TY - JOUR A1 - Guhn, Anne A1 - Dresler, Thomas A1 - Andreatta, Marta A1 - Müller, Laura D. A1 - Hahn, Tim A1 - Tupak, Sara V. A1 - Polak, Thomas A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Medial prefrontal cortex stimulation modulates the processing of conditioned fear N2 - The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS−) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS− discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT). KW - fear conditioning KW - memory consolidation and extinction KW - learning KW - transcranial magnetic stimulation (TMS) KW - medial prefrontal cortex (mPFC) Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111309 ER - TY - JOUR A1 - Herrmann, Thomas A1 - Karunakaran, Mohindar M. T1 - The Vγ9Vδ2 T cell antigen receptor and butyrophilin-3 A1: models of interaction, the possibility of co-evolution, and the case of dendritic epidermal T cells N2 - Most circulating human gamma delta T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains show a Vγ9-JP (Vγ2-Jγ1.2) rearrangement and are paired with Vδ2-containing δ-chains, a dominantTCR configuration, which until recently seemed to occur in primates only. Vγ9Vδ2 T cells respond to phosphoantigens (PAg) such as (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is produced by many pathogens and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. A prerequisite for PAg-induced activation is the contact of Vγ9Vδ2 T cells with cells expressing butyrophilin-3 A1 (BTN3A1). We will first critically review models of how BTN3 might act in PAg-mediated Vγ9Vδ2 T cell activation and then address putative co-evolution of Vγ9, Vδ2, and BTN3 genes. In those rodent and lagomorphs used as animal models, all three genes are lost but a data-base analysis showed that they emerged together with placental mammals. A strong concomitant conservation of functional Vγ9, Vδ2, and BTN3 genes in other species suggests co-evolution of these three genes. A detailed analysis was performed for the new world camelid alpaca (Vicugna pacos). It provides an excellent candidate for a non-primate species with presumably functional Vγ9Vδ2 T cells since TCR rearrangements share features characteristic for PAg-reactive primate Vγ9Vδ2 TCR and proposed PAg-binding sites of BTN3A1 have been conserved. Finally, we analyze the possible functional relationship between the butyrophilin-family member Skint1 and the γδTCR-V genes used by murine dendritic epithelialT cells (DETC). Among placental mammals, we identify five rodents, the cow, a bat, and the cape golden mole as the only species concomitantly possessing potentially functional homologs of murineVγ3,Vδ4 genes, and Skint1 gene and suggest to search for DETC like cells in these species. KW - γδ T cells KW - Vγ9Vδ2 T cell KW - phosphoantigen KW - BTN3 KW - alpaca KW - co-evolution KW - DETC KW - Skint1 Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111141 ER - TY - JOUR A1 - Schecklmann, Martin A1 - Giani, Anette A1 - Tupak, Sara A1 - Langguth, Berthold A1 - Raab, Vincent A1 - Polak, Thomas A1 - Varallyay, Csanad A1 - Harnisch, Wilma A1 - Herrmann, Martin J. A1 - Fallgatter, Andreas J. T1 - Functional Near-Infrared Spectroscopy to Probe State- and Trait-Like Conditions in Chronic Tinnitus: A Proof-of-Principle Study JF - Neural Plasticity N2 - Objective. Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. Methods. Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls (n = 12). Results. Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. Conclusions. By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait-and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response. KW - transcranial magnetic stimulation KW - positron-emission-tomography KW - auditory cortex KW - FNIRS KW - RTMS KW - neural activity KW - FMRI KW - brain KW - activation KW - humans Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117801 SN - 1687-5443 IS - 894203 ER -