Increased Excitability of Somatosensory Cortex in Aged Humans is Associated with Impaired Tactile Acuity

Abstract

Aging affects all levels of neural processing, including changes of intracortical inhibition and cortical excitability. Paired-pulse stimulation, the application of two stimuli in close succession, is a useful tool to investigate cortical excitability in humans. The paired-pulse behavior is characterized by the second response being significantly suppressed at short stimulus onset asynchronies. While in rat somatosensory cortex, intracortical inhibition has been demonstrated to decline with increasing age, data from human motor cortex of elderly subjects are controversial and there are no data for the human somatosensory cortex (SI). Moreover, behavioral implications of age-related changes of cortical excitability remain elusive. We therefore assessed SI excitability by combining paired-pulse median nerve stimulation with recording somatosensory evoked potentials in 138 healthy subjects aged 17-86 years. We found that paired-pulse suppression was characterized by substantial interindividual variability, but declined significantly with age, confirming reduced intracortical inhibition in elderly subjects. To link the age-related increase of cortical excitability to perceptual changes, we measured tactile two-point discrimination in a subsample of 26 aged participants who showed either low or high paired-pulse suppression. We found that tactile performance was particularly impaired in subjects showing markedly enhanced cortical excitability. Our data demonstrate that paired-pulse suppression of human SI is significantly reduced in older adults, and that age-related enhancement of cortical excitability correlates with degradation of tactile perception. These findings indicate that cortical excitability constitutes an important mechanism that links age-related neurophysiological changes to behavioral alterations in humans.

Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels

“…Several recent studies (Hua et al, 2008; Leventhal et al, 2003; Stanley et al, 2012) have suggested a decline in GABAergic function with age and that is associated with a loss of function (Betts et al, 2007; Lenz et al, 2012; Leventhal et al, 2003; Wilson et al, 2011; Zhang et al, 2011). While GABA levels can be measured non-invasively in the human brain using magnetic resonance spectroscopy (MRS) (Puts and Edden, 2012), to date there has been a paucity of studies exploring the normal age-related variations in regional GABA levels…”

Disinhibition of the primary somatosensory cortex in patients with fibromyalgia

“…16,25,26,52 This study aimed to investigate intracortical inhibition of the primary somatosensory cortex (S1), as measured by paired-pulse suppression (PPS) ratio of the N20m-P35m response, in patients with FM by using pairedpulse median nerve stimulation and magnetoencephalography (MEG). We hypothesized that intracortical inhibition of the S1 would be reduced in patients with FM, ie, patients with FM would demonstrate higher PPS ratios than healthy control (HC) subjects, and that the higher reductions of inhibition would be associated with increased clinical pain.…”

Disinhibitory shift of recovery curve of somatosensory-evoked response in elderly: A magnetoencephalographic study

“…Although some effects of age and disease on the SEP after median nerve stimulation have been reported (Allison et al, 1984;Ugawa et al, 1996;Lenz et al, 2012), this may be the first systematic study of the relationship between RF and aging.…”

“…In 2012, Lenz et al used a paired stimulation interval of only one ISI on elderly human subjects and found a reduction in SEP suppression (Lenz et al, 2012). Systematic studies of aging effects on inhibitory neural activity in somatosensory evoked responses have not yet been conducted.…”

“…Cortical inhibitory neuronal function can be evaluated using somatosensory-evoked potentials (SEPs) by paired-pulse stimulation. Paired-pulse SEPs were used to demonstrate changes in excitability or to investigate recovery functions (RFs) of the nervous system (Schwartz and Shagass, 1964;Hoffken et al, 2007;Lenz et al, 2012). Paired-pulse suppression is quantified by the ratio of the second response amplitude to the first response amplitude.…”