Why do users continue to contribute to darknet Child Sexual Abuse Material forums? Examining social exchange, social capital, and social learning explanations using digital forensic artifacts.

BACKGROUND: The darknet hosts an increasing number of hidden services dedicated to the distribution of child sexual abuse material (CSAM). Given that by contributing CSAM to the forum members subject themselves to criminal prosecution, questions regarding the motivation for members contributing to darknet CSAM forums arise. OBJECTIVE: Building on insights gained from research into clearnet communities, here we examine the extent to which social incentives generated by the online CSAM community may explain members' posting behavior on darknet CSAM forums. PARTICIPANTS AND SETTING: We analyze digital forensic artifacts on the online behavior of members of a darknet CSAM forum that was shut down by law enforcement agencies in July 2015. METHODS: We apply group-based trajectory modelling (GBTM), social network analysis, and mixed-effect survival models. RESULTS: Applying GBTM three posting trajectories can be distinguished. Social network analyses finds the reply network to be more centralized than predicted by chance. Mixed-effect survival models show positive associations between the length of members' first post and the time since members' first registration on the forum and subsequent posting. Contrarily, the number of replies received appears to mitigate subsequent posting. CONCLUSIONS: Findings show posting activity on the forum to be concentrated in a minority of forum members who show posting trajectories that are both frequent and persistent. Results further suggest persistence in posting is motivated by social identity and, to a lesser extent, differential association processes.

A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment or mild Alzheimer's disease dementia (ROMEMA): study protocol of a double-blind, randomized, placebo-controlled, between-subjects trial.

BACKGROUND: Research into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer's disease (AD) dementia. METHODS: The study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 µg roflumilast, and 100 µg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants' performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants. DISCUSSION: The outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders. TRIAL REGISTRATION: The Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NL ) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1 ) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.

Treatment with the selective PDE4B inhibitor A-33 or PDE4D inhibitor zatolmilast prevents sleep deprivation-induced deficits in spatial pattern separation.

Sleep deprivation (SD) disrupts hippocampus-dependent memory, particularly in the dentate gyrus (DG) region, an area crucial for pattern separation. Previous research showed that non-selective phosphodiesterase type 4 (PDE4) inhibitors like roflumilast can alleviate these deficits. However, it remains unclear whether these outcomes are specific to a particular subfamily of PDE4. Hence, this study examined the specific impact of PDE4B inhibitor (A-33) and PDE4D inhibitor (zatolmilast) on spatial pattern separation in sleep deprived mice. Results demonstrated that SD impairs pattern separation, but both zatolmilast and A-33 alleviate these effects. However, A-33 impaired pattern separation in non-sleep deprived animals. The cognitive benefits of these inhibitors after SD may arise from alterations in relevant signaling pathways in the DG. This study provides initial evidence that inhibiting PDE4B or PDE4D holds promise for mitigating memory deficits due to SD.

The Reliability and Clinical Validation of Automatically-Derived Verbal Memory Features of the Verbal Learning Test in Early Diagnostics of Cognitive Impairment.

BACKGROUND: Previous research has shown that verbal memory accurately measures cognitive decline in the early phases of neurocognitive impairment. Automatic speech recognition from the verbal learning task (VLT) can potentially be used to differentiate between people with and without cognitive impairment. OBJECTIVE: Investigate whether automatic speech recognition (ASR) of the VLT is reliable and able to differentiate between subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: The VLT was recorded and processed via a mobile application. Following, verbal memory features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to distinguish between participants with SCD versus MCI/dementia. RESULTS: The ICC for inter-rater reliability between the clinical and automatically derived features was 0.87 for the total immediate recall and 0.94 for the delayed recall. The full model including the total immediate recall, delayed recall, recognition count, and the novel verbal memory features had an AUC of 0.79 for distinguishing between participants with SCD versus MCI/dementia. The ten best differentiating VLT features correlated low to moderate with other cognitive tests such as logical memory tasks, semantic verbal fluency, and executive functioning. CONCLUSIONS: The VLT with automatically derived verbal memory features showed in general high agreement with the clinical scoring and distinguished well between SCD and MCI/dementia participants. This might be of added value in screening for cognitive impairment.

Who's Keeping an Eye on the Kids? Changes in Monitoring During Emerging Adulthood.

Previous research indicates that parental monitoring protects adolescents from delinquency. While, emerging adults spend increasing amounts of time outside the family setting, they often remain in or return to reside in the parental home, possibly prolonging the period of parental monitoring. We examine whether parental monitoring, differentiating between child disclosure, parental solicitation, and parental control, is a protective factor for delinquency for emerging adults. We also examine whether monitoring occurs in educational settings, by the partner or in employment settings, and whether this monitoring is associated with delinquency. We use data from a longitudinal survey of 970 Dutch emerging adults (18-24 years), to examine monitoring, using instruments based on Stattin and Kerr's parental monitoring scale. Results indicate that parental monitoring is not associated with delinquency in emerging adulthood. Furthermore, we find no evidence of the protective role of monitoring in educational settings, by the partner or in employment settings. However, the negative relationship between monitoring of the self, self-control, delinquency during emerging adulthood increases in strength.

Prelimbic Cortical Stimulation Induces Antidepressant-like Responses through Dopaminergic-Dependent and -Independent Mechanisms.

High-frequency stimulation (HFS) is a promising therapy for patients with depression. However, the mechanisms underlying the HFS-induced antidepressant-like effects on susceptibility and resilience to depressive-like behaviors remain obscure. Given that dopaminergic neurotransmission has been found to be disrupted in depression, we investigated the dopamine(DA)-dependent mechanism of the antidepressant-like effects of HFS of the prelimbic cortex (HFS PrL). We performed HFS PrL in a rat model of mild chronic unpredictable stress (CUS) together with 6-hydroxydopamine lesioning in the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA). Animals were assessed for anxiety, anhedonia, and behavioral despair. We also examined levels of corticosterone, hippocampal neurotransmitters, neuroplasticity-related proteins, and morphological changes in dopaminergic neurons. We found 54.3% of CUS animals exhibited decreased sucrose consumption and were designated as CUS-susceptible, while the others were designated CUS-resilient. HFS PrL in both the CUS-susceptible and CUS-resilient animals significantly increased hedonia, reduced anxiety, decreased forced swim immobility, enhanced hippocampal DA and serotonin levels, and reduced corticosterone levels when compared with the respective sham groups. The hedonic-like effects were abolished in both DRN- and VTA-lesioned groups, suggesting the effects of HFS PrL are DA-dependent. Interestingly, VTA-lesioned sham animals had increased anxiety and forced swim immobility, which was reversed by HFS PrL. The VTA-lesioned HFS PrL animals also had elevated DA levels, and reduced p-p38 MAPK and NF-κB levels when compared to VTA-lesioned sham animals. These findings suggest that HFS PrL in stressed animals leads to profound antidepressant-like responses possibly through both DA-dependent and -independent mechanisms.

Can placebo or nocebo pills improve or impair cognition performance?

OBJECTIVE: Although the placebo effect is well known to affect many behaviors, the effects on cognitive performance are less well investigated. METHODS: In this study, the effects of a placebo and a nocebo manipulation on cognitive performance was investigated in healthy young participants in an unblinded between-subjects study. In addition, the participants were asked about their subjective experience in the placebo and nocebo condition. RESULTS: The data suggested that the placebo condition induced the feeling of being more attentive and more motivated and the nocebo condition induced a feeling of being less attentive and alert and that they performed less well than normal. However, no placebo or nocebo effects were found on the actual performance on word learning, working memory, Tower of London task, or spatial pattern separation. CONCLUSIONS: These findings further support the notion that placebo or nocebo effects are not likely to occur in young healthy volunteers. However, other studies suggest that placebo effects can be found in implicit memory tasks and in participants with memory problems. Further placebo/nocebo studies are indicated using different experimental designs and different populations in order to better understand the placebo effect on cognitive performance.

Sex Differences between Neuronal Loss and the Early Onset of Amyloid Deposits and Behavioral Consequences in 5xFAD Transgenic Mouse as a Model for Alzheimer's Disease.

A promising direction in the research on Alzheimer's Disease (AD) is the identification of biomarkers that better inform the disease progression of AD. However, the performance of amyloid-based biomarkers in predicting cognitive performance has been shown to be suboptimal. We hypothesise that neuronal loss could better inform cognitive impairment. We have utilised the 5xFAD transgenic mouse model that displays AD pathology at an early phase, already fully manifested after 6 months. We have evaluated the relationships between cognitive impairment, amyloid deposition, and neuronal loss in the hippocampus in both male and female mice. We observed the onset of disease characterized by the emergence of cognitive impairment in 6-month-old 5xFAD mice coinciding with the emergence of neuronal loss in the subiculum, but not amyloid pathology. We also showed that female mice exhibited significantly increased amyloid deposition in the hippocampus and entorhinal cortex, highlighting sex-related differences in the amyloid pathology of this model. Therefore, parameters based on neuronal loss might more accurately reflect disease onset and progression compared to amyloid-based biomarkers in AD patients. Moreover, sex-related differences should be considered in studies involving 5xFAD mouse models.

The value of maintaining cognition in patients with mild cognitive impairment: The innovation headroom and potential cost-effectiveness of roflumilast.

INTRODUCTION: Early health-technology assessment can support discussing scarce resource allocation among stakeholders. We explored the value of maintaining cognition in patients with mild cognitive impairment (MCI) by estimating: (1) the innovation headroom and (2) the potential cost effectiveness of roflumilast treatment in this population. METHODS: The innovation headroom was operationalized by a fictive 100% efficacious treatment effect, and the roflumilast effect on memory word learning test was assumed to be associated with 7% relative risk reduction of dementia onset. Both were compared to Dutch setting usual care using the adapted International Pharmaco-Economic Collaboration on Alzheimer's Disease (IPECAD) open-source model. RESULTS: The total innovation headroom expressed as net health benefit was 4.2 (95% bootstrap interval: 2.9-5.7) quality-adjusted life years (QALYs). The potential cost effectiveness of roflumilast was k€34 per QALY. DISCUSSION: The innovation headroom in MCI is substantial. Although the potential cost effectiveness of roflumilast treatment is uncertain, further research on its effect on dementia onset is likely valuable.

Delay-dependent forgetting in object recognition and object location test is dependent on strain and test.

The object recognition and object location task (ORT and OLT, respectively) have been applied in preclinical research to evaluate the effects of treatments on memory. Although both tasks look quite similar, they differ with respect to the brain structures involved in the memory performance. The characterization of the memory performance in both tasks is important to understand treatment effects. Since there are no previous studies that compared strain differences in delay-dependent forgetting in both tasks, Wistar and Long Evans rats were tested in both the ORT and the OLT at different intervals. The data showed that in the ORT the delay-dependent forgetting was similar for Wistar and Long Evans rats. However, the forgetting curve was different for both strains in the OLT: the Long Evans rats the forgetting took a longer interval. This study indicates that delay-dependent forgetting in the ORT and OLT is strain and test dependent. It is suggested that before testing treatments the forgetting curve of a specific strain should be tested in this type of tasks.

Stay Home, Stay Safe? The Impact of the COVID-19 Restrictions on the Prevalence, Nature, and Type of Reporter of Domestic Violence in the Netherlands.

Purpose: Insecurities and social isolation resulting from the COVID-19 restrictions, may have elevated tensions at home, consequently increasing the risk of domestic violence. The present study aims to examine changes in the prevalence, nature, and type of reporter of domestic violence following the various restrictions implemented to control the spread of the COVID-19 virus in the Netherlands. Methods: All official domestic violence reports recorded by the 26 Dutch domestic violence agencies in 2019 and 2020 were collected and analyzed. Time-series forecasting analyses, using a SARIMAX model, were conducted to predict the trend of domestic violence reports during the first lockdown and to compare the predicted trend with the observed trend. Results: The observed trend of the registered prevalence of domestic violence did not substantially differ from the predicted trend based on pre-pandemic data. Similarly, findings regarding the nature of domestic violence suggest no clear divergence of pre-pandemic trends during the lockdown period. Nonetheless, a shift was found from professional reporters (e.g., the police) to non-professional reporters (e.g., neighbors). Conclusions: The prevalence of domestic violence reports in the Netherlands did not increase. However, the COVID-19 restrictions may have led citizens, especially neighbors, to detect domestic violence more often.

Soluble guanylate cyclase stimulator riociguat improves spatial memory in mice via peripheral mechanisms.

Soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) signalling is important for healthy memory function and a healthy vascular system. Targeting sGC-cGMP signalling can therefore be a potential strategy to enhance memory processes. sGC can be targeted by using agonists, such as sGC stimulator riociguat. Therefore, this study aimed to target sGC using riociguat to investigate its acute effects on memory function and neuronal plasticity in mice. The effects of riociguat on long-term memory and a biperiden-induced memory deficit model for assessing short-term memory were tested in the object location task, and working memory was tested in the Y-maze continuous alternation task. Pharmacokinetic measurements were performed within brain tissue of mice, and hippocampal plasticity measures were assessed using western blotting. Acute oral administration with a low dose of 0.03 mg/kg riociguat was able to enhance working-, short-, and long-term spatial memory. Under cerebral vasoconstriction higher doses of riociguat were still effective on memory. Pharmacokinetic measurements revealed poor brain penetration of riociguat and its metabolite M-1. Increased activation of VASP was found, while no effects were found on other memory-related hippocampal plasticity measures. Memory enhancing effects of riociguat are most likely regulated by vascular peripheral effects on cGMP signalling. Yet, further research is needed to investigate the possible contribution of hemodynamic or metabolic effects of sGC stimulators on memory performance.

Age Effects on Old/New Recognition Memory Involving Abstract Figures and Non-words.

Age-related memory problems posit a growing concern in our society. This study investigated the impact of age and memory strength on recognition memory of pre-experimentally unfamiliar abstract figures and non-words. We applied a three-phase old/new recognition memory paradigm and manipulated memory strength as a function of the Levels of Processing (deep vs. shallow) and repetition. Older adults relative to the young showed impairment in the correct identification of new items. As indicated by the lower discriminability indexes, the older adults also had difficulties discriminating the strongly (drawn/semantically processed) and the weakly (studied) embedded abstract figures but not the non-words. Age-related differences in reaction times were only evident with the abstract figures. Finally, our results revealed that the recognition performance was equally affected by memory strength in both age groups. The current findings agree with previous research on age-related impairment in new item recognition, which can be attributed to misrecollection and decreased sensitivity to novelty in the older adults than the young. The detected age effects on the discriminability of the drawn and studied abstract figures agree with the age-related impairment in the perceptual encoding hypothesis and support the notion related to the need for environmental support to reduce age effects. The lack of age effects with the non-words indicates that age effects on discriminability are stimulus-dependent. The current results support the notion that recognition memory in aging is only impaired under certain conditions and depends on the stimuli used.

Cholinergic models of memory impairment in animals and man: scopolamine vs. biperiden.

Scopolamine has been used as a pharmacologic model for cognitive impairments in dementia and Alzheimer's disease. The validity of this model seems to be limited because findings in animals do not readily translate to novel treatments in humans. Biperiden is also a cholinergic deficit model for cognitive impairments but specifically blocks muscarinic M1 receptors. The effects of scopolamine and biperiden (and pirenzepine) are compared in animal studies and related to findings in humans. It is concluded that the effects on cognitive functions are different for scopolamine and biperiden, and they should be considered as different cognitive deficit models. Scopolamine may model more advanced stages of Alzheimer's disease whereas biperiden may model the early deficits in declarative memory in aging and mild cognitive impairment.

The effects of selective serotonin reuptake inhibitors on memory functioning in older adults: A systematic literature review.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to older adults. In contrast to young subjects, it is unclear whether older adults may be vulnerable to cognitive side effects. Serotonin is involved in cognitive functions (e.g. memory). It is of great importance to examine the effects of SSRIs on memory functioning in older adults. OBJECTIVES: The objective of this systematic literature review is to summarize studies in which the effects of SSRI treatment on all aspects of memory functioning in older adults are investigated. METHODS: PubMed, PsycINFO, CINAHL, and Embase were searched for all studies published until 18th of October 2021. Articles were included if they fulfilled the inclusion criteria as follows: (1) study design is (randomized) controlled trial, cross-sectional, or prospective cohort study; (2) study population consists of older adults (mean age ⩾65 years), or results for this age-group are reported separately; (3) intervention is use of an SSRI; and (4) effects on performance of any memory domain are measured and clearly described. RESULTS: The search yielded 1888 articles, of which 136 were included for the full-text review. Eventually, 40 articles were included. Most studies reported no association between SSRI use and memory functioning. The studies that found a positive association mainly investigated older adults with mental or neurological disorders (e.g. depression or stroke). A few studies found a negative association in the following subgroups: non-responders (depression), patients with frontal brain disease, and women. CONCLUSION: Overall, no consistent negative effects of SSRIs on memory functioning in older adults were found after SSRI treatment. Most studies reported no change in memory functioning after SSRI use. Some studies even showed an improvement in memory performance. Positive effects of SSRIs on memory functioning were especially found in older adults with mental or neurological disorders, such as subjects with depression or stroke.

Remembering Molly: Immediate and delayed false memory formation after acute MDMA exposure.

The entactogen 3,4-Methylenedioxymethamphetamine (MDMA) is increasingly being recognized for its therapeutic potential but is also widespread in nightlife settings where it may co-occur with crime. Since previous research detected impaired verbal memory during acute MDMA intoxication, understanding the drug's ramifications in an applied legal context becomes crucial. We conducted a double-blind, placebo-controlled trial to examine acute and delayed effects of MDMA (75 mg) on false memory in 60 healthy volunteers with a history of MDMA use, using three well-established false memory methods: a basic, associative word list (Deese/Roediger-McDermott (DRM)) paradigm and two applied misinformation tasks using a virtual reality crime. Memory was tested immediately (encoding and retrieval under drug influence) and 1 week later (retrieval when sober). Small MDMA-induced impairments of true memory in the word list task were detected at both time points. MDMA increased false memory for related but non-critical lures during the immediate test, and decreased false memory for critical lures after a delay. Episodic memory assessed in the misinformation tasks was not consistently affected. Findings indicate a complex memory profile but no heightened vulnerability to external suggestion in response to MDMA intoxication. Recommendations for future applied legal psychological research include adding measures of recall on top of recognition, using study designs that separate the different memory phases, and potentially testing higher doses. Further research on false memories and suggestibility using imagination procedures can also be relevant for the clinical context.

General Offending and Intimate Partner Violence Perpetration in Young Adulthood: A Dutch Longitudinal Study.

This study examines the relationship between general offending and intimate partner violence (IPV) perpetration in young adulthood, using a Dutch longitudinal study. Young adults were followed over four waves, and self-reported data on general offending, IPV perpetration, and a number of individual characteristics were collected. Results of random effects models demonstrated that young adults involved in more diverse offending behavior reported higher levels of different types of IPV perpetration, even when individual factors were taken into account. Moreover, logistic regression analyses showed that general offending was also related to an increased likelihood of continuity in IPV perpetration. Taken together, the findings indicate that it is useful to view IPV perpetration as part of a broader criminal career.

Longitudinal Validation of the Levenson Self-Report Psychopathy (LSRP) Scale in a High-Risk Dutch Community Sample.

The Levenson Self-Report Psychopathy (LSRP) scale is a self-report measure that can be used to assess psychopathic traits in community samples, and recent research suggested that its three-factor model (Egocentricity, Callousness, and Antisocial) has promising psychometric properties. However, no study to date has validated the LSRP in a longitudinal framework. The present study sought to validate the LSRP scale in a longitudinal design using a sample of Dutch emerging adults (ns = 970 and 693 at time points 1 and 2, respectively). We assessed longitudinal measurement invariance and the stability of psychopathic traits over an 18-month time period, from age 20 to age 21.6. Furthermore, we replicated and extended findings on the factor structure, reliability, and construct validity of the Dutch LSRP scale. Confirmatory factor analysis revealed that the three-factor model fit the data well. Evidence of partial longitudinal measurement invariance was observed, which means that the Dutch translation of the LSRP scale is measuring an equivalent construct (and overall latent factor structure) over time. Psychopathic traits were relatively stable over time. The three LSRP subscales showed largely acceptable levels of internal consistency at both time points and showed conceptually expected patterns of construct validity and predictive validity, with a few notable exceptions.

The antimuscarinic agent biperiden selectively impairs recognition of abstract figures without affecting the processing of non-words.

OBJECTIVES: The present study investigated the effects of biperiden, a muscarinic type 1 antagonist, on the recognition performance of pre-experimentally unfamiliar abstract figures and non-words in healthy young volunteers. The aim was to examine whether 4 mg biperiden could model the recognition memory impairment seen in healthy aging. METHODS: A double-blind, placebo-controlled, two-way crossover study was conducted. We used a three-phase (deep memorization, shallow memorization, and recognition) old/new discrimination paradigm in which memory strength was manipulated. Strong memories were induced by deep encoding and repetition. Deep encoding was encouraged by redrawing the abstract figures and mentioning existing rhyme words for the non-words (semantic processing). Weak memories were created by merely instructing the participants to study the stimuli (shallow memorization). RESULTS: Biperiden impaired recognition accuracy and prolonged reaction times of the drawn and the studied abstract figures. However, participants were biased towards "old" responses in the placebo condition. The recognition of the new abstract figures was unaffected by the drug. Biperiden did not affect the recognition of the non-words. CONCLUSIONS: Although biperiden may model age-related deficits in episodic memory, the current findings indicate that biperiden does not mimic age-related deficits in recognition performance.

The continued need for animals to advance brain research.

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised.