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

Single prolonged stress: toward an animal model of posttraumatic stress disorder

Although selective serotonin reuptake inhibitors (SSRIs) are reported to be effective in decreasing posttraumatic stress disorder (PTSD) symptoms, a subgroup of PTSD patients remain chronically symptomatic and maintain conditioned fear responses to traumatic stimuli. In this context, the establishment of an appropriate animal model of PTSD is necessary to promote better understanding of the mechanisms of the disorder and to facilitate the development of more effective therapeutic alternatives to SSRIs. Although no single widely accepted animal model of PTSD has been established to date, the single prolonged stress (SPS) animal model has been partially validated as a model for PTSD. SPS rats mimic the pathophysiological abnormalities and behavioral characteristics of PTSD, such as enhanced anxiety-like behavior and glucocorticoid negative feedback, and they exhibit the expected therapeutic response to paroxetine on enhanced fear memory. In addition, SPS rats exhibit enhanced freezing in response to contextual fear conditioning, and impaired extinction of fear memory, which is alleviated by D -cycloserine. The enhanced consolidation and impaired extinction of fear memory found in SPS rats suggests that this model has additional value because recent studies of PTSD indicate that memory abnormalities are a central feature. In this study, we summarize the behavioral and pathophysiological PTSD-like symptoms in SPS, focusing on memory abnormalities, and evaluate the validity of SPS as an animal model of PTSD. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64546/1/20629_ftp.pd

Protective Action of Neurotrophic Factors and Estrogen against Oxidative Stress-Mediated Neurodegeneration

Oxidative stress is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Low levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important for maintenance of neuronal function, though elevated levels lead to neuronal cell death. A complex series of events including excitotoxicity, Ca2+ overload, and mitochondrial dysfunction contributes to oxidative stress-mediated neurodegeneration. As expected, many antioxidants like phytochemicals and vitamins are known to reduce oxidative toxicity. Additionally, growing evidence indicates that neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and estrogens significantly prevent neuronal damage caused by oxidative stress. Here, we review and discuss recent studies addressing the protective mechanisms of neurotrophic factors and estrogen within this system

Subjectivity of the Anomalous Sense of Self Is Represented in Gray Matter Volume in the Brain

The self includes complicated and heterogeneous functions. Researchers have divided the self into three distinct functions called “agency,” “ownership,” and “narrative self”. These correspond to psychiatric symptoms, behavioral characteristics and neural responses, but their relationship with brain structure is unclear. This study examined the relationship between the subjectivity of self-related malfunctions and brain structure in terms of gray matter (GM) volume in 96 healthy people. They completed a recently developed self-reported questionnaire called the Embodied Sense of Self Scale (ESSS) that measures self-related malfunctions. The ESSS has three subscales reflecting the three distinct functions of the self. We also determined the participants’ brain structures using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM). Multiple regression analysis revealed a significant negative correlation between ownership malfunction and the insular cortex GM volume. A relationship with brain structure could thus only be confirmed for the ESSS “ownership” subscale. This finding suggests that distinct brain structures feel ownership and that the ESSS could partly screen for distinct brain structures

Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

<p>Abstract</p> <p>Background</p> <p>Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.</p> <p>Methods</p> <p>Forty-three patients with TRD were treated with 12 weekly sessions of group-CBT. Patients were assessed with the Global Assessment of Functioning scale (GAF), the 36-item Short-Form Health Survey (SF-36), the Hamilton Rating Scale for Depression (HRSD), the Dysfunctional Attitudes Scale (DAS), and the Automatic Thought Questionnaire-Revised (ATQ-R) at baseline, at the termination of treatment, and at the 12-month follow-up.</p> <p>Results</p> <p>Thirty-eight patients completed treatment; five dropped out. For the patients who completed treatment, post-treatment scores on the GAF and SF-36 were significantly higher than baseline scores. Scores on the HRSD, DAS, and ATQ-R were significantly lower after the treatment. Thus patients improved on all measurements of psychosocial functioning and mood symptoms. Twenty patients participated in the 12-month follow-up. Their improvements for psychosocial functioning, depressive symptoms, and dysfunctional cognitions were sustained at 12 months following the completion of group-CBT.</p> <p>Conclusions</p> <p>These findings suggest a positive effect that the addition of cognitive behavioural group therapy to medication on depressive symptoms and social functioning of mildly depressed patients, showing treatment resistance.</p

TJS-010, a New Prescription of Kampa Medicine with Putative Antidepressive and Anxiolytic Properties. : A behavioral study using experimental models for depression and anxiety

We investigated the effect of TJS-010, a new prescription of Kampo or oriental medicine, on the locomotor activity and body temperature in rats in order to determine its antidepressive and anxiolytic effects. Tetrabenazine(TBZ), which sometimes induces depression in humans, decreased the spontaneous locomotion in rats, and attenuated the content of amines in several regions in the rat brain when intraperitoneally injected. TJS-010 was orally administered at a concentration of 750 mg/kg, and inhibited the locomotor suppression. The content of amines was not, however, altered. These results indicate that TJS-010 postsynaptically modulates the transmission or transduction. Imipramine, 5mg/kg, also enhanced locomotion in TBZ-treated rats, which was similar to the effect of TJS-010. These results suggest that TJS-010 has an antidepressive effect. TJS-010 also facilitated the hypothermia induced by subcutaneous injection of 0.1 mg/kg ( ± )-8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), which is known to be mediated by serotonin-1A receptors. The hypothermia in the rats via an activation of serotonin-1A receptors is often observed with anxiolytic drugs. These results may raise the possibility that TJS-010 has an anxiolytic property. TJS-010 may serve as a useful drug for the treatment of those who suffer from depressive and anxiety disorders

Quantitative Evaluation of Pain during Electrocutaneous Stimulation using a Log-Linearized Peripheral Arterial Viscoelastic Model

In clinical practice, subjective pain evaluations, e.g., the visual analogue scale and the numeric rating scale, are generally employed, but these are limited in terms of their ability to detect inaccurate reports, and are unsuitable for use in anesthetized patients or those with dementia. We focused on the peripheral sympathetic nerve activity that responds to pain, and propose a method for evaluating pain sensation, including intensity, sharpness, and dullness, using the arterial stiffness index. In the experiment, electrocardiogram, blood pressure, and photoplethysmograms were obtained, and an arterial viscoelastic model was applied to estimate arterial stiffness. The relationships among the stiffness index, self-reported pain sensation, and electrocutaneous stimuli were examined and modelled. The relationship between the stiffness index and pain sensation could be modelled using a sigmoid function with high determination coefficients, where R2 ≥ 0.88, p < 0.01 for intensity, R2 ≥ 0.89, p < 0.01 for sharpness, and R2 ≥ 0.84, p < 0.01 for dullness when the stimuli could appropriately evoke dull pain.This work was supported by the Center of Innovation Program from Japan Science and Technology Agency.Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-21223-1

Altered Gamma-Band Activity in Recovered Depression

Background: The neurophysiological mechanisms of cognitive reactivity, the primary vulnerability factor of major depressive disorder (MDD) recurrence, remain unclear in individuals with recovered MDD (rMDD). Because gamma-band responses (GBRs) can be used to measure cognitive processing, they may also be useful for elucidating the mechanisms underlying cognitive reactivity. Identifying these mechanisms may permit the development of an index for predicting and preempting MDD recurrence. Here, to identify the neurophysiological mechanisms of cognitive reactivity, we examined the characteristics of the GBRs evoked/induced by emotional words in participants with and without rMDD after inducing a negative mood. Methods: Thirty-three healthy control participants and 18 participants with rMDD completed a lexical emotion identification task during electroencephalography along with assessments of cognitive reactivity after negative mood induction. Results: No between-group differences were identified for the task reaction times; however, the rMDD group had significantly higher cognitive reactivity scores than did the control group. Furthermore, the power of late GBRs to positive words was significantly greater in the rMDD group, with the greater power of late GBRs being related to higher cognitive reactivity. Limitations: Considering the population studied, our findings cannot be completely generalized to populations other than adolescents, people with rMDD, and those without a history of co-morbid disorders and early life stress. Conclusions: Our findings indicate that the dysfunction of neural circuits related to higher-order processes like memory and attention might underlie cognitive reactivity. Altered late GBRs to positive information may be persistent biomarkers of the depression recurrence risk