Dobel, C.

Eden, A.

Keuper, K.

Schreiber, J.

Zwanzger, P.

MPG.PuRe

Structural and behavioural differences between Otto Creutzfeldt Centerfor Cognitive and Behavioral NeurosciencemedizinischefakultätWestfälischeWilhelms-Universität Münsterhigh and low trait-anxious individualsAnnuschka Eden1,2, Jan Schreiber3, Peter Zwanzger4, Kati Keuper1,2, and Christian Dobel1,21Institute for Biomagnetism and Biosignalanalysis, University Hospital Münster, 2Otto Creutzfeldt Center for Cognitive and Behavioural Neuroscience, 3Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, 4Department of Psychiatry, University Hospital MünsterIntroductionLearning, conditioning and a genetic predisposition influence the processing of negativei l i li ( h l 2004) f i h l iTo date, studies on memory-bias in subclinical anxiety patients do not add up to a consistent picture.Whil h l h i f bi h bl fi diMethodThe State Trait Anxiety Inventory (Spielberger et al., 1983) served to formtwo groups, one high and one low in trait-anxiety (fig. 1a). An associativestatistical word-learning (training) was applied to investigate the developmentof memory bias for negatively arousing stimuli. Within this framework, 60neutral word stimuli (e.g. binu) were linked with negative arousing colouri ( l i ) (fi 1b) T h k f bi i li i lemot ona st mu e.g. P e ps, . Here, we are ocus ng on t e earn ng-process, memory-consolidation and the associated neural fibre-connections in individuals with elevated trait-anxiety. These people are especially prone to develop anxiety-disorders and differ from peoplewith reduced or average trait-anxiety with regard to the processing, evaluation and memory ofthreat-related stimulus-material (McCabe, 1999; Russo et al, 2006; Mitte, 2008).e some aut ors strong y support t e ex stence o a memory as, ot ers ame n ngs onunpropitious experimental designs or insufficient criterions (Russo et al 1999). It is the intent of thisstudy to finally clarify if subclinical high and low individuals significantly differ from each other or not.To achieve this, shortcomings of earlier studies are addressed, circumvented and behavioural testing iscombined with a state-of-the art imaging technique.Testing procedures Training (example of a trial)ABCp ctures e.g. exp os on g. . o c ec or memory- ases, we mp c t yand explicitly tested the learned word-material. These tests were carried outdirectly after training and two weeks later (fig. 1c). The latter wasimplemented to investigate the impact of consolidation on the development ofmemory biases A subgroup of n= 34 subjects was additionally scanned viaDiffusion Tensor Imaging (DTI). The program Tract-based spacial statisticsfrom FSL was used to investigate white matter differences between groups viaFractional Anisotropy (FA) Values.Behavioral ResultsResults of the recall test yielded a significantmain effect for word type, F(1, 52) = 8.787; p = 0.005, andinteraction effect for anxiety x word-type, F(1, 52) =These memory-bias effects were not yet visible during the learning process itself. Here, resultsyielded increasing learning curves for all subjects (fig. 3) but did not show differences betweenanxiety-groups. Thus, no evidence for the development of a bias during the acquisition of the newword-material was found.A remarkable finding emerged two weeks after the training when high anxiety subjects rated theFigure 1: STAI-trait results of 311 subjects. Scores ≥ 50 were defined as high anxiety. Scores ≤ 30 as low anxiety. N= 54subjects took part in the main experiment (A). Visualisation of a word-learning-trial from training. After listening to a pseudoword and viewing a picture-object, participants had to decide via button-press if word and object did match or did not match (B).Schematic diagram, visualising the behavioural testing-procedures (C).Training4.687; p = 0.035. As hypothesized, higher recall-rateswere exclusively found in high anxiousindividuals (fig. 2a). Results of the valence-ratingshowed main effects for group, F(1, 529) = 34.534; p <0.001, and anxiety F(1, 52) = 7.153; p = 0.010, aninteraction effect session x word type F(2, 104) =28.697; p <0.001 but no interaction between anxiety xword-type (fig. 2b) .Structural ResultsAnalysis of the DTI-data revealed significant structural differences between high and low-anxious subjects. These were particularly visible in dorsolateral Prefrontal Cortex (dlPFC) andthalamic regions. Here, the low-anxiety group exhibited higher FA-Values, hence strongerintegrity of white matter (fig. 4).Valence rating (B)Recall test (A)neutrally linked words in a strongly negative manner, suggesting a generalization-bias (fig. 2b).Figure 3: Development of accuracy in %during training (n=54).****Figure 2: Percentage of correct responses in the cued recall test (A) and valence ratings of words (B). Highanxiety subjects remembered negatively linked words better than neutrally linked words.A trend of this discrimination effect was visible immediately after training. Two weeks after training, theeffect had strengthened. No comparable effect was found in the low-anxiety subjects (A).Before training, subjects did not differentiate between word types and rated words of both categoriescomparable to each other. Immediately after training, high and low anxiety subjects rated negatively linkedwords in a more negative way. This discrimination-effect was still visible two weeks after training. At thistime, the high anxiety group displayed a generalization effect by additionally rating neutrally linked words ina negative manner. This was not seen in the low anxiety group (B).Figure 4: Significant differences in fractional anisotropy (FA) between high and low-anxious subjects(shown in red/yellow). FA-differences are located in right hemispheric dlPFC and thalamic regions.R L R LReferences1) Phelps, E. A. (2004). „Human emotion and memory: Interactions of the amygdala and hippocampal complex“. Current Opinion in Neurobiology, 14(2), 198-202. 2) McCabe (1999). “Implicit and Explicit Memory for Threat Words in High and Low-Anxiety-Sensitive Participants“. Cognitive Therapy and Research, Vol. 23, No.1, 21-38.3) Russo et al. (2006). “Mood-congruent free recall bias in anxious individuals is not a consequence of response bias“. Memory, 14 (4), 393-399.4) Mitte (2008). “Memory bias for Threatening Information in Anxiety and Anxiety Disorders: A Meta-Analytic Review“. Vol. 134, No.6, 886-911.5) Russo (1999). “On the Status of Implicit Memory Bias in Anxiety“. Cognition and Emotion, 1999, 13 (4), 435-456.6) Spielberger et al. (1983). “Manual for the State-Tarit Anxiety Inventory (Form Y)“. Consulting Psychologists Press, Inc.: Palo Alto.Funding: Interdisziplinäres Zentrum für klinischeForschung (IZKF), Projekt: Do3/021/10Contact: Annuschka_eden@yahoo.comConclusionOverall, the results clearly emphasize neuroanatomical and behavioral differences betweensubclinical high and low trait-anxious individuals. Behavioural differences regarding learning(memory bias) are stronger for explicit than implicit memory. The absence of group-differences during the training suggests that development of the memory-bias takes place atlater learning-stages such as consolidation or retrieval.Consolidated implicit responses of the high anxiety group indicate a generalization-bias, which mightbe due to anxiety-specific consolidation-mechanisms and which is associated with lower white matterintegrity in right-hemispheric dlPFC and thalamic regions. The results of this study could haveimplications for therapeutic treatment and have to be discussed in relation to current theories onanxiety disorders.

Structural and behavioural differences between high and low trait-anxious individuals

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