Singing training predicts increased insula connectivity with speech and respiratory sensorimotor areas at rest.

The insula contributes to the detection of salient events during goal-directed behavior and participates in the coordination of motor, multisensory, and cognitive systems. Recent task-fMRI studies with trained singers suggest that singing experience can enhance the access to these resources. However, the long-term effects of vocal training on insula-based networks are still unknown. In this study, we employed resting-state fMRI to assess experience-dependent differences in insula co-activation patterns between conservatory-trained singers and non-singers. Results indicate enhanced bilateral anterior insula connectivity in singers relative to non-singers with constituents of the speech sensorimotor network. Specifically, with the cerebellum (lobule V-VI) and the superior parietal lobes. The reversed comparison showed no effects. The amount of accumulated singing training predicted enhanced bilateral insula co-activation with primary sensorimotor areas representing the diaphragm and the larynx/phonation area-crucial regions for cortico-motor control of complex vocalizations-as well as the bilateral thalamus and the left putamen. Together, these findings highlight the neuroplastic effect of expert singing training on insula-based networks, as evidenced by the association between enhanced insula co-activation profiles in singers and the brain's speech motor system components.

How restful is it with all that noise? Comparison of Interleaved silent steady state (ISSS) and conventional imaging in resting-state fMRI.

Resting-state fMRI studies have become very important in cognitive neuroscience because they are able to identify BOLD fluctuations in brain circuits involved in motor, cognitive, or perceptual processes without the use of an explicit task. Such approaches have been fruitful when applied to various disordered populations, or to children or the elderly. However, insufficient attention has been paid to the consequences of the loud acoustic scanner noise associated with conventional fMRI acquisition, which could be an important confounding factor affecting auditory and/or cognitive networks in resting-state fMRI. Several approaches have been developed to mitigate the effects of acoustic noise on fMRI signals, including sparse sampling protocols and interleaved silent steady state (ISSS) acquisition methods, the latter being used only for task-based fMRI. Here, we developed an ISSS protocol for resting-state fMRI (rs-ISSS) consisting of rapid acquisition of a set of echo planar imaging volumes following each silent period, during which the steady state longitudinal magnetization was maintained with a train of relatively silent slice-selective excitation pulses. We evaluated the test-retest reliability of intensity and spatial extent of connectivity networks of fMRI BOLD signal across three different days for rs-ISSS and compared it with a standard resting-state fMRI (rs-STD). We also compared the strength and distribution of connectivity networks between rs-ISSS and rs-STD. We found that both rs-ISSS and rs-STD showed high reproducibility of fMRI signal across days. In addition, rs-ISSS showed a more robust pattern of functional connectivity within the somatosensory and motor networks, as well as an auditory network compared with rs-STD. An increased connectivity between the default mode network and the language network and with the anterior cingulate cortex (ACC) network was also found for rs-ISSS compared with rs-STD. Finally, region of interest analysis showed higher interhemispheric connectivity in Heschl's gyri in rs-ISSS compared with rs-STD, with lower variability across days. The present findings suggest that rs-ISSS may be advantageous for detecting network connectivity in a less noisy environment, and that resting-state studies carried out with standard scanning protocols should consider the potential effects of loud noise on the measured networks.

Introduction to The neurosciences and music IV: learning and memory.

The conference entitled "The Neurosciences and Music-IV: Learning and Memory'' was held at the University of Edinburgh from June 9-12, 2011, jointly hosted by the Mariani Foundation and the Institute for Music in Human and Social Development, and involving nearly 500 international delegates. Two opening workshops, three large and vibrant poster sessions, and nine invited symposia introduced a diverse range of recent research findings and discussed current research directions. Here, the proceedings are introduced by the workshop and symposia leaders on topics including working with children, rhythm perception, language processing, cultural learning, memory, musical imagery, neural plasticity, stroke rehabilitation, autism, and amusia. The rich diversity of the interdisciplinary research presented suggests that the future of music neuroscience looks both exciting and promising, and that important implications for music rehabilitation and therapy are being discovered.

Functional neuroimaging of odor imagery.

We used positron emission tomography (PET) to investigate brain regions associated with odor imagery. Changes in regional cerebral blood flow (CBF) during odor imagery were compared with changes during nonspecific expectation of olfactory stimuli and with those during odor perception. Sixty-seven healthy volunteers were screened for their odor imagery (with a paradigm developed in a previous study), and 12 of them, assessed to be "good odor imagers," participated in the neuroimaging part of the study. Imagination of odors was associated with increased activation in several olfactory regions in the brain: the left primary olfactory cortical (POC) region including piriform cortex, the left secondary olfactory cortex or posterior orbitofrontal cortex (OFC), and the rostral insula bilaterally. Furthermore, blood flow in two regions within the right orbitofrontal cortex correlated significantly with the behavioral measure of odor imagery during scanning. Overall, the findings indicated that neural networks engaged during odor perception and imagery overlap partially.

Odor-induced changes in taste perception.

We investigated odor-induced changes in taste perception (OICTP), by examining the influence of strawberry and soy sauce odors on perceived sweetness (Experiment 1) and saltiness (Experiment 2). We explored whether taste-smell interactions occur at the central level, by delivering odorants (strawberry, soy sauce, odorless water) and tastants (sucrose, sodium chloride) separately, and whether effects of imagined odors are comparable to those of physically presented odors. We found specific taste-smell interactions: sweetness enhancement induced by strawberry odor and saltiness enhancement induced by soy sauce odor. These interactions were elicited with separate delivery of olfactory and gustatory stimuli. Secondly, we found a similar but rather limited effect with the imagined odors: imagined strawberry enhanced perceived sweetness of water solutions, and imagined soy sauce enhanced perceived saltiness of weak sodium chloride solutions. We concluded that OICTP is a centrally mediated phenomenon, and that imagined odors can to some extent induce changes in perceived taste intensity comparable to those elicited by perceived odors.

The mind's nose: Effects of odor and visual imagery on odor detection.

We examined odor imagery by looking for its effects on detection of weak odors. Seventy-two healthy subjects performed a forced-choice odor detection task in one of three conditions: after being told to imagine an odor (odor imagery), after being told to imagine an object (visual imagery), or without having received imagery instructions (no-imagery control). For the two imagery conditions, the presented and imagined stimuli were either the same (matched) or different (mismatched). There was a significant difference between detection in the matched and mismatched conditions for odor imagery, but not for visual imagery. We conclude that our paradigm does measure odor imagery and that the effect of imagery on detection is both content- and modality-specific. Further, the difference between conditions was due to lower detection with mismatched odor imagery than without imagery, indicating that interference underlies the effect.

Effects of perceived and imagined odors on taste detection.

We assessed the influence of different odors on detection of a sweet tastant, and the ability of imagined odors to elicit the same effects as perceived odors on taste perception. The tastant used was sucrose, and the two odorants were strawberry and ham. In the first experiment, participants either smelled or imagined one of two odors during taste detection tasks (between-subject design), whereas in the second one, subjects completed both the odor imagery and perception conditions with taste detection tasks (within-subject design). The effect was odorant-specific: detection of sucrose was significantly better when subjects smelled strawberry than when they smelled ham. Furthermore, imagined odors influenced taste perception in the same way as did perceived odors. We concluded that the odor-specific effect on taste perception is an authentic perceptual phenomenon. Our results also support the notion that odor-induced changes in taste perception are mediated centrally. Finally, our findings are in agreement with reports supporting the existence of odor imagery.

Spectral and temporal processing in human auditory cortex.

We used positron emission tomography to examine the response of human auditory cortex to spectral and temporal variation. Volunteers listened to sequences derived from a standard stimulus, consisting of two pure tones separated by one octave alternating with a random duty cycle. In one series of five scans, spectral information (tone spacing) remained constant while speed of alternation was doubled at each level. In another five scans, speed was kept constant while the number of tones sampled within the octave was doubled at each level, resulting in increasingly fine frequency differences. Results indicated that (i) the core auditory cortex in both hemispheres responded to temporal variation, while the anterior superior temporal areas bilaterally responded to the spectral variation; and (ii) responses to the temporal features were weighted towards the left, while responses to the spectral features were weighted towards the right. These findings confirm the specialization of the left-hemisphere auditory cortex for rapid temporal processing, and indicate that core areas are especially involved in these processes. The results also indicate a complementary hemispheric specialization in right-hemisphere belt cortical areas for spectral processing. The data provide a unifying framework to explain hemispheric asymmetries in processing speech and tonal patterns. We propose that differences exist in the temporal and spectral resolution of corresponding fields in the two hemispheres, and that they may be related to anatomical hemispheric asymmetries in myelination and spacing of cortical columns.

Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion.

We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of "shivers-down-the-spine" or "chills." Subjective reports of chills were accompanied by changes in heart rate, electromyogram, and respiration. As intensity of these chills increased, cerebral blood flow increases and decreases were observed in brain regions thought to be involved in reward/motivation, emotion, and arousal, including ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex. These brain structures are known to be active in response to other euphoria-inducing stimuli, such as food, sex, and drugs of abuse. This finding links music with biologically relevant, survival-related stimuli via their common recruitment of brain circuitry involved in pleasure and reward.

Spatial localization after excision of human auditory cortex.

Neurophysiological and animal ablation studies concur that primary auditory cortex is necessary for computation of the spatial coordinates of a sound source. Human studies have reported conflicting findings but have often suffered from inadequate psychophysical measures and/or poor lesion localization. We tested patients with unilateral temporal lobe excisions either encroaching on or sparing Heschl's gyrus (HG), quantifying lesion extent using anatomical magnetic resonance imaging measures. Subjects performed two tasks. In the localization task, they heard single clicks in a free-field spatial array subtending 180 degrees of azimuth and indicated the perceived location with a laser pointer. In the discrimination task, two clicks were presented, and subjects indicated if they were in the same or different position. As a group, patients with right temporal excision, either encroaching onto HG or not, were significantly impaired in both hemifields in both tasks, although this was not true for all individuals. Patients with left temporal resections generally performed normally, although some of the patients with left HG excision showed impaired performance bilaterally, especially in the discrimination task. This pattern stands in marked contrast to previous studies showing significant preservation of localization in hemispherectomized patients. We conclude that (1) contrary to hypotheses derived from animal studies, human auditory spatial processes are dependent primarily on cortical areas within right superior temporal cortex, which encompass both spatial hemifields; (2) functional reorganization may not take place after restricted focal damage but only after more extensive early damage; and (3) the existence of individual differences likely illustrates differential patterns of functional lateralization and/or recovery.

Do you see what I'm saying? Interactions between auditory and visual cortices in cochlear implant users.

Primary sensory cortices are generally thought to be devoted to one sensory modality-vision, hearing, or touch, for example. Surprising interactions between these sensory modes have recently been reported. One example demonstrates that people with cochlear implants show increased activity in visual cortex when listening to speech; this may be related to enhanced lipreading ability.

Working memory in another dimension: functional imaging of human olfactory working memory.

The majority of working memory research has been carried out within the visual and auditory modalities, leaving it unclear how other modalities would map onto currently proposed working memory models. In this study we examined the previously uninvestigated area of olfactory working memory. Our aim was to investigate if olfactory working memory would engage prefrontal regions known to be involved in working memory for other sensory modalities. Using positron emission tomography we measured cerebral blood flow changes in 12 volunteers during an olfactory working memory task and a comparison visual working memory task. Our findings indicate that both olfactory and face working memory engaged dorsolateral and ventrolateral frontal cortex when the task requirements were matched; a conjunction analysis indicated overlap in the distribution of activity in the two tasks. Similarities and differences in activity were noted in parietal lobe regions, with both tasks engaging inferior areas of 40/7, but only visual working memory showing increased activity within left superior parietal cortex. The findings support the idea that working memory processes engage frontal cortical areas independent of the modality of input, but do not rule out the possibility of modality-specific neural populations within dorsolateral or ventrolateral cortex.

Changes in brain activity related to eating chocolate: from pleasure to aversion.

We performed successive H(2)(15)O-PET scans on volunteers as they ate chocolate to beyond satiety. Thus, the sensory stimulus and act (eating) were held constant while the reward value of the chocolate and motivation of the subject to eat were manipulated by feeding. Non-specific effects of satiety (such as feelings of fullness and autonomic changes) were also present and probably contributed to the modulation of brain activity. After eating each piece of chocolate, subjects gave ratings of how pleasant/unpleasant the chocolate was and of how much they did or did not want another piece of chocolate. Regional cerebral blood flow was then regressed against subjects' ratings. Different groups of structures were recruited selectively depending on whether subjects were eating chocolate when they were highly motivated to eat and rated the chocolate as very pleasant [subcallosal region, caudomedial orbitofrontal cortex (OFC), insula/operculum, striatum and midbrain] or whether they ate chocolate despite being satiated (parahippocampal gyrus, caudolateral OFC and prefrontal regions). As predicted, modulation was observed in cortical chemosensory areas, including the insula and caudomedial and caudolateral OFC, suggesting that the reward value of food is represented here. Of particular interest, the medial and lateral caudal OFC showed opposite patterns of activity. This pattern of activity indicates that there may be a functional segregation of the neural representation of reward and punishment within this region. The only brain region that was active during both positive and negative compared with neutral conditions was the posterior cingulate cortex. Therefore, these results support the hypothesis that there are two separate motivational systems: one orchestrating approach and another avoidance behaviours.

Neural specializations for tonal processing.

The processing of pitch, a central aspect of music perception, is neurally dissociable from other perceptual functions. Studies using behavioral-lesion techniques as well as brain imaging methods demonstrate that tonal processing recruits mechanisms in areas of the right auditory cortex. Specifically, the right primary auditory area appears to be crucial for fine-grained representation of pitch information. Processing of pitch patterns, such as occurs in melodies, requires higher-order cortical areas, and interactions with the frontal cortex. The latter are likely related to tonal working memory functions that are necessary for the on-line maintenance and encoding of tonal patterns. One hypothesis that may explain why right-hemisphere auditory cortices seem to be so important to tonal processing is that left auditory regions are better suited for rapidly changing broad-band stimuli, such as speech, whereas the right auditory cortex may be specialized for slower narrow-band stimuli, such as tonal patterns. Evidence favoring this hypothesis was obtained in a functional imaging study in which spectral and temporal parameters were varied independently. The hypothesis also receives support from structural studies of the auditory cortex, which indicate that spectral and temporal processing may depend on interhemispheric differences in grey/white matter distribution and other anatomical features.

Increased intensity perception of aversive taste following right anteromedial temporal lobe removal in humans.

We used a modified version of the Spatial Taste Test to assess taste intensity perception in patients with either left or right temporal resection from the anteromedial temporal lobe (AMTL), and a group of control subjects. Sweet, sour, salty and bitter solutions were applied onto discrete locations of the tongue to stimulate either left or right fungiform, or left or right foliate papillae. Intensity ratings were assessed with the Labeled Magnitude Scale. Subjects also sipped 5 ml of each solution for whole mouth stimulation. Genetically based determinants of taste sensitivity were assessed with ratings of 6-n-propylthiouracil, and covaried from all analyses. As in previous studies, analysis of covariance indicated that the subjects in the right temporal group rated an aversive bitter taste as more intense than did subjects in the control group. In contrast, there were no group differences for sucrose ratings, suggesting that the AMTL may be involved preferentially in processing aversive compared with hedonic tastes. No group x side, or group x location effects were present. These results confirm that removal of the right AMTL in humans results in increased taste intensity/aversiveness perception. This finding complements existing literature indicating that the AMTL is important for processing aversive taste, and suggests that inhibitory mechanisms may play an important role in such processing.

Changes in taste intensity perception following anterior temporal lobe removal in humans.

To investigate the role of the anterior temporal lobe in taste perception, we compared taste intensity estimations made by patients who had removal from either the left or the right anterior temporal lobe for the treatment of intractable epilepsy with a group of healthy control subjects. Estimations were made for five concentrations of each of four different tastes, as well as for five cards of varying saturations of gray, which served as a control task. A cross-modal magnitude estimation procedure was employed in which subjects used distance on a measuring tape to reflect intensity estimation. Distances were then transformed into logs, and the slope and the correlation with stimulus concentration or saturation was calculated. Correlation was taken as a measure of accuracy of estimation and slope was taken as a measure of perceived intensity. As predicted, repeated measures analysis of variance (ANOVA) revealed a significant difference between the control group and both patient groups in taste intensity estimations, but not for grayness, reflecting the importance of the anterior temporal lobe in low-level gustatory but not visual perception. Additionally, repeated measures ANOVA for slopes indicated that subjects in the right temporal group rated the bitter taste as more intense than did subjects in other groups, possibly reflecting increased intensity perception of the unpleasant bitter taste.

Sexual dimorphism in the corpus callosum: methodological considerations in MRI morphometry.

Studies of sexual dimorphism in the corpus callosum (CC) have employed a variety of methodologies for measurement and normalization but have yielded disparate results. The present work demonstrates how in some cases different manipulations of the same raw data, corresponding to different commonly used methodologies, produce discordant results. Midsagittal CC area was measured from magnetic resonance images (MRIs) of 137 young normal volunteers. Three strategies intended to normalize for average differences in brain size between the sexes, as well as five different normalization variables, were contrasted and evaluated. The stereotaxic method normalizes for intersubject differences in overall brain size by scaling MRIs into a standardized space. The ratio method uses one of five different indices of brain size and divides it into CC area. The covariate method uses one of the indices as a covariate in statistical analyses. Male subjects show significantly larger absolute total area, as well as anterior third and posterior midbody. However, in two of three normalization strategies, namely the stereotaxic and ratio methods, females show relatively larger total area, anterior midbody, and splenium. The covariate method did not show any significant differences at the 0.05 level. Results suggest that different approaches to normalization and analysis are not necessarily equivalent and interchangeable.

A cross-linguistic PET study of tone perception in Mandarin Chinese and English speakers.

PET was used in a cross-linguistic study to determine whether neural mechanisms subserving pitch perception differ as a function of linguistic relevance. We compared tone perception in 12 native Mandarin speakers, who use tonal patterns to distinguish lexical meaning, with that of 12 native speakers of a nontone language, English. Subjects were scanned under two conditions: a silent resting baseline and a tonal task involving discrimination of pitch patterns in Mandarin words. Both groups showed common regions of CBF increase, but only Mandarin speakers showed additional activation in frontal, parietal, and parieto-occipital regions of the left hemisphere; this latter finding indicates that language experience may influence brain circuitry in the processing of auditory cues. In contrast, only the English group showed activity in the right inferior frontal cortex, consistent with a right-hemispheric role in pitch perception.

Speech-like cerebral activity in profoundly deaf people processing signed languages: implications for the neural basis of human language.

For more than a century we have understood that our brain's left hemisphere is the primary site for processing language, yet why this is so has remained more elusive. Using positron emission tomography, we report cerebral blood flow activity in profoundly deaf signers processing specific aspects of sign language in key brain sites widely assumed to be unimodal speech or sound processing areas: the left inferior frontal cortex when signers produced meaningful signs, and the planum temporale bilaterally when they viewed signs or meaningless parts of signs (sign-phonetic and syllabic units). Contrary to prevailing wisdom, the planum temporale may not be exclusively dedicated to processing speech sounds, but may be specialized for processing more abstract properties essential to language that can engage multiple modalities. We hypothesize that the neural tissue involved in language processing may not be prespecified exclusively by sensory modality (such as sound) but may entail polymodal neural tissue that has evolved unique sensitivity to aspects of the patterning of natural language. Such neural specialization for aspects of language patterning appears to be neurally unmodifiable in so far as languages with radically different sensory modalities such as speech and sign are processed at similar brain sites, while, at the same time, the neural pathways for expressing and perceiving natural language appear to be neurally highly modifiable.