[Cognitive impairments in patients with depression]. / Kognitive Störungen bei Patienten mit Depression.

Cognitive impairments are frequent in patients suffering from major depressive disorders. They are among the first symptoms, often persist independently of improvement even after remission of the affective symptoms and are an important predictor of psychosocial functioning. In the clinical practice it is mandatory to ask about subjective complaints of the patient as well as to assess the cognitive abilities with the help of a standardized neuropsychological test battery. Cognitive remediation, selective serotonin reuptake inhibitors (SSRI) and vortioxetine as well as repetitive transcranial magnetic stimulation have proven their effectiveness as treatment options.

[Mental disorders after acquired CNS damage]. / Psychische Störungen nach erworbener ZNS-Schädigung.

Mental disorders are a frequent consequence of acquired central nervous damage. If not recognized and treated early, they have a negative impact on the course of neurological rehabilitation. This article deals with the diagnosis and treatment of mental disorders after acquired damage to the central nervous system.

Enhanced stress response by a bilateral feet compared to a unilateral hand Cold Pressor Test.

The Cold Pressor Test (CPT) is a frequently employed laboratory stress protocol. However, with many experimental designs the application in its classic form (immersion of the dominant hand into ice-water) is problematic as unilateral stimulation may need to be avoided and/or hands are required for further measurements. Here, we describe a simple modification of the classic CPT in which both feet are immersed into ice-water and compare the evoked neuroendocrine stress response to the classic CPT in a within-subjects design. Twenty-four healthy participants were exposed to each of both CPT versions on two subsequent days in randomized order. Heart rate, blood pressure, salivary alpha-amylase and cortisol were measured at baseline and during or after CPT exposition, respectively, along with subjective ratings of pain and stress. The bilateral feet CPT induced marked increases in all measured stress parameters. Moreover, with the exception of blood pressure, autonomic and endocrine responses were enhanced compared to the classic CPT. The bilateral feet CPT thus is a valid and simple modification and may be useful when the application of the classic CPT is unfeasible or a stronger neuroendocrine stress response is of interest.

Intranasal insulin increases regional cerebral blood flow in the insular cortex in men independently of cortisol manipulation.

Insulin and cortisol play a key role in the regulation of energy homeostasis, appetite, and satiety. Little is known about the action and interaction of both hormones in brain structures controlling food intake and the processing of neurovisceral signals from the gastrointestinal tract. In this study, we assessed the impact of single and combined application of insulin and cortisol on resting regional cerebral blood flow (rCBF) in the insular cortex. After standardized periods of food restriction, 48 male volunteers were randomly assigned to receive either 40 IU intranasal insulin, 30 mg oral cortisol, both, or neither (placebo). Continuous arterial spin labeling (CASL) sequences were acquired before and after pharmacological treatment. We observed a bilateral, locally distinct rCBF increase after insulin administration in the insular cortex and the putamen. Insulin effects on rCBF were present regardless of whether participants had received cortisol or not. Our results indicate that insulin, but not cortisol, affects blood flow in human brain structures involved in the regulation of eating behavior.

Heart rate response to post-learning stress predicts memory consolidation.

Stressful experiences are often well remembered, an effect that has been explained by beta-adrenergic influences on memory consolidation. Here, we studied the impact of stress induced heart rate (HR) responses on memory consolidation in a post-learning stress paradigm. 206 male and female participants saw 52 happy and angry faces immediately before being exposed to the Cold Pressor Test or a non-stressful control procedure. Memory for the faces and their respective expression was tested twice, after 30 min and on the next day. High HR responders (in comparison to low HR responders as well as to the non-stressful control group) showed enhanced recognition memory one day after learning. Our results show that beta-adrenergic activation elicited shortly after learning enhances memory consolidation and that the stress induced HR response is a predictor for this effect.

Acute effects of a single dose of 2 mA of anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex on executive functions in patients with schizophrenia-A randomized controlled trial.

OBJECTIVE: Cognitive impairments are a frequent and difficult to treat symptom in patients with schizophrenia and the strongest predictor for a successful reintegration in occupational and everyday life. Recent research suggests transcranial direct current stimulation (tDCS) to enhance cognition in this patient group. However, the question regarding its acute effectiveness on executive functions remains largely unanswered. Here, we examined in a randomized, double blind, sham-controlled repeated-measures design the impact of tDCS on performance in several executive functions in patients with schizophrenia, schizoaffective disorder or acute transient psychotic disorder. METHODS: Patients (N = 48) were tested twice using standardized, well-constructed and clinically validated neuropsychological tests assessing verbal working memory, response inhibition, mental flexibility and problem solving. In session 1 they solely underwent the neuropsychological assessment, whereas in session 2 they additionally received 2 mA of anodal tDCS stimulation over the left dorsolateral prefrontal cortex (DLPFC), cathode right supraorbital ridge, or sham stimulation for 20 minutes. RESULTS: Patients of both groups were not able to correctly discriminate the type of stimulation received confirming the success of the blinding procedure. However, analyzing the whole sample the change in performance from session 1 to session 2 was the same in the verum as in the sham condition (all p >.5). Moreover, a subsequent exploratory analysis showed that performance in the response inhibition task was worse for patients that engaged in the task within 20 minutes after the end of the verum stimulation. CONCLUSION: Hence, 2 mA of anodal tDCS applied over the left DLPFC did not acutely enhance executive functions in patients with schizophrenia or related disorders but impaired performance in the response inhibition task shortly after. Future studies should continue to seek for effective stimulation configurations for this patient group. CLINICAL TRIAL REGISTRATION: The study is registered in the "Deutsches Register Klinischer Studien DRKS", German Clinical Trial Register and has been allocated the following number: DRKS00022126.

Combining mental and physical stress: Synergy or interference?

Both cognitive stressors (such as mental arithmetic tasks) and physical stressors (such as the cold pressor test, CP) are among the most widely employed tools in acute stress research, and there is growing evidence for a high degree of stimulus-response specificity, rather than uniformity, in the human stress response. However, little is known about potential synergistic or interfering effects during concurrent administration. While cognitive tasks have been hypothesized to attenuate pain perception during CP, they are also thought to enhance physiological reactivity. Conversely, physical stress might interfere with effective stress induction by cognitive challenges. To address these questions, 56 participants underwent either the CP (3-min ice-water immersion of feet) or a warm-water control condition. In half of the sample, the Paced Auditory Serial Addition Task (PASAT) was performed simultaneously (fully crossed interventions). Salivary cortisol, cardiovascular parameters, and subjective ratings as well as voice pitch (F0) were assessed. Results show that cortisol responses, self-reported pain and subjective arousal were mainly driven by cold exposure, which also led to increased F0. The PASAT incrementally enhanced cardiovascular reactions, but did not affect pain ratings nor cortisol responses to the CP. However, intra-individual concordance between elevated blood pressure and other reactivity measures was enhanced by PASAT administration during the CP. Importantly, performance decrements in the mental-arithmetic task were not associated with diminished stress responses. In conclusion, our results speak against any strong interference when administering cognitive and painful physical stressors simultaneously, pointing rather to specific additive effects, particularly regarding cardiovascular reactivity.

Computer-Assisted Cognitive Remediation in Schizophrenia: Efficacy of an Individualized vs. Generic Exercise Plan.

Computer-assisted cognitive remediation (CACR) is an economical, adjustable, and effective treatment for individuals with schizophrenia. The current randomized controlled study examined whether an individualized or generic exercise plan in CACR is superior in patients with multiple cognitive deficits compared to treatment-as-usual (TAU). Fifty-nine inpatients diagnosed with schizophrenia were randomly assigned to 1) TAU, 2) TAU plus an individualized exercise plan in CACR, or 3) TAU plus a generic exercise plan in CACR. Neuropsychological performance, psychopathology, and functional outcome were assessed at baseline and post-treatment. The results show a medium to large training effect for all neuropsychological performance measures. Contrary to our expectations the neuropsychological improvement over time did not differ between groups. Self-reported depression, global level of functioning, and activity and participation functioning showed a significant improvement from baseline to post-treatment. However no further group, time, or interaction effects for other psychopathology and functional outcome could be demonstrated. Possible implications for clinical use of CACR and future studies are discussed.

Visceral-afferent signals from the cardiovascular system, but not urinary urge, affect startle eye blink.

The aim of the current study was to investigate if startle methodology is suitable to reflect urinary urgency. Eighteen healthy men were tested on two separate days, each including an ingestion of fluid until 80% of the subjective urge to micturate was reached. EMG responses to acoustic startle stimuli were assessed before and after micturition, as well as in the early and late cardiac cycle phases (230 vs. 530 ms after a cardiac R-wave). Sonographic assessment confirmed bladder-filling status. Emotional arousal, stress, urge and unpleasantness ratings, as well as mean blood pressure were higher before than after micturition. Startle eye blink responses were lower during the early than during the late cardiac cycle phase, but were not affected by bladder filling status. We conclude that startle methodology is suitable for the investigation of afferent signals from the cardiovascular system, but not to reflect urinary urgency. This result may be due to different neurophysiological mechanisms underlying afferent signals from the bladder compared to other visceral organs or interference with affective states or sympathetic activation associated with bladder filling. Notwithstanding, the present research protocol of fluid intake, sonographic assessment of the bladder, and subjective reports, can be applied to examine effects of urinary urge on physiological and psychological processes.

Emotional stress regulation: The role of relative frontal alpha asymmetry in shaping the stress response.

Frontal EEG asymmetry has been proposed as an index of emotional regulation, reflecting both state and trait components, and there is evidence that these factors influence the cortisol response to stress. Here, we asked whether cold pressor stress modulates frontal asymmetry and whether this is predictive of the neuroendocrine stress response. Twenty-four male participants underwent an automatized bilateral feet cold pressor test (bfCPT) and a warm water control procedure in counterbalanced order on two separate days, one week apart. EEG, heart rate and blood pressure were assessed at baseline as well as during and after the bfCPT. Salivary cortisol and subjective ratings of stress and arousal were assessed before and after the bfCPT. The bfCPT led to a significant increase in cortisol, cardiovascular parameters and in subjective ratings of stress and arousal that was absent in the control condition. Furthermore, analysis of relative frontal alpha-band asymmetry revealed a stronger relative right frontal activation during the bfCPT compared to the control condition at electrode pairs F7/8 but not F3/4. However, frontal asymmetry scores during the bfCPT were not predictive for neither physiological responses nor subjective ratings. Moreover, an association between physiological responses and frontal asymmetry assessed during rest at baseline could be observed at electrode pairs F3/F4, with stronger responses being associated with stronger relative right frontal activation. Our results show that cold pressor stress leads to an alteration of emotional processes as reflected in frontal EEG asymmetry at F7/F8. Moreover, physiological responses to the CPT seem to be differentially moderated by trait and state components present in frontal asymmetry.

Respiratory modulation of startle eye blink: a new approach to assess afferent signals from the respiratory system.

Current approaches to assess interoception of respiratory functions cannot differentiate between the physiological basis of interoception, i.e. visceral-afferent signal processing, and the psychological process of attention focusing. Furthermore, they typically involve invasive procedures, e.g. induction of respiratory occlusions or the inhalation of CO2-enriched air. The aim of this study was to test the capacity of startle methodology to reflect respiratory-related afferent signal processing, independent of invasive procedures. Forty-two healthy participants were tested in a spontaneous breathing and in a 0.25 Hz paced breathing condition. Acoustic startle noises of 105 dB(A) intensity (50 ms white noise) were presented with identical trial frequency at peak and on-going inspiration and expiration, based on a new pattern detection method, involving the online processing of the respiratory belt signal. The results show the highest startle magnitudes during on-going expiration compared with any other measurement points during the respiratory cycle, independent of whether breathing was spontaneous or paced. Afferent signals from slow adapting phasic pulmonary stretch receptors may be responsible for this effect. This study is the first to demonstrate startle modulation by respiration. These results offer the potential to apply startle methodology in the non-invasive testing of interoception-related aspects in respiratory psychophysiology.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.

The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects.

The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression. Forty participants (50% males and 50% females) were randomly assigned to groups receiving a saline placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was drawn every 15 min to measure quantitative gene expression of PER1, PER2 and PER3. A potential role of the GR was determined by an ex vivo study stimulating whole blood with hydrocortisone and RU486 (a GR antagonist). As a result, moderate doses of hydrocortisone produced an acute and temporary induction of PER1 and PER3 mRNA levels, whereas PER2 was not responsive to the hormone administration. The cortisol-dependent induction of PER1 was blocked by the GR antagonist in whole blood after treatment with hydrocortisone and RU486 ex vivo. In conclusion, acute pharmacological stress modulated the expression of PER1 and PER3 in whole blood temporarily in our short-term sampling design, suggesting that these circadian genes mediate stable molecular mechanisms in the periphery.

Startle eye-blink modulation by facial self-resemblance and current mood.

Although salient stimuli are known to modulate startle eye-blink responses, and one's own face is considered of particular salience, effects of facial self-resemblance on startle responsiveness have not been systematically investigated. For the present study, pictures from the FACES database (rated as neutral) were digitally morphed to resemble the participants' (N=37) faces to varying degrees (25-50-75%). Perceptually matched geometrical shapes served as a control condition. At SOAs of either 300ms or 3000ms after picture onset, startle responses were elicited by white noise (50ms, 105dB), and recorded at the orbicularis oculi via EMG. Prior to the experiment, self-reported mood was assessed by means of the PANAS. Relative to non-face stimuli, the presentation of faces reduced startle magnitude at short, but not long, lead intervals. Furthermore, for probes presented at a SOA of 300ms, a linear decrease in startle magnitude with higher levels of self-resemblance was observed, presumably reflecting higher salience of the self-face. The startle modulating effect of self-resembling faces during longer lead intervals was moderated by the participants' current mood: negative affect predicted stronger patterns of attenuation, which might be interpreted as an increase in self-focus resulting from more negative mood.

Rapid cortisol enhancement of psychomotor and startle reactions to side-congruent stimuli in a focused cross-modal choice reaction time paradigm.

The stress hormone cortisol has been shown to affect hemodynamic activity of human brain structures, presumably via a nongenomic mechanism. However, behavioral implications of this finding remain unknown. In a placebo-controlled, blinded, cross-over design the rapid effects of IV hydrocortisone (5mg) on cross-modal integration of simultaneous, unilateral visual and acoustic signals in a challenging startle and reaction time (RT) paradigm were studied. On two separate days 1 week apart, 24 male volunteers responded by button push to either up- or down pointing triangles presented in random sequence in the periphery of one of the visual hemi-fields. Visual targets were accompanied by unilateral acoustic startle noise bursts, presented at the same or opposite side. Saccadic latency, manual RT, and startle eye blink responses were recorded. Faster manual reactions and increased startle eye blink responses were observed 11-20 min after hydrocortisone administration when visual targets and unilateral acoustic startle noises were presented in the same sensory hemi-field, but not when presented in opposite sensory hemi-fields. Our results suggest that a nongenomic, cortisol-sensitive mechanism enhances psychomotor and startle reactions when stimuli occur in the same sensory hemi-field. Such basic cognitive effects of cortisol may serve rapid adaptation and protection against danger stimuli in stressful contexts.

Startle effects on saccadic responses to emotional target stimuli.

Startle stimuli elicit various physiological and cognitive responses. This study investigated whether acoustic startle stimuli affect saccadic reactions in an emotional pro- or antisaccade task. Startle probes were presented either 500 ms before or simultaneous with an imperative stimulus that indicated whether a saccade towards or away from positive, neutral, or negative peripheral target pictures had to be performed. Valence interacted with saccade direction according to an approach-avoidance pattern of gaze behavior, with delayed prosaccades to negative targets and antisaccades away from positive targets. Acoustic startle stimuli preceding the presentation of peripheral target pictures speeded up the initiation saccades, irrespective of stimulus valence. Results indicate a speeding of cognitive-motor processing by preceding startle stimuli.

For whom the bell (curve) tolls: cortisol rapidly affects memory retrieval by an inverted U-shaped dose-response relationship.

Stress and cortisol are generally considered to impair declarative memory retrieval, although opposite results have also been reported. Dose-dependent effects and differences between genomic and non-genomic cortisol effects are possible reasons for these discrepancies. The aim of the current experiment was to assess the non-genomic effects of escalating doses of intravenous cortisol on cued recall of socially relevant information in humans. 40 participants (age range 20-30 years; 20 females) learned associations between male faces with a neutral facial expression and descriptions of either positive or negative social behaviors and were tested one week later in a cued recall paradigm. Escalating doses of cortisol (0, 3, 6, 12, 24 mg) were administered 8 min before testing according to a between-subjects design. An inverted U-shaped dose-response relationship between salivary cortisol levels and recall performance was observed, with moderate elevation of salivary cortisol resulting in the best recall performance. This is the first study in humans demonstrating that cortisol rapidly modulates declarative memory retrieval via a dose-dependent, non-genomic mechanism that follows an inverted U-shaped curve. Our result further emphasizes the importance of fast cortisol effects for human cognition.