Evidence map›Paper›PMID 26837462›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors.

Digavalli V Sivarao, Ping Chen, Arun Senapati, Yili Yang, Alda Fernandes, Yulia Benitex, Valerie Whiterock, Yu-Wen Li, Michael K Ahlijanian

Abstract read
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019
    Trial
  4. Trial
  5. Single-Dose Memantine Improves Cortical Oscillatory Response Dynamics in Patients with Schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017
    Trial
  6. Article
  7. Altered Auditory Maturation in Fragile X Syndrome and Its Involvement in Audiogenic Seizure Susceptibility.Autism research : official journal of the International Society for Autism Research · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Ultra-high Field fMRI Reveals Effect of Ketamine on Vocal Processing in Common Marmosets.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Discovery of VU6024578/BI02982816: An mGluJournal of medicinal chemistry · 2024
    Article
  17. Article
  18. 40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by Gabaergic Neuronal Inhibition.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  19. Article
  20. Article

19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Digavalli V SivaraoGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Ping ChenGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Arun SenapatiGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Yili YangGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Alda FernandesGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Yulia BenitexGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Valerie WhiterockGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Yu-Wen LiGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.
Michael K AhlijanianGenetically Defined Diseases and Genomics, Bristol Myers Squibb Company, Wallingford, CT, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Schizophrenia patients exhibit dysfunctional gamma oscillations in response to simple auditory stimuli or more complex cognitive tasks, a phenomenon explained by reduced NMDA transmission within inhibitory/excitatory cortical networks. Indeed, a simple steady-state auditory click stimulation paradigm at gamma frequency (~40 Hz) has been reproducibly shown to reduce entrainment as measured by electroencephalography (EEG) in patients. However, some investigators have reported increased phase locking factor (PLF) and power in response to 40 Hz auditory stimulus in patients. Interestingly, preclinical literature also reflects this contradiction. We investigated whether a graded deficiency in NMDA transmission can account for such disparate findings by administering subanesthetic ketamine (1-30 mg/kg, i.v.) or vehicle to conscious rats (n=12) and testing their EEG entrainment to 40 Hz click stimuli at various time points (~7-62 min after treatment). In separate cohorts, we examined in vivo NMDA channel occupancy and tissue exposure to contextualize ketamine effects. We report a robust inverse relationship between PLF and NMDA occupancy 7 min after dosing. Moreover, ketamine could produce inhibition or disinhibition of the 40 Hz response in a temporally dynamic manner. These results provide for the first time empirical data to understand how cortical NMDA transmission deficit may lead to opposite modulation of the auditory steady-state response (ASSR). Importantly, our findings posit that 40 Hz ASSR is a pharmacodynamic biomarker for cortical NMDA function that is also robustly translatable. Besides schizophrenia, such a functional biomarker may be of value to neuropsychiatric disorders like bipolar and autism spectrum where 40 Hz ASSR deficits have been documented.

Indexed as

Evoked Potentials, AuditoryGamma RhythmAcoustic StimulationAnimalsBiomarkersCerebral CortexDizocilpine MaleateElectroencephalographyExcitatory Amino Acid AntagonistsKetamineMaleRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal Processing, Computer-AssistedBiomarkersDizocilpine MaleateExcitatory Amino Acid AntagonistsKetamineReceptors, N-Methyl-D-Aspartate

Identifiers

PMID26837462
PMCPMC4946051

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.