An explorative single-arm clinical study to assess craving in patients with alcohol use disorder using Virtual Reality exposure (CRAVE)-study protocol.

BACKGROUND: Alcohol use disorder (AUD) belongs to the most burdensome clinical disorders worldwide. Current treatment approaches yield unsatisfactory long-term effects with relapse rates up to 85%. Craving for alcohol is a major predictor for relapse and can be intentionally induced via cue exposure in real life as well as in Virtual Reality (VR). The induction and habituation of craving via conditioned cues as well as extinction learning is used in Cue Exposure Therapy (CET), a long-known but rarely used strategy in Cognitive Behavioral Therapy (CBT) of AUD. VR scenarios with alcohol related cues offer several advantages over real life scenarios and are within the focus of current efforts to develop new treatment options. As a first step, we aim to analyze if the VR scenarios elicit a transient change in craving levels and if this is measurable via subjective and psychophysiological parameters. METHODS: A single-arm clinical study will be conducted including n = 60 patients with AUD. Data on severity of AUD and craving, comorbidities, demographics, side effects and the feeling of presence in VR will be assessed. Patients will use a head-mounted display (HMD) to immerse themselves into three different scenarios (neutral vs. two target situations: a living room and a bar) while heart rate, heart rate variability, pupillometry and electrodermal activity will be measured continuously. Subjective craving levels will be assessed before, during and after the VR session. DISCUSSION: Results of this study will yield insight into the induction of alcohol craving in VR cue exposure paradigms and its measurement via subjective and psychophysiological parameters. This might be an important step in the development of innovative therapeutic approaches in the treatment of patients with AUD. TRIAL REGISTRATION: This study was approved by the Charité-Universitätsmedizin Berlin Institutional Review Board (EA1/190/22, 23.05.2023). It was registered on ClinicalTrials.gov (NCT05861843).

Evidence for allocentric boundary and goal direction information in the human entorhinal cortex and subiculum.

In rodents, cells in the medial entorhinal cortex (EC) and subiculum code for the allocentric direction to environment boundaries, which is an important prerequisite for accurate positional coding. Although in humans boundary-related signals have been reported, there is no evidence that they contain allocentric direction information. Furthermore, it has not been possible to separate boundary versus goal direction signals in the EC/subiculum. Here, to address these questions, we had participants learn a virtual environment containing four unique boundaries. Participants then underwent fMRI scanning where they made judgements about the allocentric direction of a cue object. Using multivariate decoding, we found information regarding allocentric boundary direction in posterior EC and subiculum, whereas allocentric goal direction was decodable from anterior EC and subiculum. These data provide the first evidence of allocentric boundary coding in humans, and are consistent with recent conceptualisations of a division of labour within the EC.

A protocol for manual segmentation of medial temporal lobe subregions in 7 Tesla MRI.

Recent advances in MRI and increasing knowledge on the characterization and anatomical variability of medial temporal lobe (MTL) anatomy have paved the way for more specific subdivisions of the MTL in humans. In addition, recent studies suggest that early changes in many neurodegenerative and neuropsychiatric diseases are better detected in smaller subregions of the MTL rather than with whole structure analyses. Here, we developed a new protocol using 7 Tesla (T) MRI incorporating novel anatomical findings for the manual segmentation of entorhinal cortex (ErC), perirhinal cortex (PrC; divided into area 35 and 36), parahippocampal cortex (PhC), and hippocampus; which includes the subfields subiculum (Sub), CA1, CA2, as well as CA3 and dentate gyrus (DG) which are separated by the endfolial pathway covering most of the long axis of the hippocampus. We provide detailed instructions alongside slice-by-slice segmentations to ease learning for the untrained but also more experienced raters. Twenty-two subjects were scanned (19-32 yrs, mean age = 26 years, 12 females) with a turbo spin echo (TSE) T2-weighted MRI sequence with high-resolution oblique coronal slices oriented orthogonal to the long axis of the hippocampus (in-plane resolution 0.44 × 0.44 mm2) and 1.0 mm slice thickness. The scans were manually delineated by two experienced raters, to assess intra- and inter-rater reliability. The Dice Similarity Index (DSI) was above 0.78 for all regions and the Intraclass Correlation Coefficients (ICC) were between 0.76 to 0.99 both for intra- and inter-rater reliability. In conclusion, this study presents a fine-grained and comprehensive segmentation protocol for MTL structures at 7 T MRI that closely follows recent knowledge from anatomical studies. More specific subdivisions (e.g. area 35 and 36 in PrC, and the separation of DG and CA3) may pave the way for more precise delineations thereby enabling the detection of early volumetric changes in dementia and neuropsychiatric diseases.

Structure-function-behavior relationship in estrogen-induced synaptic plasticity.

This article is part of a Special Issue "Estradiol and Cognition". In estrogen-induced synaptic plasticity, a correlation of structure, function and behavior in the hippocampus has been widely established. 17ß-estradiol has been shown to increase dendritic spine density on hippocampal neurons and is accompanied by enhanced long-term potentiation and improved performance of animals in hippocampus-dependent memory tests. After inhibition of aromatase, the final enzyme of estradiol synthesis, with letrozole we consistently found a strong and significant impairment of long-term potentiation (LTP) in female mice as early as after six hours of treatment. LTP impairment was followed by loss of hippocampal spine synapses in the hippocampal CA1 area. Interestingly, these effects were not found in male animals. In the Morris water maze test, chronic administration of letrozole did not alter spatial learning and memory in either female or male mice. In humans, analogous effects of estradiol on hippocampal morphology and physiology were observed using neuroimaging techniques. However, similar to our findings in mice, an effect of estradiol on memory performance has not been consistently observed.

Contralateral coding of imagined body parts in the superior parietal lobe.

In monkeys, neurons in the superior parietal lobe (area 5) code for spatial position of contralateral body parts by combining visual and somatosensory signals. Using a modified version of the classical mental rotation task, we were able to demonstrate that in humans activation in the contralateral superior parietal lobe could be evoked when mental rotation was combined with motor imagery of hands. These findings show that even in the absence of visual and somatosensory input, information provided by motor imagery suffices to induce contralateral superior parietal lobe monitoring of the imagined limb configuration. This constitutes an important prerequisite for effective imagined motor practice that can be used to improve actual motor performance.

[Interactive driving simulation--a new approach to diagnosis and rehabilitation of driving skills]. / Interaktive Fahrsimulation--ein neuer Weg zur Diagnose und Rehabilitation der Fahrtauglichkeit.

Until recently, major methodological problems were faced in the assessment and rehabilitation of driving ability in neurological patients, concerning practical driving lessons and driving tests as well as neuropsychological tests and therapies. The use of highly-advanced driving simulators may solve parts of this problem. However, a basic requirement for effective rehabilitation is the patients' acceptance of this method. In a semi-standardized interview with 56 patients we found that the driving simulator recently installed in the Neurological Rehabilitation Centre "Godeshöhe" was rated mainly positively. Also, patients experienced the simulator to be motivating, effective and informative. Hence, a very important prerequisite for successful use of driving simulators in neurological rehabilitation is given.