The Effect of Singular Nonverbal Behaviours of Experimenters on Pain Reports.

Introduction: Studies suggest facial expressions of caregivers may be important in placebo effects; however, this has not been systematically tested. This experiment investigated the effects of caregivers' singular positive nonverbal behaviours (NBs) on pain reports. Methods: Fifty-one males and 53 females (total of 104) participants were randomized to four groups that were displayed positive facial expressions, tone of voice, body movement, or neutral NBs of videotaped experimenters. Subjective reports of pain, stress, arousal, and cardiac activity were obtained in a pre-test, a conditioning phase, and at a post-test. Four minutes of heat pain was induced in each test, and a placebo cream was administered before the conditioning and post-test in all groups. Results: There were no differences between the NB groups in the reduced pain. Males had larger reduction in pain in the post-test, and females had lower arousal than the opposite sex. During the conditioning, females had larger reduction in pain ie, unconditioned pain response (UPR). In females, the UPR predicted the reinforced expectation ie, increase in expectations from conditioning to post-test, and fear of minor pain negatively predicted both the UPR and reinforced expectation. Discussion: Singular NBs of caregiver were weak to enhance placebo effects. Females had lower pain during conditioning, and the UPR amplitude in females was associated with positive expectations. Moreover, for females, fear of minor pain weakened the UPR and expectations of cream. Conclusion: No NB of caregivers is more effective in reducing pain. Caregivers' NBs are less effective when displayed individually. Males and females may be different in underlying mechanisms of placebo effects.

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. METHODS: In this trial, outpatients (N = 96, aged 22-65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score ≥ 20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The first participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. DISCUSSION: The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05516095. Retrospectively registered on August 25, 2022.

A four-month home-based tDCS study on patients with Alzheimer's disease.

In the present open-label study, our first aim was to study the tolerability and feasibility of long-term treatment with transcranial direct current stimulation (tDCS) and the second aim was to measure whether the treatment led to cognitive improvement. Participants with AD used a tDCS home-treatment kit inducing a low current (2 mA) via two scalp electrodes 30 minutes daily for 4 months. A total of 8 participants were recruited. The treatment technique was manageable for the participants and their spouses, and no troublesome side effects were reported. No significant effects of treatment were found after 4 months.

Altered functional connectivity in adolescent anorexia nervosa is related to age and cortical thickness.

INTRODUCTION: Functional networks develop throughout adolescence when anorexia nervosa (AN) normally debuts. In AN, cerebral structural alterations are found in most brain regions and may be related to the observed functional brain changes. Few studies have investigated the functional networks of the brain in adolescent AN patients.. The aim of this explorative study was to investigate multiple functional networks in adolescent AN patients compared to healthy age-matched controls (HC) and the relationship with age, eating disorder symptoms and structural alterations. METHODS: Included were 29 female inpatients with restrictive AN, and 27 HC. All participants were between the ages of 12 to 18 years. Independent component analysis (ICA) identified 21 functional networks that were analyzed with multivariate and univariate analyses of components and group affiliation (AN vs HC). Age, age × group interaction and AN symptoms were included as covariates. Follow-up correlational analyses of selected components and structural measures (cortical thickness and subcortical volume) were carried out. RESULTS: Decreased functional connectivity (FC) in AN patients was found in one cortical network, involving mainly the precuneus, and identified as a default mode network (DMN). Cortical thickness in the precuneus was significantly correlated with functional connectivity in this network. Significant group differences were also found in two subcortical networks involving mainly the hippocampus and the amygdala respectively, and a significant interaction effect of age and group was found in both these networks. There were no significant associations between FC and the clinical measures used in the study. CONCLUSION: The findings from the present study may imply that functional alterations are related to structural alterations in selected regions and that the restricted food intake in AN patients disrupt normal age-related development of functional networks involving the amygdala and hippocampus.

Cutoff criteria for the placebo response: a cluster and machine learning analysis of placebo analgesia.

Computations of placebo effects are essential in randomized controlled trials (RCTs) for separating the specific effects of treatments from unspecific effects associated with the therapeutic intervention. Thus, the identification of placebo responders is important for testing the efficacy of treatments and drugs. The present study uses data from an experimental study on placebo analgesia to suggest a statistical procedure to separate placebo responders from nonresponders and suggests cutoff values for when responses to placebo treatment are large enough to be separated from reported symptom changes in a no-treatment condition. Unsupervised cluster analysis was used to classify responders and nonresponders, and logistic regression implemented in machine learning was used to obtain cutoff values for placebo analgesic responses. The results showed that placebo responders can be statistically separated from nonresponders by cluster analysis and machine learning classification, and this procedure is potentially useful in other fields for the identification of responders to a treatment.

Comparison of Two Multidisciplinary Occupational Rehabilitation Programs Based on Multimodal Cognitive Behavior Therapy on Self-Rated Health and Work Ability.

Objective: Musculoskeletal pain and common mental disorders constitute the largest proportion of people who are on sick leave. This study investigated the efficacy of two multidisciplinary occupational rehabilitation programs on self-rated health and work-related outcomes. The interventions were identical in content but differed in length. It was hypothesized that a longer inpatient program would yield greater improvements than a shorter outpatient program. Methods: Patients were sick-listed workers referred to occupational rehabilitation by the Norwegian Labor and Welfare Administration. A non-randomized 2 Condition (20 days, n = 64 versus 12 days, n = 62) × 4 repeated measures (start, end, 3 months, 12 months) between-subject design was used. Both programs were based on multimodal cognitive behavior therapy with a return-to-work focus. Health-related questionnaires were the Subjective Health Complaints inventory, Hospital Anxiety and Depression Scale, and SF-36 Bodily Pain. Work-related questionnaires were the Work Ability Index, the Fear-Avoidance Beliefs Questionnaire, Return To Work Self-Efficacy, and Return To Work expectations. Intervention effects were estimated using linear mixed models and Cohen's d. Results: The results revealed that both groups improved on the selected outcomes. Within-group contrasts and effect sizes showed that the inpatient group showed larger effect sizes at the end of rehabilitation and 12 months post-intervention for work-related outcomes than the outpatient group. Conclusion: Both programs were efficacious in improving health- and work-related outcomes during and after rehabilitation, but the inpatient group generally displayed stronger and more rapid improvements and was more stable at one-year postintervention.

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer's Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position.

BACKGROUND: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer's disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. OBJECTIVE: To measure the effect of individualized HD-tDCS in AD patients. METHODS: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient's brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. RESULTS: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. CONCLUSION: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

Cerebral cortical thickness and surface area in adolescent anorexia nervosa: Separate and joint analyses with a permutation-based nonparametric method.

OBJECTIVE: Reduction in cerebral volume is often found in underweight patients with anorexia nervosa (AN), but few studies have investigated other morphological measures. Cortical thickness (CTh) and surface area (CSA), often used to produce the measure of cortical volume, are developmentally distinct measures that may be differentially affected in AN, particularly in the developing brain. In the present study, we investigated CTh and CSA both separately and jointly to gain further insight into structural alterations in adolescent AN patients. METHOD: Thirty female AN inpatients 12-18 years of age, and 27 age-matched healthy controls (HC) underwent structural magnetic resonance imaging. Group differences in CTh and CSA were investigated separately and jointly with a permutation-based nonparametric combination method (NPC) which may be more sensitive in detecting group differences compared to traditional volumetric methods. RESULTS: Results showed significant reduction in in both CTh and CSA in several cortical regions in AN compared to HC and the reduction was related to BMI. Different results for the two morphological measures were found in a small number of cortical regions. The joint NPC analyses showed significant group differences across most of the cortical mantle. DISCUSSION: Results from this study give novel insight to areal reduction in adolescent AN patients and indicate that both CTh and CSA reduction is related to BMI. The study is the first to use the NPC method to reveal large structural alterations covering most of the brain in adolescent AN.

Can accelerated transcranial direct current stimulation improve memory functions? An experimental, placebo-controlled study.

The aim of this study was to investigate whether transcranial Direct Current Stimulation (tDCS) could improve verbal memory functions in healthy old and younger participants. We hypothesized that active tDCS led to significantly improved memory function, compared to placebo tDCS. Forty healthy participants (20 old and 20 younger participants) were included in the study. We applied a novel stimulation protocol, where six sessions of anodal tDCS were administrated during two consecutive days. Each tDCS session lasted 30 min. The current intensity was 2mA and the stimulation area was the left temporal lobe at T3 in the 10-20 EEG system. Immediate recall, delayed recall and recognition memory were assessed with California Verbal Learning Test II (CVLT-II) and executive functions were assessed with the Trail Making Test (TMT) before the first tDCS session and after the last tDCS session. Half of the participants received placebo tDCS, whereas the other half received active tDCS. We did not reveal any significant differences between active and placebo tDCS in memory functions. However, there was a significant difference between active and placebo tDCS in executive function measured by the Trail Making Test (TMT). This experimental study failed to reveal significant differences between active and placebo accelerated tDCS for verbal memory functions. However, accelerated tDCS was found to be well-tolerated in this study.

Pain Processing in Elite and High-Level Athletes Compared to Non-athletes.

BACKGROUND: Previous studies shows that elite and high-level athletes possess consistently higher pain tolerance to ischemic and cold pain stimulation compared to recreationally active. However, the data previously obtained within this field is sparse and with low consistency. PURPOSE: The aim of the present study was to examine the difference in pain perception between elite and high-level endurance athletes (cross country skiers and runners), elite soccer players and non-athletes, as well to explore the impact of psychological factors on pain processing. METHODS: Seventy one healthy volunteers (33 females and 38 males) participated in the study. Soccer players (n = 17), cross country skiers (n = 12), and long-distance runners (n = 3) formed the athlete group, with 39 non-athletes as controls. Big-five personality traits, fear of pain and Grit (perseverance and passion for long-term goals) were measured prior to induction of experimental pain. Pain threshold and intensity was induced by a PC-controlled heat thermode and measured by a computerized visual analog scale. Pain tolerance was measured by the cold pressor test (CPT). RESULTS: Elite and high-level athletes had increased pain tolerance, higher heat pain thresholds, and reported lower pain intensity to thermal stimulation. Endurance athletes (cross country skiers and long-distance runners) had better tolerance for cold pain compared to both soccer-players and non-athletes. Furthermore, endurance athletes reported lower pain intensity compared to non-athletes, whereas both endurance athletes and soccer players had higher heat pain thresholds compared to non-athletes. Fear of Pain was the only psychological trait that had an impact on all pain measures. CONCLUSION: The present findings suggest that sports with long durations of physically intense activity, leveling aerobic capacity, are associated with increased ability to tolerate pain and that the amount of training hours has an impact on this tolerance. However, the small sample size implies that the results from this study should be interpreted with caution.

Reactive Heart Rate Variability and Cardiac Entropy in Children with Internalizing Disorder and Healthy Controls.

Atypical vagal reactivity has been linked to internalizing psychopathology and less adaptive emotion regulation, but reactive cardiac entropy is largely unexplored. Therefore, this study investigated reactive vagally-mediated heart-rate variability (vmHRV) and cardiac entropy in relation to emotion regulation. Electrocardiograms of 32 children (9-13 years) with internalizing difficulties and 25 healthy controls were recorded during a baseline and a sad film. Reactivity-measures were calculated from the root mean square of successive differences (RMSSD) and sample entropy (SampEn). Emotion regulation was assessed using the emotion regulation checklist (ERC). Determinants of reactive SampEn and RMSSD were analyzed with marginal and generalized linear models. The study also modeled the relationship between cardiac reactivity and emotion regulation while controlling for psychopathology. The two groups differed significantly in vmHRV-reactivity, with seemingly higher vagal-withdrawal in the control group. SampEn increased significantly during the film, but less in subjects with higher psychopathology. Higher reactive entropy was a significant predictor of better emotion regulation as measured by the ERC. Internalizing subjects and controls showed significantly different vmHRV-reactivity. Higher reactive cardiac entropy was associated with lower internalizing psychopathology and better emotion regulation and may reflect on organizational features of the neurovisceral system relevant for adaptive emotion regulation.

Blame it on the weather? The association between pain in fibromyalgia, relative humidity, temperature and barometric pressure.

Self-reported pain levels in patients with fibromyalgia may change according to weather conditions. Previous studies suggest that low barometric pressure (BMP) is significantly related to increased pain, but that the contribution of changes in BMP has limited clinical relevance. The present study examined whether BMP influenced variability in perceived stress, and if stress levels moderated or mediated the relationship between BMP and pain. Forty-eight patients with fibromyalgia enrolled in a randomized controlled trail (RCT) reported pain and emotional state three times daily with mobile phone messages for a 30-consecutive day period prior to the start of the treatment in the RCT. The patients were unaware that weather data were collected simultaneously with pain and emotional reports. The results showed that lower BMP and increased humidity were significantly associated with increased pain intensity and pain unpleasantness, but only BMP was associated with stress levels. Stress levels moderated the impact of lower BMP on pain intensity significantly, where higher stress was associated with higher pain. Significant individual differences were present shown by a sub-group of patients (n = 8) who reacted opposite compared to the majority of patients (n = 40) with increased pain reports to an increase in BMP. In sum, lower BMP was associated with increased pain and stress levels in the majority of the patients, and stress moderated the relationship between BMP and pain at the group-level. Significant individual differences in response to changes in BMP were present, and the relation between weather and pain may be of clinical relevance at the individual level.

Cortical Thickness and Cognitive Performance After Out-of-Hospital Cardiac Arrest.

BACKGROUND: Cognitive impairment is common in long-term survivors of out-of-hospital cardiac arrest (OHCA) but corresponding neuroimaging data are lacking. OBJECTIVES: This study explored the relationship among the cortical brain structure, cognitive performance, and clinical variables after OHCA. METHODS: Three months after resuscitation, 13 OHCA survivors who had recovered from a coma to living independently and 19 healthy controls were assessed by cerebral magnetic resonance imaging and neuropsychological tests quantifying memory, fine-motor coordination, and attention/executive functions. Cortical thickness (Cth) and surface area (SA) were compared between groups and analyzed for relationships with cognitive performance as well as the clinical variables of coma duration and the time to return of spontaneous circulation (ROSC). All analyses were controlled for age and sex. RESULTS: Analyses of SA revealed no significant differences. Compared with controls, survivors had significantly reduced memory and fine-motor coordination and significantly thinner cortex in large clusters in the frontal, parietal, and inferior temporal cortices, with additional regions in the left occipital lobe and the left temporal lobe. Widespread thinner cortical regions were significantly associated with decreased memory performance in survivors when compared with those in controls and were significantly associated with an increased time to ROSC and increased coma duration in the OHCA group. Increased coma duration, but not increased time to ROSC, was significantly correlated with cognitive test performance. CONCLUSIONS: The results suggest that widespread Cth reductions correspond to the cognitive impairments observed after OHCA. Neuroimaging studies of long-term OHCA survivors are warranted to guide the development of diagnostics and treatment options.

Hippocampal subfields in adolescent anorexia nervosa.

Patients with anorexia nervosa (AN) exhibit volume reduction in cerebral gray matter (GM), and several studies report reduced hippocampus volume. The hippocampal subfields (HS) are functionally and structurally distinct, and appear to respond differently to neuropathology. The aim of this study was to investigate HS volumes in adolescent females with restrictive AN compared to a healthy age-matched control group (HC). The FreeSurfer v6.0 package was used to extract brain volumes, and segment HS in 58 female adolescents (AN = 30, HC = 28). We investigated group differences in GM, white matter (WM), whole hippocampus and 12 HS volumes. AN patients had significantly lower total GM and total hippocampal volume. No group difference was found in WM. Volume reduction was found in 11 of the 12 HS, and most results remained significant when adjusting for global brain volume reduction. Investigations of clinical covariates revealed statistically significant relationships between the whole hippocampus, several HS and scores on depression and anxiety scales in AN. Results from this study show that young AN patients exhibit reduced volume in most subfields of the hippocampus, and that this reduction may be more extensive than the observed global cerebral volume loss.

Failure to Find a Conditioned Placebo Analgesic Response.

Background: Associative learning has, in several studies, been modulated by the sex of the participant. Consistent with this, a recent review found that conditioned nocebo effects are stronger in females than in males. Purpose: It has been suggested that conditioned placebo responses are stronger in females, and this hypothesis was investigated in the present study. Cortisol and measures of negative emotions were taken to investigate if these processes could mediate any conditioned placebo effects. Methods: Cold pain was applied to the volar forearm. The Conditioned group received inert capsules prior to two presentations of less painful stimulations, to associate intake of the capsules with reduced pain. The pain control group received the same painful stimulation as the Conditioned group, but no capsules. The Capsule control group received the capsules in the same way as the Conditioned group, but no decrease in the painful stimulation. Participant sex was crossed across groups. It was hypothesized that in the Conditioned group, an expectation of reduced pain should be induced after administration of the capsules, and this should generate placebo analgesia, and mostly so in females. Results: The Conditioned group reported lower pain during conditioning, and rated the capsules as more effective painkillers than the capsule control group. However, placebo analgesia was not reliably observed in the Conditioned group. Conclusion: The placebo capsules were rated as effective painkillers, but this did not translate into a placebo analgesic effect. This could be due to violation of response expectancies, too few conditioning trials, and differences in pain ratings in the pre-test that could be due to previous experience with painkillers.

The opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 as genetic markers for placebo analgesia.

The placebo effect is considered the core example of mind-body interactions. However, individual differences produce large placebo response variability in both healthy volunteers and patients. The placebo response in pain, placebo analgesia, may be dependent on both the opioid system and the dopaminergic system. Previous studies suggest that genetic variability affects the function of these 2 systems. The aim of this study was therefore to address the interaction between the single nucleotide polymorphisms opioid receptor mu 1 (OPRM1) rs1799971 and catechol-O-methyltransferase (COMT) rs4680 on placebo analgesia. Two hundred ninety-six healthy volunteers participated in a repeated-measures experimental design where thermal heat pain stimuli were used as pain stimuli. Participants were randomized either to a placebo group receiving placebo cream together with information that the cream would reduce pain, or to a natural history group receiving the same pain stimuli as the placebo group without any application of cream or manipulation of expectation of pain levels. The results showed that the interaction between OPRM1 rs1799971 and COMT rs4680 was significantly associated with the placebo analgesic response. Participants with OPRM1 Asn/Asn combined with COMT Met/Met and Val/Met reported significant pain relief after placebo administration, whereas those with other combinations of the OPRM1 and COMT genotypes displayed no significant placebo effect. Neither OPRM1 nor COMT had any significant influence on affective changes after placebo administration. As shown in this study, genotyping with regard to OPRM1 and COMT may predict who will respond favorably to placebo analgesic treatment.

Non-linear Heart Rate Variability as a Discriminator of Internalizing Psychopathology and Negative Affect in Children With Internalizing Problems and Healthy Controls.

Background: Internalizing psychopathology and dysregulated negative affect are characterized by dysregulation in the autonomic nervous system and reduced heart rate variability (HRV) due to increases in sympathetic activity alongside reduced vagal tone. The neurovisceral system is however, a complex nonlinear system, and nonlinear indices related to psychopathology are so far less studied in children. Essential nonlinear properties of a system can be found in two main domains: the informational domain and the invariant domain. sample entropy (SampEn) is a much-used method from the informational domain, while detrended fluctuation analysis (DFA) represents a widely-used method from the invariant domain. To see if nonlinear HRV can provide information beyond linear indices of autonomic activation, this study investigated SampEn and DFA as discriminators of internalizing psychopathology and negative affect alongside measures of vagally-mediated HRV and sympathetic activation. Material and Methods: Thirty-Two children with internalizing difficulties and 25 healthy controls (aged 9-13) were assessed with the Child Behavior Checklist and the Early Adolescent Temperament Questionnaire, Revised, giving an estimate of internalizing psychopathology, negative affect and effortful control, a protective factor against psychopathology. Five minute electrocardiogram and impedance cardiography recordings were collected during a resting baseline, giving estimates of SampEn, DFA short-term scaling exponent α1, root mean square of successive differences (RMSSD), and pre-ejection period (PEP). Between-group differences and correlations were assessed with parametric and non-parametric tests, and the relationships between cardiac variables, psychopathology and negative affect were assessed using generalized linear modeling. Results: SampEn and DFA were not significantly different between the groups. SampEn was weakly negatively related to heart rate (HR) in the controls, while DFA was moderately negatively related to RMSSD in both groups, and moderately positively related to HR in the clinical sample. SampEn was significantly associated with internalizing psychopathology and negative affect. DFA was significantly related to internalizing psychopathology. Conclusions: Higher invariant self-similarity was linked to less psychopathology. Higher informational entropy was related to less psychopathology and less negative affect, and may provide an index of the organizational flexibility of the neurovisceral system.

The relation of hippocampal subfield volumes to verbal episodic memory measured by the California Verbal Learning Test II in healthy adults.

Total hippocampal volume has previously been shown to correlate with performance on tests for verbal episodic memory. However, there are sparse evidence on how hippocampal subfield volumes are related to verbal episodic memory in healthy adults. The present study investigated the association between volumes of separate hippocampal subfields and verbal episodic memory performance in healthy volunteers. Forty-seven participants (31 females) between 20-71 years age underwent testing with the California Verbal Learning Test II (CVLT II), and the Wechsler Abbreviated Scale of Intelligence (WASI) to obtain an estimate of cognitive functioning. T1-weighted MR images were obtained after cognitive testing, and volumetric estimates adjusted for age and estimated total intracranial volume were calculated in the FreeSurfer 6.0 software suite for cerebral -and hippocampal structures. The sample performed within the statistical normal range on both CVLT II and WASI. Significant correlations adjusted for multiple testing were found between CVLT II subtests of total learning, free immediate recall and free delayed recall and volumes of the left Cornu Ammonis (CA) 1-4 subfields. There were no significant correlations between right hippocampal subfields and CVLT II performance, and no significant correlation between WASI results and hippocampal subfields. The present results suggest that better verbal episodic memory measured by the CVLT II is associated with relative larger volumes of specific left CA hippocampal subfields in healthy adults. Due to the small sample size and large age-span of the participants, the present findings are preliminary and should be confirmed in larger samples.

Memory performance, global cerebral volumes and hippocampal subfield volumes in long-term survivors of Out-of-Hospital Cardiac Arrest.

AIM: We explored the associations between global brain volumes, hippocampal subfield volumes and verbal memory performance in long-term survivors of out-of-hospital cardiac arrest (OHCA). METHODS: Three months after OHCA, survivors and healthy, age-matched controls were assessed with cerebral MRI and the California Verbal Learning Test-II (CVLT-II). Volumetric brain segmentation was performed automatically by FreeSurfer. RESULTS: Twenty-six OHCA survivors who were living independently in regular homes at the time of assessment and 19 controls participated in the study. Thirteen of the survivors had been conscious upon arrival to the emergency department. The other 13 survivors had 0.5-7 days of inpatient coma before recovery. Memory was poorer in the OHCA group that had been comatose beyond initial hospital admission compared to both other groups. Total cortical volumes, total hippocampus volumes and several hippocampal subfield volumes were significantly smaller in the OHCA group comatose beyond initial hospital admission compared to controls. No significant differences between the OHCA group conscious upon emergency department arrival and the other two groups were found for brain volumes. No significant differences were observed between any groups for white matter or total subcortical volumes. In OHCA survivors with recovery from inpatient coma, the various CVLT-II trials were significantly, but differentially, correlated to total gray matter volume, cortical volume and the hippocampal subfield subiculum. CONCLUSION: In this small, single-site study, both hippocampal volume and cortical volume were smaller in good outcome OHCA survivors 3 months after resuscitation in comparison to healthy controls. Smaller cerebral volumes were correlated with poorer memory performance.