Anita Must

Reduced facilitation effect of collinear flankers on contrast detection reveals impaired lateral connectivity in the visual cortex of schizophrenia patients

The aim of this study was to investigate lateral connectivity in early visual cortex of schizophrenia patients. Contrast thresholds were measured for centrally presented Gabor patches which were surrounded by two collinear or orthogonal flankers. The healthy subjects (n = 15) showed lower contrast thresholds for central Gabor patches when collinear flankers were presented. This effect was significantly reduced in unmedicated highly functioning schizophrenia patients (n = 20) who performed normally on the continuous performance test. The performance of the patients did not correlate with the positive and negative symptoms. The facilitation effect of collinear flankers is believed to reflect lateral interactions between feature-specific units in early visual cortex (V1). Our results therefore suggest abnormal lateral interactions in early visual cortex of schizophrenia patients.

The Iowa Gambling Task in depression - what have we learned about sub-optimal decision-making strategies?

Our earlier study found patients with depression to show a preference for larger reward as measured by the Iowa Gambling Task (IGT). In this IGT version, larger rewards were associated with even larger consequent losses. In the light of the clinical markers defining depressive disorder, this finding might appear controversial at first. Performance of depressed patients on various decision-making (DM) tasks is typically found to be impaired. Evidence points toward reduced reward learning, as well as the difficulty to shift strategy and integrate environmental changes into DM contingencies. This results in an impaired ability to modulate behavior as a function of reward, or punishment, respectively. Clinical symptoms of the disorder, the genetic profile, as well as personality traits might also influence DM strategies. More severe depression increased sensitivity to immediate large punishment, thus predicting future decisions, and was also associated with higher harm avoidance. Anhedonic features diminished reward learning abilities to a greater extent, even predicting clinical outcome. Several questions about how these aspects relate remain to be clarified. Is there a genetic predisposition for the DM impairment preceding mood symptoms? Is it the consequence of clinical signs or even learned behavior serving as a coping strategy? Are patients prone to develop an aversion of loss or are they unable to sense or deal with reward or the preference of reward? Does the DM deficit normalize or is a persisting impairment predictor for clinical outcome or relapse risk? To what extent is it influenced by medication effects? How does a long-lasting DM deficit affect daily life and social interactions? Strikingly, research evidence indicates that depressed patients tend to behave less deceptive and more self-focused, resulting in impaired social DM. The difficulty in daily interpersonal interactions might contribute to social isolation, further intensifying depressive symptoms.

Eye-Movement Behavior Reveals Relational Memory Impairment in Schizophrenia

BACKGROUND Previous studies have demonstrated impaired relational memory in schizophrenia. We studied eye-movement behavior as an indirect measure of relational memory, together with forced-choice recognition as an explicit measure. METHODS Thirty-five patients with schizophrenia and 35 healthy participants were trained to associate a face with a background scene. During testing, scenes were presented as a cue and then overlaid with three previously studied faces. Participants were asked to recall the matching face, and both eye movements and forced-choice recognition were recorded. During Non-Match trials, no faces matched the scene. During Match trials, one of the faces had previously been paired with the scene. RESULTS On Non-Match trials, when no relational memory trace was present, both groups viewed the three faces equally. In contrast, on Match trials, control participants quickly (within 500 msec) and consistently (70%-75% of test trial viewing) showed preferential viewing of the matching face. Viewing of the matching face was significantly delayed and reduced in schizophrenia participants. Forced-choice recognition of the matching face was also impaired in the patient group. An analysis of all correct Match trials revealed that preferential viewing was significantly reduced and delayed in participants with schizophrenia. CONCLUSIONS This study provides novel evidence for a specific relational memory impairment in schizophrenia. Patients showed deficits in their forced-choice recognition responses, as well as abnormal eye-movement patterns during memory recall, even on trials when behavioral responses were accurate. We propose that eye movements provide a promising new avenue for studying relational memory in schizophrenia.

Male brain ages faster: the age and gender dependence of subcortical volumes

Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson’s disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders.

Gender-Specific Degeneration of Dementia-Related Subcortical Structures Throughout the Lifespan

Age-related changes in brain structure are a question of interest to a broad field of research. Structural decline has been consistently, but not unambiguously, linked to functional consequences, including cognitive impairment and dementia. One of the areas considered of crucial importance throughout this process is the medial temporal lobe, and primarily the hippocampal region. Gender also has a considerable effect on volume deterioration of subcortical grey matter (GM) structures, such as the hippocampus. The influence of age×gender interaction on disproportionate GM volume changes might be mediated by hormonal effects on the brain. Hippocampal volume loss appears to become accelerated in the postmenopausal period. This decline might have significant influences on neuroplasticity in the CA1 region of the hippocampus highly vulnerable to pathological influences. Additionally, menopause has been associated with critical pathobiochemical changes involved in neurodegeneration. The micro- and macrostructural alterations and consequent functional deterioration of critical hippocampal regions might result in clinical cognitive impairment-especially if there already is a decline in the cognitive reserve capacity. Several lines of potential vulnerability factors appear to interact in the menopausal period eventually leading to cognitive decline, mild cognitive impairment, or Alzheimers disease. This focused review aims to delineate the influence of unmodifiable risk factors of neurodegenerative processes, i.e., age and gender, on critical subcortical GM structures in the light of brain derived estrogen effects. The menopausal period appears to be of key importance for the risk of cognitive decline representing a time of special vulnerability for molecular, structural, and functional influences and offering only a narrow window for potential protective effects.

Continuous theta-burst stimulation over the dorsolateral prefrontal cortex inhibits improvement on a working memory task

Theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) may be more effective for modulating cortical excitability compared to standard repetitive transcranial magnetic stimulation. However, the impact of intermittent (iTBS) and continuous TBS (cTBS) on working memory (WM) is poorly studied. The aim of our study was to compare the effects of iTBS and cTBS on WM over the left and right DLPFC. iTBS, cTBS or sham stimulation was administered over the right and left hemisphere of fifty-one healthy human subjects. WM was assessed before and after TBS using the 1-back, 2-back, and 3-back tasks. We found classical practice effects in the iTBS and the sham group: WM performance improved following stimulation as measured by the discriminability index. However, this effect could not be observed in the cTBS group. We did not find any hemisphere-dependent effects, suggesting that the practice effect is not lateralized, and TBS affects WM performance in a comparable manner if administered either over the left or the right hemisphere. We propose that our findings represent a useful addition to the literature of TBS-induced effects on WM. Moreover, these results indicate the possibility of clarifying processes underlying WM performance changes by using non-invasive brain stimulation.

The Report of p.Val717Phe Mutation in the APP Gene in a Hungarian Family With Alzheimer Disease: A Phenomenological Study

Autosomal dominantly inherited Alzheimer disease (AD) is characterized by early onset (under the age of 65 y) and accounts for approximately 0.5% of all AD cases.1 The underlying genetic alterations include mutations in the presenilin-1 (PSEN-1), PSEN-2, and amyloid precursor protein (APP) genes and duplication in the APP gene, of which APP gene mutations are responsible for 18% of these genetic cases with a wide geographical distribution2 (http:// www.molgen.vib-ua.be/ADMutations; http://www.alzforum. org/mutations). Although the clinical features of APP gene mutations may be heterogeneous (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/WAD/ A175), the most prevalent symptoms are memory impairment, disorientation, language disturbances, apraxia, myoclonus, seizures, dyscalculia, Parkinsonism, apathy, depressive mood, and aggressive behavior1 (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/WAD/A175). The age of onset and disease duration are variable as well, with a typical onset in their 40s and 50s (range, 30 to 82y of age) and 10 years of duration (range, 2 to 18y), respectively (Supplemental Digital Content 1, http://links.lww.com/WAD/A175 Table 1). Although the site of the mutation and the type of amino acid change clearly seems to affect the clinical characteristics (Supplementary Table 1, Supplemental Digital Content 1, http://links.lww.com/WAD/A175), there may be several other influencing factors as well. The report of new families is clearly relevant in terms of better understanding of disease characteristics. Accordingly, the aim of the current study is to provide a detailed phenotypic description of the first Hungarian patient diagnosed with familial AD caused by the Val717Phe mutation in the APP gene.

Spirituality mediates state anxiety but not trait anxiety and depression in alcohol recovery

Abstract Background and objectives: Twelve-step based interventions promote the recovery from alcohol dependence, support relapse prevention and are associated with improved mental status indices (e.g. depression). This treatment model largely relies on spiritual experience. We tested three different alcohol treatment settings, which differently involve elements of spirituality in order to reveal its possible mediator effect on the level of depressive and anxiety symptoms. Methods: Patients were involved from (1) detoxification (n = 34), (2) long-term – 12-step based – therapeutic community treatment (n = 89), (3) and from Alcoholics Anonymous (AA) groups after at least 3 years of attendance (n = 46). Anxiodepressive symptoms and spirituality/transcendence were compared and the potential mediator role of spirituality was assessed in the levels of depressive and anxiety symptoms. Results: Long-term 12-step based rehabilitation and sustained AA attendance was connected to lower levels of anxiodepressive symptoms and to more pronounced spirituality. The spiritual component of the different treatments played a mediator role in the decrease of state anxiety but this mediation was not detected in the case of depressive symptoms and trait anxiety. Conclusions/Importance: The role of spirituality in the decrease of state anxiety indicates acute beneficial effect. Therefore, long term, regular attendance in AA groups is essential.

The effect of emotion and reward contingencies on relational memory in major depression: An eye-movement study with follow-up

Background: Episodic memory disturbances were found to constitute a potential trait marker for major depression (MD). The recall of positive or rewarding information in a relational context is specifically impaired. Eye-movement recording constitutes a novel, direct approach to examine implicit memory performance. Here we aimed to assess the effect of emotional context and implicit virtual monetary reward or loss on viewing patterns in association with relational memory in a 6-months follow-up study in MD. Materials and Methods: Twenty-eight patients with MD and 30 healthy participants were trained to associate a face (happy/sad/neutral) with a background scene. After each pair a virtual monetary reward or loss appeared briefly. During testing, scenes were presented as a cue and then overlaid with three previously studied faces. Participants were asked to recall the matching face if present (Match trials), with eye-movements and subsequent forced-choice recognition being recorded. Results: Explicit recognition of the matching face was impaired in the MD group as compared to controls. In correlation with this, viewing of the matching face was significantly reduced in the MD group. We found a significant interaction of group (MD vs HC) with the relational memory condition (Match and Non-match), facial emotion and monetary reward and loss. MD patients attended longer to previously rewarded stimuli, but significantly less to sad faces in the Match condition. The relational memory impairment persisted at follow-up and correlated with symptom severity both at baseline and follow-up. Viewing patterns associated with previous virtual reward were associated with clinical symptoms at follow-up. Conclusion: Our current results provide novel evidence for a specific relational memory impairment in MD as supported by abnormal eye-movement behavior and a deficit in explicit recognition. MD patients showed an attentional bias to rewarded stimuli and decreased viewing of sad faces when relational memory information was present.

The impact of intermediate-term alcohol abstinence on memory retrieval and suppression.

Background: The nature of episodic memory deficit in intermediate-term abstinence from alcohol in alcohol dependence (AD) is not yet clarified. Deficits in inhibitory control are commonly reported in substance use disorders. However, much less is known about cognitive control suppressing interference from memory. The Think/No-think (TNT) paradigm is a well established method to investigate inhibition of associative memory retrieval. Methods: Thirty-six unmedicated patients with AD and 36 healthy controls (HCs) performed the TNT task. Thirty image–word pairs were trained up to a predefined accuracy level. Cued recall was examined in three conditions: Think (T) for items instructed to-be-remembered, No-think (NT) assessing the ability to suppress retrieval and Baseline (B) for general relational memory. Premorbid IQ, clinical variables and impulsivity measures were quantified. Results: AD patients had a significantly increased demand for training. Baseline memory abilities and effect of practice on retrieval were not markedly different between the groups. We found a significant main effect of group (HC vs. AD) × condition (B, T, and NT) and a significant difference in mean NT–B scores for the two groups. Discussion: AD and HC groups did not differ essentially in their baseline memory abilities. Also, the instruction to focus on retrieval improved episodic memory performance in both groups. Crucially, control participants were able to suppress relational words in the NT condition supporting the critical effect of cognitive control processes over inhibition of retrieval. In contrast to this, the ability of AD patients to suppress retrieval was found to be impaired.