Elsevier

NeuroImage

Volume 44, Issue 1, 1 January 2009, Pages 182-189
NeuroImage

The neural networks underlying auditory sensory gating

https://doi.org/10.1016/j.neuroimage.2008.08.025Get rights and content

Abstract

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.

Introduction

The ability to filter out irrelevant stimuli that are repeated in close temporal proximity is essential for the selection, processing, and storage of more salient information (Alho, 1992, Cadenhead et al., 2000, Cullum et al., 1993). Sensory gating, as measured by the paired-click paradigm, has been commonly used to measure these basic inhibitory processes in several clinical populations, including schizophrenia (Adler et al., 1982, Adler and Waldo, 1991, Boutros et al., 2004, Bramon et al., 2004, Hanlon et al., 2005, Huang et al., 2003, Thoma et al., 2003). Two recent meta-analyses suggest that the gating deficit is present in the majority of studies comparing schizophrenia patients with normal controls (de Wilde et al., 2007, Patterson et al., 2008) and others have suggested that the deficit may be an endophenotypical marker (Adler et al., 1999, Freedman et al., 2003). However, there is considerable heterogeneity in the magnitude of the effect across different studies and substantial debate remains regarding the underlying neuronal substrates. Specifically, both animal and invasive human neuroimaging techniques (Boutros et al., 2005, Freedman et al., 1996, Grunwald et al., 2003, Korzyukov et al., 2007) suggest that sensory gating is mediated by a network including the auditory cortex (AC), prefrontal cortex and hippocampus. In contrast, the majority of results from non-invasive electrophysiological studies have not implicated the prefrontal cortex and/or hippocampus in gating.

In the standard paired-click paradigm (Adler et al., 1982), a gating ratio is derived from the proportion of the electrophysiological responses to the first (S1) and second (S2) of the paired stimuli (S2/S1  100), which are typically separated by an inter-stimulus interval (ISI) of 500 ms. Although the superb temporal resolution of electrophysiological techniques permits for the disambiguation of S1 and S2 responses, these techniques are somewhat limited by their spatial resolution, such as their ability to image deep sources, radially oriented sources, or simultaneously occurring sources (Huang et al., 2003, Huotilainen et al., 1998, Korzyukov et al., 2007). Moreover, non-invasive electrophysiological studies have focused almost exclusively on earlier components of the gating response (EEG: P50 and N100; MEG: M50 and M100) instead of longer latencies (200–300 ms) where hippocampal involvement has been recorded with more invasive techniques (Boutros et al., 2005, Grunwald et al., 2003). Neuroimaging techniques with higher spatial resolution and the ability to independently evaluate activation on a voxel-wise basis, such as functional magnetic resonance imaging (FMRI), should therefore provide additional critical information on the role of the prefrontal cortex and hippocampus in sensory gating.

Numerous FMRI studies (Friston et al., 1998, Glover, 1999, Huettel and McCarthy, 2000, Inan et al., 2004) have demonstrated a non-linearity in the summation of the hemodynamic response function (HRF) for stimuli that occur in close temporal proximity (i.e., ISIs of less than 4 s). However, none has directly examined sensory gating using similar parameters commonly employed in the electrophysiological literature (i.e., two stimuli; 3–5 ms stimulus duration, 500 ms ISI; 7–10 seconds inter-trial interval (ITI)). One study compared two identical 1000 Hz tones (100 ms duration) separated by one, four or six-second ISIs and reported both a reduced amplitude and delayed onset for the second stimulus at all ISIs (Inan et al., 2004). A more recent FMRI study attempted to compensate for the temporal sluggishness of the hemodynamic response by utilizing a click-train paradigm in which 9 clicks were presented over a 4-second interval (Tregellas et al., 2007). This study found increased dorsolateral prefrontal cortex, thalamic and hippocampal gating activity in patients with schizophrenia compared to normal controls.

A more complete understanding of the neural generators involved in normal sensory gating is critical for elucidating the pathological response that is often observed in clinical populations (Edgar et al., 2003, Patterson et al., 2008). In the current study, participants listened to pairs of identical and non-identical tones to examine the effects of distinct, compared to repeated, paired stimuli. Electrophysiological results from a similar paradigm indicate larger gating effects for the identical (P50 gating ratio = 44%) compared to non-identical tone condition (P50 gating ratio = 67%) in normal controls, with a reversal of effects in patients with schizophrenia (Boutros et al., 1999). In addition, participants also listened to single, unpaired tones of the same two fundamental frequencies. The resultant HRFs for the single-tone conditions were then summed to obtain an estimation of the “true” hemodynamic response to pairs of identical (single 2000 Hz tone + single 2000 Hz tone) or non-identical (single 2000 Hz tone + single 3000 Hz tone) tones. In an ANOVA framework, the estimated HRFs could then be compared to the empirically determined (observed) HRFs to identify regions that exhibited a gating response for both non-identical and identical tones. In addition, a comparison between the observed HRF for identical compared to non-identical tones should directly replicate previous electrophysiological work indicating larger gating ratios for non-identical stimuli compared to identical stimuli (Boutros et al., 1999).

We predicted that the magnitude of the estimated HRF would be greater than the magnitude of observed HRF in the bilateral AC, prefrontal cortex and hippocampi for identical stimuli, indicative of sensory gating. In addition, we predicted that the magnitude of the observed HRF would be greater in these regions for the non-identical condition compared to the identical condition based on the assumption of a reduced gating response (i.e., increased S2) and subsequent increase in BOLD activity, for novel compared to repeated stimuli (see Fig. 1).

Section snippets

Subjects

Twenty-one (11 female, 10 male) healthy adult volunteers participated in the current study. One female was identified as an outlier (above three standard deviations) on head motion parameters corresponding to image-to-image motion and was therefore excluded from further analyses (Mayer et al., 2007). All subjects (mean age = 26 ± 5.8 years) were right-handed (mean Edinburgh Handedness Inventory score = 90.3% ± 12.4%) and had no self-reported history of neurological disease, major psychiatric

Results

Several frontal and temporal areas that have been previously implicated in sensory gating exceeded the two significance thresholds outlined above (p < .005; 440 μl) during the comparison of the estimated (non-gating) vs. observed (gating) HRFs (Table 1; Fig. 2). As predicted, the bilateral AC (insula and superior temporal gyrus (BAs 13/42) extending into the inferior parietal lobule (BA 40)) and dorsolateral prefrontal cortex (including anterior aspects of the insula, inferior frontal gyrus and

Discussion

To our knowledge, this was the first event-related FMRI study to examine both the cortical and deep neuronal sources that mediate the sensory gating response in a population of healthy controls during the processing of pairs of identical and non-identical tone pips. Current results indicated that a large network of cortical and subcortical structures, including both the bilateral dorsolateral prefrontal cortex and the AC, were implicated in auditory sensory gating during both non-identical and

Acknowledgments

This research was supported by grants NIH 1 R03 DA022435-01A1 from the National Institute of Drug Abuse and DOE Grant No. DE-FG02-99ER62764 from The Mind Research Network. Special thanks to Charles Gasparovich, Ph.D., Jing Xu and Diana South for their technical support.

References (55)

  • de WildeO.M. et al.

    A meta-analysis of P50 studies in patients with schizophrenia and relatives: differences in methodology between research groups

    Schizophr. Res.

    (2007)
  • EdgarJ.C. et al.

    Interpreting abnormality: an EEG and MEG study of P50 and the auditory paired-stimulus paradigm

    Biol. Psychol.

    (2003)
  • FordJ.M. et al.

    Delayed hemodynamic responses in schizophrenia

    Neuroimage

    (2005)
  • GloverG.H.

    Deconvolution of impulse response in event-related BOLD fMRI

    Neuroimage

    (1999)
  • GrunwaldT. et al.

    Neuronal substrates of sensory gating within the human brain

    Biol. Psychiatry

    (2003)
  • GutermanY. et al.

    Attentional influence on the P50 component of the auditory event-related brain potential

    Int. J. Psychophysiol.

    (1992)
  • HuangM.X. et al.

    Predicting EEG responses using MEG sources in superior temporal gyrus reveals source asynchrony in patients with schizophrenia

    Clin. Neurophysiol.

    (2003)
  • HuettelS.A. et al.

    Evidence for a refractory period in the hemodynamic response to visual stimuli as measured by MRI

    Neuroimage

    (2000)
  • HuotilainenM. et al.

    Combined mapping of human auditory EEG and MEG responses

    Electroencephalogr. Clin. Neurophysiol.

    (1998)
  • InanS. et al.

    Hemodynamic correlates of stimulus repetition in the visual and auditory cortices: an fMRI study

    Neuroimage

    (2004)
  • KnightR.T. et al.

    Prefrontal cortex regulates inhibition and excitation in distributed neural networks

    Acta Psychol. (Amst)

    (1999)
  • KorzyukovO. et al.

    Generators of the intracranial P50 response in auditory sensory gating

    Neuroimage

    (2007)
  • OranjeB. et al.

    Modulating sensory gating in healthy volunteers: the effects of ketamine and haloperidol

    Biol. Psychiatry

    (2002)
  • PattersonJ.V. et al.

    P50 sensory gating ratios in schizophrenics and controls: a review and data analysis

    Psychiatry Res.

    (2008)
  • PausT.

    Location and function of the human frontal eye-field: a selective review

    Cogn. Neuropsychol.

    (1996)
  • RentzschJ. et al.

    Test-retest reliability of P50, N100 and P200 auditory sensory gating in healthy subjects

    Int. J. Psychophysiol.

    (2008)
  • SeifritzE. et al.

    Enhancing BOLD response in the auditory system by neurophysiologically tuned fMRI sequence

    Neuroimage

    (2006)
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