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Highlights • IL-6 has been associated with poorer facial emotion recognition. • fMRI was performed during a faces task and IL-6 measured from blood samples. • IL-6 predicted increased neural response during facial emotion recognition., Background Deficits in facial emotion recognition are a core feature of schizophrenia and predictive of functional outcome. Higher plasma levels of the cytokine interleukin 6 (IL-6) have recently been associated with poorer facial emotion recognition in individuals with schizophrenia and healthy participants, but the neural mechanisms affected remain poorly understood. Methods Forty-nine individuals with schizophrenia or schizoaffective disorder and 158 healthy participants were imaged using functional magnetic resonance imaging during a dynamic facial emotion recognition task. Plasma IL-6 was measured from blood samples taken outside the scanner. Multiple regression was used in statistical parametric mapping software to test whether higher plasma IL-6 predicted increased neural response during task performance. Results Higher plasma IL-6 predicted increased bilateral medial prefrontal response during neutral face processing compared to angry face processing in the total sample (N = 207, tmax = 5.67) and increased left insula response during angry face processing compared to neutral face processing (N = 207, tmax = 4.40) (p

Highlights • The Brain/MINDS beyond project plans to collect multi-site/scanner brain MRI data. • Prospective harmonization of MRI was achieved by standardizing scanning protocols. • The preliminary data showed moderate reliability of brain connectome data. • Completing traveling subject plan will allow robust statistical harmonization. • Scanning protocols are publicly available and data will also be shared by 2024., Psychiatric and neurological disorders are afflictions of the brain that can affect individuals throughout their lifespan. Many brain magnetic resonance imaging (MRI) studies have been conducted; however, imaging-based biomarkers are not yet well established for diagnostic and therapeutic use. This article describes an outline of the planned study, the Brain/MINDS Beyond human brain MRI project (BMB-HBM, FY2018 ~ FY2023), which aims to establish clinically-relevant imaging biomarkers with multi-site harmonization by collecting data from healthy traveling subjects (TS) at 13 research sites. Collection of data in psychiatric and neurological disorders across the lifespan is also scheduled at 13 sites, whereas designing measurement procedures, developing and analyzing neuroimaging protocols, and databasing are done at three research sites. A high-quality scanning protocol, Harmonization Protocol (HARP), was established for five high-quality 3 T scanners to obtain multimodal brain images including T1 and T2-weighted, resting-state and task functional and diffusion-weighted MRI. Data are preprocessed and analyzed using approaches developed by the Human Connectome Project. Preliminary results in 30 TS demonstrated cortical thickness, myelin, functional connectivity measures are comparable across 5 scanners, suggesting sensitivity to subject-specific connectome. A total of 75 TS and more than two thousand patients with various psychiatric and neurological disorders are scheduled to participate in the project, allowing a mixed model statistical harmonization. The HARP protocols are publicly available online, and all the imaging, demographic and clinical information, harmonizing database will also be made available by 2024. To the best of our knowledge, this is the first project to implement a prospective, multi-level harmonization protocol with multi-site TS data. It explores intractable brain disorders across the lifespan and may help to identify the disease-specific pathophysiology and imaging biomarkers for clinical practice.

Production of actions is highly dependent on concurrent sensory information. In speech production, for example, movement of the articulators is guided by both auditory and somatosensory input. It has been demonstrated in non-human primates that self-produced vocalizations and those of others are differentially processed in the temporal cortex. The aim of the current study was to investigate how auditory and motor responses differ for self-produced and externally produced speech. Using functional neuroimaging, subjects were asked to produce sentences aloud, to silently mouth while listening to a different speaker producing the same sentence, to passively listen to sentences being read aloud, or to read sentences silently. We show that that separate regions of the superior temporal cortex display distinct response profiles to speaking aloud, mouthing while listening, and passive listening. Responses in anterior superior temporal cortices in both hemispheres are greater for passive listening compared with both mouthing while listening, and speaking aloud. This is the first demonstration that articulation, whether or not it has auditory consequences, modulates responses of the dorsolateral temporal cortex. In contrast posterior regions of the superior temporal cortex are recruited during both articulation conditions. In dorsal regions of the posterior superior temporal gyrus, responses to mouthing and reading aloud were equivalent, and in more ventral posterior superior temporal sulcus, responses were greater for reading aloud compared with mouthing while listening. These data demonstrate an anterior–posterior division of superior temporal regions where anterior fields are suppressed during motor output, potentially for the purpose of enhanced detection of the speech of others. We suggest posterior fields are engaged in auditory processing for the guidance of articulation by auditory information., Highlights ► Using neuroimaging, we compare responses to normal speech production and perception. ► Sentences were voiced normally or mouthed silently while concurrently listening. ► Distinct regions of temporal cortex respond to auditory input from different sources. ► Inferior parietal regions are more sensitive to non-self generated auditory input. ► Silent articulation modifies auditory responses in superior temporal gyrus.

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., Highlights • Speech networks are altered in PD patients before they develop speech symptoms. • Hypophonia relates to reduced energization due to reduced striato-prefrontal coupling. • PD patients show signatures of reduced monitoring of auditory feedback. • Dysarthria may result from imprecise shaping of motor representations by feedback. • External therapeutic models help normalizing speech-related neural anomalies.