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Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels. ispartof: NEUROIMAGE vol:191 pages:537-548 ispartof: location:United States status: published

In schizophrenia, auditory verbal hallucinations (AVHs) are likely to be perceived as gender-specific. Given that functional neuro-imaging correlates of AVHs involve multiple brain regions principally including auditory cortex, it is likely that those brain regions responsible for attribution of gender to speech are invoked during AVHs. We used functional magnetic resonance imaging (fMRI) and a paradigm utilising 'gender-apparent' (unaltered) and 'gender-ambiguous' (pitch-scaled) male and female voice stimuli to test the hypothesis that male and female voices activate distinct brain areas during gender attribution. The perception of female voices, when compared with male voices, affected greater activation of the right anterior superior temporal gyrus, near the superior temporal sulcus. Similarly, male voice perception activated the mesio-parietal precuneus area. These different gender associations could not be explained by either simple pitch perception or behavioural response because the activations that we observed were conjointly activated by both 'gender-apparent' and 'gender-ambiguous' voices. The results of this study demonstrate that, in the male brain, the perception of male and female voices activates distinct brain regions.

We introduce two independent component analysis (ICA) methods, spatiotemporal ICA (stICA) and skew-ICA, and demonstrate the utility of these methods in analyzing synthetic and event-related fMRI data. First, stICA simultaneously maximizes statistical independence over both time and space. This contrasts with conventional ICA methods, which maximize independence either over time only or over space only; these methods often yield physically improbable solutions. Second, skew-ICA is based on the assumption that images have skewed probability density functions (pdfs), an assumption consistent with spatially localized regions of activity. In contrast, conventional ICA is based on the physiologically unrealistic assumption that images have symmetric pdfs. We combine stICA and skew-ICA, to form skew-stICA, and use it to analyze synthetic data and data from an event-related, left-right visual hemifield fMRI experiment. Results obtained with skew-stICA are superior to those of principal component analysis, spatial ICA (sICA), temporal ICA, stICA, and skew-sICA. We argue that skew-stICA works because it is based on physically realistic assumptions and that the potential of ICA can only be realized if such prior knowledge is incorporated into ICA methods.

Discerning a speaker's gender from their voice is a basic and crucial aspect of human communication. Voice pitch height, the perceptual correlate of fundamental frequency, is higher in females and provides a cue for gender discrimination. However, male and female voices are also differentiated by multiple other spectral and temporal characteristics, including mean formant frequency and spectral flux. The robust perceptual segregation of male and female voices is thought to result from processing the combination of discriminating features, which in neural terms may correspond to early sound object analysis occurring in non-primary auditory cortex. However, the specific mechanism for gender perception has been unclear. Here, using functional magnetic resonance imaging, we show that discrete sites in non-primary auditory cortex are differentially activated by male and female voices, with female voices consistently evoking greater activation in the upper bank of the superior temporal sulcus and posterior superior temporal plane. This finding was observed at the individual subject-level in all 24 subjects. The neural response was highly specific: no auditory regions were more activated by male than female voices. Further, the activation associated with female voices was 1) larger than can be accounted for by a sole effect of fundamental frequency, 2) not due to psychological attribution of female gender and 3) unaffected by listener gender. These results demonstrate that male and female voices are represented as distinct auditory objects in the human brain, with the mechanism for gender discrimination being a gender-dependent activation-level cue in non-primary auditory cortex.

Investigating auditory hallucinations that occur in health may help elucidate brain mechanisms which lead to the pathological experience of auditory hallucinations in neuropsychiatric disorders such as schizophrenia. In this study, we investigated healthy individuals who reported auditory hallucinations whilst falling asleep (hypnagogic hallucinations; HG) and waking up (hypnopompic hallucinations; HP). In an initial behavioural study, we found that subjects with a history of auditory HG/HP hallucinations (n = 26) reported significantly greater subjective sensitivity to environmental sounds than non-hallucinator controls (n = 74). Then, two fMRI experiments were performed. The first examined speech-evoked brain activation in 12 subjects with a history of auditory HG/HP hallucinations and 12 non-hallucinator controls matched for age, gender and IQ. The second fMRI experiment, in the same subjects, probed how brain activation was modulated by auditory attention using a bimodal selective attention paradigm. In the first experiment, the hallucinator group demonstrated significantly greater speech-evoked activation in the left supramarginal gyrus than the control group. In the second experiment, directing attention towards the auditory (vs. visual) modality induced significantly greater activation of the anterior cingulate gyrus in the hallucinator group than in the control group. These results suggest that hallucination proneness is associated with increased sensitivity of auditory and polysensory association cortex to auditory stimulation, an effect which might arise due to enhanced attentional bias from the anterior cingulate gyrus. Our data support the overarching hypothesis that top-down modulation of auditory cortical response characteristics may be a key mechanistic step in the generation of auditory hallucinations.

It is widely accepted that dorsolateral prefrontal cortex (DLPFC) is activated at the time of action generation in humans. However, the previous functional neuroimaging studies that have supported this hypothesis temporally integrated brain dynamics and therefore could not demonstrate when DLPFC underwent activation relative to the emergence of voluntary behavior. Data that are time-locked to the instant of voluntary action execution do not reveal DLPFC activation at that moment. Rather, activated foci are seen at the frontal poles. We investigated this apparent conundrum through three differentially constrained experiments, utilizing functional magnetic resonance imaging to identify those prefrontal areas exhibiting functional change at the moment of spontaneous action execution. We observed profound functional dissociation between anterior and dorsolateral regions, compatible with their involvement at different points during the temporal evolution of action: bilaterally the frontal poles activated at the moment of execution, while simultaneously (and relative to a prior activation state) left DLPFC 'deactivated.'

We used functional magnetic resonance imaging of healthy subjects to investigate the neural basis for spontaneous “willed” action. We hypothesised that such action involves prefrontal cortex (PFC) and supplementary motor area (SMA), in addition to primary motor cortex. Furthermore, we predicted that PFC and SMA would demonstrate similar temporal response dynamics, distinct from primary motor cortex. Specifically, we predicted earlier activation in PFC and SMA, manifest as shorter response latencies compared with primary motor cortex. Six right-handed males participated in an event-related design and were required to generate spontaneous motor acts inside the scanner. By deciding “which” of two buttons to press, and “when” to press them, subjects generated sequences of action that were of high information content (“novelty” or “randomness”). Utilising a short repetition time (1 s), we acquired functional images that covered most of the frontal and parietal cortices. The onset of action was associated with significant activation in bilateral PFC, left primary motor cortex, and, close to the midline, SMA. Following action, mean time to half-maximum blood oxygenation level-dependent response was significantly earlier in left PFC and SMA than primary motor cortex. Our findings suggest that neural correlates of spontaneous willed action are distributed in executive and motor centres, and that temporal response dynamics differentiate “higher” regions from subordinate motor areas.