PMID- 29453445
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20190610
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 43
IP  - 7
DP  - 2018 Jun
TI  - Alterations in interhemispheric gamma-band connectivity are related to the 
      emergence of auditory verbal hallucinations in healthy subjects during 
      NMDA-receptor blockade.
PG  - 1608-1615
LID - 10.1038/s41386-018-0014-z [doi]
AB  - Auditory verbal hallucinations (AVH) are a common positive symptom of 
      schizophrenia. Excitatory-to-inhibitory (E/I) imbalance related to disturbed 
      N-methyl-D-aspartate receptor (NMDAR) functioning has been suggested as a 
      possible mechanism underlying altered connectivity and AVH in schizophrenia. The 
      current study examined the effects of ketamine, a NMDAR antagonist, on 
      glutamate-related mechanisms underlying interhemispheric gamma-band connectivity, 
      conscious auditory perception during dichotic listening (DL), and the emergence 
      of auditory verbal distortions and hallucinations (AVD/AVH) in healthy 
      volunteers. In a single-blind, pseudo-randomized, placebo-controlled crossover 
      design, nineteen male, right-handed volunteers were measured using 64 channel 
      electroencephalography (EEG). Psychopathology was assessed with the PANSS 
      interview and the 5D-ASC questionnaire, including a subscale to detect auditory 
      alterations with regard to AVD/AVH (AUA-AVD/AVH). Interhemispheric connectivity 
      analysis was performed using eLORETA source estimation and lagged phase 
      synchronization (LPS) in the gamma-band range (30-100 Hz). Ketamine induced 
      positive symptoms such as hallucinations in a subgroup of healthy subjects. In 
      addition, interhemispheric gamma-band connectivity was found to be altered under 
      ketamine compared to placebo, and subjects with AUA-AVD/AVH under ketamine showed 
      significantly higher interhemispheric gamma-band connectivity than subjects 
      without AUA-AVD/AVH. These findings demonstrate a relationship between NMDAR 
      functioning, interhemispheric connectivity in the gamma-band frequency range 
      between bilateral auditory cortices and the emergence of AVD/AVH in healthy 
      subjects. The result is in accordance with the interhemispheric miscommunication 
      hypothesis of AVH and argues for a possible role of glutamate in AVH in 
      schizophrenia.
FAU - Thiebes, Stephanie
AU  - Thiebes S
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Steinmann, Saskia
AU  - Steinmann S
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Curic, Stjepan
AU  - Curic S
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Polomac, Nenad
AU  - Polomac N
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Andreou, Christina
AU  - Andreou C
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
AD  - Center for Gender Research and Early Detection, University of Basel Psychiatric 
      Clinics, Basel, Switzerland.
FAU - Eichler, Iris-Carola
AU  - Eichler IC
AD  - Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Eichler, Lars
AU  - Eichler L
AD  - Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Zollner, Christian
AU  - Zollner C
AD  - Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, 
      Hamburg, Germany.
FAU - Gallinat, Jurgen
AU  - Gallinat J
AD  - Department of Psychiatry and Psychotherapy, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Leicht, Gregor
AU  - Leicht G
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Mulert, Christoph
AU  - Mulert C
AD  - Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, 
      University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 
      c.mulert@uke.uni-hamburg.de.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180205
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Auditory Perception/drug effects
MH  - Cross-Over Studies
MH  - Dichotic Listening Tests
MH  - Electroencephalography/drug effects
MH  - Gamma Rhythm/*drug effects
MH  - Hallucinations/*chemically induced
MH  - Healthy Volunteers
MH  - Humans
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Single-Blind Method
MH  - Young Adult
PMC - PMC5983549
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/02/18 06:00
MHDA- 2019/02/09 06:00
PMCR- 2019/06/01
CRDT- 2018/02/18 06:00
PHST- 2017/07/04 00:00 [received]
PHST- 2018/01/05 00:00 [accepted]
PHST- 2017/12/19 00:00 [revised]
PHST- 2018/02/18 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2018/02/18 06:00 [entrez]
PHST- 2019/06/01 00:00 [pmc-release]
AID - 10.1038/s41386-018-0014-z [pii]
AID - 14 [pii]
AID - 10.1038/s41386-018-0014-z [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2018 Jun;43(7):1608-1615. doi: 
      10.1038/s41386-018-0014-z. Epub 2018 Feb 5.