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Background: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied.Methods: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes).Results: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities.Limitations: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results.Conclusions: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective. [ABSTRACT FROM AUTHOR]

In order to better understand the descending voluntary vocal control pathway, the efferent subcortical projections of the laryngeal motorcortex were studied in the rhesus monkey (Macaca mulatta). For this purpose, the left motorcortex was exposed in three animals under narcosis. By electrical brain stimulation, sites were identified yielding vocal fold adduction. Effective sites were injected with the anterograde tracer biotin dextran amine. Subcortical projections could be traced within the forebrain to the putamen, caudate nucleus, claustrum, zona incerta, field H of Forel and a number of thalamic nuclei, with the heaviest projections to the nuclei ventralis lateralis, ventralis posteromedialis, including its parvocellular part, medialis dorsalis, centralis medialis, centrum medianum and reuniens. In the midbrain, labeling was found in the deep mesencephalic nucleus. In the lower brainstem, fibers terminated in the pontine and medullary reticular formation, locus coeruleus, nucleus subcoeruleus, medial parabrachial nucleus, nucleus of the spinal trigeminal tract, solitary tract nucleus and facial nucleus. No projections were found to the nucl. ambiguus. The fact that monkeys, in contrast to humans, lack a direct connection of the motorcortex with the laryngeal motoneurons suggests that this connection has evolved in the last few million years and might represent one of the factors that made speech evolution possible. [Copyright &y& Elsevier]

Behavioral studies have provided evidence that the processing of a musical target is faster and more accurate when it is harmonically related to the preceding prime context. We investigated the neural correlates of processing related and unrelated musical targets that were presented at the end of musical sequences. Participants were scanned with functional magnetic resonance imaging (fMRI) while performing speeded intonation judgments (consonant versus dissonant) on the target chords. Behavioral results acquired in the scanner replicated the facilitation effect of related over unrelated consonant targets. The overall activation pattern associated with target processing showed commonalities with networks previously described for target detection and novelty processing. The blood oxygen level-dependent (BOLD) signal linked to target processing revealed activation of bilateral inferior frontal regions (i.e. inferior frontal gyrus, frontal operculum, insula) that was stronger for unrelated than for related targets. We discuss our results with regard to the role of these areas in the processing and integration of temporal information. [Copyright &y& Elsevier]

Applying whole-head functional magnetic resonance imaging (fMRI) in 11 neurologically intact subjects, hemodynamic responses to mon- or binaurally presented auditory stimuli were measured. To expand on previous studies in this research area, we used tones and consonant–vowel (CV) syllables. In one group of subjects (n=6) the perceived loudness of the monaurally presented stimuli were adjusted so that they matched the loudness of the binaurally presented stimuli. In a second group (n=5) no loudness adjustment was performed, thus the monaural stimuli were perceived less loud (∼10 dB) than the binaural stimuli. These extensions allowed us to test whether CV syllables and tones produce different contralaterality effects (stronger hemodynamic responses in the auditory cortex contralateral to the stimulated ear) and whether binaural stimulation results in stronger activations in the auditory areas than during both monaural stimulation conditions (binaural summation) independent of loudness influences. In summary, we obtained the following findings: (1) strong contralaterality effects during monaural acoustic stimulation in the posterior superior temporal gyrus (STG) comprising the planum temporale and the dorsal bank of the superior temporal sulcus to CV syllables and tones; (2) the hemodynamic responses to contralaterally presented stimuli (during the monaural conditions) were mostly stronger than those to binaurally presented CV syllables; (3) there was no interaction between stimulus type and the size of the contralaterality effect; (4) there was no indication of binaural summation, rather we found stronger hemodynamic responses to the sum of both monaural stimulations (right and left ear) than to binaural stimulation in all auditory areas; (5) there were generally stronger hemodynamic responses to CV syllables than to tones in the posterior STG, while the hemodynamic responses to tones were stronger in the anterior part of the STG (temporal pole); and finally (6) there was no general difference in terms of hemodynamic response in the auditory cortex between the two groups when receiving either loudness-matched or non-loudness-matched monaural stimulation. These findings are discussed in the context of the underlying neurophysiological mechanisms, the peculiarities of functional fMRI, and the direct access and callosal relay models of hemispheric lateralization. [Copyright &y& Elsevier]

Positron emission tomography imaging was used to investigate the brain activation patterns of listeners presented monaurally (right ear) with speech and nonspeech stimuli. The major objectives were to identify regions involved with speech and nonspeech processing, and to develop a stimulus paradigm suitable for studies of cochlear-implant subjects. Scans were acquired under a silent condition and stimulus conditions that required listeners to press a response button to repeated words, sentences, time-reversed (TR) words, or TR sentences. Group-averaged data showed activated foci in the posterior superior temporal gyrus (STG) bilaterally and in or near the anterior insula/frontal operculum across all stimulus conditions compared to silence. The anterior STG was activated bilaterally for speech signals, but only on the right side for TR sentences. Only nonspeech conditions showed frontal-lobe activation in both the left inferior frontal gyrus [Brodmann’s area (BA) 47] and ventromedial prefrontal areas (BA 10/11). An STG focus near the superior temporal sulcus was observed for sentence compared to word. The present findings show that both speech and nonspeech engaged a distributed network in temporal cortex for early acoustic and prelexical phonological analysis. Yet backward speech, though lacking semantic content, is perceived as speechlike by engaging prefrontal regions implicated in lexico-semantic processing. [Copyright &y& Elsevier]

Voice and speech in Parkinson's disease (PD) patients are classically affected by a hypophonia, dysprosody, and dysarthria. The underlying pathomechanisms of these disabling symptoms are not well understood. To identify functional anomalies related to pathophysiology and compensation we compared speech-related brain activity and effective connectivity in early PD patients who did not yet develop voice or speech symptoms and matched controls. During fMRI 20 PD patients ON and OFF levodopa and 20 control participants read 75 sentences covertly, overtly with neutral, or with happy intonation. A cue-target reading paradigm allowed for dissociating task preparation from execution. We found pathologically reduced striato-prefrontal preparatory effective connectivity in early PD patients associated with subcortical (OFF state) or cortical (ON state) compensatory networks. While speaking, PD patients showed signs of diminished monitoring of external auditory feedback. During generation of affective prosody, a reduced functional coupling between the ventral and dorsal striatum was observed. Our results suggest three pathomechanisms affecting speech in PD: While diminished energization on the basis of striato-prefrontal hypo-connectivity together with dysfunctional self-monitoring mechanisms could underlie hypophonia, dysarthria may result from fading speech motor representations given that they are not sufficiently well updated by external auditory feedback. A pathological interplay between the limbic and sensorimotor striatum could interfere with affective modulation of speech routines, which affects emotional prosody generation. However, early PD patients show compensatory mechanisms that could help improve future speech therapies.