Auditory Steady State Response; nature and utility as a translational science tool

Abstract

The auditory steady-state response (ASSR) has been used to detect auditory processing deficits in patients with psychiatric disorders. However, the methodology of ASSR recording from the brain surface has not been standardized in preclinical studies, limiting its use as a translational biomarker. The sites of maximal ASSR in humans are the vertex and/or middle frontal area, although it has been suggested that the auditory cortex is the source of the ASSR. We constructed and validated novel methods for ASSR recording using a switchable pedestal which allows ASSR recording alternatively from temporal or parietal cortex with a wide range of frequencies in freely moving rats. We further evaluated ASSR as a translational tool by assessing the effect of ketamine. The ASSR measured at parietal cortex did not show clear event-related spectral perturbation (ERSP) or inter-trial coherence (ITC) in any frequency bands or a change with ketamine. In contrast, the ASSR at temporal cortex showed clear ERSP and ITC where 40 Hz was maximal in both gamma-band frequencies. Ketamine exerted a biphasic effect in ERSP at gamma bands. These findings suggest that temporal cortex recording with a wide frequency range is a robust methodology to detect ASSR, potentially enabling application as a translational biomarker in psychiatric and developmental disorders.

Gamma power abnormalities in a Fmr1-targeted transgenic rat model of fragile X syndrome

“…WT and Fmr1 -KO rats showed clear ITC and ERSP responses at 10–80 Hz. Peak ITC and ERSP responses observed at 40–50 Hz in the gamma frequency band (30–80 Hz) are consistent with previous reports in rats 32 and humans 15 , 47 , 48 . ASSR recordings revealed clear impairment of ITC at 30–70 Hz in Fmr1 -KO rats compared with WT rats.…”

“…Further, there was also clear impairment of ERSP at 30–60 Hz in Fmr1 -KO rats. We used a previously developed ASSR paradigm that adopted click sounds as stimuli in freely moving rats 32 , with a similar method having been used in subjects with schizophrenia 49 . However, no robust impairment of ERSP in the gamma frequency band has been observed in subjects with FXS or Fmr1 KO mice.…”

“…Accumulated evidence demonstrates the excellent test–retest reliability of ASSR in clinical setting, indicating the use of this method for drug development trial 28 – 31 . We employed the methodology of ASSR with ERSP and ITC that we recently established in rodent model 32 .…”

Haploinsufficiency of Cyfip2 Causes Lithium‐Responsive Prefrontal Dysfunction

“…However, some investigators have reported disparate findings, such as increased ASSR in psychosis patients, 46 positive correlations between hallucinations and gamma oscillations, 47 and state‐dependent ASSR switch 48 . In addition, a recent study of graded doses of ketamine has presented a dose‐dependent biphasic ASSR, 49 suggesting that the ASSR abnormalities include both decreased and increased gamma activity. Therefore, it is also possible that the enhanced ASSR of Cyfip2 +/− mice might reflect a pathological condition of the mice rather than augmentation of PFC functions.…”

Translational research identifies a metabolism pathway involved in first-episode of schizophrenia: Towards precision medicine

“…e b i o m e d i c i n e . c o m brain structure, in particular in the anterior cingulate cortex and the insula [7], signals from visual [8] and auditory pathways [9]. Both structural changes using MRI approaches and methodologies to explore either visual or auditory pathways are available in mice.…”