Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia

Abstract

Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex. Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants’ level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants’ arcuate fasciculus was used to predict their level of cortical suppression in the three conditions. While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient’s level of N1 suppression was linearly related to the FA of their arcuate fasciculus. These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.

The effects of stimulus complexity on the preattentive processing of self-generated and nonself voices: An ERP study

“…Since most of the studies on self-voice processing have used simple voice stimuli, such as vocalizations (e.g., Ford et al, 2007;Graux et al, 2015;Graux et al, 2013;Sitek et al, 2013;Whitford et al, 2011), future studies should test the specific contribution of stimulus complexity to these processes by including different stimuli varying in their amounts of linguistic and paralinguistic information. Furthermore, stimulus length is an important marker of linguistic complexity, and our experimental design does not allow for disentangling the effects of stimulus duration from linguistic information effects in the WCC.…”

“…Following previous studies (e.g., Ford et al, 2007;Graux et al, 2015;Graux et al, 2013;Heinks-Maldonado, Nagarajan, & Houde, 2006;Sitek et al, 2013;Whitford et al 2011), the vowel /a/ (duration = 300 ms) was selected for the VCC condition, thus allowing more direct comparisons with those experiments. For the WCC, a word was selected from the Affective Norms for English Words (ANEW; Soares, Comesaña, Pinheiro, Simões, & Frade, 2012) and P-PAL (Soares et al, 2010) sets, according to the following criteria: neutral valence (5.34), low arousal (3.36), high frequency (>100 per million), grammatical class (noun), and short extension (two syllables and four letters).…”

“…In these studies, the N1 ERP component (or its magnetic counterpart, the N100m) has been used to examine the auditory cortical responsiveness during voice production relative to the passive listening to one's own voice. This component indexes the sensory registration of auditory stimuli (Ford, Roach, & Mathalon, 2010;Whitford et al, 2011), and it is thought to be generated in the auditory cortex (Godey, Schwartz, de Graaf, Chauvel, & Liégeois-Chauvel, 2001). These studies have found an N1 amplitude suppression effect during vocal production when compared with the condition of passively listening to prerecorded self-generated voice stimuli Curio, Neuloh, Numminen, Jousmaki, & Hari, 2000;Ford & Mathalon, 2004Ford et al, 2001;Ford et al, 2002;Ford et al, 2007;HeinksMaldonado, Mathalon, Gray, & Ford, 2005;HeinksMaldonado et al, 2007;Houde, Nagarajan, Sekihara, & Merzenich, 2002;H.…”

Towards integrating phenomenology and neurocognition: Possible neurocognitive correlates of basic self-disturbance in schizophrenia

“…[76] and Whitford et al [77] observed that while healthy controls exhibited significantly smaller event-related potentials (ERPs) to self-initiated, button-press initiated sounds compared to identical, externally-initiated sounds, patients with schizophrenia did not exhibit this ERP suppression. This again suggests that schizophrenia patients fail to distinguish between internally-generated and externally-generated sensations, even when the association between action and sensation is not direct (e.g., sounds caused by willed speech) but is instead indirect and more likely to be associatively learned (e.g., sounds generated by pressing a button).…”

Reduced integrity of the left arcuate fasciculus is specifically associated with auditory verbal hallucinations in schizophrenia

“…The AF L was extracted from DT images using deterministic tractography (as per Whitford et al, 2011) and implemented in the Slicer-3 software package (version 4.2.0, nightly build, www.slicer. org).…”