Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex

Stagg, Charlotte J.; Bestmann, Sven; Constantinescu, Alexandra O.; Moreno, L Moreno; Allman, Claire; Mekle, Ralf; Woolrich, Mark W.; Near, Jamie; Johansen‐Berg, Heidi; Rothwell, John C.

doi:10.1113/jphysiol.2011.216978

Cited by 344 publications

(281 citation statements)

References 34 publications

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“…By temporally resolving cortical responses to each TMS pulse, we demonstrate that starting from the initial "basin of suppression," consecutive TMS pulses (10 Hz) produce a stepwise buildup of activity, reaching signal levels that suggest massive spiking across large populations of neurons. These results promote the view that subsequent TMS pulses, each within a 100-ms time window, weaken inhibitory drive (57) and activate excitatory circuits that outbalance inhibition involving NMDAreceptor activation (61), overall leading to an excitatory state of the cortex (62).…”

Section: Discussionmentioning

confidence: 81%

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

Kozyrev

Eysel

Jancke

2014

Proc. Natl. Acad. Sci. U.S.A.

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Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. To circumvent these constraints, we performed optical imaging with voltage-sensitive dye (VSD) in an animal experimental setting using anaesthetized cats. The dye signals reflect gradual changes in the cells' membrane potential across several square millimeters of cortical tissue, thus enabling direct visualization of TMS-induced neuronal population dynamics. After application of a single TMS pulse across visual cortex, brief focal activation was immediately followed by synchronous suppression of a large pool of neurons. With consecutive magnetic pulses (10 Hz), widespread activity within this "basin of suppression" increased stepwise to suprathreshold levels and spontaneous activity was enhanced. Visual stimulation after repetitive TMS revealed long-term potentiation of evoked activity. Furthermore, loss of the "deceleration-acceleration" notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions. (1) (TMS) has become a frequently used method for noninvasive diagnostics, therapeutic treatment, and intervention for neurorehabilitation of neurological disorders (2-8). Additionally, TMS has proved a valuable tool in basic brain research as its perturbative effects allow area-selective manipulation of immediate cortical function (9-11), as well as its long-lasting alteration through plasticity and learning protocols (12, 13). However, direct measurements of the TMS-induced cortical dynamics at highly resolved spatiotemporal scales are missing because "online approaches" (14), using modern neuroimaging techniques such as functional MRI (fMRI) (15-18), magnetoencephalography (19), EEG (20), and near-infrared (21) or intrinsic optical imaging (22), are limited in either spatial or temporal resolutions or in both.Here we overcame these limitations, using optical imaging with voltage-sensitive dyes (VSD), which exploits the dye's property to transduce gradual changes in voltage across neuronal membranes into fluorescent light signals. In contrast to imaging methods applicable in humans, this method is invasive but allows avoiding the commonly experienced contamination of signals by artifacts due to the strong ...

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Section: Discussionmentioning

confidence: 81%

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

Kozyrev

Eysel

Jancke

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…SICI at 1 millisecond correlated with GABA concentration measured by magnetic resonance spectroscopy. 27 We found that there was decreased SICI at the midrange of S1 intensities in patients with PD. The results were similar to the SICI tested at SICF trough 1, suggesting that impaired GABA-mediated inhibition may be responsible.…”

mentioning

confidence: 76%

Increased motor cortical facilitation and decreased inhibition in Parkinson disease

et al. 2013

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Objective: To identify the changes in motor cortical facilitatory and inhibitory circuits in Parkinson disease (PD) by detailed studies of their time courses and interactions.Methods: Short-interval intracortical facilitation (SICF) and short-interval intracortical inhibition (SICI) were measured with a paired-pulse paradigm using transcranial magnetic stimulation. Twelve patients with PD in both ON and OFF medication states and 12 age-matched healthy controls were tested. The first experiment tested the time course of SICF in PD and controls. The second experiment tested SICI at different times corresponding to SICF peaks and troughs to investigate whether SICI was affected by SICF.Results: SICF was increased in PD OFF state and was reduced by dopaminergic medications. The reduction in SICF from the OFF to ON state correlated with the improvement in PD motor signs. SICI was reduced in PD OFF state and was only partially normalized by dopaminergic medications. At SICF peaks, improvement in SICI with medication correlated with improvement in PD motor sign. Principal component analysis showed that variations of SICF and SICI were explained by the same principal component only in the PD OFF group, suggesting that decreased SICI in the OFF state is related to increased SICF. Conclusions:Motor cortical facilitation is increased and inhibition is decreased in PD. Increased cortical facilitation partly accounts for the decreased inhibition, but there is also impairment in synaptic inhibition in PD. Increased cortical facilitation may be a compensatory mechanism in PD. Neurology â 2013;80:1746-1753 GLOSSARY AMT 5 active motor threshold; ANOVA 5 analysis of variance; GABA 5 g-aminobutyric acid; ICF 5 intracortical facilitation; ISI 5 interstimulus interval; I-wave 5 indirect wave; M1 5 primary motor cortex; MEP 5 motor-evoked potential; PD 5 Parkinson disease; RMT 5 rest motor threshold; S1 5 first stimulus; S2 5 second stimulus; SICF 5 short-interval intracortical facilitation; SICI 5 short-interval intracortical inhibition; TMS 5 transcranial magnetic stimulation; UPDRS 5 Unified Parkinson's Disease Rating Scale.The cardinal symptoms of Parkinson disease (PD) arise from dysfunctions of the motor system. 1 Cortical motor commands originate from the primary motor cortex (M1), which is a primary target of basal ganglia output. The balance and interactions between cortical inhibitory and facilitatory circuits determine motor cortical excitability and output. Short-interval intracortical inhibition (SICI) represents a cortical inhibitory process that is measured by paired-pulse transcranial magnetic stimulation (TMS) with a subthreshold first stimulus (S1) suppressing the motor-evoked potential (MEP) generated by a subsequent suprathreshold second stimulus (S2) at interstimulus intervals (ISIs) of 1 to 5 milliseconds.2 Short-interval intracortical facilitation (SICF) represents a cortical facilitatory process whereby a threshold-level S2 facilitates a suprathreshold S1 at 3 distinct peaks of ISIs (1.1-1.5, 2.3-2.9, ...

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“…A magnetic resonance spectroscopy study by Stagg and colleagues (2011a) revealed that tDCS (1mA, 10min) with the anode placed over M1 reduces local GABA concentration and tDCS with the cathode placed over M1reduces glutamatergic activity. In a subsequent study, Stagg and colleagues (2011b) found significant correlations between GABA concentration level and 1 ms ISI SICI which is thought to reflect extrasynaptic GABA tone (Stagg et al 2011b) as well as corticospinal excitability and glutamate level. However, there was no association between GABA concentration level and SICI with 2.5 ms ISI which is thought to reflect synaptic GABAA activity.…”

Section: Neurophysiological Effects Of Tdcs With the Cathode Placed Omentioning

confidence: 95%

Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults

Fujiyama

Hinder

Barzideh

et al. 2017

Neurobiology of Aging

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Functional motor declines that often occur with advancing age -including reduced efficacy to learn new skills -can have a substantial impact on the quality of life. Recent studies using non-invasive brain stimulation indicate that priming the corticospinal system by lowering the threshold for the induction of long-term potentiation (LTP)-like plasticity before skill training may facilitate subsequent skill learning. Here we utilized 'priming' protocol, in which we used transcranial direct current stimulation (tDCS) applying the cathode over the primary motor cortex (M1) prior to the anode placed over M1 during unimanual isometric force control training (FORCEtraining). Older individuals who received tDCS with the cathode placed over M1 prior to tDCS with the anode placed over M1 concurrent with FORCEtraining showed greater skill improvement and corticospinal excitability increases following the tDCS/FORCEtraining protocol compared to both young and older individuals who did not receive the preceding tDCS with the cathode placed over M1. The results suggested that priming tDCS protocols may be used in clinical settings to improve motor function and thus maintain the functional independence of older adults.

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Relationship between physiological measures of excitability and levels of glutamate and GABA in the human motor cortex

Cited by 344 publications

References 34 publications

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics

Increased motor cortical facilitation and decreased inhibition in Parkinson disease

Preconditioning tDCS facilitates subsequent tDCS effect on skill acquisition in older adults

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