Brain Areas Controlling Heart Rate Variability in Tinnitus and Tinnitus-Related Distress

Background

Tinnitus is defined as an intrinsic sound perception that cannot be attributed to an external sound source. Distress in tinnitus patients is related to increased beta activity in the dorsal part of the anterior cingulate and the amount of distress correlates with network activity consisting of the amygdala-anterior cingulate cortex-insula-parahippocampus. Previous research also revealed that distress is associated to a higher sympathetic (OS) tone in tinnitus patients and tinnitus suppression to increased parasympathetic (PS) tone.

Methodology

The aim of the present study is to investigate the relationship between tinnitus distress and the autonomic nervous system and find out which cortical areas are involved in the autonomic nervous system influences in tinnitus distress by the use of source localized resting state electroencephalogram (EEG) recordings and electrocardiogram (ECG). Twenty-one tinnitus patients were included in this study.

Conclusions

The results indicate that the dorsal and subgenual anterior cingulate, as well as the left and right insula are important in the central control of heart rate variability in tinnitus patients. Whereas the sympathovagal balance is controlled by the subgenual and pregenual anterior cingulate cortex, the right insula controls sympathetic activity and the left insula the parasympathetic activity. The perceived distress in tinnitus patients seems to be sympathetically mediated.     

Prefrontal cortex based sex differences in tinnitus perception: same tinnitus intensity, same tinnitus distress, different mood

Background

Tinnitus refers to auditory phantom sensation. It is estimated that for 2% of the population this auditory phantom percept severely affects the quality of life, due to tinnitus related distress. Although the overall distress levels do not differ between sexes in tinnitus, females are more influenced by distress than males. Typically, pain, sleep, and depression are perceived as significantly more severe by female tinnitus patients. Studies on gender differences in emotional regulation indicate that females with high depressive symptoms show greater attention to emotion, and use less anti-rumination emotional repair strategies than males.

Methodology

The objective of this study was to verify whether the activity and connectivity of the resting brain is different for male and female tinnitus patients using resting-state EEG.

Conclusions

Females had a higher mean score than male tinnitus patients on the BDI–II. Female tinnitus patients differ from male tinnitus patients in the orbitofrontal cortex (OFC) extending to the frontopolar cortex in beta1 and beta2. The OFC is important for emotional processing of sounds. Increased functional alpha connectivity is found between the OFC, insula, subgenual anterior cingulate (sgACC), parahippocampal (PHC) areas and the auditory cortex in females. Our data suggest increased functional connectivity that binds tinnitus-related auditory cortex activity to auditory emotion-related areas via the PHC-sgACC connections resulting in a more depressive state even though the tinnitus intensity and tinnitus-related distress are not different from men. Comparing male tinnitus patients to a control group of males significant differences could be found for beta3 in the posterior cingulate cortex (PCC). The PCC might be related to cognitive and memory-related aspects of the tinnitus percept. Our results propose that sex influences in tinnitus research cannot be ignored and should be taken into account in functional imaging studies related to tinnitus.     

Tinnitus: A Large VBM-EEG Correlational Study

A surprising fact in voxel-based morphometry (VBM) studies performed in tinnitus is that not one single region is replicated in studies of different centers. The question then rises whether this is related to the low sample size of these studies, the selection of non-representative patient subgroups, or the absence of stratification according to clinical characteristics. Another possibility is that VBM is not a good tool to study functional pathologies such as tinnitus, in contrast to pathologies like Alzheimer’s disease where it is known the pathology is related to cell loss. In a large sample of 154 tinnitus patients VBM and QEEG (Quantitative Electroencephalography) was performed and evaluated by a regression analysis. Correlation analyses are performed between VBM and QEEG data. Uncorrected data demonstrated structural differences in grey matter in hippocampal and cerebellar areas related to tinnitus related distress and tinnitus duration. After control for multiple comparisons, only cerebellar VBM changes remain significantly altered. Electrophysiological differences are related to distress, tinnitus intensity, and tinnitus duration in the subgenual anterior cingulate cortex, dorsal anterior cingulate cortex, hippocampus, and parahippocampus, which confirms previous results. The absence of QEEG-VBM correlations suggest functional changes are not reflected by co-occurring structural changes in tinnitus, and the absence of VBM changes (except for the cerebellum) that survive correct statistical analysis in a large study population suggests that VBM might not be very sensitive for studying tinnitus.     

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

Background

Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores.

Methods and Findings

In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05).

Conclusion

Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.     

Short and intense tailor-made notched music training against tinnitus: the tinnitus frequency matters

Tinnitus is one of the most common diseases in industrialized countries. Here, we developed and evaluated a short-term (5 subsequent days) and intensive (6 hours/day) tailor-made notched music training (TMNMT) for patients suffering from chronic, tonal tinnitus. We evaluated (i) the TMNMT efficacy in terms of behavioral and magnetoencephalographic outcome measures for two matched patient groups with either low (≤8 kHz, N = 10) or high (>8 kHz, N = 10) tinnitus frequencies, and the (ii) persistency of the TMNMT effects over the course of a four weeks post-training phase. The results indicated that the short-term intensive TMNMT took effect in patients with tinnitus frequencies ≤8 kHz: subjective tinnitus loudness, tinnitus-related distress, and tinnitus-related auditory cortex evoked activity were significantly reduced after TMNMT completion. However, in the patients with tinnitus frequencies >8 kHz, significant changes were not observed. Interpreted in their entirety, the results also indicated that the induced changes in auditory cortex evoked neuronal activity and tinnitus loudness were not persistent, encouraging the application of the TMNMT as a longer-term training. The findings are essential in guiding the intended transfer of this neuro-scientific treatment approach into routine clinical practice.     

Does Tinnitus Distress Depend on Age of Onset?

Objectives

Tinnitus is the perception of a sound in the absence of any physical source of it. About 5–15% of the population report hearing such a tinnitus and about 1–2% suffer from their tinnitus leading to anxiety, sleep disorders or depression. It is currently not completely understood why some people feel distressed by their tinnitus, while others don''t. Several studies indicate that the amount of tinnitus distress is associated with many factors including comorbid anxiety, comorbid depression, personality, the psychosocial situation, the amount of the related hearing loss and the loudness of the tinnitus. Furthermore, theoretical considerations suggest an impact of the age at tinnitus onset influencing tinnitus distress.

Methods

Based on a sample of 755 normal hearing tinnitus patients we tested this assumption. All participants answered a questionnaire on the amount of tinnitus distress together with a large variety of clinical and demographic data.

Results

Patients with an earlier onset of tinnitus suffer significantly less than patients with an onset later in life. Furthermore, patients with a later onset of tinnitus describe their course of tinnitus distress as more abrupt and distressing right from the beginning.

Conclusion

We argue that a decline of compensatory brain plasticity in older age accounts for this age-dependent tinnitus decompensation.     

Lipid pathway alterations in Parkinson's disease primary visual cortex

Background

We present a lipidomics analysis of human Parkinson''s disease tissues. We have focused on the primary visual cortex, a region that is devoid of pathological changes and Lewy bodies; and two additional regions, the amygdala and anterior cingulate cortex which contain Lewy bodies at different disease stages but do not have as severe degeneration as the substantia nigra.

Methodology/Principal Findings

Using liquid chromatography mass spectrometry lipidomics techniques for an initial screen of 200 lipid species, significant changes in 79 sphingolipid, glycerophospholipid and cholesterol species were detected in the visual cortex of Parkinson''s disease patients (n = 10) compared to controls (n = 10) as assessed by two-sided unpaired t-test (p-value <0.05). False discovery rate analysis confirmed that 73 of these 79 lipid species were significantly changed in the visual cortex (q-value <0.05). By contrast, changes in 17 and 12 lipid species were identified in the Parkinson''s disease amygdala and anterior cingulate cortex, respectively, compared to controls; none of which remained significant after false discovery rate analysis. Using gas chromatography mass spectrometry techniques, 6 out of 7 oxysterols analysed from both non-enzymatic and enzymatic pathways were also selectively increased in the Parkinson''s disease visual cortex. Many of these changes in visual cortex lipids were correlated with relevant changes in the expression of genes involved in lipid metabolism and an oxidative stress response as determined by quantitative polymerase chain reaction techniques.

Conclusions/Significance

The data indicate that changes in lipid metabolism occur in the Parkinson''s disease visual cortex in the absence of obvious pathology. This suggests that normalization of lipid metabolism and/or oxidative stress status in the visual cortex may represent a novel route for treatment of non-motor symptoms, such as visual hallucinations, that are experienced by a majority of Parkinson''s disease patients.     

Disentangling depression and distress networks in the tinnitus brain

Tinnitus is the continuous perception of an internal auditory stimulus. This permanent sound often affects a person's emotional state inducing distress and depressive feelings changes in 6-25% of the affected population. Distress and depression are two distinct emotional states. Whereas distress describes a transient aversive state, interfering with a person's ability to adequately adapt to stressors, depressive feelings should rather be considered as a more constant emotional state. Based on previous observations in chronic pain, posttraumatic stress disorder and depression, we assume that both states are related to separate neural circuits. We used the Dutch version of the Tinnitus Questionnaire to assess the global index of distress together with the Beck Depression Inventory to evaluate the depressive symptoms accompanying tinnitus. Furthermore sLORETA analysis was performed to correlate current density distribution with distress and depression scores, revealing a lateralization effect of depression versus distress. Distress is mainly correlated with alpha 2, beta 1 and beta 2 activity of the right frontopolar cortex and orbitofrontal cortex in combination with beta 2 activation of the anterior cingulate cortex. In contrast, the more permanent depressive alterations induced by tinnitus are associated with activity of alpha 2 activity in the left frontopolar and orbitofrontal cortex. These specific neural circuits are embedded in a greater neural network, with the parahippocampal region functioning as a crucial linkage between both tinnitus related pathways.     

Increased Coupling of Intrinsic Networks in Remitted Depressed Youth Predicts Rumination and Cognitive Control

Objective

Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD.

Method

fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain.

Results

Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely.

Conclusions

Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.     

Using Auditory Steady State Responses to Outline the Functional Connectivity in the Tinnitus Brain

Background

Tinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions.

Methods and Findings

Using whole-head magnetoencephalography we investigated cortical connectivity by means of phase synchronization in tinnitus subjects and healthy controls. We found evidence for a deviating pattern of long-range functional connectivity in tinnitus that was strongly correlated with individual ratings of the tinnitus percept. Phase couplings between the anterior cingulum and the right frontal lobe and phase couplings between the anterior cingulum and the right parietal lobe showed significant condition x group interactions and were correlated with the individual tinnitus distress ratings only in the tinnitus condition and not in the control conditions.

Conclusions

To the best of our knowledge this is the first study that demonstrates existence of a global tinnitus network of long-range cortical connections outside the central auditory system. This result extends the current knowledge of how tinnitus is generated in the brain. We propose that this global extend of the tinnitus network is crucial for the continuos perception of the tinnitus tone and a therapeutical intervention that is able to change this network should result in relief of tinnitus.     

Hippocampal and Left Subcallosal Anterior Cingulate Atrophy in Psychotic Depression

Background

Psychotic depression is arguably the most diagnostically stable subtype of major depressive disorder, and an attractive target of study in a famously heterogeneous mental illness. Previous imaging studies have identified abnormal volumes of the hippocampus, amygdala, and subcallosal region of the anterior cingulate cortex (scACC) in psychotic depression, though studies have not yet examined the role of family history of depression in these relationships.

Methods

20 participants with psychotic depression preparing to undergo electroconvulsive therapy and 20 healthy comparison participants (13 women and 7 men in each group) underwent structural brain imaging in a 1.5 T MRI scanner. 15 of the psychotic depression group had a first-degree relative with diagnosed affective disorders, while the healthy control group had no first-degree relatives with affective disorders. Depression severity was assessed with the Hamilton Depression Rating Scale and duration of illness was assessed in all patients. Automated neural nets were used to isolate the hippocampi and amygdalae in each scan, and an established manual method was used to parcellate the anterior cingulate cortex into dorsal, rostral, subcallosal, and subgenual regions. The volumes of these regions were compared between groups. Effects of laterality and family history of affective disorders were examined as well.

Results

Patients with psychotic depression had significantly smaller left scACC and bilateral hippocampal volumes, while no group differences in other anterior cingulate cortex subregions or amygdala volumes were present. Hippocampal atrophy was found in all patients with psychotic depression, but reduced left scACC volume was found only in the patients with a family history of depression.

Conclusions

Patients with psychotic depression showed significant reduction in hippocampal volume bilaterally, perhaps due to high cortisol states associated with this illness. Reduced left scACC volume may be a vulnerability factor related to family history of depression.     

Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates

Background

Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs.

Materials/Methodology

Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels.

Results

Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation.

Conclusion

We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants.     

Pattern of Regional Cortical Thinning Associated with Cognitive Deterioration in Parkinson’s Disease

Background

Dementia is a frequent and devastating complication in Parkinson’s disease (PD). There is an intensive search for biomarkers that may predict the progression from normal cognition (PD-NC) to dementia (PDD) in PD. Mild cognitive impairment in PD (PD-MCI) seems to represent a transitional state between PD-NC and PDD. Few studies have explored the structural changes that differentiate PD-NC from PD-MCI and PDD patients.

Objectives and Methods

We aimed to analyze changes in cortical thickness on 3.0T Magnetic Resonance Imaging (MRI) across stages of cognitive decline in a prospective sample of PD-NC (n = 26), PD-MCI (n = 26) and PDD (n = 20) patients, compared to a group of healthy subjects (HC) (n = 18). Cortical thickness measurements were made using the automatic software Freesurfer.

Results

In a sample of 72 PD patients, a pattern of linear and progressive cortical thinning was observed between cognitive groups in cortical areas functionally specialized in declarative memory (entorhinal cortex, anterior temporal pole), semantic knowledge (parahippocampus, fusiform gyrus), and visuoperceptive integration (banks of the superior temporal sulcus, lingual gyrus, cuneus and precuneus). Positive correlation was observed between confrontation naming and thinning in the fusiform gyrus, parahippocampal gyrus and anterior temporal pole; clock copy with thinning of the precuneus, parahippocampal and lingual gyrus; and delayed memory with thinning of the bilateral anteromedial temporal cortex.

Conclusions

The pattern of regional decreased cortical thickness that relates to cognitive deterioration is present in PD-MCI patients, involving areas that play a central role in the storage of prior experiences, integration of external perceptions, and semantic processing.     

Trauma-Associated Tinnitus: Audiological,Demographic and Clinical Characteristics

Background

Tinnitus can result from different etiologies. Frequently, patients report the development of tinnitus after traumatic injuries. However, to which extent this specific etiologic factor plays a role for the phenomenology of tinnitus is still incompletely understood. Additionally, it remains a matter of debate whether the etiology of tinnitus constitutes a relevant criterion for defining tinnitus subtypes.

Objective

By investigating a worldwide sample of tinnitus patients derived from the Tinnitus Research Initiative (TRI) Database, we aimed to identify differences in demographic, clinical and audiological characteristics between tinnitus patients with and without preceding trauma.

Materials

A total of 1,604 patients were investigated. Assessment included demographic data, tinnitus related clinical data, audiological data, the Tinnitus Handicap Inventory, the Tinnitus Questionnaire, the Beck Depression Inventory, various numeric tinnitus rating scales, and the World Health Organisation Quality of Life Scale (WHOQoL).

Results

Our data clearly indicate differences between tinnitus patients with and without trauma at tinnitus onset. Patients suffering from trauma-associated tinnitus suffer from a higher mental burden than tinnitus patients presenting with phantom perceptions based on other or unknown etiologic factors. This is especially the case for patients with whiplash and head trauma. Patients with posttraumatic noise-related tinnitus experience more frequently hyperacousis, were younger, had longer tinnitus duration, and were more frequently of male gender.

Conclusions

Trauma before tinnitus onset seems to represent a relevant criterion for subtypization of tinnitus. Patients with posttraumatic tinnitus may require specific diagnostic and therapeutic management. A more systematic and – at best - standardized assessment for hearing related sequelae of trauma is needed for a better understanding of the underlying pathophysiology and for developing more tailored treatment approaches as well.     

Dysfunctional Noise Cancelling of the Rostral Anterior Cingulate Cortex in Tinnitus Patients

Background

Peripheral auditory deafferentation and central compensation have been regarded as the main culprits of tinnitus generation. However, patient-to-patient discrepancy in the range of the percentage of daytime in which tinnitus is perceived (tinnitus awareness percentage, 0 – 100%), is not fully explicable only by peripheral deafferentation, considering that the deafferentation is a stable persisting phenomenon but tinnitus is intermittently perceived in most patients. Consequently, the involvement of a dysfunctional noise cancellation mechanism has recently been suggested with regard to the individual differences in reported tinnitus awareness. By correlating the tinnitus awareness percentage with resting-state source-localized electroencephalography findings, we may be able to retrieve the cortical area that is negatively correlated with tinnitus awareness percentage, and then the area may be regarded as the core of the noise cancelling system that is defective in patients with tinnitus.

Methods and Findings

Using resting-state cortical oscillation, we investigated 80 tinnitus patients by correlating the tinnitus awareness percentage with their source-localized cortical oscillatory activity and functional connectivity. The activity of bilateral rostral anterior cingulate cortices (ACCs), left dorsal- and pregenual ACCs for the delta band, bilateral rostral/pregenual/subgenual ACCs for the theta band, and left rostral/pregenual ACC for the beta 1 band displayed significantly negative correlations with tinnitus awareness percentage. Also, the connectivity between the left primary auditory cortex (A1) and the rostral ACC, as well as between the left A1 and the subgenual ACC for the beta 1 band, were negatively correlated with tinnitus awareness percentage.

Conclusions

These results may designate the role of the rostral ACC as the core of the descending noise cancellation system, and thus dysfunction of the rostral ACC may result in perception of tinnitus. The present study also opens a possibility of tinnitus modulation by neuromodulatory approaches targeting the rostral ACC.     

Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba

Objective

The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.

Design

A case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.

Results

Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.

Conclusion

This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.     

Functional and Anatomical Connectivity Abnormalities in Cognitive Division of Anterior Cingulate Cortex in Schizophrenia

Introduction

Current pathophysiological theories of schizophrenia highlight the role of altered brain functional and anatomical connectivity. The cognitive division of anterior cingulate cortex (ACC-cd) is a commonly reported abnormal brain region in schizophrenia for its importance in cognitive control process. The aim of this study was to investigate the functional and anatomical connectivity of ACC-cd and its cognitive and clinical manifestation significance in schizophrenia by using the resting-state functional magnetic resonance imaging (fMRI) and the diffusion tensor imaging (DTI).

Methods

Thirty-three medicated schizophrenics and 30 well-matched health controls were recruited. Region-of-interest (ROI)-based resting-state functional connectivity analysis and Tract-Based Spatial Statistics (TBSS) were performed on 30 patients and 30 controls, and 24 patients and 29 controls, respectively. The Pearson correlation was performed between the imaging measures and the Stroop performance and scores of the Positive and Negative Syndrome Scale (PANSS), respectively.

Results

Patients with schizophrenia showed significantly abnormal in the functional connectivity and its hemispheric asymmetry of the ACC-cd with multiple brain areas, e.g., decreased positive connectivity with the bilateral putamen and caudate, increased negative connectivity with the left posterior cingulated cortex (PCC), increased asymmetry of connectivity strength with the contralateral inferior frontal gyrus (IFG). The FA of the right anterior cingulum was significantly decreased in patients group (p = 0.014). The abnormal functional and structural connectivity of ACC-cd were correlated with Stroop performance and the severity of the symptoms in patients.

Conclusions

Our results suggested that the abnormal connectivity of the ACC-cd might play a role in the cognitive impairment and clinical symptoms in schizophrenia.     

The Neural Correlates of Mindful Awareness: A Possible Buffering Effect on Anxiety-Related Reduction in Subgenual Anterior Cingulate Cortex Activity

Background

Human personality consists of two fundamental elements character and temperament. Character allays automatic and preconceptual emotional responses determined by temperament. However, the neurobiological basis of character and its interplay with temperament remain elusive. Here, we examined character-temperament interplay and explored the neural basis of character, with a particular focus on the subgenual anterior cingulate cortex extending to a ventromedial portion of the prefrontal cortex (sgACC/vmPFC).

Methods

Resting brain glucose metabolism (GM) was measured using [¹⁸F] fluorodeoxyglucose positron emission tomography in 140 healthy adults. Personality traits were assessed using the Temperament and Character Inventory. Regions of interest (ROI) analysis and whole-brain analysis were performed to examine a combination effect of temperament and character on the sgACC/vmPFC and to explore the neural correlates of character, respectively.

Results

Harm avoidance (HA), a temperament trait (i.e., depressive, anxious, vulnerable), showed a significant negative impact on the sgACC/vmPFC GM, whereas self-transcendence (ST), a character trait (i.e., intuitive, judicious, spiritual), exhibited a significant positive effect on GM in the same region (HA β = −0.248, p = 0.003; ST: β = 0.250, p = 0.003). In addition, when coupled with strong ST, individuals with strong HA maintained the sgACC/vmPFC GM level comparable to the level of those with low scores on both HA and ST. Furthermore, exploratory whole-brain analysis revealed a significant positive relationship between ST and sgACC/vmPFC GM (peak voxel at x = −8, y = 32, z = −8, k = 423, Z = 4.41, corrected p ^FDR = 0.030).

Conclusion

The current findings indicate that the sgACC/vmPFC might play a critical role in mindful awareness to something beyond as well as in emotional regulation. Developing a sense of mindfulness may temper exaggerated emotional responses in individuals with a risk for or having anxiety and depressive disorders.     

Phenotypic Characteristics of Hyperacusis in Tinnitus

Background

Many people with tinnitus also suffer from hyperacusis. Both clinical and basic scientific data indicate an overlap in pathophysiologic mechanisms. In order to further elucidate the interplay between tinnitus and hyperacusis we compared clinical and demographic characteristics of tinnitus patients with and without hyperacusis by analyzing a large sample from an international tinnitus patient database.

Materials

The default dataset import [November 1^st, 2012] from the Tinnitus Research Initiative [TRI] Database was used for analyses. Hyperacusis was defined by the question “Do sounds cause you pain or physical discomfort?” of the Tinnitus Sample Case History Questionnaire. Patients who answered this question with “yes” were contrasted with “no”-responders with respect to 41 variables.

Results

935 [55%] out of 1713 patients were characterized as hyperacusis patients. Hyperacusis in tinnitus was associated with younger age, higher tinnitus-related, mental and general distress; and higher rates of pain disorders and vertigo. In relation to objective audiological assessment patients with hyperacusis rated their subjective hearing function worse than those without hyperacusis. Similarly the tinnitus pitch was rated higher by hyperacusis patients in relation to the audiometrically determined tinnitus pitch. Among patients with tinnitus and hyperacusis the tinnitus was more frequently modulated by external noise and somatic maneuvers, i.e., exposure to environmental sounds and head and neck movements change the tinnitus percept.

Conclusions

Our findings suggest that the comorbidity of hyperacusis is a useful criterion for defining a sub-type of tinnitus which is characterized by greater need of treatment. The higher sensitivity to auditory, somatosensory and vestibular input confirms the notion of an overactivation of an unspecific hypervigilance network in tinnitus patients with hyperacusis.     

Different Brain Activation under Left and Right Ventricular Stimulation: An fMRI Study in Anesthetized Rats

Background

Myocardial ischemia in the anterior wall of the left ventricule (LV) and in the inferior wall and/or right ventricle (RV) shows different manifestations that can be explained by the different innervations of cardiac afferent nerves. However, it remains unclear whether information from different areas of the heart, such as the LV and RV, are differently processed in the brain. In this study, we investigated the brain regions that process information from the LV or RV using cardiac electrical stimulation and functional magnetic resonance imaging (fMRI) in anesthetized rats because the combination of these two approaches cannot be used in humans.

Methodology/Principal Findings

An electrical stimulation catheter was inserted into the LV or RV (n = 12 each). Brain fMRI scans were recorded during LV or RV stimulation (9 Hz and 0.3 ms width) over 10 blocks consisting of alternating periods of 2 mA for 30 sec followed by 0.2 mA for 60 sec. The validity of fMRI signals was confirmed by first and second-level analyses and temporal profiles. Increases in fMRI signals were observed in the anterior cingulate cortex and the right somatosensory cortex under LV stimulation. In contrast, RV stimulation activated the right somatosensory cortex, which was identified more anteriorly compared with LV stimulation but did not activate the anterior cingulate cortex.

Conclusion/Significance

This study provides the first evidence for differences in brain activation under LV and RV stimulation. These different brain processes may be associated with different clinical manifestations between anterior wall and inferoposterior wall and/or RV myocardial ischemia.