of Dr. Todd Manini (mentor) and Dr. Joseph Nocera (collaborator on proposed project) we made significant improvements in the assessment of physical fitness and targeted recruitment and proper differentiation of highly fit and sedentary participants (assessed by multiple fitness questionnaires). This mentorship has resulted in a considerable strengthening of my research methodology and has provided a large leap in my understanding of exercise science. In addition to measurement of interhemispheric communication, we also are interested in the association of physical fitness with upper extremity function. Previous work has indicated that physical fitness levels has been associated with improvement in multiple measures of upper extremity function (reaction time, dexterity, psychomotor processing speed (van Heuvelen , M. et al., 2000; also see Hillman et al., 2008 for review). Based on these findings and results from my dissertation study, we hypothesize that the regular engagement of aerobic exercise causes changes to interhemispheric communication and benefits motor performance in the upper extremity. We believe our study is the first cross-sectional study to approach the effects of aerobic fitness level on tasks which inform on interhemispheric communication. We have hypothesized that aerobic fitness will alter aging related decreases in interhemispheric inhibition. As part of my CDA-1 project and in support of
this CDA-2 proposal, we have collected preliminary data which supports this hypothesis.


Motor Map Reliability and Aging: A  TMS/fMRI Study.  

As a continuation of my  interest in the aging motor system, I designed and executed a joint fMRI/TMS study under the  guidance of Dr. Crosson and Dr. Jeffrey Kleim, a noted neuroscientist with expertise in motor  mapping using TMS. Importantly, this study was a collaborative effort between investigational cores within a VA Center of Excellence (BRRC) and was recognized during the Center’s 2009 successful renewal. This purpose of this study was to compare the reliability of motor maps over 3 sessions from both neuronavigated transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) data between younger and older adults. Seven younger (ages 19-31) and seven sedentary (self-reported) older (ages 64-76) adults participated in three joint TMS/fMRI assessment sessions separated by 7 or 14 days. Sessions involved mapping of  the right first dorsal interosseous (FDI) muscle using single-pulse TMS immediately followed by  block-design fMRI scanning involving volitional right-hand index finger to thumb oppositional squeeze. We found that intersession reliability of map volume, evaluated by intraclass correlation and coefficient of variation between testing sessions, was more consistent for  younger adults in both fMRI and TMS. Importantly, motor maps of the contralateral cortex were not significantly larger in older adults in either fMRI and TMS. Published as: McGregor KM, Carpenter H, Kleim E, Sudhyadhom A, White KD, Butler AJ, Kleim J, Crosson B. (2012). Motor map reliability and aging: a TMS/fMRI study.. Experimental Brain Research, 219(1), 97-106.