We aimed to investigate the effect of a brief semantic training in episodic verbal memory of children with OCD by assessing its ... level of symptoms: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) mean of 26.7 and a SD of 6.48 (Table. 1).
POSTER Nº 18631 Section 3.20
Author Disclosure Information: - Polanczyk GV served as a speaker and/or consultant to Eli-Lilly, Novartis, Janssen-Cilag, and Shire Pharmaceuticals, developed educational material to Janssen-Cilag, and receives unrestricted research support from Novartis and from the National Council for Scientific and Technological Development (CNPq, Brazil). - The remaining authors involved in this study declare no conflict of interest.
EPISODIC VERBAL MEMORY ENCODING BEFORE AND AFTER A BRIEF COGNITIVE TRAINING: RESULTS FROM A fMRI STUDY IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER Batistuzzo MC¹³, Balardin JB², Martin MGM²³, Hoexter MQ¹, Amaro E², Savage CR³, Miguel EC¹³, Polanczyk GV¹³, Miotto EC ¹ Department of Psychiatry, Psychiatric Institute of the Medical School of São Paulo University ² Institute of Radiology, São Paulo University ³ National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, Brazil Department of Neurology, São Paulo University
INTRODUTCION
MATERIALS AND METHODS
RESULTS
Imaging results
Previous neuroimaging studies of Obsessive-Compulsive Disorder (OCD) suggest that orbitofrontal cortex (OFC) is implicated in the neurobiology of the disease, most often being hiperactivated on resting conditions¹. In spite of studies showing morphometric and functional cerebral specificities in children with OCD, in general the neurobiological model of the disease, involving the orbitofrontalstriatal circuit, can be extended from adults to pediatric samples². In parallel to these findings, neuropsychological studies of OCD patients indicates, among other cognitive difficulties, deficits on episodic verbal memory³. It is postulated that this deficit may be mediated by poor executive functions, ie. difficulties to organize different words using semantic categorization to make connections between them⁴. In this sense, the memory deficits presented by the patients would be secondary to the executive functions deficits, and not a memory deficit per se.
Subjects Twenty children with OCD recruited from our OCD clinic and 20 healthy controls were included in this study. Both groups went through a fMRI paradigm which accessed the memory encoding of words, based on a previous study by our group⁵. Both groups were paired for age, sex and lateralization (Table 1). Years of education and mean income were also not different between groups.
Clinical results Children with OCD presented a moderate level of symptoms: Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) mean of 26.7 and a SD of 6.48 (Table 1). The groups had significantly different scores on scales of depression and anxiety (CDRS-R and SCARED, p Pre, as for Pre>Post. Patients After training patients presented more activations in 2 different clusters for the SR condition, and 5 clusters for the NR condition (Table 3). For the SR condition, the first cluster involved mainly the intraparietal fissure of both hemispheres and the second cluster involved portions of left orbital, inferior and medial frontal gyrus (Figure 2). Regarding the NR condition, we observed clusters in similar locations as the SR condition, besides the presence of two other areas engaged on the task after the training: right orbital and inferior gyros and an extent cluster on the cerebellum and occipital lobe, bilaterally (Figure 3).
*This data are not shown in the tables.
Figure 2: Patients group (n=20), SR list, Post > Pre.
Figure 3: Patients group (n=20): NR list, Post > Pre.
Episodic Verbal Memory Paradigm The AB block design paradigm had two different conditions: we scanned children when they were encoding (reading) semantically related words (SR), non related words (NR) and fixation (+ or x). Each condition was composed by 16 words, presented 3 times each. Semantic lists were made of 4 different categories (Figure 1). After the visual presentation of the stimuli, subjects were instructed to recall as much words as they could. After retrieval, participants went through a recognition task outside the scanner.
Finally, our main results from ANOVA analysis revealed a significant group*training interaction only for the NR condition (Figure 4). Two clusters were detected: the biggest one situated in the left inferior frontal gyros (IFG), mainly on the pars opercularis extending to the pars triangularis; and the second cluster in the left occipital lobe (Table 4).
Semantic Training The semantic training conducted in the interval between sections was a 30-minutes procedure in which children were oriented to identify and classify the categories “hidden” inside the word lists. Children returned to the machine when they could effectively perform the categorization task.
Figure 1: Representation of the encoding words and the Paradigm Design.
CONCLUSIONS We didn't observe any difference between groups on the comparison before the training in terms of recalled words or recognition scores. This indicates that both groups could remember the same quantity of words. This was also true for after the training, where both groups presented approximately 11/12 words in the free recall.
Figure 4: Interaction effect group*training (OCD=20, controls=20): NR list. The chart represents the amount of BOLD signal in the left IFG cluster showed below.
Statistical Analysis We used the FMRIB Software Library (FSL) to perform statistical analysis of neuroimaging data of first and higher level analysis. Briefly, the first level analysis was composed by: slice correction, motion correction (MCFLIRT), spatial smoothing of 5 mm, 90 seconds high pass filtering, cerebral extraction (BET) and specific children template was utilized to register the images with 12 DOF. The Gamma hemodynamic response function was estimated by a convolution with 6 seconds peak level. General linear model (GLM) was used to calculate the paradigm regressors, and the adopted criteria was a probability value of 0.05 and a 2.3 threshold for clusters. First level analysis were made for SR > rest and NR > rest. For higher level analysis we carried out: independent ttest for comparisons between groups, paired t-tests for comparisons within groups and mixed-effects repeated ANOVA to assess the group*training interaction. In this last case we used the FEATquery function (of FSL) to extract the amount of blood oxygen level dependent (BOLD) signal in the cluster that presented differences in this comparison. The behavioral data analysis followed the same steps of the imaging data, using SPSS v19.
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Controls
Patients
On the other hand, our imaging data have shown that children with OCD recruited more the IFG after training, whereas the control group showed reduction in this area after the training (ANOVA analysis). Thus, this results indicate that children with OCD and controls benefited in different ways from the training: both could improve their memory (SR list and the semantic index), but only children with OCD increased their activation on left IFG, a crucial region for semantic categorization. Given that the training did not change the BOLD signal in controls, it is possible that they were already engaging this area before the training. In this sense, this study corroborates the impairment of frontostriatal circuits in OCD, at least before the training, in a childhood population. Furthermore, it is very likely that long term cognitive interventions or rehabilitation programs could benefit children with OCD by re-modulating their brain functions and improving their affected cognitive abilities. Curiously, in all imaging analysis the BOLD effect was larger in the NR condition compared to the SR list: both ANOVA analysis and the paired t-tests (separately) have shown more extension and more clusters in the NR condition. It is possibly that this happened in the NR list because individuals where trying, unsuccessfully, to relate unrelated words. In this way, the more challenging is the task, more engaged will be the brain. In conclusion, early diagnosis of OCD is crucial for implementation of cognitive interventions that re-modulates brain functions.
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