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.

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.

Lateralization of phonetic and pitch discrimination in speech processing.

Cerebral activation was measured with positron emission tomography in ten human volunteers. The primary auditory cortex showed increased activity in response to noise bursts, whereas acoustically matched speech syllables activated secondary auditory cortices bilaterally. Instructions to make judgments about different attributes of the same speech signal resulted in activation of specific lateralized neural systems. Discrimination of phonetic structure led to increased activity in part of Broca's area of the left hemisphere, suggesting a role for articulatory recoding in phonetic perception. Processing changes in pitch produced activation of the right prefrontal cortex, consistent with the importance of right-hemisphere mechanisms in pitch perception.

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.

Emotional responses to pleasant and unpleasant music correlate with activity in paralimbic brain regions.

Neural correlates of the often-powerful emotional responses to music are poorly understood. Here we used positron emission tomography to examine cerebral blood flow (CBF) changes related to affective responses to music. Ten volunteers were scanned while listening to six versions of a novel musical passage varying systematically in degree of dissonance. Reciprocal CBF covariations were observed in several distinct paralimbic and neocortical regions as a function of dissonance and of perceived pleasantness/unpleasantness. The findings suggest that music may recruit neural mechanisms similar to those previously associated with pleasant/unpleasant emotional states, but different from those underlying other components of music perception, and other emotions such as fear.

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.

Auditory function in Alzheimer's disease.

The pattern of cerebral degeneration in Alzheimer's disease (AD) patients suggests that basic auditory capacities should be normal in AD, whereas progressively higher levels of auditory function should be increasingly impaired. To test this hypothesis, we administered tests of auditory capacities associated with primary auditory cortex (sound localization and perception of complex tones) and auditory association cortex (phoneme discrimination, timbre discrimination, and tonal memory) to 19 mildly to moderately demented AD patients, 21 elderly control subjects (ECS), and 14 young control subjects (YCS). The results showed significant differences between YCS and ECS on phoneme discrimination with synthetic speech and on tonal memory. The AD group differed from the ECS group on sound localization, one measure of synthetic speech discrimination, and timbre discrimination. Performance did not correlate with age, dementia severity, or duration of illness on any test condition. These findings indicate that although AD is accompanied by specific auditory deficits, the increase in neuropathologic change between primary auditory and auditory association cortices is not reflected in an increased impairment of functions that are mediated by these areas. Degraded aural language comprehension, which is characteristic of AD, likely reflects disruption of language processes, rather than dysfunction specific to auditory circuits.

Perceptual asymmetry on the dichotic fused words test and cerebral speech lateralization determined by the carotid sodium amytal test.

The rhymed fused dichotic words test was administered to 61 epileptic patients whose lesions were atrophic and predominantly unilateral. Subjects were categorized according to the side of speech representation, as determined by intracarotid sodium Amytal injection (left-hemisphere representation, 35 subjects; right-hemisphere representation, 4 subjects; bilateral representation, 22 subjects). Results indicated that 33 of the patients with left-hemisphere speech representation obtained right-ear advantages, and all four of the patients with right-hemisphere speech representation obtained left-ear advantages. The distribution of scores for patients with bilateral speech straddled the zero ear-advantage point, but overlapped both of the other two groups to some extent. Neither handedness, familial handedness, sex, nor side of epileptogenic focus had any significant effect on the observed asymmetries. It was also found that stimulus dominance effects have an important influence on the results, and must be taken into account in the interpretation of dichotic listening asymmetries. It is concluded that this test yields valid estimates of speech lateralization; it is also apparent that the magnitude of ear advantage may be an important variable insofar as the more extreme asymmetries appear to be exclusively associated with speech dominance of the contralateral hemisphere, whereas small-magnitude asymmetries are often associated with bilateral speech representation.

Discrimination and recognition of tonal melodies after unilateral cerebral excisions.

Groups of surgical patients with unilateral temporal- or frontal-lobe lesions and normal control subjects were tested in melodic discrimination and recognition tasks. The discrimination task required detection of a single-note change in a pair of short unfamiliar tonal melodies. The altered note either violated or preserved the contour, the scale, or both, of the original melody. Recognition required that the melodies used in the discrimination task be recognized from among a set of similar foils. Right temporal-lobe patients performed most poorly in discrimination. Further analysis showed that excision of the primary auditory receiving area. Heschl's gyri from either side resulted in a deficit which was independent from, but additive with, the deficit caused by right temporal lobectomy. In the recognition task, both temporal-lobe groups were impaired as compared to control. The use of scale and contour cues was similar for all groups, indicating that the deficits observed are not attributable to failure to process one of these cues. Right frontal-lobe lesioned patients differed from the others in response bias, but performed as well as controls on both tasks. The results are interpreted as evidence for two processes in melodic discrimination, one due to short-term memory mechanisms, the other attributable to a deficit in processing complex auditory patterns.

Impaired stereoscopic detection thresholds after left or right temporal lobectomy.

The present study assessed global stereopsis as measured by random dot stereograms (RDS). Single stimuli were presented in order of increasing binocular correlation (40-100%) making it progressively easier to perceive the figures in depth, and then the same set of stimuli was presented in reverse order. The subjects tested included 50 patients with unilateral temporal-lobe lesions, 11 patients with right frontal-lobe lesions and 18 normal control subjects. Results indicate that either right or left temporal lobectomy leads to a higher than normal detection threshold for RDS. In contrast, right frontal lobectomy did not have a significant effect compared to the normal control subjects. All subjects were able to perceive correctly the figures at 100% binocular correlation. The results are interpreted in terms of a possible contribution of the inferior temporal cortex to global stereopsis.

Olfactory identification deficits in patients with focal cerebral excision.

The ability to identify common odors using the University of Pennsylvania Smell Identification Test was investigated in 120 patients with a focal surgical brain lesion and 20 normal control subjects. Results showed significant impairment after right or left temporal lobectomy, right or left frontal lobectomy, and right frontotemporal excision. Patients whose excision was confined to the left central, parietal or posterior area showed no significant deficit. The impairment after frontal lobectomy was demonstrated only in patients whose frontal-lobe removal invaded the orbital cortex; that group also showed a significantly greater impairment than did the temporal lobectomy group. All patient groups showed normal detection thresholds for n-butyl alcohol.

Contribution of the right temporal lobe to musical timbre discrimination.

Patients with unilateral temporal lobe excisions and normal control subjects were tested in timbre discrimination tasks in which the stimuli differed by either the number of harmonics (a spectral cue) or by the duration of the rise and fall times (a time cue). Patients with right temporal lobe lesions exhibited a significant deficit in discriminating both spectral and time information, in comparison to patients with left temporal lobe lesions and normal control subjects. This finding suggests that musical timbre perception, examined in a psychoacoustic sense, depends on neural systems found within the right temporal lobe.

Learning and retention of melodic and verbal information after unilateral temporal lobectomy.

The role of the temporal lobes in auditory memory was tested in two analogous tasks assessing learning and 24-hr delayed recognition of unfamiliar melodies and nonsense words. The performance of patients with either anterior right (RT) or left (LT) temporal lobectomy was impaired in learning and delayed recognition of both melodies and words, as compared to normal control subjects, although some preserved learning over successive trials was observed. These results suggest a bilateral temporal-lobe contribution to the learning of these auditory patterns. However, melodies and nonsense words were not recognized in the same way by the two patient groups after 24 hr: subjects in the LT group tended to improve on melodies but drop on words, whereas subjects with RT lesions displayed the reverse pattern, suggesting a differential role for each temporal lobe in long-term memory, according to the nature of the cues inherent to a given type of stimulus.

Effect of unilateral temporal-lobe excision on perception and imagery of songs.

Auditory imagery for songs was studied in two groups of patients with left or right temporal-lobe excision for control of epilepsy, and a group of matched normal control subjects. Two tasks were used. In the perceptual task, subjects saw the text of a familiar song and simultaneously heard it sung. On each trial they judged if the second of two capitalized lyrics was higher or lower in pitch than the first. The imagery task was identical in all respects except that no song was presented, so that subjects had to generate an auditory image of the song. The results indicated that all subjects found the imagery task more difficult than the perceptual task, but patients with right temporal-lobe damage performed significantly worse on both tasks than either patients with left temporal-lobe lesions or normal control subjects. These results support the idea that imagery arises from activation of a neural substrate shared with perceptual mechanisms, and provides evidence for a right temporal-lobe specialization for this type of auditory imaginal processing.

The role of auditory cortex in retention of rhythmic patterns as studied in patients with temporal lobe removals including Heschl's gyrus.

This experiment examined the participation of the auditory cortex of the temporal lobe in the perception and retention of rhythmic patterns. Four patient groups were tested on a paradigm contrasting reproduction of auditory and visual rhythms: those with right or left anterior temporal lobe removals which included Heschl's gyrus (HG), the region of primary auditory cortex (RT-A and LT-A); and patients with right or left anterior temporal lobe removals which did not include HG (RT-a and LT-a). Estimation of lesion extent in HG using an MRI-based probabilistic map indicated that, in the majority of subjects, the lesion was confined to the anterior secondary auditory cortex located on the anterior-lateral extent of HG. On the rhythm reproduction task, RT-A patients were impaired in retention of auditory but not visual rhythms, particularly when accurate reproduction of stimulus durations was required. In contrast, LT-A patients as well as both RT-a and LT-a patients were relatively unimpaired on this task. None of the patient groups was impaired in the ability to make an adequate motor response. Further, they were unimpaired when using a dichotomous response mode, indicating that they were able to adequately differentiate the stimulus durations and, when given an alternative method of encoding, to retain them. Taken together, these results point to a specific role for the right anterior secondary auditory cortex in the retention of a precise analogue representation of auditory tonal patterns.

Learning and retention of words and designs following excision from medial or lateral temporal-lobe structures.

We sought to elucidate the contributions of the amygdala, hippocampus and temporal neocortex to learning and memory for verbal and visuospatial material. Two matched learning tasks, using abstract words versus abstract designs, were administered to patients with unilateral neocorticectomy (NCE; Dublin), selective amygdalohippocampectomy (AHE; Zurich) or anterior temporal-lobe resection invading the amygdala and hippocampus (ATL; Montreal). Data were analysed according to side and type of resection. Learning and recall for words was impaired in groups with resection from the left temporal lobe, irrespective of whether mediobasal structures were spared or temporal neocortex was spared. All right-resection groups were unimpaired. Learning for abstract designs was impaired across all trials in the right AHE and NCE groups, and on the last two trials in the right ATL group. Restricted deficits of lower magnitude were observed on some trials in left-resection groups. These results show a partial dissociation between side of excision and type of material, but the finding of similar deficits in all resection types was unexpected. We propose that excision from either the hippocampal region or temporal neocortex may result in a disconnection, giving a similar functional outcome, as both types of resection interrupt a circuit likely to be essential for normal storage and retrieval of information.

Stability of regional cerebral glucose metabolism in the normal brain measured by positron emission tomography.

Cerebral glucose utilization (LCMRGI) was measured using the [18F]fluorodeoxyglucose method with PET in two groups of ten healthy young volunteers, each scanned in a resting state under different methodological conditions. In addition, five subjects had a second scan within 48 hr. Mean hemispheric values averaged 45.8 +/- 3.3 mumol/100 g/min in the right cerebral hemisphere and 47.0 +/- 3.7 mumol/100 g/min in the left hemisphere. A four-way analysis of variance (group, sex, region, hemisphere) was carried out on the results using three different methods of data manipulation: (a) the raw values of glucose utilization, (b) LCMRGI values "normalized" by the mean hemispheric gray matter LCMRGI value, and (c) log transformed LCMRGI values. For all analysis techniques, significantly higher LCMRGI values were consistently seen in the left mid and posterior temporal area and caudate nucleus relative to the right, and in the right occipital region relative to the left. The coefficient of variation of intrasubject regional differences (9.9%) was significantly smaller than the coefficient of variation for regions between subjects (16.5%). No differences were noted between the sexes and no effect of repeat procedures was seen in subjects having multiple scans. In addition, inter-regional LCMRGI correlations were examined both in values from the 20 normal subjects, as well as in a set of hypothetical "abnormal" values. Results were compared with those reported from other PET centers; despite certain methodological differences, the intersubject and inter-regional variation of LCMRGI is fairly constant.

Enhancement of the signal-to-noise ratio in H2(15)O bolus PET activation images: a combined cold-bolus, switched protocol.

UNLABELLED: To increase the signal-to-noise ratio (S/N) of H2(15)O bolus PET activation images, we designed and tested a data acquisition protocol that alters the relative distribution of tracer in the uptake and washout phases of the input function. This protocol enhances the S/N gains obtained with conventional switched protocols by combining task switching and the use of a large bolus of blood free of tracer (cold bolus). The cold bolus is formed by sequestering blood in the lower limbs with a double cuff before tracer injection. METHODS: The effect of a combined cold-bolus, switched protocol on the signal from activation images was first simulated using a compartmental model of the uptake of H2(15)O into the brain. Then, the effectiveness of the protocol was investigated in 4 healthy volunteers performing a language task. Each volunteer underwent scanning 12 times: 3 activation/ baseline and 3 baseline/activation scans using the conventional switched protocol and 3 activation/baseline and 3 baseline/activation scans using the combined cold-bolus, switched protocol. The S/N changes introduced when using the cold bolus were analyzed by comparing, across protocols, the magnitude and statistical significance of the activation foci associated with the execution of the language task identified in the averaged subtracted images, and by comparing image noise levels. RESULTS: In the simulated datasets, the combined protocol yielded a substantial increase in the activation signals for scan durations greater than 60 s, in comparison with equivalent signals yielded by the switched protocol alone. In the PET experiments, activation foci obtained using the combined protocol had significantly higher t statistic values than did equivalent foci detected using the conventional switched protocol (mean improvement, 36%). Analysis of the S/N in the averaged subtracted images revealed that the improvements in statistical significance of the activation foci were caused by increases in the signal magnitudes and not by decreases in overall image noise. CONCLUSION: We designed a data acquisition protocol for H2(15)O bolus PET activation studies that combines the use of a tracer-free bolus with a switched protocol. Simulated and experimental data suggest that this combined protocol enhances the S/N gains obtained with a conventional switched protocol. Implementation of the combined protocol in H2(15)O bolus activation studies was easy.

Signal-enhancing switched protocols to study higher-order cognitive tasks with PET.

UNLABELLED: We tested the effectiveness of a switched protocol when it is used to detect signals that result from the study of a higher-order cognitive task with PET. Using language tasks that have been studied extensively in our laboratories, we compared the signal-to-noise ratio (S/N) and statistical significance of the activation signals detected in PET images of regional cerebral blood flow (rCBF), obtained using a standard activation protocol, and of activity concentration, obtained using a switched protocol. METHODS: Four volunteers were studied with PET while they were performing synonym-generation and word-repetition tasks (activation and baseline tasks, respectively). Each volunteer had three activation/baseline and three baseline/ activation scans. Data for each scan were collected in two frames (60 and 120 sec long). During the first 60 sec, data were collected using a standard activation protocol. Subjects then switched tasks, and acquisition continued for 120 sec. Two images were obtained from each scan: an rCBF image using the first frame and an activity-concentration image using both frames. Images were transformed into Talairach space, subtracted and averaged within and across subjects. Parametric t-statistic images were generated for each protocol, and the magnitude and significance of the activation signals yielded by the two acquisition methods were compared. RESULTS: All the activation foci detected using measurements of rCBF were detected when the switched protocol was used; this protocol, in addition, yielded better S/N values. The cognitive component introduced by task-switching in switched protocols did not yield extra statistically significant foci. In single subjects, the average improvement in the signal significance from regions of activation, at a 95% confidence level, was between 6% and 25%. When scans were averaged across subjects, the switched protocol yielded improvements in signal statistical significance of up to 38%. CONCLUSION: We present evidence suggesting that switched protocols can be used to study higher-order cognitive tasks and that they yield activation foci with S/N values that are greater than those of equivalent foci detected using an rCBF protocol. Switched protocols appear to be easy to apply to the testing of higher-order cognitive functions. However, the extra cognitive requirement of switching tasks during data acquisition may be a limiting factor when switched protocols are used to study memory processes.

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.