Distortion products in auditory fMRI research: Measurements and solutions

Nonlinearities in the cochlea can introduce audio frequencies that are not present in the sound signal entering the ear. Known as distortion products (DPs), these added frequencies complicate the interpretation of auditory experiments. Sound production systems also introduce distortion via nonlinearities, a particular concern for fMRI research because the Sensimetrics earphones widely used for sound presentation are less linear than most high-end audio devices (due to design constraints). Here we describe the acoustic and neural effects of cochlear and earphone distortion in the context of fMRI studies of pitch perception, and discuss how their effects can be minimized with appropriate stimuli and masking noise. The amplitude of cochlear and Sensimetrics earphone DPs were measured for a large collection of harmonic stimuli to assess effects of level, frequency, and waveform amplitude. Cochlear DP amplitudes were highly sensitive to the absolute frequency of the DP, and were most prominent at frequencies below 300 Hz. Cochlear DPs could thus be effectively masked by low-frequency noise, as expected. Earphone DP amplitudes, in contrast, were highly sensitive to both stimulus and DP frequency (due to prominent resonances in the earphone's transfer function), and their levels grew more rapidly with increasing stimulus level than did cochlear DP amplitudes. As a result, earphone DP amplitudes often exceeded those of cochlear DPs. Using fMRI, we found that earphone DPs had a substantial effect on the response of pitch-sensitive cortical regions. In contrast, cochlear DPs had a small effect on cortical fMRI responses that did not reach statistical significance, consistent with their lower amplitudes. Based on these findings, we designed a set of pitch stimuli optimized for identifying pitch-responsive brain regions using fMRI. These stimuli robustly drive pitch-responsive brain regions while producing minimal cochlear and earphone distortion, and will hopefully aid fMRI researchers in avoiding distortion confounds

Distinct Cortical Pathways for Music and Speech Revealed by Hypothesis-Free Voxel Decomposition

The organization of human auditory cortex remains unresolved, due in part to the small stimulus sets common to fMRI studies and the overlap of neural populations within voxels. To address these challenges, we measured fMRI responses to 165 natural sounds and inferred canonical response profiles ("components") whose weighted combinations explained voxel responses throughout auditory cortex. This analysis revealed six components, each with interpretable response characteristics despite being unconstrained by prior functional hypotheses. Four components embodied selectivity for particular acoustic features (frequency, spectrotemporal modulation, pitch). Two others exhibited pronounced selectivity for music and speech, respectively, and were not explainable by standard acoustic features. Anatomically, music and speech selectivity concentrated in distinct regions of non-primary auditory cortex. However, music selectivity was weak in raw voxel responses, and its detection required a decomposition method. Voxel decomposition identifies primary dimensions of response variation across natural sounds, revealing distinct cortical pathways for music and speech.National Eye Institute (Grant EY13455

Pitch-Responsive Cortical Regions in Congenital Amusia

Congenital amusia is a lifelong deficit in music perception thought to reflect an underlying impairment in the perception and memory of pitch. The neural basis of amusic impairments is actively debated. Some prior studies have suggested that amusia stems from impaired connectivity between auditory and frontal cortex. However, it remains possible that impairments in pitch coding within auditory cortex also contribute to the disorder, in part because prior studies have not measured responses from the cortical regions most implicated in pitch perception in normal individuals. We addressed this question by measuring fMRI responses in 11 subjects with amusia and 11 age- and education-matched controls to a stimulus contrast that reliably identifies pitch-responsive regions in normal individuals: harmonic tones versus frequency-matched noise. Our findings demonstrate that amusic individuals with a substantial pitch perception deficit exhibit clusters of pitch-responsive voxels that are comparable in extent, selectivity, and anatomical location to those of control participants. We discuss possible explanations for why amusics might be impaired at perceiving pitch relations despite exhibiting normal fMRI responses to pitch in their auditory cortex: (1) individual neurons within the pitch-responsive region might exhibit abnormal tuning or temporal coding not detectable with fMRI, (2) anatomical tracts that link pitch-responsive regions to other brain areas (e.g., frontal cortex) might be altered, and (3) cortical regions outside of pitch-responsive cortex might be abnormal. The ability to identify pitch-responsive regions in individual amusic subjects will make it possible to ask more precise questions about their role in amusia in future work. SIGNIFICANCE STATEMENT The neural causes of congenital amusia, a lifelong deficit in pitch and music perception, are not fully understood. We tested the hypothesis that amusia is due to abnormalities in brain regions that respond selectively to sounds with a pitch in normal listeners. Surprisingly, amusic individuals exhibited pitch-responsive regions that were similar to normal-hearing controls in extent, selectivity, and anatomical location. We discuss how our results inform current debates on the neural basis of amusia and how the ability to identify pitch-responsive regions in amusic subjects will make it possible to ask more precise questions about their role in amusic deficits

Divergence in the functional organization of human and macaque auditory cortex revealed by fMRI responses to harmonic tones

We report a difference between humans and macaque monkeys in the functional organization of cortical regions implicated in pitch perception. Humans but not macaques showed regions with a strong preference for harmonic sounds compared to noise, measured with both synthetic tones and macaque vocalizations. In contrast, frequency-selective tonotopic maps were similar between the two species. This species difference may be driven by the unique demands of speech and music perception in humans.National Institutes of Health (U.S.) (Grant EY13455)National Science Foundation (U.S.). Science and Technology Center for Brains, Minds, and Machines (Grant CCF-1231216)Massachusetts General Hospital. Center for Functional Neuroimaging Technologies (Grant P41EB015896)National Institutes of Health (U.S.). Shared Instrumentation Grant Program (Grant S10RR021110

Cortical Pitch Regions in Humans Respond Primarily to Resolved Harmonics and Are Located in Specific Tonotopic Regions of Anterior Auditory Cortex

Pitch is a defining perceptual property of many real-world sounds, including music and speech. Classically, theories of pitch perception have differentiated between temporal and spectral cues. These cues are rendered distinct by the frequency resolution of the ear, such that some frequencies produce “resolved” peaks of excitation in the cochlea, whereas others are “unresolved,” providing a pitch cue only via their temporal fluctuations. Despite longstanding interest, the neural structures that process pitch, and their relationship to these cues, have remained controversial. Here, using fMRI in humans, we report the following: (1) consistent with previous reports, all subjects exhibited pitch-sensitive cortical regions that responded substantially more to harmonic tones than frequency-matched noise; (2) the response of these regions was mainly driven by spectrally resolved harmonics, although they also exhibited a weak but consistent response to unresolved harmonics relative to noise; (3) the response of pitch-sensitive regions to a parametric manipulation of resolvability tracked psychophysical discrimination thresholds for the same stimuli; and (4) pitch-sensitive regions were localized to specific tonotopic regions of anterior auditory cortex, extending from a low-frequency region of primary auditory cortex into a more anterior and less frequency-selective region of nonprimary auditory cortex. These results demonstrate that cortical pitch responses are located in a stereotyped region of anterior auditory cortex and are predominantly driven by resolved frequency components in a way that mirrors behavior.National Eye Institute (Grant EY13455)James S. McDonnell Foundation (Scholar Award