The cat's meow: A high-field fMRI assessment of cortical activity in response to vocalizations and complex auditory stimuli.

Sensory systems are typically constructed in a hierarchical fashion such that lower level subcortical and cortical areas process basic stimulus features, while higher level areas reassemble these features into object-level representations. A number of anatomical pathway tracing studies have suggested that the auditory cortical hierarchy of the cat extends from a core region, consisting of the primary auditory cortex (A1) and the anterior auditory field (AAF), to higher level auditory fields that are located ventrally. Unfortunately, limitations on electrophysiological examination of these higher level fields have resulted in an incomplete understanding of the functional organization of the auditory cortex. Thus, the current study uses functional MRI in conjunction with a variety of simple and complex auditory stimuli to provide the first comprehensive examination of function across the entire cortical hierarchy. Auditory cortex function is shown to be largely lateralized to the left hemisphere, and is concentrated bilaterally in fields surrounding the posterior ectosylvian sulcus. The use of narrowband noise stimuli enables the visualization of tonotopic gradients in the posterior auditory field (PAF) and ventral posterior auditory field (VPAF) that have previously been unverifiable using fMRI and pure tones. Furthermore, auditory fields that are inaccessible to more invasive techniques, such as the insular (IN) and temporal (T) cortices, are shown to be selectively responsive to vocalizations. Collectively, these data provide a much needed functional correlate for anatomical examinations of the hierarchy of cortical structures within the cat auditory cortex.

High-Field Functional Imaging of Pitch Processing in Auditory Cortex of the Cat.

The perception of pitch is a widely studied and hotly debated topic in human hearing. Many of these studies combine functional imaging techniques with stimuli designed to disambiguate the percept of pitch from frequency information present in the stimulus. While useful in identifying potential "pitch centres" in cortex, the existence of truly pitch-responsive neurons requires single neuron-level measures that can only be undertaken in animal models. While a number of animals have been shown to be sensitive to pitch, few studies have addressed the location of cortical generators of pitch percepts in non-human models. The current study uses high-field functional magnetic resonance imaging (fMRI) of the feline brain in an attempt to identify regions of cortex that show increased activity in response to pitch-evoking stimuli. Cats were presented with iterated rippled noise (IRN) stimuli, narrowband noise stimuli with the same spectral profile but no perceivable pitch, and a processed IRN stimulus in which phase components were randomized to preserve slowly changing modulations in the absence of pitch (IRNo). Pitch-related activity was not observed to occur in either primary auditory cortex (A1) or the anterior auditory field (AAF) which comprise the core auditory cortex in cats. Rather, cortical areas surrounding the posterior ectosylvian sulcus responded preferentially to the IRN stimulus when compared to narrowband noise, with group analyses revealing bilateral activity centred in the posterior auditory field (PAF). This study demonstrates that fMRI is useful for identifying pitch-related processing in cat cortex, and identifies cortical areas that warrant further investigation. Moreover, we have taken the first steps in identifying a useful animal model for the study of pitch perception.

High-field fMRI reveals tonotopically-organized and core auditory cortex in the cat.

As frequency is one of the most basic elements of sound, it is not surprising that the earliest stages of auditory cortical processing are tonotopically organized. In cats, there are four known tonotopically organized cortical areas: the anterior (AAF), posterior (PAF), and ventral posterior (VPAF) auditory fields and primary auditory cortex (A1). Electrophysiological and anatomical evidence have suggested that AAF and A1 form core auditory cortex. The purpose of this investigation was to determine if high-field functional magnetic resonance imaging (fMRI) could be used to define the borders of all four tonotopically organized areas, identify core auditory cortex, and demonstrate tonotopy similar to that found using more invasive techniques. Five adult cats were examined. Eight different pure tones or one broad-band noise (BBN) stimuli were presented in a block paradigm during continuous fMRI scanning. Analysis was performed on each animal individually using conservative familywise error thresholds. Group analysis was performed by extracting data from fMRI analysis software and performing a battery of statistical tests. In auditory cortex, a reversal of the tonotopic gradient is known to occur at the borders between tonotopically organized areas. Therefore, high and low tones were used to delineate these borders. Activations in response to BBN as opposed to tonal stimulation demonstrated that core auditory cortex consists of both A1 and AAF. Finally, tonotopy was identified in each of the four known tonotopically organized areas. Therefore, we conclude that fMRI is effective at defining all four tonotopically organized cortical areas and delineating core auditory cortex.

There's more than one way to scan a cat: imaging cat auditory cortex with high-field fMRI using continuous or sparse sampling.

When conducting auditory investigations using functional magnetic resonance imaging (fMRI), there are inherent potential confounds that need to be considered. Traditional continuous fMRI acquisition methods produce sounds >90 dB which compete with stimuli or produce neural activation masking evoked activity. Sparse scanning methods insert a period of reduced MRI-related noise, between image acquisitions, in which a stimulus can be presented without competition. In this study, we compared sparse and continuous scanning methods to identify the optimal approach to investigate acoustically evoked cortical, thalamic and midbrain activity in the cat. Using a 7 T magnet, we presented broadband noise, 10 kHz tones, or 0.5 kHz tones in a block design, interleaved with blocks in which no stimulus was presented. Continuous scanning resulted in larger clusters of activation and more peak voxels within the auditory cortex. However, no significant activation was observed within the thalamus. Also, there was no significant difference found, between continuous or sparse scanning, in activations of midbrain structures. Higher magnitude activations were identified in auditory cortex compared to the midbrain using both continuous and sparse scanning. These results indicate that continuous scanning is the preferred method for investigations of auditory cortex in the cat using fMRI. Also, choice of method for future investigations of midbrain activity should be driven by other experimental factors, such as stimulus intensity and task performance during scanning.

Cerebral origins of the auditory projection to the superior colliculus of the cat.

The superior colliculus (SC) is critical for directing accurate head and eye movements to visual and acoustic targets. In visual cortex, areas involved in orienting of the head and eyes to a visual stimulus have direct projections to the SC. In auditory cortex of the cat, four areas have been identified to be critical for the accurate orienting of the head and body to an acoustic stimulus. These areas include primary auditory cortex (A1), the posterior auditory field (PAF), the dorsal zone of auditory cortex (DZ), and the auditory field of the anterior ectosylvian sulcus (fAES). Therefore, we hypothesized that these four regions of auditory cortex would have direct projections to the SC. To test this hypothesis, deposits of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made into the superficial and deep layers of the SC to label, by means of retrograde transport, the auditory cortical origins of the corticotectal pathway. Bilateral examination of auditory cortex revealed that the vast majority of the labeled cells were located in the hemisphere ipsilateral to the SC injection. In ipsilateral auditory cortex, nearly all the labeled neurons were found in the infragranular layers, predominately in layer V. The largest population of labeled cells was located in the fAES. Few labeled neurons were identified in A1, PAF, or DZ. Thus, in contrast to the visual system, only one of the auditory cortical areas involved in orienting to an acoustic stimulus has a strong direct projection to the SC. Sound localization signals processed in primary (A1) and other non-primary (PAF and DZ) auditory cortices may be transmitted to the SC via a multi-synaptic corticotectal network.

Auditory cortex projections target the peripheral field representation of primary visual cortex.

The purpose of the present study was to identify projections from auditory to visual cortex and their organization. Retrograde tracers were used to identify the sources of auditory cortical projections to primary visual cortex (areas 17 and 18) in adult cats. Two groups of animals were studied. In the first group, large deposits were centered on the lower visual field representation of the vertical meridian located along the area 17 and 18 border. Following tissue processing, characteristic patterns of cell body labeling were identified in extrastriate visual cortex and the visual thalamus (LGN, MIN, & LPl). In auditory cortex, of the four tonotopically-organized regions, neuronal labeling was identified in the supragranular layers of the posterior auditory field (PAF). Little to no labeling was evident in the primary auditory cortex, the anterior auditory field, the ventral posterior auditory field or in the remaining six non-tonotopically organized regions of auditory cortex. In the second group, small deposits were made into the central or peripheral visual field representations of primary visual cortex. Labeled cells were identified in PAF following deposits into regions of primary visual cortex representing peripheral, but not central, visual field representations. Furthermore, a coarse topography was identified in PAF, with neurons projecting to the upper field representation being located in the gyral portion of PAF and neurons projecting to the lower field representation located in the sulcal portion of PAF. Therefore, direct projections can be identified from tonotopically organized auditory cortex to the earliest stages of visual cortical processing.

Functional specialization in non-primary auditory cortex of the cat: areal and laminar contributions to sound localization.

The purpose of this study is to: (1) examine the relative contributions of the 13 acoustically-responsive regions of the cerebral cortex to sound localization; (2) examine the laminar contributions to spatial localization behavior for each of the cortical areas identified to be critical for accurately determining the position of a sound source; and (3) synthesize the findings from sound localization studies and the underlying corticocortical and corticotectal connections to develop a processing system for sound localization information within and between the cerebral cortex and the superior colliculus. First, we examined performance on a sound localization task before, during, and after unilateral or bilateral reversible cooling deactivation of each region of acoustically-responsive cortex. Overall, unilateral deactivation of primary auditory cortex and the dorsal zone (AI/DZ), the posterior auditory field (PAF), or the auditory field of the anterior ectosylvian sulcus (AES) yielded profound sound localization deficits in the contralateral field. Bilateral deactivations of the same regions yielded bilateral sound localization deficits. Second, graded cooling of AI/DZ or PAF showed that deactivation of only the superficial layers was required to elicit sound localization deficits. However, graded cooling of AES revealed that cooling of the superficial layers alone does not cause significant sound localization deficits. Profound deficits were identified only when cooling extended through the full thickness of AES cortex. Therefore, we propose that the superficial layers of AI/DZ or PAF and the deeper layers of AES are necessary for determining the precise location of a sound source. Finally, when these results are combined with data on corticocortical and corticotectal projections, we propose that signals processed in the superficial layers of AI, DZ, or PAF feed forward to the auditory field of AES. In turn, neurons in the deeper layers of AES project to the intermediate and deeper layers of the superior colliculus. Therefore, we propose that sound localization signals processed in primary and non-primary auditory cortex are transmitted to the superior colliculus by means of the auditory field of the AES.

Cortical control of sound localization in the cat: unilateral cooling deactivation of 19 cerebral areas.

We examined the ability of mature cats to accurately orient to, and approach, an acoustic stimulus during unilateral reversible cooling deactivation of primary auditory cortex (AI) or 1 of 18 other cerebral loci. After attending to a central visual stimulus, the cats learned to orient to a 100-ms broad-band, white-noise stimulus emitted from a central speaker or 1 of 12 peripheral sites (at 15 degrees intervals) positioned along the horizontal plane. Twenty-eight cats had two to six cryoloops implanted over multiple cerebral loci. Within auditory cortex, unilateral deactivation of AI, the posterior auditory field (PAF) or the anterior ectosylvian sulcus (AES) resulted in orienting deficits throughout the contralateral field. However, unilateral deactivation of the anterior auditory field, the second auditory cortex, or the ventroposterior auditory field resulted in no deficits on the orienting task. In multisensory cortex, unilateral deactivation of neither ventral or dorsal posterior ectosylvian cortices nor anterior or posterior area 7 resulted in any deficits. No deficits were identified during unilateral cooling of the five visual regions flanking auditory or multisensory cortices: posterior or anterior ii suprasylvian sulcus, posterior suprasylvian sulcus or dorsal or ventral posterior suprasylvian gyrus. In motor cortex, we identified contralateral orienting deficits during unilateral cooling of lateral area 5 (5L) or medial area 6 (6m) but not medial area 5 or lateral area 6. In a control visual-orienting task, areas 5L and 6m also yielded deficits to visual stimuli presented in the contralateral field. Thus the sound-localization deficits identified during unilateral deactivation of area 5L or 6m were not unimodal and are most likely the result of motor rather than perceptual impairments. Overall, three regions in auditory cortex (AI, PAF, AES) are critical for accurate sound localization as assessed by orienting.