The human brain is adept at identifying new sounds in the environment and determining their potential ecologic relevance (Escera and Malmierca, 2014; Justo-Guillen et al., 2019). Detection of a potentially meaningful new sound is followed by attempts to place the sound into a pre-existing semantic category (Nobre and McCarthy, 1994; Mecklinger et al., 1997). Novelty detection in the auditory domain is of fundamental importance for learning across the lifespan (Nordt et al., 2016) and is present in early infancy (Katus et al., 2023). Aberrant detection of novel sounds is a feature of many neuropsychiatric disorders, including autism and schizophrenia, as well as altered states of consciousness, e.g., sleep, delirium, and coma (Lepistö et al., 2005; Higuchi et al., 2014; Morlet & Fischer, 2014; Strauss et al., 2015; Michie et al., 2016; Hudac et al., 2018; Perrottelli et al., 2021).

Auditory semantic novelty has typically been studied using either auditory-only paradigms with non-speech environmental sounds (e.g., Opitz et al., 1999) or audiovisual oddball paradigms with speech stimuli (e.g., Parmentier, 2008). Functional neuroimaging studies have revealed greater cortical activation in response to novel meaningful environmental sounds than to sounds that are not meaningful (e.g., tones) (Opitz et al., 1999). Behavioral studies have indicated that speech processing relies on specialized systems distinct from those involved in processing of music and other environmental sounds (Moskowitz et al., 2020). Likewise, results from audiovisual paradigms reflect complex interactions between responses to stimuli of both sensory modalities and associated selective attention mechanisms (Parmentier, 2008; see also Salmela et al., 2018). Thus, it is premature to extrapolate findings derived during identification of novel environmental stimuli or those obtained in audiovisual paradigms to auditory novelty detection associated with speech stimuli.

Most studies devoted to identifying the brain areas associated with novelty detection and semantic classification used electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) (e.g., Mecklinger et al., 1997, Opitz et al., 1999; Kotz et al., 2007). Auditory novelty detection within the context of semantic processing has been associated with several event-related potential (ERP) components, including P3a and N400. P3a, peaking at ∼300 ms after the onset of the novel stimulus, is an endogenous automatic preattentive response, thought to have a prefrontal generator (Polich, 2007; Friedman et al., 2009). The clinical importance of examining P3a with speech stimuli is exemplified by a greater degree of P3a impairment for speech than non-speech stimuli in children with autism (Lepistö et al., 2005). N400 is an attention-dependent neural response that represents semantic classification of novel sounds, including non-speech stimuli (Opitz et al., 1999; Kotz et al., 2007). N400 elicited by speech stimuli has been suggested to be a useful biomarker for the diagnosis and management of aphasia (Meechan et al., 2021).

The current intracranial EEG (iEEG) study is an expansion of our previous work examining brain regions subserving semantic classification (Steinschneider et al., 2014; Nourski et al., 2017). These studies examined semantic processing using repeatedly presented words (“common”, COM) associated with different semantic categories. The present study focused on responses to additional, single-exemplar words (“novel”, NOV) that were intermixed with the repeatedly presented COM stimuli. Extensive electrode coverage (over 5500 recording sites across 38 participants) permitted detailed characterizations, including spatial distribution of auditory novelty responses during performance of the same task as used in the previous studies (Steinschneider et al., 2014; Nourski et al., 2017). Novelty responses to unexpected words were predicted to have a higher prevalence along the ventral than dorsal auditory cortical processing stream given the semantic nature of the task (Hickok & Poeppel, 2004; Rauschecker & Scott, 2009). For the same reason, it was predicted that there would be a left hemispheric bias (cf. Nourski et al., 2017), in contrast to a right hemispheric bias for novel non-speech environmental sounds (Mecklinger et al., 1997; Opitz et al., 1999). Additionally, we focused on examining the relationship between bottom-up and top-down cortical representation of auditory novelty and behavioral task performance. To that end, we used broadband gamma (30-150 Hz) activation and alpha (8-14 Hz) suppression as physiologic markers and examined the degree to which task performance was a function of top-down modulation. These complementary measures are sensitive indices of cortical function and represent fundamental features of predictive coding (Billig et al., 2019; Bastos et al., 2020; Nourski et al., 2021b, 2022). Gamma activation reflects feedforward signaling at the cortical level, whereas alpha suppression represents the release from inhibition due to diminished feedback from higher cortical areas (Fontolan et al., 2014; Billig et al., 2019; Bastos et al., 2020). Finally, building upon the groundbreaking work of Halgren et al. (1995, 1998), the present study examined averaged evoked potentials (AEP) to facilitate identification of the putative generators of non-invasively recorded responses.