The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body.

Spatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of intero-exteroceptive information integration to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of the self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0°, 90°, and 270° relative to the upright orientation, and when the front view was presented rather than the back view. Reflecting the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC), suggesting that the activation reflects the involvement of an embodied simulation in ALJ. Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants' interoceptive sensitivity, as assessed through the heartbeat discrimination task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues to spatially transform the image of our self-body.

Bodily maps of uncertainty and surprise in musical chord progression and the underlying emotional response.

Music has profoundly shaped the human experience across cultures and generations, yet its impact on our minds and bodies remains elusive. This study examined how the perception of musical chord elicits bodily sensations and emotions through the brain's predictive processing. By deploying body-mapping tests and emotional evaluations on 527 participants exposed to chord progressions, we unveiled the intricate interplay between musical uncertainty, prediction error in eliciting specific bodily sensations and emotions. Our results demonstrated that certain chord progressions elicit cardiac and abdominal sensations, linked to interoception, and associated with aesthetic appreciation and positive valence. These findings highlight the crucial role of musical uncertainty and prediction error in emotional response and sound embodiment. This study offers insight into the potential connection between music-induced interoception and mental well-being, underscoring the musical effects on our minds and bodies.

Magnetoencephalographic detection of synchronized epileptic activity between the hippocampus and insular cortex.

Most magnetoencephalographic signals are derived from synchronized activity in the brain surface cortex. By contrast, the contribution of synchronized activity in the deep brain to magnetoencephalography (MEG) has remained unclear. We compared stereotactic electroencephalography (sEEG) with simultaneous MEG findings in a patient with temporal lobe epilepsy to determine the conditions under which MEG could also detect sEEG findings. The synchrony and similarity of the waves were evaluated using visual inspection and wavelet coherence. A 45-year-old woman with intractable temporal lobe epilepsy underwent sEEG and MEG simultaneously to determine the laterality and precise location of the epileptic focus. When spike-and-waves were seen in the right hippocampal head alone, no distinct spike-and-waves were observed visually in the right temporal MEG. The seizure then spread to the right insula on sEEG with a rhythmic theta frequency while synchronous activity was observed in the right temporal MEG channels. When polyspikes appeared in the right hippocampus, the right temporal MEG showed electrical activity with relatively high similarity to that of the right hippocampal head and insular cortex but less similarity to that of the right lateral temporal lobe cortex. MEG might detect epileptic activity synchronized between the hippocampus and insular cortex.

Clinical effects of online cognitive behavioral group therapy for chronic pain patients and developing a therapeutic alliance: A pre-post pilot trial.

Background and Aims: Research suggests that various psychosocial factors influence chronic pain, with psychotherapies like cognitive behavioral therapy  proving effective. However, the limited availability and accessibility have prolonged suffering among patients with chronic pain. This challenge has led to a growing demand for accessible online interventions. We developed an online cognitive behavioral group therapy (CBGT) program, building upon our existing face-to-face CBGT program. We compared the scores obtained by patients during the treatment-as-usual (TAU) period with those collected at the beginning and at the end of the intervention. Methods: Patients with chronic pain (N = 22) agreed to participate in the online CBGT program, which was conducted once a week for 12 sessions. The sample size was decided based on the effect sizes of our past face-to-face CBGT. We assessed pain intensity [Visual Analogue Scale (VAS)], pain catastrophizing [pain catastrophizing scale (PCS)] and psychiatric assessment [Beck Depression Inventory-Second Edition (BDI)-II], State-Trait-Anxiety Inventory (STAI), and Short Form Health Survey (SF-36) at three points: entry, pretreatment, and posttreatment. We also evaluated the participants' therapeutic alliance with the treatment staff [short-form version of the Working Alliance Inventory (WAI-S)]. We utilized analyses of variance, Friedman test, paired t-tests, Wilcoxon signed-rank test, and Pearson correlation analysis for data evaluation. Results: Results indicated a significant posttreatment improvement in VAS, PCS, and BDI-II scores compared to the TAU period. Furthermore, posttreatment WAI-S scores increased significantly compared to pretreatment scores. Also, positive correlations were observed among pre- and posttreatment changes in WAI-S, pain intensity, and pain catastrophizing scores. Conclusion: There is a possibility that a therapeutic alliance can be established, and therapeutic effects achieved through an online CBGT intervention; however, additional research is required to substantiate this potential. We have registered this clinical trial in UMIN-CTR on 04/21/2021 with the number UMIN000043982.

Changes in Resting-State Brain Activity After Cognitive Behavioral Therapy for Chronic Pain: A Magnetoencephalography Study.

Cognitive behavioral therapy (CBT) is believed to be an effective treatment for chronic pain due to its association with cognitive and emotional factors. Nevertheless, there is a paucity of magnetoencephalography (MEG) investigations elucidating its underlying mechanisms. This study investigated the neurophysiological effects of CBT employing MEG and analytical techniques. We administered resting-state MEG scans to 30 patients with chronic pain and 31 age-matched healthy controls. Patients engaged in a 12-session group CBT program. We conducted pretreatment (T1) and post-treatment (T2) MEG and clinical assessments. MEG data were examined within predefined regions of interest, guided by the authors' and others' prior magnetic resonance imaging studies. Initially, we selected regions displaying significant changes in power spectral density and multiscale entropy between patients at T1 and healthy controls. Then, we examined the changes within these regions after conducting CBT. Furthermore, we applied support vector machine analysis to MEG data to assess the potential for classifying treatment effects. We observed normalization of power in the gamma2 band (61-90 Hz) within the right inferior frontal gyrus (IFG) and multiscale entropy within the right dorsolateral prefrontal cortex (DLPFC) of patients with chronic pain after CBT. Notably, changes in pain intensity before and after CBT positively correlated with the alterations of multiscale entropy. Importantly, responders predicted by the support vector machine classifier had significantly higher treatment improvement rates than nonresponders. These findings underscore the pivotal role of the right IFG and DLPFC in ameliorating pain intensity through CBT. Further accumulation of evidence is essential for future applications. PERSPECTIVE: We conducted MEG scans on 30 patients with chronic pain before and after a CBT program, comparing results with 31 healthy individuals. There were CBT-related changes in the right IFG and DLPFC. These results highlight the importance of specific brain regions in pain reduction through CBT.

Insula-cortico-subcortical networks predict interoceptive awareness and stress resilience.

BACKGROUND: Interoception, the neural sensing of visceral signals, and interoceptive awareness (IA), the conscious perception of interoception, are crucial for life survival functions and mental health. Resilience, the capacity to overcome adversity, has been associated with reduced interoceptive disturbances. Here, we sought evidence for our Insula Modular Active Control (IMAC) model that suggest that the insula, a brain region specialized in the processing of interoceptive information, realizes IA and contributes to resilience and mental health via cortico-subcortical connections. METHODS: 64 healthy participants (32 females; ages 18-34 years) answered questionnaires that assess IA and resilience. Mental health was evaluated with the Beck Depression Inventory II that assesses depressive mood. Participants also underwent a 15 minute resting-state functional resonance imaging session. Pearson correlations and mediation analyses were used to investigate the relationship between IA and resilience and their contributions to depressive mood. We then performed insula seed-based functional connectivity analyzes to identify insula networks involved in IA, resilience and depressive mood. RESULTS: We first demonstrated that resilience mediates the relationship between IA and depressive mood. Second, shared and distinct intra-insula, insula-cortical and insula-subcortical networks were associated with IA, resilience and also predicted the degree of experienced depressive mood. Third, while resilience was associated with stronger insula-precuneus, insula-cerebellum and insula-prefrontal networks, IA was linked with stronger intra-insula, insula-striatum and insula-motor networks. CONCLUSIONS: Our findings help understand the roles of insula-cortico-subcortical networks in IA and resilience. These results also highlight the potential use of insula networks as biomarkers for depression prediction.

Assessment on interoceptive awareness on alcohol use and gambling disorders reveals dissociable interoceptive abilities linked to external and internal dependencies: Practical use of Body Perception Questionnaire Very Short Form (BPQ-VSF) in clinical settings.

Interoception is one of the pivotal cognitive functions for mechanisms of our body awareness, and malfunction of the interoceptive network is thought to be associated with mental illness, including addiction. Within addictive disorders, substance-based and non-substance-based addictions are known to hold dissociable reward systems. However, little is known about how interoceptive awareness between these addiction sub-types would differ. Subjective interoceptive awareness was assessed among patients with alcohol use disorder (n = 50) who were subsequently hospitalized or remained out-patient and gambling addiction (n = 41) by the Body Awareness component of the Japanese version of the Body Perception Questionnaire (BPQ-VSFBA-J) and compared them against healthy control (n = 809). Both addiction groups showed significantly lower BPQ than the control, with no substantial differences between inpatients and outpatients for alcohol samples. Notably, BPQ scores for gambling patients were significantly lower than those for the alcohol group. This evidence may suggest a putative role of interoceptive ability on the severity of behavioral addiction over substance-based addiction.

Insula neuroanatomical networks predict interoceptive awareness.

Interoceptive awareness (IA), the subjective and conscious perception of visceral and physiological signals from the body, has been associated with functions of cortical and subcortical neural systems involved in emotion control, mood and anxiety disorders. We recently hypothesized that IA and its contributions to mental health are realized by a brain interoception network (BIN) linking brain regions that receive ascending interoceptive information from the brainstem, such as the amygdala, insula and anterior cingulate cortex (ACC). However, little evidence exists to support this hypothesis. In order to test this hypothesis, we used a publicly available dataset that contained both anatomical neuroimaging data and an objective measure of IA assessed with a heartbeat detection task. Whole-brain Voxel-Based Morphometry (VBM) was used to investigate the association of IA with gray matter volume (GMV) and the structural covariance network (SCN) of the amygdala, insula and ACC. The relationship between IA and mental health was investigated with questionnaires that assessed depressive symptoms and anxiety. We found a positive correlation between IA and state anxiety, but not with depressive symptoms. In the VBM analysis, only the GMV of the left anterior insula showed a positive association with IA. A similar association was observed between the parcellated GMV of the left dorsal agranular insula, located in the anterior insula, and IA. The SCN linking the right dorsal agranular insula with the left dorsal agranular insula and left hyper-granular insula were positively correlated with IA. No association between GMV or SCN and depressive symptoms or anxiety were observed. These findings revealed a previously unknown association between IA, insula volume and intra-insula SCNs. These results may support development of non-invasive neuroimaging interventions, e.g., neurofeedback, seeking to improve IA and to prevent development of mental health problems, such anxiety disorders.

The neuroanatomy of social trust predicts depression vulnerability.

Trust attitude is a social personality trait linked with the estimation of others' trustworthiness. Trusting others, however, can have substantial negative effects on mental health, such as the development of depression. Despite significant progress in understanding the neurobiology of trust, whether the neuroanatomy of trust is linked with depression vulnerability remains unknown. To investigate a link between the neuroanatomy of trust and depression vulnerability, we assessed trust and depressive symptoms and employed neuroimaging to acquire brain structure data of healthy participants. A high depressive symptom score was used as an indicator of depression vulnerability. The neuroanatomical results observed with the healthy sample were validated in a sample of clinically diagnosed depressive patients. We found significantly higher depressive symptoms among low trusters than among high trusters. Neuroanatomically, low trusters and depressive patients showed similar volume reduction in brain regions implicated in social cognition, including the dorsolateral prefrontal cortex (DLPFC), dorsomedial PFC, posterior cingulate, precuneus, and angular gyrus. Furthermore, the reduced volume of the DLPFC and precuneus mediated the relationship between trust and depressive symptoms. These findings contribute to understanding social- and neural-markers of depression vulnerability and may inform the development of social interventions to prevent pathological depression.

[Vagus Nerve Stimulation for Depression].

Vagus nerve stimulation (VNS) is used for treatment of refractory epilepsy and depression, particularly in western countries. In our country, VNS is covered by insurance for treatment of refractory epilepsy. In this study, we discuss the findings of previous studies that have reported VNS for depression, based on a history of VNS. Additionally, we have briefly described the mechanisms underlying the effects of treatment options used for depression.

An insula hierarchical network architecture for active interoceptive inference.

In the brain, the insular cortex receives a vast amount of interoceptive information, ascending through deep brain structures, from multiple visceral organs. The unique hierarchical and modular architecture of the insula suggests specialization for processing interoceptive afferents. Yet, the biological significance of the insula's neuroanatomical architecture, in relation to deep brain structures, remains obscure. In this opinion piece, we propose the Insula Hierarchical Modular Adaptive Interoception Control (IMAC) model to suggest that insula modules (granular, dysgranular and agranular), forming parallel networks with the prefrontal cortex and striatum, are specialized to form higher order interoceptive representations. These interoceptive representations are recruited in a context-dependent manner to support habitual, model-based and exploratory control of visceral organs and physiological processes. We discuss how insula interoceptive representations may give rise to conscious feelings that best explain lower order deep brain interoceptive representations, and how the insula may serve to defend the body and mind against pathological depression.

Interoceptive accuracy is related to the psychological mechanisms of the burning mouth syndrome: a cross-sectional study.

BACKGROUND: Different perspectives are needed to understand the pathophysiology of burning mouth syndrome (BMS), including physiological and psychological standpoints. The significance of interoception in chronic pain has been suggested. However, few studies have investigated this relationship in BMS. Therefore, we examined the role of interoception in BMS. METHODS: This is a cross-sectional study. BMS patients (N = 64) participated in the study. We used interoceptive accuracy (IAc) based on the heartbeat counting task. Then, participants were divided into high and low IAc groups, and their scores on clinical assessment including pain and psychological evaluation were compared. RESULTS: The Visual Analogue Scale scores indicating pain in low IAc patients, but not high IAc patients, were positively correlated with the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-State (STAI-S) Scores. CONCLUSIONS: Interoception might play a role in the pathophysiology of BMS.

Neural basis for anxiety and anxiety-related physiological responses during a driving situation: an fMRI study.

Although the exteroceptive and interoceptive prediction of a negative event increases a person's anxiety in daily life situations, the relationship between the brain mechanism of anxiety and the anxiety-related autonomic response has not been fully understood. In this functional magnetic resonance imaging (fMRI) study, we examined the neural basis of anxiety and anxiety-related autonomic responses in a daily driving situation. Participants viewed a driving video clip in the first-person perspective. During the video clip, participants were presented with a cue to indicate whether a subsequent crash could occur (attention condition) or not (safe condition). Enhanced activities in the anterior insula, bed nucleus of the stria terminalis, thalamus, and periaqueductal gray, and higher sympathetic nerve responses (pupil dilation and peripheral arterial stiffness) were triggered by the attention condition but not with the safe condition. Autonomic response-related functional connectivity was detected in the visual cortex, cerebellum, brainstem, and MCC/PCC with the right anterior insula and its adjacent regions as seed regions. Thus, the right anterior insula and adjacent regions, in collaboration with other regions play a role in eliciting anxiety based on the prediction of negative events, by mediating anxiety-related autonomic responses according to interoceptive information.

Increased cerebrovascular reactivity in selected brain regions after extracranial-intracranial bypass improves the speed and accuracy of visual cancellation in patients with severe steno-occlusive disease: a preliminary study.

The effect of the change in cerebrovascular reactivity (CVR) in each brain area on cognitive function after extracranial-intracranial bypass (EC-IC bypass) was examined. Eighteen patients who underwent EC-IC bypass for severe unilateral steno-occlusive disease were included. Single-photon emission CT (SPECT) for evaluating CVR and the visual cancellation (VC) task were performed before and after surgery. The accuracy of VC was expressed by the arithmetic mean of the age-matched correct answer rate and the accurate answer rate, and the averages of the time (time score) and accuracy (accuracy score) of the four VC subtests were used. The speed of VC tended to be slower, whereas accuracy was maintained before surgery. The EC-IC bypass improved CVR mainly in the cerebral hemisphere on the surgical side. On bivariate analysis, when CVR increased post-operatively, accuracy improved on both surgical sides, but the time score was faster on the left and slower on the right surgical side. Stepwise multiple regression analysis showed that the number of the brain regions associated with the time score was 5 and that associated with the accuracy score was 4. In the hemodynamically ischemic brain, processing speed might be adjusted so that accuracy would be maintained based on the speed-accuracy trade-off mechanism that may become engaged separately in the left and right cerebral hemispheres when performing VC. When considering the treatment for hemodynamic ischemia, the relationship between CVR change and the speed-accuracy trade-off in each brain region should be considered.

Spike firing attenuation of serotonin neurons in learned helplessness rats is reversed by ketamine.

Animals suffering from uncontrollable stress sometimes show low effort to escape stress (learned helplessness). Changes in serotonin (5-hydroxytryptamine) signalling are thought to underlie this behaviour. Although the release of 5-hydroxytryptamine is triggered by the action potential firing of dorsal raphe nuclei 5-hydroxytryptamine neurons, the electrophysiological changes induced by uncontrollable stress are largely unclear. Herein, we examined electrophysiological differences among 5-hydroxytryptamine neurons in naïve rats, learned helplessness rats and rats resistant to inescapable stress (non-learned helplessness). Five-week-old male Sprague Dawley rats were exposed to inescapable foot shocks. After an avoidance test session, rats were classified as learned helplessness or non-learned helplessness. Activity-dependent 5-hydroxytryptamine release induced by the administration of high-potassium solution was slower in free-moving learned helplessness rats. Subthreshold electrophysiological properties of 5-hydroxytryptamine neurons were identical among the three rat groups, but the depolarization-induced spike firing was significantly attenuated in learned helplessness rats. To clarify the underlying mechanisms, potassium (K+) channels regulating the spike firing were initially examined using naïve rats. K+ channels sensitive to 500 µM tetraethylammonium caused rapid repolarization of the action potential and the small conductance calcium-activated K+ channels produced afterhyperpolarization. Additionally, dendrotoxin-I, a blocker of Kv1.1 (encoded by Kcna1), Kv1.2 (encoded by Kcna2) and Kv1.6 (encoded by Kcna6) voltage-dependent K+ channels, weakly enhanced the spike firing frequency during depolarizing current injections without changes in individual spike waveforms in naïve rats. We found that dendrotoxin-I significantly enhanced the spike firing of 5-hydroxytryptamine neurons in learned helplessness rats. Consequently, the difference in spike firing among the three rat groups was abolished in the presence of dendrotoxin-I. These results suggest that the upregulation of dendrotoxin-I-sensitive Kv1 channels underlies the firing attenuation of 5-hydroxytryptamine neurons in learned helplessness rats. We also found that the antidepressant ketamine facilitated the spike firing of 5-hydroxytryptamine neurons and abolished the firing difference between learned helplessness and non-learned helplessness by suppressing dendrotoxin-I-sensitive Kv1 channels. The dendrotoxin-I-sensitive Kv1 channel may be a potential target for developing drugs to control activity of 5-hydroxytryptamine neurons.

Modeling Heterogeneous Brain Dynamics of Depression and Melancholia Using Energy Landscape Analysis.

Our current understanding of melancholic depression is shaped by its position in the depression spectrum. The lack of consensus on how it should be treated-whether as a subtype of depression, or as a distinct disorder altogethe-interferes with the recovery of suffering patients. In this study, we analyzed brain state energy landscape models of melancholic depression, in contrast to healthy and non-melancholic energy landscapes. Our analyses showed significant group differences on basin energy, basin frequency, and transition dynamics in several functional brain networks such as basal ganglia, dorsal default mode, and left executive control networks. Furthermore, we found evidences suggesting the connection between energy landscape characteristics (basin characteristics) and depressive symptom scores (BDI-II and SHAPS). These results indicate that melancholic depression is distinguishable from its non-melancholic counterpart, not only in terms of depression severity, but also in brain dynamics.

Resting-state brain activity can predict target-independent aptitude in fMRI-neurofeedback training.

Neurofeedback (NF) aptitude, which refers to an individual's ability to change brain activity through NF training, has been reported to vary significantly from person to person. The prediction of individual NF aptitudes is critical in clinical applications to screen patients suitable for NF treatment. In the present study, we extracted the resting-state functional brain connectivity (FC) markers of NF aptitude, independent of NF-targeting brain regions. We combined the data from fMRI-NF studies targeting four different brain regions at two independent sites (obtained from 59 healthy adults and six patients with major depressive disorder) to collect resting-state fMRI data associated with aptitude scores in subsequent fMRI-NF training. We then trained the multiple regression models to predict the individual NF aptitude scores from the resting-state fMRI data using a discovery dataset from one site and identified six resting-state FCs that predicted NF aptitude. Subsequently, the reproducibility of the prediction model was validated using independent test data from another site. The identified FC model revealed that the posterior cingulate cortex was the functional hub among the brain regions and formed predictive resting-state FCs, suggesting that NF aptitude may be involved in the attentional mode-orientation modulation system's characteristics in task-free resting-state brain activity.

Brain changes associated with impaired attention function in chronic pain.

Attention function is thought to be important in chronic pain, with the pathology of chronic pain closely associated with cognitive-emotional components. However, there have been few neuroimaging studies of the relationship between attention function and chronic pain. We used the method of functional connectivity analysis for resting-state fMRI (rs-fMRI) data and the Attention Network Test-Revision (ANT-R) to clarify the attention-related pathology of chronic pain. We performed rs-fMRI and ANT-R on a group of 26 chronic pain (somatoform pain disorder) patients and 28 age-matched healthy controls. A significant group difference in validity effects, a component of ANT-R, emerged (F1,46 = 5.91, p = 0.019), and the chronic pain group exhibited slower reaction times. Decreased brain connectivity of the left insula and left frontal regions was confirmed in chronic pain patients (pFWE < 0.05), and connectivity was negatively correlated with validity effects (r = -0.29, permutation test p = 0.033). Further, decreased functional connectivity strength of the right insula and left temporal gyrus in the chronic pain group were confirmed (pFWE < 0.05). We conclude that poor control of attention function results from deficits of functional connectivity in the left insula and left frontal regions in chronic pain.

Modulatory Effects of Prediction Accuracy on Electroencephalographic Brain Activity During Prediction.

Prediction is essential for the efficiency of many cognitive processes; however, this process is not always perfect. Predictive coding theory suggests that the brain generates and updates a prediction to respond to an upcoming event. Although an electrophysiological index of prediction, the stimulus preceding negativity (SPN), has been reported, it remains unknown whether the SPN reflects the prediction accuracy, or whether it is associated with the prediction error, which corresponds to a mismatch between a prediction and an actual input. Thus, the present study aimed to investigate this question using electroencephalography (EEG). Participants were asked to predict the original pictures from pictures that had undergone different levels of pixelation. The SPN amplitude was affected by the level of pixelation and correlated with the subjective evaluation of the prediction accuracy. Furthermore, late positive components (LPC) were negatively correlated with SPN. These results suggest that the amplitude of SPN reflects the prediction accuracy; more accurate prediction increases the SPN and reduces the prediction error, resulting in reduced LPC amplitudes.

Cardiorespiratory synchronisation and systolic blood pressure correlation of peripheral arterial stiffness during endoscopic thoracic sympathectomy.

Muscle sympathetic nerve activity (MSNA) is known as an effective measure to evaluate peripheral sympathetic activity; however, it requires invasive measurement with the microneurography method. In contrast, peripheral arterial stiffness affected by MSNA is a measure that allows non-invasive evaluation of mechanical changes of arterial elasticity. This paper aims to clarify the features of peripheral arterial stiffness to determine whether it inherits MSNA features towards non-invasive evaluation of its activity. To this end, we propose a method to estimate peripheral arterial stiffness [Formula: see text] at a high sampling rate. Power spectral analysis of the estimated [Formula: see text] was then performed on data acquired from 15 patients ([Formula: see text] years) who underwent endoscopic thoracic sympathectomy. We examined whether [Formula: see text] exhibited the features of MSNA where its frequency components synchronise with heart and respiration rates and correlates with the low-frequency component of systolic blood pressure. Regression analysis revealed that the local peak frequency in the range of heartbeat frequency highly correlate with the heart rate ([Formula: see text], [Formula: see text]) where the regression slope was approximately 1 and intercept was approximately 0. Frequency analysis then found spectral peaks of [Formula: see text] approximately 0.2 Hz that correspond to the respiratory cycle. Finally, cross power spectral analysis showed a significant magnitude squared coherence between [Formula: see text] and systolic blood pressure in the frequency band from 0.04 to 0.2 Hz. These results indicate that [Formula: see text] inherits the features observed in MSNA that require invasive measurements, and thus [Formula: see text] can be an effective non-invasive substitution for MSNA measure.