GABA levels and measures of intracortical and interhemispheric excitability in healthy young and older adults: an MRS-TMS study (original) (raw)
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NeuroImage, 2020
Establishing the associations between magnetic resonance spectroscopy (MRS)-assessed gamma-aminobutyric acid (GABA) levels and transcranial magnetic stimulation (TMS)-derived 'task-related' modulations in GABA A receptor-mediated inhibition and how these associations change with advancing age is a topic of interest in the field of human neuroscience. In this study, we identified the relationship between GABA levels and task-related modulations in GABA A receptor-mediated inhibition in the dominant (left) and non-dominant (right) sensorimotor (SM) cortices. GABA levels were measured using edited MRS and task-related GABA A receptor-mediated inhibition was measured using a short-interval intracortical inhibition (SICI) TMS protocol during the preparation and premotor period of a choice reaction time (CRT) task in 25 young (aged 18-33 years) and 25 older (aged 60-74 years) adults. Our results demonstrated that GABA levels in both SM voxels were lower in older adults as compared to younger adults; and higher SM GABA levels in the dominant as compared to the non-dominant SM voxel pointed to a lateralization effect, irrespective of age group. Furthermore, older adults showed decreased GABA A receptor-mediated inhibition in the preparation phase of the CRT task within the dominant primary motor cortex (M1), as compared to young adults. Finally, results from an exploratory correlation analysis pointed towards positive relationships between MRS-assessed GABA levels and TMS-derived task-related SICI measures. However, after correction for multiple comparisons none of the correlations remained significant.
Neuroscience & Biobehavioral Reviews, 2014
Please cite this article as: Levin, O., Fujiyama, H., Boisgontier, M.P., Swinnen, S.P., Summers, J.J.,Aging and motor inhibition: a converging perspective provided by brain stimulation and imaging approaches, Neuroscience and Biobehavioral Reviews (2014), http://dx.
Age-related decrease in paired-pulse intracortical inhibition in the human primary motor cortex
Neuroscience Letters, 2001
Using biphasic magnetic stimuli, paired-pulse transcranial magnetic stimulation (TMS) at short interstimulus intervals (ISIs) was employed to investigate age-related changes in the balance between intracortical inhibition and facilitation. In 26 right-handed healthy individuals, motor evoked potentials were recorded from the relaxed right first dorsal interosseus muscle after paired-pulse TMS of the left primary motor hand area. The magnitude of intracortical paired-pulse inhibition at ISIs of 1-5 ms was markedly reduced in elderly individuals, whereas no age effect was observed for intracortical paired-pulse facilitation at ISIs of 11-15 ms. This finding demonstrates that normal aging is associated with a relative decrease in the excitability of intracortical inhibitory circuits. In conclusion, paired-pulse TMS provides a non-invasive means of studying age-related functional changes in the motor cortex. q
tDCS-Induced Modulation of GABA Levels and Resting-State Functional Connectivity in Older Adults
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2017
Transcranial direct current stimulation (tDCS) modulates human behavior, neuronal patterns, and metabolite concentrations, with exciting potential for neurorehabilitation. However, the understanding of tDCS-induced alterations on the neuronal level is incomplete, and conclusions from young adults, in whom the majority of studies have been conducted, cannot be easily transferred to older populations. Here, we investigated tDCS-induced effects in older adults (N = 48; age range, 50-79 years) using magnetic resonance spectroscopy to quantify GABA levels as well as resting-state functional magnetic resonance imaging to assess sensorimotor network strength and interhemispheric connectivity. In a randomized, counterbalanced, crossover design, we applied anodal tDCS (atDCS), cathodal tDCS (ctDCS), and sham tDCS (stDCS) over the left sensorimotor region. We observed a significant reduction of GABA levels after atDCS compared with stDCS, reflecting the preserved neuromodulatory effect of atD...
Journal of Neuroscience, 2013
Since GABA A -mediated intracortical inhibition has been shown to underlie plastic changes throughout the lifespan from development to aging, here, the aging motor system was used as a model to analyze the interdependence of plastic alterations within the inhibitory motorcortical network and level of behavioral performance. Double-pulse transcranial magnetic stimulation (dpTMS) was used to examine inhibition by means of short-interval intracortical inhibition (SICI) of the contralateral primary motor cortex in a sample of 64 healthy right-handed human subjects covering a wide range of the adult lifespan (age range 20 -88 years, mean 47.6 Ϯ 20.7, 34 female). SICI was evaluated during resting state and in an event-related condition during movement preparation in a visually triggered simple reaction time task. In a subgroup , manual motor performance was tested with tasks of graded dexterous demand.
Neuroscience Letters, 2002
Using single and paired-pulse transcranial magnetic stimulation we compared the cortical excitability in two different age groups of healthy subjects (mean^SD age: 28.5^5.2 vs. 56.1^4.9 years). Motor evoked potentials were recorded from right extensor and flexor carpi radialis muscles. The effect of paired-pulse stimulation was assessed by the ratio conditioned/unconditioned response area with interstimulus intervals of 3 and 13 ms to test for intracortical inhibition and facilitation, respectively. To test the influence of sensory input the experiments were conducted without and with vibration of the extensor carpi radialis muscle. The intracortical inhibition was significantly greater in older subjects; however, during muscle vibration this difference between the two groups vanished. The different effect of vibration favors compensatory mechanisms to be responsible for a different paired-pulse excitability in middle-aged subjects. q
Cortical excitability and age-related volumetric MRI changes
Clinical Neurophysiology, 2006
Objective: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in nondemented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. Methods: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. Results: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. Conclusions: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. Significance: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.
The Journal of Physiology, 2011
Inter-individual differences in regional GABA as assessed by magnetic resonance spectroscopy (MRS) relate to behavioural variation in humans. However, it is not clear what the relationship is between MRS measures of the concentration of neurotransmitters in a region and synaptic activity. Transcranial magnetic stimulation (TMS) techniques provide physiological measures of cortical excitation or inhibition. Here, we investigated the relationship between MRS and TMS measures of glutamatergic and GABAergic activity within the same individuals. We demonstrated a relationship between MRS-assessed glutamate levels and a TMS measure of global cortical excitability, suggesting that MRS measures of glutamate do reflect glutamatergic activity. However, there was no clear relationship between MRS-assessed GABA levels and TMS measures of synaptic GABA A or GABA B activity. A relationship was found between MRS-assessed GABA and a TMS protocol with less clearly understood physiological underpinnings. We speculate that this protocol may therefore reflect extrasynaptic GABA tone.
Scientific Reports
Transcranial magnetic stimulation (TMS) is used to probe inhibitory intracortical neurotransmission and has been used to infer the neurobiological dysfunction that may underly several neurological disorders. One technique, short-interval intracortical inhibition (SICI), indexes gamma-aminobutyric acid (GABA) mediated inhibitory activity and is a promising biomarker. However emerging evidence suggests SICI does not exclusively represent GABAergic activity because it may be influenced by inter-individual differences in the specific excitatory neural populations activated by TMS. Here we used the latency of TMS motor evoked potentials (MEPs) to index these inter-individual differences, and found that a significant proportion of the observed variability in SICI magnitude was accounted for by MEP latency, r = − 0.57, r2 = 0.33, p = .014. We conclude that SICI is influenced by inter-individual differences in the excitatory neural populations activated by TMS, reducing the precision of thi...
Frontiers in Aging Neuroscience, 2018
Background: Transcranial magnetic stimulation (TMS) is a non-invasive technique that can be used to evaluate cortical function and corticospinal pathway in normal and pathological aging. Yet, the metrologic properties of TMS-related measurements is still limited in the aging population. Objectives: The aim of this cross-sectional study was to document the reliability and smallest detectable change of TMS measurements among community-dwelling seniors. A secondary objective was to test if TMS measurements differ between elders based on lifestyle, medical and socio-demographic factors. Methods: Motor evoked potentials (MEPs) elicited by single-pulse TMS were recorded in the first dorsal interosseous (FDI) in 26 elderly individuals (mean age = 70 ± 3.8 years). Resting motor threshold (rMT), MEP amplitudes and contralateral silent period (cSP) were measured on two separate occasions (1-week interval), and the standard error of the measurement (SEM eas), intraclass correlation coefficient (ICC), and smallest detectable change in an individual (SDC indv) were calculated. Lifestyle, medical and socio-demographic factors were collected using questionnaires. TMS-related outcomes were compared using independent sample t-test based on the presence of chronic health diseases, chronic medication intake, obesity, history of smoking, physical activity levels, gender, and level of education. Results: rMT and cSP measures were the most reliable outcomes, with the lowest SEM eas and highest ICCs, whereas MEP amplitude-related measures were less reliable. SDC indv levels were generally high, even for rMT (7.29 %MSO) and cSP (43.16-50.84 ms) measures. Although not systematically significant, results pointed toward a higher corticospinal excitability in elderly individuals who were regularly active, who had no chronic medical conditions and who did not take any medication.