Dataset Information

Characterization of the influence of age on GABA_A and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.

ABSTRACT: Gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmissions in the prefrontal cortex decreases with age. Further, cognitive function mediated through the dorsolateral prefrontal cortex (DLPFC) also declines with age. Although neuroimaging studies have demonstrated decreased levels of these substances, direct neurophysiological data investigating the effect of aging in the DLPFC in human subjects is lacking. The advent of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) has allowed for the assessment of functional neurotransmission in vivo. In the present study, we examined short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in a group of older adults (> 60 yrs) to evaluate the strength of GABA_A and glutamate-mediated neurotransmission in the DLPFC, compared to younger adults (18-59 yrs). Older adults showed an increase of amplitude of N100 by the SICI paradigm, while N45 amplitude was increased and N100 amplitude was decreased by ICF. Moreover, these modulations significantly correlated with age. Our findings provide evidence for age-related alterations of excitatory and inhibitory functions in the prefrontal cortex in healthy adults. Future studies may aim to explore these neurophysiological relationships in the DLPFC in pathological forms of aging that affect cortical functioning such as mild cognitive impairment and Alzheimer's disease.

SUBMITTER: Noda Y

PROVIDER: S-EPMC5361681 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Characterization of the influence of age on GABA<sub>A</sub> and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.

Noda Yoshihiro Y Zomorrodi Reza R Cash Robin F H RF Barr Mera S MS Farzan Faranak F Rajji Tarek K TK Chen Robert R Daskalakis Zafiris J ZJ Blumberger Daniel M DM

Aging 20170201 2

Gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmissions in the prefrontal cortex decreases with age. Further, cognitive function mediated through the dorsolateral prefrontal cortex (DLPFC) also declines with age. Although neuroimaging studies have demonstrated decreased levels of these substances, direct neurophysiological data investigating the effect of aging in the DLPFC in human subjects is lacking. The advent of transcranial magnetic stimulation (TMS) combined with electroe ...[more]

PMID: 28209926

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Project description:IntroductionTranscranial magnetic stimulation (TMS)-evoked potentials (TEPs) allow for probing cortical functions in health and pathology. However, there is uncertainty whether long-latency TMS-evoked potentials reflect functioning of the targeted cortical area. It has been suggested that components such as the TMS-evoked N100 are stereotypical and related to nonspecific sensory processes rather than transcranial effects of the changing magnetic field. In contrast, TEPs that vary according to the targeted brain region and are systematically lateralized toward the stimulated hemisphere can be considered to reflect activity in the stimulated brain region resulting from transcranial electromagnetic induction.MethodsTMS with concurrent 64-channel electroencephalography (EEG) was sequentially performed in homologous areas of both hemispheres. One sample of healthy adults received TMS to the dorsolateral prefrontal cortex; another sample received TMS to the temporo-occipital cortex. We analyzed late negative TEP deflections corresponding to the N100 component in motor cortex stimulation.ResultsTEP topography varied according to the stimulation target site. Long-latency negative TEP deflections were systematically lateralized (higher in ipsilateral compared to contralateral electrodes) in electrodes over the stimulated brain region. A calculation that removes evoked components that are not systematically lateralized relative to the stimulated hemisphere revealed negative maxima located around the respective target sites.ConclusionTEPs contain long-latency negative components that are lateralized toward the stimulated hemisphere and have their topographic maxima at the respective stimulation sites. They can be differentiated from co-occurring components that are invariable across different stimulation sites (probably reflecting coactivation of peripheral sensory afferences) according to their spatiotemporal patterns. Lateralized long-latency TEP components located at the stimulation site likely reflect activity evoked in the targeted cortex region by direct transcranial effects and are therefore suitable for assessing cortical functions.

Project description:In subjects with schizophrenia, impairments in working memory are associated with dysfunction of the dorsolateral prefrontal cortex (DLPFC). This dysfunction appears to be due, at least in part, to abnormalities in gamma-aminobutyric acid (GABA)-mediated inhibitory circuitry. To test the hypothesis that altered GABA-mediated circuitry in the DLPFC of subjects with schizophrenia reflects expression changes of genes that encode selective presynaptic and postsynaptic components of GABA neurotransmission, we conducted a systematic expression analysis of GABA-related transcripts in the DLPFC of 14 pairs of schizophrenia and age-, sex- and post-mortem interval-matched control subjects using a customized DNA microarray with enhanced sensitivity and specificity. Subjects with schizophrenia exhibited expression deficits in GABA-related transcripts encoding (1) presynaptic regulators of GABA neurotransmission (67 kDa isoform of glutamic acid decarboxylase (GAD(67)) and GABA transporter 1), (2) neuropeptides (somatostatin (SST), neuropeptide Y (NPY) and cholecystokinin (CCK)) and (3) GABA(A) receptor subunits (alpha1, alpha4, beta3, gamma2 and delta). Real-time qPCR and/or in situ hybridization confirmed the deficits for six representative transcripts tested in the same pairs and in an extended cohort, respectively. In contrast, GAD(67), SST and alpha1 subunit mRNA levels, as assessed by in situ hybridization, were not altered in the DLPFC of monkeys chronically exposed to antipsychotic medications. These findings suggest that schizophrenia is associated with alterations in inhibitory inputs from SST/NPY-containing and CCK-containing subpopulations of GABA neurons and in the signaling via certain GABA(A) receptors that mediate synaptic (phasic) or extrasynaptic (tonic) inhibition. In concert with previous findings, these data suggest that working memory dysfunction in schizophrenia is mediated by altered GABA neurotransmission in certain DLPFC microcircuits.

Dataset Information

Characterization of the influence of age on GABA_A and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.

Publications

Characterization of the influence of age on GABA<sub>A</sub> and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.

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Dataset Information

Characterization of the influence of age on GABAA and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.

Publications

Characterization of the influence of age on GABA<sub>A</sub> and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Characterization of the influence of age on GABA_A and glutamatergic mediated functions in the dorsolateral prefrontal cortex using paired-pulse TMS-EEG.