Effects of Psychotherapy on Glutamatergic Neurotransmission.

INTRODUCTION: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. METHODS: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). RESULTS: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. DISCUSSION: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery.

Effective handling of nonlinear distortions in CO-OFDM using affinity propagation clustering.

We experimentally demonstrate a system-agnostic and training-data-free nonlinearity compensator, using affinity propagation (AP) clustering in single- and multi-channel coherent optical OFDM (CO-OFDM) for up to 3200 km transmission. We show that AP outperforms benchmark deterministic and clustering algorithms by effectively tackling stochastic nonlinear distortions and inter-channel nonlinearities. AP offers up to almost 4 dB power margin extension over linear equalization in single-channel 16-quadrature amplitude-modulated CO-OFDM and a 1.4 dB increase in Q-factor over digital back-propagation in multi-channel quaternary phase-shift keying CO-OFDM. Simulated results indicate transparency to higher modulation format orders and better efficiency when a multi-carrier structure is considered.

Anticipating control over aversive stimuli is mediated by the medial prefrontal cortex: An fMRI study with healthy adults.

The anticipation of control over aversive events in life is relevant for our mental health. Insights on the underlying neural mechanisms remain limited. We developed a new functional magnetic resonance imaging (fMRI) task that uses auditory stimuli to explore the neural correlates of (1) the anticipation of control over aversion and (2) the processing of aversion. In a sample of 25 healthy adults, we observed increased neural activation in the medial prefrontal cortex (ventromedial prefrontal cortex and rostral anterior cingulate cortex), other brain areas relevant for reward anticipation (ventral striatum, brainstem [ventral tegmental area], midcingulate cortex), and the posterior cingulate cortex when they anticipated control over aversion compared with anticipating no control (1). The processing of aversive sounds compared to neutral sounds (2) was associated with increased neural activation in the bilateral posterior insula. Our findings provide evidence for the important role of medial prefrontal regions in control anticipation and highlight the relevance of conceiving the neural mechanisms involved within a reward-based framework.

Statistical quantification of nonlinear interference noise components in coherent systems.

We present and validate a statistical method able to separate nonlinear interference noise (NLIN) into a residual Gaussian (ResN) and a phase noise (NLPN) component. We take into account the interaction of the NLIN with the receiver's DSP, mainly through carrier phase recovery (CPR), by considering the amount of correlation of the NLPN component. This allows obtaining in a straightforward way an accurate prediction of the achievable post-DSP transmission performance. We apply our method on simulated data in different scenarios. For this purpose: (i) several different quadrature amplitude modulation (QAM) and probabilistically shaped (PS) formats are investigated and (ii) simulations with standard single mode fiber (SSMF) and dispersion shifted fiber (DSF) are performed. In all these cases we validate the results provided by our method through comparison with ideal data-aided CPR and a more practical blind phase search (BPS) algorithm. The results obtained are finally compared with the predictions of existing theoretical models and the differences with our approach are pointed out.

Impact of pump-signal overlap in S+C+L band discrete Raman amplifiers.

We experimentally investigate the impact of pump-signal overlap in ultra-wideband (>13THz) Raman amplifiers and measure the transmission penalty on 30GBaud PM-QPSK signals due to adjacent Raman pumps in a 15dB gain, 150nm (∼18.8THz) S+C+L-band discrete Raman amplifier. We present an efficient numerical model to predict the performance penalty induced by crosstalk from Rayleigh backscattered light from backward-propagating Raman pumps showing good agreement with the experimental results. A 4nm guard-band must be retained around an overlapping Raman pump based on typical, commercial semiconductor laser pump diodes to ensure a negligible transmission penalty in S-band.

Delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale (RASS): Inattention and visuo-spatial impairment as potential screening domains.

OBJECTIVE: In the intensive care setting, delirium is a common occurrence; however, the impact of the level of alertness has never been evaluated. Therefore, this study aimed to assess the delirium characteristics in the drowsy, as well as the alert and calm patient. METHOD: In this prospective cohort study, 225 intensive care patients with Richmond Agitation and Sedation Scale (RASS) scores of -1 - drowsy and 0 - alert and calm were evaluated with the Delirium Rating Scale-Revised-1998 (DRS-R-98) and the Diagnostic and Statistical Manual 4th edition text revision (DSM-IV-TR)-determined diagnosis of delirium. RESULTS: In total, 85 drowsy and 140 alert and calm patients were included. Crucial items for the correct identification of delirium were sleep-wake cycle disturbances, language abnormalities, thought process alterations, psychomotor retardation, disorientation, inattention, short- and long-term memory, as well as visuo-spatial impairment, and the temporal onset. Conversely, perceptual disturbances, delusions, affective lability, psychomotor agitation, or fluctuations were items, which identified delirium less correctly. Further, the severities of inattentiveness and visuo-spatial impairment were indicative of delirium in both alert- or calmness and drowsiness. SIGNIFICANCE OF RESULTS: The impairment in the cognitive domain, psychomotor retardation, and sleep-wake cycle disturbances correctly identified delirium irrespective of the level alertness. Further, inattentiveness and - to a lesser degree - visuo-spatial impairment could represent a specific marker for delirium in the intensive care setting meriting further evaluation.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): Symptom profile and utility of individual items in the identification of delirium dependent on the level of sedation.

OBJECTIVE: The importance of the proper identification of delirium, with its high incidence and adversities in the intensive care setting, has been widely recognized. One common screening instrument is the Intensive Care Delirium Screening Checklist (ICDSC); however, the symptom profile and key features of delirium dependent on the level of sedation have not yet been evaluated. METHOD: In this prospective cohort study, the ICDSC was evaluated versus the Diagnostic and Statistical Manual, 4th edition, text revision, diagnosis of delirium set as standard with respect to the symptom profile, and correct identification of delirium. The aim of this study was to identify key features of delirium in the intensive care setting dependent on the Richmond Agitation and Sedation Scale levels of sedation: drowsiness versus alert and calmness.ResultThe 88 delirious patients of 225 were older, had more severe disease, and prolonged hospitalization. Irrespective of the level of sedation, delirium was correctly classified by items related to inattention, disorientation, psychomotor alterations, inappropriate speech or mood, and symptom fluctuation. In the drowsy patients, inattention reached substantial sensitivity and specificity, whereas psychomotor alterations and sleep-wake cycle disturbances were sensitive lacked specificity. The positive prediction was substantial across items, whereas the negative prediction was only moderate. In the alert and calm patient, the sensitivities were substantial for psychomotor alterations, sleep-wake cycle disturbances, and symptom fluctuations; however, these fluctuations were not specific. The positive prediction was moderate and the negative prediction substantial. Between the nondelirious drowsy and alert, the symptom profile was similar; however, drowsiness was associated with alterations in consciousness.Significance of resultsIn the clinical routine, irrespective of the level of sedation, delirium was characterized by the ICDSC items for inattention, disorientation, psychomotor alterations, inappropriate speech or mood and symptom fluctuation. Further, drowsiness caused altered levels of consciousness.

Subsyndromal delirium in the intensive care setting: Phenomenological characteristics and discrimination of subsyndromal delirium versus no and full-syndromal delirium.

OBJECTIVE: Similar to delirium, its subsyndromal form has been recognized as the cause of diverse adverse outcomes. Nonetheless, the nature of this subsyndromal delirium remains vastly understudied. Therefore, in the following, we evaluate the phenomenological characteristics of this syndrome versus no and full-syndromal delirium. METHOD: In this prospective cohort study, we evaluated the Delirium Rating Scale-Revised, 1998 (DRS-R-98) versus the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnostic criteria and examined the diagnosis of delirium with respect to phenomenological distinctions in the intensive care setting. RESULTS: Out of 289 patients, 36 with subsyndromal delirium versus 86 with full-syndromal and 167 without delirium were identified. Agreement with respect to the DSM-IV-TR diagnosis of delirium was perfect. The most common subtype in those with subsyndromal delirium was hypoactive, in contrast to mixed subtype in those with full-syndromal delirium versus no motor alterations in those without delirium. By presence and severity of delirium symptoms, subsyndromal delirium was intermediate. The ability of the DRS-R-98 items to discriminate between either form of delirium was substantial. Between subsyndromal and no delirium, the cognitive domain and sleep-wake cycle were more impaired and allowed a distinction with no delirium. Further, between full- and subsyndromal delirium, the prevalence and severity of individual DRS-R-98 items were greater. Although the differences between these two forms of delirium was substantial, the items were not very specific, indicating that the phenomenology of subsyndromal delirium is closer to full-syndromal delirium. SIGNIFICANCE OF RESULTS: Phenomenologically, subsyndromal delirium was found to be distinct from and intermediate between no delirium and full-syndromal delirium. Moreover, the greater proximity to full-syndromal delirium indicated that subsyndromal delirium represents an identifiable subform of full-syndromal delirium.

Delirium in the intensive care setting: A reevaluation of the validity of the CAM-ICU and ICDSC versus the DSM-IV-TR in determining a diagnosis of delirium as part of the daily clinical routine.

BACKGROUND: In the intensive care setting, delirium is a common occurrence that comes with subsequent adversities. Therefore, several instruments have been developed to screen for and detect delirium. Their validity and psychometric properties, however, remain controversial. METHOD: In this prospective cohort study, the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) were evaluated versus the DSM-IV-TR in the diagnosis of delirium with respect to their validity and psychometric properties. RESULTS: Out of some 289 patients, 210 with matching CAM-ICU, ICDSC, and DSM-IV-TR diagnoses were included. Between the scales, the prevalence of delirium ranged from 23.3% with the CAM-ICU, to 30.5% with the ICDSC, to 43.8% with the DSM-IV-TR criteria. The CAM-ICU showed only moderate concurrent validity (Cohen's κ = 0.44) and sensitivity (50%), but high specificity (95%). The ICDSC also reached moderate agreement (Cohen's κ = 0.60) and sensitivity (63%) while being very specific (95%). Between the CAM-ICU and the ICDSC, the concurrent validity was again only moderate (Cohen's κ = 0.56); however, the ICDSC yielded higher sensitivity and specificity (78 and 83%, respectively). SIGNIFICANCE OF RESULTS: In the daily clinical routine, neither the CAM-ICU nor the ICDSC, common tools used in screening and detecting delirium in the intensive care setting, reached sufficient concurrent validity; nor did they outperform the DSM-IV-TR diagnostic criteria with respect to sensitivity or positive prediction, but they were very specific. Thus, the non-prediction by the CAM-ICU or ICDSC did not refute the presence of delirium. Between the CAM-ICU and ICDSC, the ICDSC proved to be the more accurate instrument.

Brief assessment of delirium subtypes: Psychometric evaluation of the Delirium Motor Subtype Scale (DMSS)-4 in the intensive care setting.

OBJECTIVE: The management of and prognosis for delirium are affected by its subtype: hypoactive, hyperactive, mixed, and none. The DMSS-4, an abbreviated version of the Delirium Motor Symptom Scale, is a brief instrument for the assessment of delirium subtypes. However, it has not yet been evaluated in an intensive care setting. METHOD: We performed a prospective/descriptive cohort study in order to determine the internal consistency, reliability, and validity of the relevant items of the DMSS-4 versus the Delirium Rating Scale-Revised-98 (DRS-R-98) and the original DMSS in a surgical intensive care setting. RESULTS: A total of 289 elderly, predominantly male patients were screened for delirium, and 122 were included in our sample. The internal consistency of the DMSS-4 items was excellent (Cronbach's α = 0.92), and between the DMSS-4 and DRS-R-98 the overall concurrent validity was substantial (Cramer's V = 0.67). Within individual motor subtypes, concurrent validity remained at least substantial (Cohen's κ = 0.65-0.81) and sensitivity high (69.8 to 82.2%), in contrast to those of the no-motor subtype, with less validity and sensitivity (κ = 0.28, 22%). Similarly, total concurrent validity between the DMSS-4 and the original DMSS reached perfection (Cramer's V = 0.83), as did agreement between the subtypes (κ = 0.83-0.92), while sensitivity remained high (88.2-100%). Only in those with delirium with no-motor subtype was agreement moderate (κ = 0.56) and sensitivity lower (67%). Specificity was high across all subtypes (91.2-99.1%). The DMSS-4 yielded very sensitive ratings, particularly for hypoactive and hyperactive motor symptoms, and interrater agreement was excellent (Fleiss's κ = 0.83). SIGNIFICANCE OF RESULTS: We found the DMSS-4 to be a most reliable and valid brief assessment of delirium in characterizing the subtypes of delirium in an intensive care setting, with increased sensitivity to hypoactive and hyperactive motor alterations.

OFDM and PAM comparison using a high baudrate low resolution IM/DD interface for 400G Ethernet access.

We compare OFDM and PAM for 400G Ethernet based on a 3-bit high baudrate IM/DD interface at 1550nm. We demonstrate 27Gb/s and 32Gb/s transmission over 10km SSMF using OFDM and PAM respectively. We show that capacity can be improved through adaptation/equalization to achieve 42Gb/s and 64Gb/s for OFDM and PAM respectively. Experimental results are used to create realistic simulations to extrapolate the performance of both modulation formats under varied conditions. For the considered interface we found that PAM has the best performance, OFDM is impaired by quantization noise. When the resolution limitation is relaxed, OFDM shows better performance.

Are preoperative sex-related differences of affective symptoms in primary brain tumor patients associated with postoperative histopathological grading?

Our objective was to explore the impact of the histopathological tumor type on affective symptoms before surgery among male and female patients with supratentorial primary brain tumors. A total of 44 adult patients were included in the study. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory. Additionally, clinical interviews, including the Hamilton Depression Rating Scale (HDRS), were conducted. The general function of patients was measured with the Karnofsky Performance Status scale (KPS). All measures were obtained before surgery and therefore before the final histopathological diagnosis. All self-rating questionnaires but not the HDRS, showed significantly higher scores in female patients. The functional status assessed with the KPS was lower in female patients and correlated to the somatic part of the BDI. We further found a tendency for higher HDRS scores in male patients with a WHO grade 4 tumor stage compared to female patients. This finding was supported by positive correlations between HDRS scores and WHO grade in male and negative correlations between HDRS scores and WHO grade in female patients. In conclusion the preoperative evaluation of affective symptoms with self-rating questionnaires in patients with brain tumors may be invalidated by the patient's functional status. Depression should be explored with clinical interviews in these patients. Sex differences of affective symptoms in this patient group may also be related to the malignancy of the tumor, but further studies are needed to disentangle this relationship.

Adaptive nonlinear Volterra equalizer for mitigation of chirp-induced distortions in cost effective IMDD OFDM systems.

We report experimental validations of an adaptive 2nd order Volterra equalization scheme for cost effective IMDD OFDM systems. This equalization scheme was applied to both uplink and downlink transmission. Downlink settings were optimized for maximum bitrate where we achieved 34 Gb/s over 10 km of SSMF using an EML with 10 GHz bandwidth. For the uplink, maximum reach was optimized achieving 14 Gb/s using a low-cost DML with 2.5 GHz bandwidth.

Sustained cognitive impairments after clinical recovery of severe depression.

Neuropsychological impairment is prominent in patients with depression, but it is unclear whether deficits persist after clinical response. This study aimed to investigate neuropsychological functions in the course of the illness. Depressive patients were investigated in the acute state and after clinical response using an extensive neuropsychological test battery. After clinical response, there was only a partial improvement in learning and memory and there were no changes regarding working memory, executive functions, and attention. Transient impairments in visual learning and memory suggest a depression-related state effect. The continuing deficits in attention, working memory, and executive function might be considered a trait marker.

Gender characteristics of cerebral hemodynamics during complex cognitive functioning.

Functional Transcranial Doppler sonography (fTCD) has been applied to assess peak mean cerebral blood flow velocity (MFV) with a high temporal resolution during cognitive activation. Yet, little attention has been devoted to gender-related alterations of MFV, including spectral analysis. In healthy subjects, fTCD was used to investigate a series of cerebral hemodynamic parameters in the middle cerebral arteries (MCA) during the Trail Making Tests (TMT), a means of selective attention and complex cognitive functioning. In females, there was a frequency peak at 0.375 Hz in both MCA, and we observed a dynamic shift in hemispheric dominance during that condition. Further, after the start phase, there was an MFV decline during complex functioning for the entire sample. These novel results suggest condition-specific features of cerebral hemodynamics in females, and it adds to the notion that gender is a fundamental confounder of brain physiology.

Differential Alterations in Resting State Functional Connectivity Associated with Depressive Symptoms and Early Life Adversity.

Depression and early life adversity (ELA) are associated with aberrant resting state functional connectivity (FC) of the default mode (DMN), salience (SN), and central executive networks (CEN). However, the specific and differential associations of depression and ELA with FC of these networks remain unclear. Applying a dimensional approach, here we analyzed associations of FC between major nodes of the DMN, SN, and CEN with severity of depressive symptoms and ELA defined as childhood abuse and neglect in a sample of 83 healthy and depressed subjects. Depressive symptoms were linked to increased FC within the SN and decreased FC of the SN with the DMN and CEN. Childhood abuse was associated with increased FC within the SN, whereas childhood neglect was associated with decreased FC within the SN and increased FC between the SN and the DMN. Our study thus provides evidence for differential associations of depressive symptoms and ELA with resting state FC and contributes to a clarification of previously contradictory findings. Specific FC abnormalities may underlie specific cognitive and emotional impairments. Future research should link specific clinical symptoms resulting from ELA to FC patterns thereby characterizing depression subtypes with specific neurobiological signatures.

Lorazepam modulates orbitofrontal signal changes during emotional processing in catatonia.

OBJECTIVE: Catatonia is a psychomotor syndrome characterized by concomitant emotional, behavioural and motor symptoms. In many cases clinical symptoms disappear almost immediately with administration of lorazepam, which acts on GABA(A) receptors. METHODS: Using functional magnetic resonance imaging (fMRI) we investigated prefrontal activation patterns during emotion processing in catatonic patients with and without lorazepam in a double-blind study design. For emotional stimulation the International Affective Picture System (IAPS) was used. BOLD-signals were determined using regions of interest (ROI) and were statistically compared between groups. RESULTS: For negative emotional pictures lorazepam induced higher signal decreases in the orbitofrontal cortex (OFC) in catatonic patients than in healthy subjects resulting in a regularization of activity patterns comparable to healthy subjects with placebo. CONCLUSIONS: Results indicate disturbances in the functioning of OFC in catatonia. GABAergic modified emotion regulation with decreased inhibition of affective stimuli could lead to the intense emotions reported by many catatonic patients.

The awareness of the scared - context dependent influence of oxytocin on brain function.

Oxytocin is both a hormone and a neurotransmitter and has been originally recognized for its role in childbirth and lactation. Later, it became widely known as a "cuddle hormone" that induces trusting behavior towards strangers and reduces social stress and anxiety. Several studies showed that oxytocin influences empathic behavior and has prosocial effects. The anterior cingulate cortex and the anterior insula are brain regions that are active when humans observe fear in others. Therefore, the aim of this study was to investigate whether oxytocin administration affects activity in these regions depending on whether a threat is directed at another person (empathy) compared to when the threat is directed at the subject itself (fear). Our findings demonstrate increased anterior cingulate cortex activation after oxytocin administration in the fear, but not in the empathy condition. Furthermore, oxytocin administration was associated with deceased anterior insula activity in the empathy condition. However, our findings do not support the idea that oxytocin generally augments activity in brain regions associated with empathy. Thereby this study supports current research questioning that oxytocin has exclusively prosocial effects on human behavior. Rather, the effect of oxytocin depends on various contextual (e.g. presence of a familiar person) and interindividual (e.g. sex, mental disorder) factors. Therefore, to consider oxytocin an empathy inducing hormone is an oversimplification and future research should focus on factors moderating oxytocin effects.

Validation and Psychometric Properties of the German Version of the Delirium Motor Subtype Scale (DMSS).

Objective: Delirium has been characterized into its subtypes-hypoactive, hyperactive, mixed, or no motor subtype-along with the use of the Delirium Motor Symptom Scale (DMSS). The German version of this scale (DMSS-G), however, has not yet been validated. Method: We determined internal consistency, reliability, and validity of the DMSS-G in the surgical intensive care unit, using DSM-IV-TR criteria and the Delirium Rating Scale-Revised-98. Results: In total, 289 patients were included, and out of these, 122 were delirious. The DMSS-G showed excellent internal consistency (Cronbach's α = 0.92) and interrater reliability (Fleiss κ = 0.83). Additionally, the overall concurrent validity was substantial (Cramer's V = 0.69); within subtypes, hyperactive, hypoactive, or mixed, the concurrent validity remained at least substantial (Cohen's κ = 0.73-0.82) and the sensitivity ranged from 60% to 97%. In contrast, in those with no motor subtype, we found the concurrent validity (Cohen's κ = 0.31) and sensitivity to be low (22%). Overall, specificity for all individual subtypes was high (82% to 100%). The DMSS was very sensitive in both rating hyperactive and hypoactive motor symptoms of delirium. Conclusion: The DMSS-G is a highly reliable and valid instrument for detecting motor symptoms in delirium, which provides an accurate instrument to classify the motor subtypes of delirium.

Screening for delirium with the Intensive Care Delirium Screening Checklist (ICDSC): a re-evaluation of the threshold for delirium.

BACKGROUND: With its high incidence and subsequent adverse consequences in the intensive care setting, several instruments have been developed to screen for and detect delirium. One of the more commonly used is the Intensive Care Delirium Screening Checklist (ICDSC); however, the optimal cut-off score indicating delirium has been debated. METHODS: In this prospective cohort study, the ICDSC threshold for delirium set at ≥3, ≥4, or ≥5 was compared with the DSM-IV-TR-determined diagnosis of delirium (used as standard), and with the Confusion Assessment Method for the ICU (CAM-ICU), with respect to their concurrent validity. RESULTS: In total, 289 patients were assessed, including 122 with delirium. The cut-off score of ≥4 had several shortcomings: although 90% of patients with delirium were correctly classified, 23% remained undetected. The agreement with the DSM-IV-TR diagnosis of delirium was only moderate (Cohen's κ 0.59) and the sensitivity was only 62%. In contrast, when the cut-off was ≥3, 83% of patients with delirium were correctly classified and only 14.5% remained undetected. The agreement with DSM-IV-TR was substantial (Cohen's κ 0.68) and the sensitivity increased to 83%. The benefit of setting the cut-off at ≥5 was not convincing: although 90% of patients with delirium were correctly classified, 30% remained undetected. The concurrent validity was only moderate (Cohen's κ 0.44), and the sensitivity reached only 44%. Changing the ICDSC cut-off score did not strengthen the moderate agreement with the CAM-ICU (Cohen's κ 0.45-0.56). CONCLUSION: In clinical routine, decreasing the ICDSC threshold for delirium to ≥3 increased the accuracy in detecting delirium at the cost of over-identification and is therefore recommended as the optimal threshold. Increasing the cut-off score to ≥5 decreased the concurrent validity and sensitivity; in addition, the under-detection of delirium was substantial.