Multimodal Assessment of Smoking cue Reactivity During a Smoking Cue Exposure Task.

Background. Cue-reactivity as a characteristic symptom of substance use disorders (SUD) is highly context dependent. Paradigms with high context validity need to be established for the investigation of underlying neurobiological mechanisms. While craving can be assessed by self-report as one aspect of cue-reactivity (CR), the assessment of biological measures such as the autonomous response and EEG promises a holistic perspective including CR at an automatized level. In a multimodal approach, smoking cue exposure (CE) effects on heart rate variability (HRV), EEG frequency power, and craving as well as their interrelation were assessed. This pilot study focused on the validity of CR measurements in a naturalistic CE paradigm. Methods. EEG frequency power, HRV, and craving were assessed during resting state (RS) and smoking CE in smokers (n = 14) and nonsmoking controls (n = 10) to investigate the psychophysiological and subjective reactions to CE. Results. Increased beta power was found only in smokers during CE compared to the control condition. There was an inverse correlation of beta power and maximum craving. Likewise, HRV correlated negatively with maximum smoking urges in smokers immediately after the measurements, without differentiation between CE and control condition. Conclusion. The increased beta power in smokers during CE is discussed as increased inhibitory control related to reduced craving in smokers. Furthermore, increased craving during CE seems to be associated to decreased vagal activity. The multimodal measurements during the CE showed ecological validity to be fundamental for CE assessment in clinical populations to evaluate its predictive value.

Orthostatic hypotension as a risk factor for longitudinal deterioration of cognitive function in the elderly.

BACKGROUND AND PURPOSE: Orthostatic hypotension is frequent with aging with a prevalence of 20%-30% in people aged 65 or older and is considered to increase the risk for coronary events, strokes and dementia. Our objective was to characterize the association of orthostatic hypotension and cognitive function longitudinally over 6 years in a large cohort of the elderly aged over 50 years. METHODS: In all, 495 participants were assessed longitudinally with the Schellong test and comprehensive cognitive testing using the extended CERAD neuropsychological test battery at baseline and after 6 years. In a subgroup of 92 participants, cerebral magnetic resonance imaging was evaluated for white matter changes using a modified version of the Fazekas score. RESULTS: The prevalence of orthostatic hypotension increases with aging reaching up to 30% in participants aged >70 years. Participants with orthostatic hypotension presented with a higher vascular burden index (1.03 vs. 0.69, P ≤ 0.001), tended to have a higher prevalence of cerebral white matter hyperintensities (91.7% vs. 68.8%, P = 0.091) and showed a faster deterioration in executive and memory function (Trail Making Test B 95 vs. 87 s, P ≤ 0.001; word list learning sum -0.53 vs. 0.38, P = 0.002) compared to participants without orthostatic hypotension. CONCLUSION: Orthostatic hypotension seems to be associated with cognitive decline longitudinally.

Beneficial effects of anodal transcranial direct current stimulation (tDCS) on spatial working memory in patients with schizophrenia.

Schizophrenia is a severe and often detrimental psychiatric disorder. The individual patients' level of functioning is essentially determined by cognitive, particularly working memory (WM), deficits that are critically linked to dysfunctional activity of the dorsolateral prefrontal cortex (dlPFC). Transcranial direct current stimulation (tDCS) can transiently modulate activity of the dlPFC and remote areas and has been shown to improve WM functions. It may therefore provide a new, targeted treatment option. For this aim, the present study investigated the effect of anodal tDCS of different intensities on spatial WM in patients with schizophrenia. In two experiments, 32 patients performed a spatial n-back task with increasing WM load (1-, 2-, and 3-back) at baseline and in two sessions with anodal or sham tDCS (EXP I [n = 16]: 1 mA; EXP II [n = 16]: 2 mA) to the right dlPFC (cathode: left m. deltoideus). With 1 mA anodal tDCS, no effect on WM performance could be detected. However, 2 mA anodal tDCS increased accuracy (measured by d') of the task with the highest WM load (3-back). This effect was larger in patients with a lower level of general neurocognitive functioning. These results demonstrate a beneficial effect of 2 mA anodal tDCS on deficient WM accuracy in patients with schizophrenia particularly under challenging conditions and in subjects with higher cognitive impairments. This data will inform future clinical trials on tDCS-enhanced cognitive training to improve treatment of schizophrenia.

[Rationality and freedom in medicine: the case of electroconvulsive therapy]. / Rationalität und Freiheit in der Medizin: Der Fall der Elektrokrampftherapie.

There are no rational reasons why electroconvulsive therapy (ECT) should not be subject to the same criteria in its clinical application as any other treatment in medicine. Associations referring to historical events and their presentation in the media do not provide convincing arguments against the clinical use of ECT. In order to offer ECT to patients, scientifically solid evidence with respect to its clinical results must be available. As this scientific evidence is clearly given, ECT must be offered to the patients. A well-informed, reflected medicine must not withhold an effective treatment like ECT from the patients and medicine should not be influenced by associations but only by scientific evidence, even though the exact mechanisms of action of ECT are not known in detail. The image of ECT has clearly improved during the last decades thereby increasing the hope that unjustified arguments against ECT will lose their impact.

Whole brain MP2RAGE-based mapping of the longitudinal relaxation time at 9.4T.

Mapping of the longitudinal relaxation time (T1) with high accuracy and precision is central for neuroscientific and clinical research, since it opens up the possibility to obtain accurate brain tissue segmentation and gain myelin-related information. An ideal, quantitative method should enable whole brain coverage within a limited scan time yet allow for detailed sampling with sub-millimeter voxel sizes. The use of ultra-high magnetic fields is well suited for this purpose, however the inhomogeneous transmit field potentially hampers its use. In the present work, we conducted whole brain T1 mapping based on the MP2RAGE sequence at 9.4T and explored potential pitfalls for automated tissue classification compared with 3T. Data accuracy and T2-dependent variation of the adiabatic inversion efficiency were investigated by single slice T1 mapping with inversion recovery EPI measurements, quantitative T2 mapping using multi-echo techniques and simulations of the Bloch equations. We found that the prominent spatial variation of the transmit field at 9.4T (yielding flip angles between 20% and 180% of nominal values) profoundly affected the result of image segmentation and T1 mapping. These effects could be mitigated by correcting for both flip angle and inversion efficiency deviations. Based on the corrected T1 maps, new, 'flattened', MP2RAGE contrast images were generated, that were no longer affected by variations of the transmit field. Unlike the uncorrected MP2RAGE contrast images acquired at 9.4T, these flattened images yielded image segmentations comparable to 3T, making bias-field correction prior to image segmentation and tissue classification unnecessary. In terms of the T1 estimates at high field, the proposed correction methods resulted in an improved precision, with test-retest variability below 1% and a coefficient-of-variation across 25 subjects below 3%.

[Architectural modernization of psychiatric hospitals influences the use of coercive measures]. / Bauliche Modernisierungen in psychiatrischen Kliniken beeinflussen Zwangsmaßnahmen.

BACKGROUND: Coercive measures are widely applied in psychiatric hospitals as a last resort to prevent patients seriously harming themselves or others, with negative psychological and somatic consequences for those affected. OBJECTIVE: In a naturalistic observational study it was investigated whether relocation of the structural milieu of a psychiatric hospital to an architectonically improved new building influenced the application of coercive measures. MATERIAL AND METHODS: The frequency and duration of coercive measures (e.g. fixation, coercive medication and preventive restraints) were routinely documented and compared in the periods before and after the relocation. RESULTS: After the relocation the utilization of coercive measures was significantly reduced by 48-84 %. CONCLUSION: Despite the limitations of the study design the results suggest that the architectural improvements reduced the application of coercive measures. It is speculated that the positive structural milieu enhanced the well-being of patients and staff and their social relations, which in turn prevented coercive measures.

Effects of transcranial direct current stimulation on craving, heart-rate variability and prefrontal hemodynamics during smoking cue exposure.

OBJECTIVE: Drug-related cue exposure elicits craving and risk for relapse during recovery. Transcranial direct current stimulation is a promising research tool and possible treatment for relapse prevention. Enhanced functional neuroconnectivity is discussed as a treatment target. The goal of this research was to examine whether transcranial direct current stimulation affected cortical hemodynamic indicators of functional connectivity, craving, and heart rate variability during smoking-related cue exposure in non-treatment-seeking smokers. METHOD: In vivo smoking cue exposure supported by a 2mA transcranial direct current stimulation (anode: dorsolateral prefrontal cortex, cathode: orbitofrontal cortex; placebo-controlled, randomized, double-blind) in 29 (age: M=25, SD=5) German university students (smoking at least once a week). Cue reactivity was assessed on an autonomous (heart rate variability) and a subjective level (craving ratings). Functional near-infrared spectroscopy measured changes in the concentration of deoxygenated hemoglobin, and seed-based correlation analysis was used to quantify prefrontal connectivity of brain regions involved in cue reactivity. RESULTS: Cue exposure elicited increased subjective craving and heart rate variability changes in smokers. Connectivity between the orbitofrontal and dorsolateral prefrontal cortex was increased in subjects receiving verum compared to placebo stimulation (d=0.66). Hemodynamics in the left dorsolateral prefrontal cortex, however, increased in the group receiving sham stimulation (η2=0.140). Transcranial direct current stimulation did not significantly alter craving or heart rate variability during cue exposure. CONCLUSION: Prefrontal connectivity - between regions involved in the processing of reinforcement value and cognitive control - was increased by anodal transcranial direct current stimulation during smoking cue exposure. Possible clinical implications should be considered in future studies.

Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia.

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further.

Psychophysiological effects of an iTBS modulated virtual reality challenge including participants with spider phobia.

Preliminary evidence suggests beneficial effects of transcranial magnetic stimulation (TMS) on anxiety. The objective of this study was to investigate the effects of intermittent theta burst stimulation (iTBS) as a form of TMS on acute anxiety provoked by a virtual reality (VR) scenario. Participants with spider phobia (n=41) and healthy controls (n=42) were exposed to a spider scenario in VR after one session of iTBS over the prefrontal cortex or sham treatment. Participants with spider phobia reacted with more anxiety compared to healthy controls. Their heart rate and skin conductance increased compared to baseline. Contrary to expectations, iTBS did not influence these reactions, but modulated heart rate variability (HRV). Sympathetic influence on HRV showed an increase in the active iTBS group only. This study does not support the idea of beneficial effects of a single session of iTBS on anxiety, although other protocols or repeated sessions might be effective.

[Non-invasive brain stimulation for treatment of schizophrenic psychoses]. / Hirnstimulationsverfahren zur Behandlung schizophrener Psychosen.

Despite many different available pharmacological and psychosocial treatment options, an optimal control of symptoms is only partly possible for most schizophrenia patients. Especially, persistent auditory hallucinations, negative symptoms and cognitive impairment are difficult to treat symptoms. Several non-invasive brain stimulation techniques are increasingly being considered as new therapeutic add on options for the management of schizophrenia, targeting these symptom domains. The technique which has been available for the longest time and that is best established in clinical care is electroconvulsive therapy (ECT). New stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) allow a more pathophysiological-based approach. This review article introduces various non-invasive brain stimulation techniques and discusses recent treatment studies on schizophrenia. In total, the novel brain stimulation techniques discussed here can be considered relevant add on therapeutic approaches for schizophrenia. In this context, the best evidence is available for the application of rTMS for the treatment of negative symptoms and persistent auditory hallucinations; however, negative studies have also been published for both indications. Studies using other non-invasive brain stimulation techniques showed promising results but further research is needed to establish the clinical efficacy. Based on a growing pathophysiological knowledge, non-invasive brain stimulation techniques provide new treatment perspectives for patients with schizophrenia.

Brain correlates of verbal fluency in subthreshold psychosis assessed by functional near-infrared spectroscopy.

The prevalence of subthreshold psychotic symptoms in the general population has gained increasing interest as a possible precursor of psychotic disorders. The goal of the present study was to evaluate whether neurobiological features of subthreshold psychotic symptoms can be detected using verbal fluency tasks and functional near-infrared spectroscopy (fNIRS). A large data set was obtained from the Zurich Program for Sustainable Development of Mental Health Services (ZInEP). Based on the SCL-90-R subscales 'Paranoid Ideation' and 'Psychoticism' a total sample of 188 subjects was assigned to four groups with different levels of subthreshold psychotic symptoms. All subjects completed a phonemic and semantic verbal fluency task while fNIRS was recorded over the prefrontal and temporal cortices. Results revealed larger hemodynamic (oxy-hemoglobin) responses to the phonemic and semantic conditions compared to the control condition over prefrontal and temporal cortices. Subjects with high subthreshold psychotic symptoms exhibited significantly reduced hemodynamic responses in both conditions compared to the control group. Further, connectivity between prefrontal and temporal cortices revealed significantly weaker patterns in subjects with high subthreshold psychotic symptoms compared to the control group, possibly indicating less incisive network connections associated with subthreshold psychotic symptoms. The present findings provide evidence that subthreshold forms of psychotic symptoms are associated with reduced hemodynamic responses and connectivity in prefrontal and temporal cortices during verbal fluency that can be identified using fNIRS.

Stress-induced neuroplasticity: (mal)adaptation to adverse life events in patients with PTSD--a critical overview.

Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and associated neurochemical reactions, following glucocorticoid release from the adrenal glands, accompanied by rapid physiological responses. Stimulation of this pathway results in the activation of specific brain regions, including the hippocampus, amygdala and prefrontal cortex which are enriched with glucocorticoid receptors (GRs). Recent findings indicate that the activation of GRs mediates the regulation of the brain-derived neurotrophic factor (BDNF). BDNF is crucial for neural plasticity, as it promotes cellular growth and synaptic changes. Hence stress-induced activation of these pathways leads to neuroplastic changes, including the formation of long-lasting memories of the experiences. As a consequence, organisms can learn from stressful events and respond in an adaptive manner to similar demands in the future. Whereas an optimal stress level leads to enhancement of memory performance, the exposure to extreme, traumatic or chronic stressors is a risk factor for psychopathologies which are associated with memory impairment and cognitive deficits such as posttraumatic stress disorder (PTSD). In this review article, we will outline the implications of stress exposure on memory formation involving the role of glucocorticoids and BDNF. Within this context, potential adverse effects of neuroplastic alterations will be discussed using the example of PTSD.

Reconstructing functional near-infrared spectroscopy (fNIRS) signals impaired by extra-cranial confounds: an easy-to-use filter method.

Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging method that detects temporal concentration changes of oxygenated and deoxygenated hemoglobin within the cortex, so that neural activation can be inferred. However, even though fNIRS is a very practical and well-tolerated method with several advantages particularly in methodically challenging measurement situations (e.g., during tasks involving movement or open speech), it has been shown to be confounded by systemic compounds of non-cerebral, extra-cranial origin (e.g. changes in blood pressure, heart rate). Especially event-related signal patterns induced by dilation or constriction of superficial forehead and temple veins impair the detection of frontal brain activation elicited by cognitive tasks. To further investigate this phenomenon, we conducted a simultaneous fNIRS-fMRI study applying a working memory paradigm (n-back). Extra-cranial signals were obtained by extracting the BOLD signal from fMRI voxels within the skin. To develop a filter method that corrects for extra-cranial skin blood flow, particularly intended for fNIRS data sets recorded by widely used continuous wave systems with fixed optode distances, we identified channels over the forehead with probable major extra-cranial signal contributions. The averaged signal from these channels was then subtracted from all fNIRS channels of the probe set. Additionally, the data were corrected for motion and non-evoked systemic artifacts. Applying these filters, we can show that measuring brain activation in frontal brain areas with fNIRS was substantially improved. The resulting signal resembled the fMRI parameters more closely than before the correction. Future fNIRS studies measuring functional brain activation in the forehead region need to consider the use of different filter options to correct for interfering extra-cranial signals.

Voluntary suppression of thoughts is influenced by anxious and ruminative tendencies in healthy volunteers.

Replicating thought suppression effects with the Think/No-Think paradigm (TNT) has failed in some studies investigating the phenomenon of below-baseline recall of suppressed stimuli. Attempts have been made to isolate factors that might explain inter-individual differences in suppression performance. Certain personality traits, whether associated with a pathological state or investigated in a community sample, have been shown to interfere with successful thought suppression and might be responsible for some of the negative results obtained in TNT studies. In the present study we investigate the influence of psychometric measures of depression and anxiety in a fairly large sample of healthy volunteers. We show that high brooding and anxious tendencies predict worse suppression performance. While no suppression was shown when investigating the TNT not taking the psychometric measures into account, including these two traits in the analysis resulted in a pattern of below-baseline recall only for low brooders and low anxious participants. We argue that inclusion of variables measuring personality traits is warranted using the TNT and that these variables already exert their influence at minimal levels of variance, significantly improving the interpretability of the results. Future research should therefore cautiously investigate potential confounding personality characteristics before analysing their data.

Similar autobiographical memory impairment in long-term secondary progressive multiple sclerosis and Alzheimer's disease.

BACKGROUND: Memory disturbance is a common symptom of multiple sclerosis (MS), but little is known about autobiographical memory deficits in the long-term course of different MS subtypes. Inflammatory activity and demyelination is pronounced in relapsing-remitting multiple sclerosis (RRMS) whereas, similar to Alzheimer's disease, neurodegeneration affecting autobiographical memory-associated areas is seen in secondary progressive multiple sclerosis (SPMS). OBJECTIVE: In light of distinct disease mechanisms, we evaluated autobiographical memory in different MS subtypes and hypothesized similarities between elderly patients with SPMS and Alzheimer's disease. METHODS: We used the Autobiographical Memory Interview to assess episodic and semantic autobiographical memory in 112 education- and gender-matched participants, including healthy controls and patients with RRMS, SPMS, amnesic mild cognitive impairment (aMCI) and early Alzheimer's dementia (AD). RESULTS: Patients with SPMS, AD, and aMCI, but not with RRMS, exhibited a pattern of episodic autobiographical memory impairment that followed Ribot's Law; older memories were better preserved than more recent memories. In contrast to aMCI and AD, neither SPMS nor RRMS was associated with semantic autobiographical memory impairment. CONCLUSION: Our neuropsychological findings suggest that episodic autobiographical memory is affected in long-term patients with SPMS, possibly due to neurodegenerative processes in functional relevant brain regions.

Reliability of the emotional Stroop task: an investigation of patients with panic disorder.

Despite its popularity in clinical research, the emotional Stroop task's reliability in patient groups is unknown. Given the low reliability of interference scores in healthy subjects, correlations with other variables pose a problem, especially as reliability in clinical samples is unknown. To assess reliability in panic disorder for the first time, we used the spilt-half method in two independent samples of patients and controls. As expected, only patients showed the behavioral interference effect. Reliability of interference scores (i.e. mean response latency emotional minus neutral words) was insufficiently low for patient and control samples; however, reliability scores derived from the conditions' response latencies (i.e. mean response latency emotional or neutral words) were much higher. The assumption that reliability scores in patients might differ from controls was not supported. This finding questions the use of correlations with external variables and suggests the use of response latencies instead of interference scores.

Functional near-infrared spectroscopy for the assessment of speech related tasks.

Over the past years functional near-infrared spectroscopy (fNIRS) has substantially contributed to the understanding of language and its neural correlates. In contrast to other imaging techniques, fNIRS is well suited to study language function in healthy and psychiatric populations due to its cheap and easy application in a quiet and natural measurement setting. Its relative insensitivity for motion artifacts allows the use of overt speech tasks and the investigation of verbal conversation. The present review focuses on the numerous contributions of fNIRS to the field of language, its development, and related psychiatric disorders but also on its limitations and chances for the future.

Auditory cortex activation is modulated by emotion: a functional near-infrared spectroscopy (fNIRS) study.

Visual emotional stimuli evoke enhanced activation in early visual cortex areas which may help organisms to quickly detect biologically salient cues and initiate appropriate approach or avoidance behavior. Functional neuroimaging evidence for the modulation of other sensory modalities by emotion is scarce. Therefore, the aim of the present study was to test whether sensory facilitation by emotional cues can also be found in the auditory domain. We recorded auditory brain activation with functional near-infrared-spectroscopy (fNIRS), a non-invasive and silent neuroimaging technique, while participants were listening to standardized pleasant, unpleasant, and neutral sounds selected from the International Affective Digitized Sound System (IADS). Pleasant and unpleasant sounds led to increased auditory cortex activation as compared to neutral sounds. This is the first study to suggest that the enhanced activation of sensory areas in response to complex emotional stimuli is apparently not restricted to the visual domain but is also evident in the auditory domain.