Article

Dysfunctions of Cortical Excitability in Drug-Naïve Posttraumatic Stress Disorder Patients

Department of Neuroscience, Neurology Section, University of Siena School of Medicine, Siena, Italy.
Biological psychiatry (Impact Factor: 9.47). 05/2009; 66(1):54-61. DOI: 10.1016/j.biopsych.2009.03.008
Source: PubMed

ABSTRACT The investigation of a wide set of transcranial magnetic stimulation (TMS)-related variables in both hemispheres might help to identify a pattern of cortical excitability changes in posttraumatic stress disorder (PTSD) patients, reflecting gamma-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features.
In 20 drug-naive PTSD patients without comorbidity and 16 matched healthy control subjects we tested bilaterally with standard TMS procedures: resting motor threshold (RMT) to single-pulse TMS (reflecting ion channel function), paired-pulse short-latency intracortical inhibition (SICI; mainly reflecting GABA(A) function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABA(B)-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABA(A)-mediated modulation).
The PTSD patients showed widespread impairment of GABA(A)-ergic SICI, which was reversed toward facilitation in both hemispheres in one-half of the patients, marked increase of glutamatergic ICF in the right hemisphere, and right-sided impairment of SAI. Illness duration and avoidance symptoms but not anxiety correlated with right-lateralized dysfunctions of cortical excitability.
Although the neurobiological complexity of each TMS variable makes current results theoretical, the pattern of cortical excitability accompanying PTSD symptoms suggests a bilateral decrease of the GABA(A)-ergic function. This prevails in the right hemisphere, in association with a relative prevalence of the glutamatergic tone, a new finding that current neuroimaging investigations cannot provide due to the lack of reliable glutamate tracers. Results might help to disclose new pathophysiological aspects of PTSD symptoms, providing a rationale for future neuromodulatory strategies of treatment.

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    • "The efficiency of this motor cortical inhibition circuit is influenced by benzodiazepines (Di Lazzaro et al., 2007a), consistent with a role of the GABAergic system in controlling acetylcholine release in the cortex (Giorgetti et al., 2000). Also, SAI is decreased in patients with obsessive-compulsive disorder (Russo et al., 2014) and posttraumatic stress disorder (Rossi et al., 2009), which are both psychiatric conditions involving a GABAergic imbalance but with limited cholinergic involvement. The age-related reductions in SAI described in this study may thus reflect not only declines in cholinergic activity but also alterations in GABAergic transmission , though this system appears to be relatively spared in aging (Rissman et al., 2007). "
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    • "Alterations in the insula, orbitofrontal cortex, posterior cingulate and parietal somatosensory regions have also been described (Bremner et al., 2008; Liberzon and Sripada, 2008). In addition to regionalized brain dysfunction in PTSD, cortical excitability changes in PTSD have been demonstrated by the application of single-pulse transcranial magnetic stimulation (TMS) to the motor cortex of drug naı¨ve patients (Rossi et al., 2009). The authors contend that prolonged illness could be associated with lasting (GABAa related) functional or structural changes even in brain regions such as the motor cortex that are outside, although functionally connected with, regions usually found dysfunctional in PTSD, such as the anterior cingulate cortex, amygdala, limbic and paralimbuc regions. "
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    • "This is particularly relevant since both depression and PTSD have specific cortical excitability dysfunction profiles that are different from that of TBI. In PTSD, hemispheric-specific reductions in SICI and SAI (Rossi et al., 2009) have been reported, whereas depressive patients show a consistent pattern of right-left hemisphere motor threshold INHIBITORY DYSFUNCTION IN SPORTS CONCUSSION 499 differences (Maeda et al., 2000) and reduced CSP durations (Bajbouj et al., 2006). Further studies will be necessary to determine the value of TMS measures in the differential diagnosis of these pathologies. "
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