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

The mechanisms of tinnitus: perspectives from human functional neuroimaging

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power

Quantification of venous blood signal contribution to BOLD functional activation in the auditory cortex at 3 T

Most modern techniques for functional magnetic resonance imaging (fMRI) rely on blood-oxygen-level-dependent (BOLD) contrast as the basic principle for detecting neuronal activation. However, the measured BOLD effect depends on a transfer function related to neurophysiological changes accompanying electrical neural activation. The spatial accuracy and extension of the region of interest are determined by vascular effect, which introduces incertitude on real neuronal activation maps. Our efforts have been directed towards the development of a new methodology that is capable of combining morphological, vascular and functional information; obtaining new insight regarding foci of activation; and distinguishing the nature of activation on a pixel-by-pixel basis. Six healthy volunteers were studied in a parametric auditory functional experiment at 3 T; activation maps were overlaid on a high-resolution brain venography obtained through a novel technique. The BOLD signal intensities of vascular and nonvascular activated voxels were analyzed and compared: it was shown that nonvascular active voxels have lower values for signal peak (Pb10−7) and area (Pb10−8) with respect to vascular voxels. The analysis showed how venous blood influenced the measured BOLD signals, supplying a technique to filter possible venous artifacts that potentially can lead to misinterpretation of fMRI results. This methodology, although validated in the auditory cortex activation, maintains a general applicability to any cortical fMRI study, as the basic concepts on which it relies on are not limited to this cortical region. The results obtained in this study can represent the basis for new methodologies and tools that are capable of adding further characterization to the BOLD signal properties

Two distinct profiles of fMRI and neurophysiological activity elicited by acetylcholine in visual cortex

Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays. We found that local injection of ACh elicited two distinct profiles of fMRI and neurophysiological activity, depending on the distance from the injector. Near the injection site, we observed an increase in the baseline blood oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) responses, while their visual modulation decreased. In contrast, further from the injection site, we observed an increase in the visually induced BOLD and CBF modulation without changes in baseline. Neurophysiological recordings suggest that the spatial correspondence between fMRI responses and neural activity does not change in the gamma, high-gamma, and multiunit activity (MUA) bands. The results near the injection site suggest increased inhibitory drive and decreased metabolism, contrasting to the far region. These changes are thought to reflect the kinetics of ACh and its metabolism to choline

Resting state networks of the canine brain under sevoflurane anaesthesia

Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs’ brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases

Methodological challenges and solutions in auditory functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) studies involve substantial acoustic noise. This review covers the difficulties posed by such noise for auditory neuroscience, as well as a number of possible solutions that have emerged. Acoustic noise can affect the processing of auditory stimuli by making them inaudible or unintelligible, and can result in reduced sensitivity to auditory activation in auditory cortex. Equally importantly, acoustic noise may also lead to increased listening effort, meaning that even when auditory stimuli are perceived, neural processing may differ from when the same stimuli are presented in quiet. These and other challenges have motivated a number of approaches for collecting auditory fMRI data. Although using a continuous echoplanar imaging (EPI) sequence provides high quality imaging data, these data may also be contaminated by background acoustic noise. Traditional sparse imaging has the advantage of avoiding acoustic noise during stimulus presentation, but at a cost of reduced temporal resolution. Recently, three classes of techniques have been developed to circumvent these limitations. The first is Interleaved Silent Steady State (ISSS) imaging, a variation of sparse imaging that involves collecting multiple volumes following a silent period while maintaining steady-state longitudinal magnetization. The second involves active noise control to limit the impact of acoustic scanner noise. Finally, novel MRI sequences that reduce the amount of acoustic noise produced during fMRI make the use of continuous scanning a more practical option. Together these advances provide unprecedented opportunities for researchers to collect high-quality data of hemodynamic responses to auditory stimuli using fMRI