Eye-tracking-aided characterization of saccades and antisaccades in SYNE1 ataxia patients: a pilot study.

BACKGROUND: SYNE1 ataxia is an autosomal recessive hereditary condition, the main characteristic features of which are gait and limb ataxia and cerebellar dysarthria. Reports have revealed that the clinical phenotype of SYNE1 ataxia is more complex than the first published cases with pure cerebellar signs indicated. The aim of this study was to characterize eye movement alterations in the first diagnosed Hungarian SYNE1 ataxia patients. RESULTS: Saccades and antisaccades were examined with an eye tracker device in 3 SYNE1 (one patient has two frameshift mutations [c.8515_8516insA, p.Met2839Asnfs*53 and c.11594_11595insG, p.Glu3866*] in a compound heterozygous state, whereas two subjects have a splicing variant [c.23146-2A > G] in a homozygous state), 6 Friedreich ataxia (FA) patients and 12 healthy controls. Besides that, detailed clinical phenotyping and comprehensive neuropsychological assessment were carried out in all patients with ataxia. In addition to the characteristic cerebellar alterations, pyramidal signs and polyneuropathy were observed at least in 2 SYNE1 ataxia patients, for which no other underlying reason was found. The eye tracking assessment revealed hypometric saccades in the longer amplitude (18.4°) saccadic paradigm in all SYNE1 patients, whereas 2 out of 3 SYNE1 subjects performed slow saccades as well. In the antisaccade task, higher incorrect ratios of antisaccades were demonstrated in SYNE1 patients compared to healthy controls, showing inverse correlation with working memory test results. The corresponding data of FA patients was dispersed over a wide range, partially overlapping with control data. CONCLUSIONS: The current study draws attention to the presence of eye movement disorders in patients with SYNE1 ataxia and demonstrates that alterations in the antisaccade paradigm may be related to working memory deficits.

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.

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.