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Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression
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P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation
P.1.i.011 Prefrontal cortex haemodynamic responses in severe major depression and the effects of ECT: an fNIRS study D. Downey1 , S. Brigadoi2,3 , L. Trevithick4 , R. Elliott1 , C. Elwell3 , R.H. McAllister-Williams4 , I.M. Anderson1,5 ° 1 University of Manchester, Neuroscience and Psychiatry Unit, Manchester, United Kingdom; 2 University of Padova, Department of Developmental and Social Psychology, Padova, Italy; 3 University College London, Biomedical Optics Research Laboratory, London, United Kingdom; 4 Newcastle University, Institute of Neuroscience, Newcastle, United Kingdom; 5 Manchester Mental Health and Social Care Trust, Division of Psychiatry, Manchester, United Kingdom Background: The cognitive deficits found in depressed patients have been associated with impaired prefrontal cortical function, and limited evidence suggests that electroconvulsive therapy (ECT) leads to its further suppression. This may contribute to the acute detrimental effects of ECT on cognition [1]. Haemodynamic responses to cognitive tasks can be measured in the lateral prefrontal cortex using functional near-infrared spectroscopy (fNIRS), and an expanding evidence base has shown that depressed patients, compared to healthy controls, have impaired responses during verbal fluency (VF) [2] and working memory (WM) [3] tasks, suggesting that this methodology can be used as a measure of prefrontal cortical function. Objective: We hypothesised that severely ill depressed patients will have decreased lateral frontal activation to verbal fluency and working memory tasks and that a low dose of ketamine, given as part of the general anaesthetic, will alleviate the further suppression of frontal activation by ECT, in line with its benefits in preserving cognitive function. Methods: As part of a placebo-controlled trial investigating whether ketamine might alleviate the cognitive impairments caused by ECT [4], 18 depressed patients and 51 healthy controls (HC) were studied using fNIRS. Patients were tested before commencing ECT, and 12 were also assessed after 4 ECT treatments. Participants performed a short (10 min) paced category VF task consisting of blocks of 30 seconds of stimulus, followed by 30 seconds of rest, repeated 10 times and a 10 minute N-Back WM task consisting of 10 blocks each of 30 seconds of 2 back stimuli and rest. Haemodynamic optical data were acquired with the miniNTS fNIRS system (UCL Biomedical Optics Research/Gower Labs) consisting of 4 detectors and 24 sources. A symmetric probe was created covering lateral prefrontal areas, with a total of 12 channels per hemisphere. Homer2 [5] was used to preprocess the data using spline motion correction and band-pass filtering. Mean regional haemodynamic responses were calculated by blockaveraging trials following a baseline correction, and analysed using ANCOVA co-varied for age and sex. Results: Preliminary results show patients had blunted bilateral prefrontal cortex oxyhaemoglobin responses to the VF task compared to HC, and this was further decreased after 4 ECT. Patients who responded to ECT tended to have relatively preserved responses, and greater suppression by ECT, to this task. On the WM task, patients tended to show prefrontal cortex inhibition at baseline and an altered time course of oxy- and deoxyhaemoglobin after 4 ECTs. No significant effect of ketamine was found in either task but the number of patients in each arm limited this comparison. Conclusions: Haemodynamic prefrontal cortical responses appear to be impaired in severe depression and further suppressed
by ECT treatment in a preliminary analysis. The usefulness of fNIRS to predict response to ECT warrants further investigation. References [1] MacPherson, R.D., Loo, C.K., 2008. Cognitive impairment following electroconvulsive therapy − does the choice of anesthetic agent make a difference? J ECT 24, 52−56. [2] Herrmann, M.J., Ehlis, A.C., Fallgatter, A.J., 2004. Bilaterally reduced frontal activation during a verbal fluency task in depressed patients as measured by near-infrared spectroscopy. J Neuropsychiatry Clin Neurosci 16, 170–175. [3] Pu, S., Yamada, T., Yokoyama, K., Matsumura, H., Kobayashi, H., Sasaki, N., et al., 2011. A multi-channel near-infrared spectroscopy study of prefrontal cortex activation during working memory task in major depressive disorder. Neurosci Res 70, 91−97. [4] Trevithick, L., McAllister-Williams, R.H., Blamire, A., Branton, T., Clark, R., Downey, D., Dunn, G., Easton, A., et al., 2015. Study protocol for the randomised controlled trial: Ketamine augmentation of ECT to improve outcomes in depression (Ketamine-ECT study). BMC Psychiatry 21(15), 257. [5] Huppert, T.J., Diamond, S.G., Franceschini, M.A., Boas, D.A. 2009. HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain, Appl Opt 48, D280–298. Disclosure statement: Current Controlled Trials ISRCTN14689382. The study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership. The views expressed are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health, UK.
P.1.i.012 Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression A. Jørgensen1 , P. Magnusson2 , L. Hanson2 , T. Kirkegaard1 , H. Benveniste3 , H. Lee3 , C. Svarer4 , J. Mikkelsen4 , A. FinkJensen1 , G. Knudsen4 , O.B. Paulson4 ° , T. Bolwig1 , M. Jørgensen1 1 Psychiatric Centre Copenhagen- Copenhagen University Hospital, Department O Rigshospitalet, Copenhagen, Denmark; 2 Hvidovre Hospital- Copenhagen University Hospital, Danish Research Center for Magnetic Resonance, Hvidovre, Denmark; 3 Stony Brook Medicine, Anesthesiology and Radiology, Stony Brook- NY, USA; 4 Copenhagen University Hospital Rigshospitalet, Neurobiology Research Unit- build. N-6931, Copenhagen, Denmark Introduction: Severe depression is a serious disease with a significant risk of suicide. Electroconvulsive therapy (ECT) has been used in the treatment of psychiatric disorders for more than 70 years. Despite numerous studies focusing on a variety of biological mechanisms acting during and after ECT, its underlying mechanism of action is far from fully elucidated. Earlier MR studies further have demonstrated a reduction in hippocampal volume in patients with long-standing symptoms of severe depression [1]. The hippocampal volume reduction appears after onset of illness and is therefore most likely the result of depression rather than a pre-existing trait. Recent research has focused on the neurotrophic effects of ECT, especially those occurring in the hippocampus [2]. In support of a role for the hippocampus in the pathogenesis of depression, MR studies have shown an increase in hippocampal volume following successful ECT in severely depressed patients [3]. Further, the relevance of the hippocampus in understanding the effects of ECT is substantiated by a number of animal studies demonstrating that electroconvulsive stimulations (ECS, an animal model of clinical ECT) induces the formation of new neurons (neuronal progenitor cells) in the dentate gyrus of the hippocampus [4]. A recent study described a metabolic biomarker for the detection and quantification of neural stem and progenitor cells (NPCs) using in vivo proton magnetic resonance spectroscopy (1H-MRS) [5].
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation Aims: To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). Methods: We used Magnetic Resonance (MR) Imaging, including Diffusion Tensor Imaging (DTI) and proton MR Spectroscopy (1H-MRS) to investigate hippocampal volume, diffusivity and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), one week (TP2) and four weeks (TP3) after completion of the ECT series. Results: Hippocampal and amygdala volume increased significantly at TP2, and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations (1H-MRS), and we were unable to identify a spectral signature at ≈1.30 ppm previously suggested to reflect neurogenesis induced by ECT [5]. None of the brain imaging measures correlated to the clinical response. Conclusions: Our findings show that ECT causes a remodelling of brain structures involved in affective regulation, but due to their lack of correlation with the antidepressant effect, this remodelling does not appear to be directly underlying the antidepressant action of ECT. Brain metabolites were not significantly altered by ECT. We were unable to identify a previously described spectroscopic marker of hippocampal neurogenesis before or after ECT. The study contributes significantly to our knowledge of the biological brain changes occurring in association with ECT. References [1] Sheline, Y.I., Wang, P.W., Gado, M.H., Csernansky, J.G., Vannier, M.W., 1996. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93, 3908–3913. [2] Hageman, I., Nielsen, M., Wortwein, G., Diemer, N.H., Jorgensen, M.B., 2008. Electroconvulsive stimulations prevent stressinduced morphological changes in the hippocampus. Stress 11, 282– 289. [3] Nordanskog, P., Dahlstrand, U., Larsson, M.R., Larsson, E.M., Knutsson, L., Johanson, A., 2010. Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. J ECT 26, 62−67. [4] Madsen, T.M., Treschow, A., Bengzon, J., Bolwig, T.G., Lindvall, O., Tingstrom, A., 2000. Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 47, 1043–1049. [5] Manganas, L.N., Zhang, X., Li, Y., Hazel, R.D., Smith, S.D., Wagshul, M.E., Henn, F., Benveniste, H., Djuric, P.M., Enikolopov, G., Maletic-Savatic, M., 2007. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science. 318, 980–985.
P.1.i.013 Do obsessive compulsive disorder patients have difficulty forming an internal model of the completed state of an action? O.M. Kocak1 ° , K. Ozdel2 , B. Kırkıcı3 , M. U˘gurlu4 , E. Kale5 , 6 , S. Buturak6 , D. Oymak4 1 Kirikkale ¨ A. Yılmaz Ozpolat University, Psychiatry, Kirikkale, Turkey; 2 Dı¸skapı Yıldırım Beyazıt Education and Research Hospital, Psychiatry, Ankara, Turkey; 3 Middle East Technical University- Faculty of Education, Department of Foreign Language Education, Ankara, Turkey; 4 Atat¨ urk Education and Research Hospital, Psychiatry, Ankara, Turkey; 5 Ankara university, Brain Research Center, Ankara, Turkey; 6 Kırıkkale University School of Medicine, Psychiatry, Kırıkkale, Turkey Background: Earlier findings suggest that in obsessive compulsive disorder (OCD) the completion of an action is problematic [1,2] and forward motor control seems impaired [3]. Against this background, the present study used fMRI to test
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whether compulsions are associated with inadequate activation of the completed state of an action in the sensory-motor system. In order to test this hypothesis, a novel paradigm, which involves a lexical decision test, was designed. It was assumed that language comprehension requires the activation of the perceptual and motor systems, which is accepted as a “mental simulation” of the content of sentences in the mind [4]. One component that has been expected to be central to the formation of such a mental simulation is the aspect encoded in the sentence. Aspect describes the different ways of viewing the temporal properties of a situation or the internal temporal state (completed, sustained etc.) of an event, typically encoded through verbal constructions. A basic distinction is made between perfective and imperfective aspect. Thus it has been hypothesis that OCD patients had a different functional activity pattern in perfective aspect. Method: Sixteen patients with OCD and 13 non-OCD volunteers took part in the study. While functional images were acquired, subjects performed a series of lexical decisions following the presentation of stimuli. The stimuli consisted of a picture and a verb on the screen. The verb was inflected with one of the aspect markers of the prospective, the perfective aspect or the imperfective aspect in Turkish language. The picture, on the other hand, presented a two-directional arrow that contained a red ring on the right (indicating intention to perform an action), in the middle (indicating sustained action), or left (indicating a completed action). The subjects were asked to decide whether the aspect of the word and the place of ring on the arrow were congruent or not via pressing one of two buttons. Half of the stimuli verbs were nonwords and the subjects were required to not press any button as response to these (hence, to make a lexical decision). Results: Congruent stimuli of each aspect were analysed through a One-Way ANOVA in the control group. This analysis revealed that there were significantly different activity patterns belonging to perfective and imperfective aspects (p < 0.001, uncorrected). A flexible factorial design with three factors (aspect, state of congruency and group) revealed significant main effects of group and state of congruency [for both main effects p(FDR) < 0.05, corrected]. In addition, a significant group × aspect interaction was observed for both the perfective and the imperfective aspects [for both interactions p(FDR) < 0.05]. Accordingly, the OCD group was less able to activate the dorsolateral PFC and their medial prefrontal regions were more activated in comparison to the control group. Conclusion: The intersection of the activated regions of perfective aspect in control group and the regions in which flexible factorial design revealed a significant group × perfective aspect interaction directly supports the hypothesis that patients with OCD have an inadequacy of the representation of completed state of an action. References [1] Zor, R., Szechtman, H., Hermesh, H., Fineberg, N.A., Eilam, D., 2011. Manifestation of incompleteness in obsessive-compulsive disorder (OCD) as reduced functionality and extended activity beyond task completion. PLoS One 6, e25217. [2] Hinds, A.L., Woody, E.Z., Van Ameringen, M., Schmidt, L.A., Szechtman, H., 2012. When too much is not enough: obsessive-compulsive disorder as a pathology of stopping, rather than starting. PLoS One 2012, 7:e30586. [3] Gentsch, A., Sch¨utz-Bosbach, S., Endrass, T., Kathmann, N. 2012. Dysfunctional forward model mechanisms and aberrant sense of agency in obsessive-compulsive disorder. Biol Psychiatry 71, 652–659. [4] Tettamanti, M., Buccino, G., Saccuman, M.C., Gallese, V., Danna, M., Scifo, P., Fazio, F., Rizzolatti, G., Cappa, S.F., Perani, D. 2005. Listening to action-related sentences activates fronto-parietal motor circuits. J Cogn Neurosci 17, 273–281.
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation
P.1.i.011 Prefrontal cortex haemodynamic responses in severe major depression and the effects of ECT: an fNIRS study D. Downey1 , S. Brigadoi2,3 , L. Trevithick4 , R. Elliott1 , C. Elwell3 , R.H. McAllister-Williams4 , I.M. Anderson1,5 ° 1 University of Manchester, Neuroscience and Psychiatry Unit, Manchester, United Kingdom; 2 University of Padova, Department of Developmental and Social Psychology, Padova, Italy; 3 University College London, Biomedical Optics Research Laboratory, London, United Kingdom; 4 Newcastle University, Institute of Neuroscience, Newcastle, United Kingdom; 5 Manchester Mental Health and Social Care Trust, Division of Psychiatry, Manchester, United Kingdom Background: The cognitive deficits found in depressed patients have been associated with impaired prefrontal cortical function, and limited evidence suggests that electroconvulsive therapy (ECT) leads to its further suppression. This may contribute to the acute detrimental effects of ECT on cognition [1]. Haemodynamic responses to cognitive tasks can be measured in the lateral prefrontal cortex using functional near-infrared spectroscopy (fNIRS), and an expanding evidence base has shown that depressed patients, compared to healthy controls, have impaired responses during verbal fluency (VF) [2] and working memory (WM) [3] tasks, suggesting that this methodology can be used as a measure of prefrontal cortical function. Objective: We hypothesised that severely ill depressed patients will have decreased lateral frontal activation to verbal fluency and working memory tasks and that a low dose of ketamine, given as part of the general anaesthetic, will alleviate the further suppression of frontal activation by ECT, in line with its benefits in preserving cognitive function. Methods: As part of a placebo-controlled trial investigating whether ketamine might alleviate the cognitive impairments caused by ECT [4], 18 depressed patients and 51 healthy controls (HC) were studied using fNIRS. Patients were tested before commencing ECT, and 12 were also assessed after 4 ECT treatments. Participants performed a short (10 min) paced category VF task consisting of blocks of 30 seconds of stimulus, followed by 30 seconds of rest, repeated 10 times and a 10 minute N-Back WM task consisting of 10 blocks each of 30 seconds of 2 back stimuli and rest. Haemodynamic optical data were acquired with the miniNTS fNIRS system (UCL Biomedical Optics Research/Gower Labs) consisting of 4 detectors and 24 sources. A symmetric probe was created covering lateral prefrontal areas, with a total of 12 channels per hemisphere. Homer2 [5] was used to preprocess the data using spline motion correction and band-pass filtering. Mean regional haemodynamic responses were calculated by blockaveraging trials following a baseline correction, and analysed using ANCOVA co-varied for age and sex. Results: Preliminary results show patients had blunted bilateral prefrontal cortex oxyhaemoglobin responses to the VF task compared to HC, and this was further decreased after 4 ECT. Patients who responded to ECT tended to have relatively preserved responses, and greater suppression by ECT, to this task. On the WM task, patients tended to show prefrontal cortex inhibition at baseline and an altered time course of oxy- and deoxyhaemoglobin after 4 ECTs. No significant effect of ketamine was found in either task but the number of patients in each arm limited this comparison. Conclusions: Haemodynamic prefrontal cortical responses appear to be impaired in severe depression and further suppressed
by ECT treatment in a preliminary analysis. The usefulness of fNIRS to predict response to ECT warrants further investigation. References [1] MacPherson, R.D., Loo, C.K., 2008. Cognitive impairment following electroconvulsive therapy − does the choice of anesthetic agent make a difference? J ECT 24, 52−56. [2] Herrmann, M.J., Ehlis, A.C., Fallgatter, A.J., 2004. Bilaterally reduced frontal activation during a verbal fluency task in depressed patients as measured by near-infrared spectroscopy. J Neuropsychiatry Clin Neurosci 16, 170–175. [3] Pu, S., Yamada, T., Yokoyama, K., Matsumura, H., Kobayashi, H., Sasaki, N., et al., 2011. A multi-channel near-infrared spectroscopy study of prefrontal cortex activation during working memory task in major depressive disorder. Neurosci Res 70, 91−97. [4] Trevithick, L., McAllister-Williams, R.H., Blamire, A., Branton, T., Clark, R., Downey, D., Dunn, G., Easton, A., et al., 2015. Study protocol for the randomised controlled trial: Ketamine augmentation of ECT to improve outcomes in depression (Ketamine-ECT study). BMC Psychiatry 21(15), 257. [5] Huppert, T.J., Diamond, S.G., Franceschini, M.A., Boas, D.A. 2009. HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain, Appl Opt 48, D280–298. Disclosure statement: Current Controlled Trials ISRCTN14689382. The study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership. The views expressed are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health, UK.
P.1.i.012 Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression A. Jørgensen1 , P. Magnusson2 , L. Hanson2 , T. Kirkegaard1 , H. Benveniste3 , H. Lee3 , C. Svarer4 , J. Mikkelsen4 , A. FinkJensen1 , G. Knudsen4 , O.B. Paulson4 ° , T. Bolwig1 , M. Jørgensen1 1 Psychiatric Centre Copenhagen- Copenhagen University Hospital, Department O Rigshospitalet, Copenhagen, Denmark; 2 Hvidovre Hospital- Copenhagen University Hospital, Danish Research Center for Magnetic Resonance, Hvidovre, Denmark; 3 Stony Brook Medicine, Anesthesiology and Radiology, Stony Brook- NY, USA; 4 Copenhagen University Hospital Rigshospitalet, Neurobiology Research Unit- build. N-6931, Copenhagen, Denmark Introduction: Severe depression is a serious disease with a significant risk of suicide. Electroconvulsive therapy (ECT) has been used in the treatment of psychiatric disorders for more than 70 years. Despite numerous studies focusing on a variety of biological mechanisms acting during and after ECT, its underlying mechanism of action is far from fully elucidated. Earlier MR studies further have demonstrated a reduction in hippocampal volume in patients with long-standing symptoms of severe depression [1]. The hippocampal volume reduction appears after onset of illness and is therefore most likely the result of depression rather than a pre-existing trait. Recent research has focused on the neurotrophic effects of ECT, especially those occurring in the hippocampus [2]. In support of a role for the hippocampus in the pathogenesis of depression, MR studies have shown an increase in hippocampal volume following successful ECT in severely depressed patients [3]. Further, the relevance of the hippocampus in understanding the effects of ECT is substantiated by a number of animal studies demonstrating that electroconvulsive stimulations (ECS, an animal model of clinical ECT) induces the formation of new neurons (neuronal progenitor cells) in the dentate gyrus of the hippocampus [4]. A recent study described a metabolic biomarker for the detection and quantification of neural stem and progenitor cells (NPCs) using in vivo proton magnetic resonance spectroscopy (1H-MRS) [5].
P.1.i. Basic and clinical neuroscience − Brain imaging and neuro-modulation Aims: To investigate the role of hippocampal plasticity in the antidepressant effect of electroconvulsive therapy (ECT). Methods: We used Magnetic Resonance (MR) Imaging, including Diffusion Tensor Imaging (DTI) and proton MR Spectroscopy (1H-MRS) to investigate hippocampal volume, diffusivity and metabolite changes in 19 patients receiving ECT for severe depression. Other regions of interest included the amygdala, dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex, and hypothalamus. Patients received a 3T MR scan before ECT (TP1), one week (TP2) and four weeks (TP3) after completion of the ECT series. Results: Hippocampal and amygdala volume increased significantly at TP2, and continued to be increased at TP3. DLPFC exhibited a transient volume reduction at TP2. DTI revealed a reduced anisotropy and diffusivity of the hippocampus at TP2. We found no significant post-ECT changes in brain metabolite concentrations (1H-MRS), and we were unable to identify a spectral signature at ≈1.30 ppm previously suggested to reflect neurogenesis induced by ECT [5]. None of the brain imaging measures correlated to the clinical response. Conclusions: Our findings show that ECT causes a remodelling of brain structures involved in affective regulation, but due to their lack of correlation with the antidepressant effect, this remodelling does not appear to be directly underlying the antidepressant action of ECT. Brain metabolites were not significantly altered by ECT. We were unable to identify a previously described spectroscopic marker of hippocampal neurogenesis before or after ECT. The study contributes significantly to our knowledge of the biological brain changes occurring in association with ECT. References [1] Sheline, Y.I., Wang, P.W., Gado, M.H., Csernansky, J.G., Vannier, M.W., 1996. Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93, 3908–3913. [2] Hageman, I., Nielsen, M., Wortwein, G., Diemer, N.H., Jorgensen, M.B., 2008. Electroconvulsive stimulations prevent stressinduced morphological changes in the hippocampus. Stress 11, 282– 289. [3] Nordanskog, P., Dahlstrand, U., Larsson, M.R., Larsson, E.M., Knutsson, L., Johanson, A., 2010. Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. J ECT 26, 62−67. [4] Madsen, T.M., Treschow, A., Bengzon, J., Bolwig, T.G., Lindvall, O., Tingstrom, A., 2000. Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 47, 1043–1049. [5] Manganas, L.N., Zhang, X., Li, Y., Hazel, R.D., Smith, S.D., Wagshul, M.E., Henn, F., Benveniste, H., Djuric, P.M., Enikolopov, G., Maletic-Savatic, M., 2007. Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science. 318, 980–985.
P.1.i.013 Do obsessive compulsive disorder patients have difficulty forming an internal model of the completed state of an action? O.M. Kocak1 ° , K. Ozdel2 , B. Kırkıcı3 , M. U˘gurlu4 , E. Kale5 , 6 , S. Buturak6 , D. Oymak4 1 Kirikkale ¨ A. Yılmaz Ozpolat University, Psychiatry, Kirikkale, Turkey; 2 Dı¸skapı Yıldırım Beyazıt Education and Research Hospital, Psychiatry, Ankara, Turkey; 3 Middle East Technical University- Faculty of Education, Department of Foreign Language Education, Ankara, Turkey; 4 Atat¨ urk Education and Research Hospital, Psychiatry, Ankara, Turkey; 5 Ankara university, Brain Research Center, Ankara, Turkey; 6 Kırıkkale University School of Medicine, Psychiatry, Kırıkkale, Turkey Background: Earlier findings suggest that in obsessive compulsive disorder (OCD) the completion of an action is problematic [1,2] and forward motor control seems impaired [3]. Against this background, the present study used fMRI to test
S305
whether compulsions are associated with inadequate activation of the completed state of an action in the sensory-motor system. In order to test this hypothesis, a novel paradigm, which involves a lexical decision test, was designed. It was assumed that language comprehension requires the activation of the perceptual and motor systems, which is accepted as a “mental simulation” of the content of sentences in the mind [4]. One component that has been expected to be central to the formation of such a mental simulation is the aspect encoded in the sentence. Aspect describes the different ways of viewing the temporal properties of a situation or the internal temporal state (completed, sustained etc.) of an event, typically encoded through verbal constructions. A basic distinction is made between perfective and imperfective aspect. Thus it has been hypothesis that OCD patients had a different functional activity pattern in perfective aspect. Method: Sixteen patients with OCD and 13 non-OCD volunteers took part in the study. While functional images were acquired, subjects performed a series of lexical decisions following the presentation of stimuli. The stimuli consisted of a picture and a verb on the screen. The verb was inflected with one of the aspect markers of the prospective, the perfective aspect or the imperfective aspect in Turkish language. The picture, on the other hand, presented a two-directional arrow that contained a red ring on the right (indicating intention to perform an action), in the middle (indicating sustained action), or left (indicating a completed action). The subjects were asked to decide whether the aspect of the word and the place of ring on the arrow were congruent or not via pressing one of two buttons. Half of the stimuli verbs were nonwords and the subjects were required to not press any button as response to these (hence, to make a lexical decision). Results: Congruent stimuli of each aspect were analysed through a One-Way ANOVA in the control group. This analysis revealed that there were significantly different activity patterns belonging to perfective and imperfective aspects (p < 0.001, uncorrected). A flexible factorial design with three factors (aspect, state of congruency and group) revealed significant main effects of group and state of congruency [for both main effects p(FDR) < 0.05, corrected]. In addition, a significant group × aspect interaction was observed for both the perfective and the imperfective aspects [for both interactions p(FDR) < 0.05]. Accordingly, the OCD group was less able to activate the dorsolateral PFC and their medial prefrontal regions were more activated in comparison to the control group. Conclusion: The intersection of the activated regions of perfective aspect in control group and the regions in which flexible factorial design revealed a significant group × perfective aspect interaction directly supports the hypothesis that patients with OCD have an inadequacy of the representation of completed state of an action. References [1] Zor, R., Szechtman, H., Hermesh, H., Fineberg, N.A., Eilam, D., 2011. Manifestation of incompleteness in obsessive-compulsive disorder (OCD) as reduced functionality and extended activity beyond task completion. PLoS One 6, e25217. [2] Hinds, A.L., Woody, E.Z., Van Ameringen, M., Schmidt, L.A., Szechtman, H., 2012. When too much is not enough: obsessive-compulsive disorder as a pathology of stopping, rather than starting. PLoS One 2012, 7:e30586. [3] Gentsch, A., Sch¨utz-Bosbach, S., Endrass, T., Kathmann, N. 2012. Dysfunctional forward model mechanisms and aberrant sense of agency in obsessive-compulsive disorder. Biol Psychiatry 71, 652–659. [4] Tettamanti, M., Buccino, G., Saccuman, M.C., Gallese, V., Danna, M., Scifo, P., Fazio, F., Rizzolatti, G., Cappa, S.F., Perani, D. 2005. Listening to action-related sentences activates fronto-parietal motor circuits. J Cogn Neurosci 17, 273–281.