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: 8.93). 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.

0 Bookmarks
 · 
154 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: While polarity-specific after-effects of monopolar transcranial direct current stimulation (tDCS) on corticospinal excitability are well-documented, modulation of vital parameters due to current spread through the brainstem is still a matter of debate, raising potential concerns about its use through the general public, as well as for neurorehabilitation purposes. We monitored online and after-effects of monopolar tDCS (primary motor cortex) in 10 healthy subjects by adopting a neuronavigated transcranial magnetic stimulation (TMS)/tDCS combined protocol. Motor evoked potentials (MEPs) together with vital parameters [e.g., blood pressure, heart-rate variability (HRV), and sympathovagal balance] were recorded and monitored before, during, and after anodal, cathodal, or sham tDCS. Ten MEPs, every 2.5-min time windows, were recorded from the right first dorsal interosseous (FDI), while 5-min epochs were used to record vital parameters. The protocol included 15 min of pre-tDCS and of online tDCS (anodal, cathodal, or sham). After-effects were recorded for 30 min. We showed a polarity-independent stabilization of cortical excitability level, a polarity-specific after-effect for cathodal and anodal stimulation, and an absence of persistent excitability changes during online stimulation. No significant effects on vital parameters emerged both during and after tDCS, while a linear increase in systolic/diastolic blood pressure and HRV was observed during each tDCS condition, as a possible unspecific response to experimental demands. Taken together, current findings provide new insights on the safety of monopolar tDCS, promoting its application both in research and clinical settings.
    Frontiers in Psychiatry 01/2014; 5:86.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application. Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS.
    Frontiers in Aging Neuroscience 01/2014; · 5.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Abstract The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10 mg/Kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti-inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic α7 receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or -in wild-type animals- upon application sgp130Fc. Similar results were obtained by activating the “anti-inflammatory reflex” -a neural circuit regulating peripheral immune response- by stimulation of the vagal nerve or through peripheral administration of the α7 nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated trans-signaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression.
    Brain Behavior and Immunity 01/2015; 43:149–158. · 5.61 Impact Factor

Full-text

Download
114 Downloads
Available from
May 29, 2014