Corrigendum: Mirror neuron activity during audiovisual appreciation of opera performance.

[This corrects the article DOI: 10.3389/fpsyg.2020.563031.].

Functional connectivity in autism spectrum disorder evaluated using rs-fMRI and DKI.

We evaluated functional connectivity (FC) in patients with adult autism spectrum disorder (ASD) using resting-state functional MRI (rs-fMRI) and diffusion kurtosis imaging (DKI). We acquired rs-fMRI data from 33 individuals with ASD and 33 healthy controls (HC) and DKI data from 18 individuals with ASD and 17 HC. ASD showed attenuated FC between the right frontal pole (FP) and the bilateral temporal fusiform cortex (TFusC) and enhanced FC between the right thalamus and the bilateral inferior division of lateral occipital cortex, and between the cerebellar vermis and the right occipital fusiform gyrus (OFusG) and the right lingual gyrus, compared with HC. ASD demonstrated increased axial kurtosis (AK) and mean kurtosis (MK) in white matter (WM) tracts, including the right anterior corona radiata (ACR), forceps minor (FM), and right superior longitudinal fasciculus (SLF). In ASD, there was also a significant negative correlation between MK and FC between the cerebellar vermis and the right OFusG in the corpus callosum, FM, right SLF and right ACR. Increased DKI metrics might represent neuroinflammation, increased complexity, or disrupted WM tissue integrity that alters long-distance connectivity. Nonetheless, protective or compensating adaptations of inflammation might lead to more abundant glial cells and cytokine activation effectively alleviating the degeneration of neurons, resulting in increased complexity. FC abnormality in ASD observed in rs-fMRI may be attributed to microstructural alterations of the commissural and long-range association tracts in WM as indicated by DKI.

Distorted neurocomputation by a small number of extra-large spines in psychiatric disorders.

Human genetics strongly support the involvement of synaptopathy in psychiatric disorders. However, trans-scale causality linking synapse pathology to behavioral changes is lacking. To address this question, we examined the effects of synaptic inputs on dendrites, cells, and behaviors of mice with knockdown of SETD1A and DISC1, which are validated animal models of schizophrenia. Both models exhibited an overrepresentation of extra-large (XL) synapses, which evoked supralinear dendritic and somatic integration, resulting in increased neuronal firing. The probability of XL spines correlated negatively with working memory, and the optical prevention of XL spine generation restored working memory impairment. Furthermore, XL synapses were more abundant in the postmortem brains of patients with schizophrenia than in those of matched controls. Our findings suggest that working memory performance, a pivotal aspect of psychiatric symptoms, is shaped by distorted dendritic and somatic integration via XL spines.

Development of Connective Tissue Area Increases by Initial Impact With High-Intensity Exercise After Reloading in Rat Soleus Muscle.

OBJECTIVE: The aim of the study is to clarify whether high-intensity exercise in atrophied skeletal muscle after reloading (1) increases the injury and promotes the development of the muscle connective tissue area in the soleus muscle and (2) delays muscle strength recovery. DESIGN: Rats had their hindlimbs suspended for 14 days followed by hindlimb reloading and squat exercise of 30% or 70%-one-repetition maximum exercise until 14 days of reloading. The influences of reloading and exercise in muscles were examined by histological and immunofluorescence analyses based on the exercise load. RESULTS: Seventy percent-one-repetition maximum exercise increased the extramyofiber area more than the control group and the central nuclear fiber number than the other groups after 7 days of reloading. Seventy percent-one-repetition maximum exercise resulted in a larger muscle connective tissue area than the control and reload groups after 14 days of reloading. Myogenin and M2-type macrophages after 7 days of reloading increased by reloading but were not increased by the exercise load. CONCLUSIONS: Seventy percent-one-repetition maximum exercise to atrophied muscle increased injury early in postreloading and increased the muscle connective tissue area after 14 days of reloading, but evidence that it delays muscle strength recovery was lacking. Therefore, muscle connective tissue area induced by high-intensity exercise after reloading seems to be associated with initial exercise damage but not with repetition over 14 days.

Right-Lateralized Enhancement of the Auditory Cortical Network During Imagined Music Performance.

Although the primary role of the auditory cortical areas is to process actual sounds, these areas are also activated by tasks that process imagined music, suggesting that the auditory cortical areas are involved in the processes underlying musical imagery. However, the mechanism by which these areas are involved in such processes is unknown. To elucidate this feature of the auditory cortical areas, we analyzed their functional networks during imagined music performance in comparison with those in the resting condition. While imagined music performance does not produce any musical sounds, the participants heard the same actual sounds from the MRI equipment in both experimental conditions. Therefore, if the functional connectivity between these conditions differs significantly, one can infer that the auditory cortical areas are actively involved in imagined music performance. Our functional connectivity analysis revealed a significant enhancement in the auditory network during imagined music performance relative to the resting condition. The reconfiguration profile of the auditory network showed a clear right-lateralized increase in the connectivity of the auditory cortical areas with brain regions associated with cognitive, memory, and emotional information processing. On the basis of these results, we hypothesize that auditory cortical areas and their networks are actively involved in imagined music performance through the integration of auditory imagery into mental imagery associated with music performance.

Effects of long-term treatment with dietary theobromine on rat skeletal muscles.

BACKGROUND: Plastic changes of skeletal muscles, such as hypertrophy and atrophy, are dependent on physiological activities and regulated by a variety of signaling pathways, including cyclic adenosine monophosphate (cAMP) pathway. The cAMP inducing agents, such as the ß2-adrenergic agonist clenbuterol, are known to induce muscle hypertrophy, and has been reported to induce slow-to-fast transitions in rat soleus muscle. Theobromine, one of the active components of cacao, functions as an inhibitor of phosphodiesterase and increases cAMP. This study hypothesized that theobromine, like clenbuterol, can induce muscle hypertrophy and influence contractile properties. METHODS AND RESULTS: Male Wistar rats were fed a normal diet or a diet containing 0.05% theobromine for 20 weeks. Using biochemical, anatomical, and physiological techniques, effects of dietary theobromine on skeletal muscles (soleus, extensor digitorum longus, plantaris, and gastrocnemius) were examined. There were no significant differences in body weight, serum levels of proteins and lipids, muscle weights, dry/wet ratio of muscle weights, mitochondrial oxidation enzyme activity of muscles, isometric contractile properties of muscles, and muscle fatigue between control and theobromine-fed rats. Quantitative analysis of mRNA, however, revealed upregulation of myosin heavy chain 2x and myogenic differentiation 1, as previously reported in clenbuterol-treated muscles. CONCLUSION: The long-term theobromine (0.05%) diet in rats had no effect in inducing muscle hypertrophy and in changing contractile properties, although it had some similar effects of clenbuterol on muscle gene expression.

The Precuneus Contributes to Embodied Scene Construction for Singing in an Opera.

Performing an opera requires singers on stage to process mental imagery and theory of mind tasks in conjunction with singing and action control. Although it is conceivable that the precuneus, as a posterior hub of the default mode network, plays an important role in opera performance, how the precuneus contributes to opera performance has not been elucidated yet. In this study, we aimed to investigate the contribution of the precuneus to singing in an opera. Since the precuneus processes mental scenes, which are multimodal and integrative, we hypothesized that it is involved in opera performance by integrating multimodal information required for performing a character in an opera. We tested this hypothesis by analyzing the functional connectivity of the precuneus during imagined singing and rest. This study included 42 opera singers who underwent functional magnetic resonance imaging when performing "imagined operatic singing" with their eyes closed. During imagined singing, the precuneus showed increased functional connectivity with brain regions related to language, mirror neuron, socio-cognitive/emotional, and reward processing. Our findings suggest that, with the aid of its widespread connectivity, the precuneus and its network allow embodiment and multimodal integration of mental scenes. This information processing is necessary for imagined singing as well as performing an opera. We propose a novel role of the precuneus in opera performance.

Blood lipid profile changes in type 2 diabetic rats after tail suspension and reloading.

PURPOSE: The effects of the tail suspension and reloading on the protein and lipid metabolism in muscle and blood in type 2 diabetes mellitus (T2DM) are unclear. This study evaluated the hypothesis that skeletal muscle catabolism is greater in T2DM than in non-diabetes mellitus (non-DM) rats and that the activity-dependent changes in the intramuscular lipid accumulation and blood lipid profile are poorer in T2DM than in non-DM rats. METHODS: T2DM and non-DM rats were suspended for two weeks followed by reloading for two weeks. The muscle and blood were then examined. RESULTS: In contrast to our hypothesis, there was no marked difference between the T2DM and non-DM groups in terms of the skeletal muscle catabolism and activity-dependent changes in intramuscular lipid accumulation. However, the blood lipid profile increased in the T2DM group compared to the non-DM group. One interesting finding in this study was the decrease in non-high-density lipoprotein (non-HDL) cholesterol levels after one week of reloading followed by a significant increase in the non-HDL cholesterol levels after two weeks of reloading in the T2DM group. CONCLUSION: These results suggest that a dramatic increase in activity after a period of inactivity may rapidly improve the blood lipid profile in T2DM rats.

Corrigendum: Increased Functional Connectivity of the Angular Gyrus During Imagined Music Performance.

[This corrects the article DOI: 10.3389/fnhum.2019.00092.].

Fast repetitive stretch suppresses denervation-induced muscle fibrosis.

BACKGROUND: We aimed to examine the influence of different speeds of stretching on denervation-induced skeletal muscle fibrosis. METHODS: Stretching was passively applied to rat plantaris muscle denervated by sciatic nerve excision in three different cycles of 0.5, 3, or 12 cycles/min, for 20 min/d for 2 weeks. RESULTS: Gene analysis results showed greater expression of fibrosis-related factors with fast stretching compared with non-stretched muscle. Laser Doppler blood flow analysis indicated reduced intramuscular blood flow during stretching. Histological analysis demonstrated fibrotic area decreases in 12 cycles/min stretched muscle compared with non-stretched muscle. CONCLUSIONS: Slower stretching induced greater mRNA expression of collagen and fibroblasts and greater decrement of blood flow. Histologically, faster stretching suppressed fibrosis. These results suggest that fast repetitive stretching of denervated muscle might suppress processes of muscle fibrosis.

Music Intervention Reduces Persistent Fibromyalgia Pain and Alters Functional Connectivity Between the Insula and Default Mode Network.

OBJECTIVE: The aims of the present study were to examine the effects of short-term music interventions among patients with fibromyalgia (FM) and to clarify the alterations in functional connectivity and persistent pain. DESIGN: Pilot study. SETTING: All participants were evaluated at Juntendo University from November 2017 to January 2019. SUBJECTS: We enrolled female patients who had been clinically diagnosed with FM (N = 23). METHODS: All participants listened to Mozart's Duo for Violin and Viola No. 1, K. 423, in a quiet room for 17 minutes. We compared the degree of pain using resting-state functional magnetic resonance imaging and the numeric rating scale before and after listening to music. RESULTS: Pain scores were significantly reduced after listening to music. Further, we observed there was a significant difference in connectivity between the right insular cortex (IC) and posterior cingulate cortex (PCC)/precuneus (PCu) before and after listening to music. We also found that the difference between the right IC-PCu connectivity and the difference in pain scores were significantly correlated. CONCLUSIONS: We found that a short period of music intervention reduced chronic pain and altered functional IC-default mode network connectivity. Furthermore, music potentially normalized the neural network via IC-default mode network connectivity, yielding temporary pain relief in patients with FM. Further longitudinal studies with larger sample sizes are required to confirm these results.

Mirror Neuron Activity During Audiovisual Appreciation of Opera Performance.

Opera is a performing art in which music plays the leading role, and the acting of singers has a synergistic effect with the music. The mirror neuron system represents the neurophysiological mechanism underlying the coupling of perception and action. Mirror neuron activity is modulated by the appropriateness of actions and clarity of intentions, as well as emotional expression and aesthetic values. Therefore, it would be reasonable to assume that an opera performance induces mirror neuron activity in the audience so that the performer effectively shares an embodied performance with the audience. However, it is uncertain which aspect of opera performance induces mirror neuron activity. It is hypothesized that although auditory stimuli could induce mirror neuron activity, audiovisual perception of stage performance is the primary inducer of mirror neuron activity. To test this hypothesis, this study sought to correlate opera performance with brain activity as measured by electroencephalography (EEG) in singers while watching an opera performance with sounds or while listening to an aria without visual stimulus. We detected mirror neuron activity by observing that the EEG power in the alpha frequency band (8-13 Hz) was selectively decreased in the frontal-central-parietal area when watching an opera performance. In the auditory condition, however, the alpha-band power did not change relative to the resting condition. This study illustrates that the audiovisual perception of an opera performance engages the mirror neuron system in its audience.

[Brain as a Dynamical System].

This article aims at understanding the essential dynamical characteristics of the brain by modeling the brain as a simplified dynamical control system. Although the brain is a highly complex system, such a simplified model provides us insights into its essential features. Using a control system model, the first half of this article describes the dynamics of a system comprising the dorsolateral prefrontal cortex and striatum with dopaminergic modulation and argue its relevance to the functions of the brain with schizophrenia. The second half of this article introduces a model-based analysis of molecular imaging data.

White matter alterations in adult with autism spectrum disorder evaluated using diffusion kurtosis imaging.

PURPOSE: Autism spectrum disorder (ASD) is related to impairment in various white matter (WM) pathways. Utility of the recently developed two-compartment model of diffusion kurtosis imaging (DKI) to analyse axial diffusivity of WM is restricted by several limitations. The present study aims to validate the utility of model-free DKI in the evaluation of WM alterations in ASD and analyse the potential relationship between DKI-evident WM alterations and personality scales. METHODS: Overall, 15 participants with ASD and 15 neurotypical (NT) controls were scanned on a 3 T magnetic resonance (MR) scanner, and scores for autism quotient (AQ), systemising quotient (SQ) and empathising quotient (EQ) were obtained for both groups. Multishell diffusion-weighted MR data were acquired using two b-values (1000 and 2000 s/mm2). Differences in mean kurtosis (MK), radial kurtosis (RK) and axial kurtosis (AK) between the groups were evaluated using tract-based spatial statistics (TBSS). Finally, the relationships between the kurtosis indices and personality quotients were examined. RESULTS: The ASD group demonstrated significantly lower AK in the body and splenium of corpus callosum than the NT group; however, no other significant differences were identified. Negative correlations were found between AK and AQ or SQ, predominantly in WM areas related to social-emotional processing such as uncinate fasciculus, inferior fronto-occipital fasciculus, and inferior and superior longitudinal fasciculi. CONCLUSIONS: Model-free DKI and its indices may represent a novel, objective method for detecting the disease severity and WM alterations in patients with ASD.

Highly Planar and Completely Insulated Oligothiophenes: Effects of π-Conjugation on Hopping Charge Transport.

Elucidating the nature of long-range intramolecular charge transport in π-conjugated molecules is of great importance for the development of organic electronic materials. However, the effects of the degree of π-conjugation on the hopping charge transport have not been experimentally explored so far owing to the lack of π-conjugated backbones with different conjugation degrees and several-nanometer lengths. Here we develop highly planar and completely insulated oligothiophenes between 0.85 and 9.64 nm in length. As compared to distorted oligothiophenes, single-molecule conductance measurements of the planar molecules show (i) a smaller activation energy and larger electrical conductance in the hopping transport regime and (ii) a shift in crossover between tunneling and hopping conduction toward a short molecular length. Theoretical calculations indicate that small reorganization energies and narrow energy gaps derived from the planar backbones result in these superior characteristics. This study reveals that the planarity of π-conjugation has significant advantages for hopping charge transport.

Increased Functional Connectivity of the Angular Gyrus During Imagined Music Performance.

The angular gyrus (AG) is a hub of several networks that are involved in various functions, including attention, self-processing, semantic information processing, emotion regulation, and mentalizing. Since these functions are required in music performance, it is likely that the AG plays a role in music performance. Considering that these functions emerge as network properties, this study analyzed the functional connectivity of the AG during the imagined music performance task and the resting condition. Our hypothesis was that the functional connectivity of the AG is modulated by imagined music performance. In the resting condition, the AG had connections with the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and precuneus as well as the superior and inferior frontal gyri and with the temporal cortex. Compared with the resting condition, imagined music performance increased the functional connectivity of the AG with the superior frontal gyrus (SFG), mPFC, precuneus, PCC, hippocampal/parahippocampal gyrus (H/PHG), and amygdala. The anterior cingulate cortex (ACC) and superior temporal gyrus (STG) were newly engaged or added to the AG network during the task. In contrast, the supplementary motor area (SMA), sensorimotor areas, and occipital regions, which were anti-correlated with the AG in the resting condition, were disengaged during the task. These results lead to the conclusion that the functional connectivity of the AG is modulated by imagined music performance, which suggests that the AG plays a role in imagined music performance.

Functional Connectivity of the Caudate in Schizophrenia Evaluated with Simultaneous Resting-State Functional MRI and Electroencephalography Recordings.

BACKGROUND: Aberrant functional connectivity (FC) is increasingly implicated in the clinical phenomenology of schizophrenia. This study focused on the FC of the cortico-striatal network, which is thought to be disrupted in schizophrenia and to contribute to its clinical manifestations. METHODS: We used simultaneous resting-state functional magnetic resonance imaging (rsfMRI) and electroencephalography (EEG) recordings to investigate FC in patients with schizophrenia. The study included 20 patients with schizophrenia and 20 healthy controls (HCs). Simultaneously recorded rsfMRI and EEG data were collected with an MR-compatible amplifier, and rsfMRI data were analyzed with the CONN toolbox to calculate FC. The study focused on the caudate, which was defined as the seed. We also performed between-group comparisons of standardized low-resolution electromagnetic tomography intracortical lagged coherence for each EEG frequency band. RESULTS: Compared to HCs, patients with schizophrenia showed enhanced FC between the caudate nucleus and the posterior cingulate cortex, temporal, and occipital regions on rsfMRI. It is thus possible that HCs have negative FC between these regions, whereas patients with schizophrenia have non-negative FC. The EEG results showed no significant differences in oscillations or in FC between the groups in any frequency band in any region. CONCLUSIONS: Increased FC in the caudate may represent aberrant between-network FC resulting from the disruption of segregation between networks.

Mechanistic insights from sequential combination therapy with a sodium glucose co-transporter-2 inhibitor and a dipeptidyl peptidase-4 inhibitor: Results from the CANARIS Trial using canagliflozin and teneligliptin.

AIM: To elucidate the mechanisms involved in the sequential use of SGLT2 and DPP4 inhibitors (SGLT2i and DPP-4i). METHODS: Twenty-six type-2 diabetes mellitus patients were recruited into a stepped regimen of 100 mg of canagliflozin daily from day 1, supplemented with 20 mg of teneligliptin daily from day 4. Glucose (Glu), insulin and glucagon were measured at fasting and after ingesting a mixed meal on days 1, 4 and 6. RESULTS: Canagliflozin decreased fasting plasma glucose to an extent inversely proportional to the change in the glucagon-to-insulin (G/I) ratio. This correlation at fasting was maintained when adding teneligliptin, while the change in the area under the curve of Glu (GluAUC) correlated closely with that in the G/I ratio at fasting and 60 min with canagliflozin. Moreover, these correlations persisted at 60 and 120 min postprandially, but not at fasting on day 6 when teneligliptin was added. CONCLUSION: The result suggested that the dominant mechanism responsible for the glucose metabolism reflected in the G/I ratio was attributable to SGLT2i and that its active mechanism persisted, despite adding a DPP-4i.

Effect of moderate exercise intensities on the cortical activity in young adults.

[Purpose] To examine the influence of different exercise intensities on cortical activity. [Participants and Methods] Twenty-six healthy adults aged 20-30 years performed exercise at three intensities on a bicycle ergometer as follows: (a) 15-minute exercise at 40% peak oxygen uptake, (b) same as (a) but at 60% peak oxygen uptake, and (c) 15 minutes of rest. The cognitive function of the participants was measured before and after exercise by the Paced Auditory Serial Addition Test (PASAT) under these three conditions. The cerebral blood flow in the left prefrontal and temporal cortices was measured using near-infrared spectroscopy during the PASAT. [Results] The PASAT score was significantly higher after exercise under condition (b) than before exercise (41.4 ± 9.1 vs. 47.7 ± 8.3). The cerebral blood flow in the prefrontal cortex under condition (b) was significantly increased compared to that under condition (c), as determined by the Tukey method (0.019 ± 0.030 vs. -0.008 ± 0.044). Significant differences were not observed in the cerebral blood flow in the temporal cortex under these three conditions. [Conclusion] Cortical activation of the frontal lobe increased after high-intensity aerobic exercise with no change in the cortical activity of the temporal lobe.

Effect of hindlimb unloading and reloading on the soleus and plantaris muscles in diabetic rats.

[Purpose] This study aimed to induce disuse muscle atrophy in Goto-Kakizaki rats, a type 2 diabetes model, to investigate the effects of reloading on the soleus and plantaris muscles. [Materials and Methods] Wistar and Goto-Kakizaki (GK) rats were divided into 6 groups: Wistar Control (WC), GK Control (GC), Wistar Tail suspension (WS), GK Tail suspension (GS), and Wistar Reload (WR), GK Reload (GR). [Results] Investigation of myofiber cross-sectional area in Goto-Kakizaki rat soleus muscles indicated that the GS group showed significantly lower values than the GC and GR groups. No significant differences were observed between the GC and GR groups. However, investigation of plantaris muscles in Goto-Kakizaki rats indicated that the GS and GR groups showed a significant decrease compared to the GC group. No significant differences were found between the GS and GR groups. [Conclusion] Investigation of muscle weight/body weight ratios and myofiber cross-sectional area in tail suspension groups confirmed the induction of muscular atrophy. The differences in the degree of atrophy and recovery in terms of myofiber cross-sectional area observed in Goto-Kakizaki rat plantaris muscles may be influenced by the myofiber type and diabetes.