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94. Extinction of cognitively conditioned fear in borderline personality disorder
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Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88
93. Structural brain abnormalities in attention-deficit/hyperactivity disorder: A voxel-based MRI study in adult patients—A. Konrad 1, T.F. Dielentheis 1, M. Bayerl 1, D. El Masri 1, T. Bauermann 2, G. Vucurevic 2, P. Stoeter 2, G. Winterer 3 (1 Johannes Gutenberg-Universität, Klinik für Psychiatrie und Psychotherapie, Mainz, Germany, 2 Johannes Gutenberg-Universität Mainz, Institut für Neuroradiologie, Mainz, Germany, 3 Heinrich-HeineUniversität Düsseldorf, Klinik für Psychiatrie, Düsseldorf, Germany) Objective: Most structural neuroimaging studies of subjects with attention-deficit/hyperactivity disorder (ADHD) have been conducted in children. The most replicated findings in ADHD children include significantly smaller volumes in the prefrontal cortex, basal ganglia, corpus callosum and cerebellum. In this study, we investigated structural brain abnormalities in the adult subjects with ADHD using voxel-based morphometry (VBM). Methods: Twenty-five ADHD patients (14 males, mean age 32 years) and 25 age- and gender-matched healthy control subjects (Table 1) underwent a detailed clinical interview as well as neuropsychological investigation of intelligence, memory, attention, psychomotor performance and executive functioning. We acquired MPRAGE (Magnetization Prepared Rapid Gradient Echo)-sequences for high-resolution structural magnetic resonance imaging (MRI) on a 1.5 T scanner. The MRI data sets were first normalized to a standard template using SPM5 software. Images were segmented into gray matter (GM), white matter and cerebrospinal fluid (Fig. 1) and were smoothed with an 8 mm FWHM kernel. Voxel-wise comparisons were then performed between the groups with two contrasts (2 sample unpaired t-test) to test for significant differences of local brain tissue concentration and volume. Following the established procedures, contrast maps were thresholded at a P < 0.001 without correction for multiple comparisons and the extent threshold for significant clusters was set to 100 voxels. Results: Typical group differences in ADHD measures were found (Table 1). Voxel-based morphometry analysis revealed regional volume differences in the gray matter of the right cerebellum showing significantly smaller GM volume in ADHD patients (Fig. 2; peak voxel coordinates MNI 16,-60,-38; cluster extend 125 voxels).
Table 1
Gender (m/f) Age (years) IQ WURS BADDS TOVA
ADHD patients mean ± SD
Controls mean ± SD
P value
14/ 11 32.0 ± 10.5 109.4 ± 8.9 108.9 ± 26.2 74.6 ± 18.7 5.0 ± 6.7
14/ 11 32.1 ± 8.5 111.4 ± 7.8 51.4 ± 20.7 14.4 ± 16.8 1.3 ± 2.6
NS NS NS P < 0.001 P < 0.001 P < 0.001
Fig. 1.
Fig. 2.
Conclusion: Our results provide additional support for the role of cerebellar abnormalities in the pathophysiology of ADHD. Together with the previous findings, there is growing evidence for the impact of the cerebellar-prefrontal-striatal network in ADHD pathophysiology. References Ashburner J, Friston KJ. Neuroimage 2000;11:805–21. Seidman LJ et al. Biol Psychiatry 2005;57:1263–72. Seidman LJ et al. Biol Psychiatry 2006;60:1071–80. Valera EM et al. Biol Psychiatry 2007;61:1361–9. doi:10.1016/j.clinph.2008.07.092
94. Extinction of cognitively conditioned fear in borderline personality disorder—Kamphausen 1, Schroeder 1, Maier 1, Bader 1, Tebartz van Elst 1, Jacob 1, Lieb 2, Tüscher 3 (1 Department of Psychiatry and Psychotherapy, University of Freiburg, Germany, 2 Department of Psychiatry and Psychotherapy, University of Mainz, Germany, 3 Department of Neurology, University of Freiburg, Germany) Background: Despite the prominent role of emotion dysregulation in the theoretical accounts of BPD, so far only few imaging studies have examined emotion dysregulation in BPD. Learning to combine a previously neutral stimulus with a possible aversive event by means of verbal instruction is an everyday experience which humans encounter. Symbolically acquired fear results in physiological fear responses and functional neuroimaging data comparable to the responses in classical fear conditioning. This study aims to investigate the neural underpinnings of extinction learning in female borderline patients to test the hypothesis of different emotion regulation during the extinction process. Methods: We explored the neural mechanisms of fear extinction by means of an instructed fear conditioning task (Phelps et al. 2001). Prior to scanning, was determined in the participants the level of electrodermal stimulation said to be received during the scan session via a standardized dial-up procedure. The scanning session consisted of a ‘‘threat condition’’, about which subjects were told that an electrodermal stimulation could occur at any time and a ‘‘safety condition’’, during which participants knew that they would not receive any stimulation. Threat and safety were signified by the presentation of easily distinguishable coloured squares. The expression of fear responses was controlled by measuring the skin conductance response (SCR). As no stimulation was given at any time during the experiment, extinction processes were recorded throughout the scanning session. So
Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88
far, 14 female patients with borderline personality disorder and 14 matched healthy controls have been included. Results: In the debriefing, all the subjects indicated that they expected to receive a stimulation during the presentation of the threat stimulus until some point in time when their expectancy was started to decrease. Interaction analysis (group condition time) of brain regions (ROI) previously shown to be associated with extinction processes revealed stronger activation of the lateral amygdalae in the patient group compared to controls, regardless of stimulus type. In both the groups, the amygdala response to the threat stimulus was largest at the beginning of the scanning procedure, but, in the patient group, the decline of activation turned out to be less pronounced over the extinction period. As hypothesized, all the control subjects revealed a stronger activation of the (lateral) orbitofrontal cortex (OFC) during extinction, possibly indicating the change of stimulus value that is encoded. Patients did not show a comparable activity increase, indicating the failure of stimulus value reversal. Conclusion: Analyses confirmed a hyperactivity of the amygdala in the borderline patients suggesting a more general responsiveness to threat stimuli. Furthermore, activations of the lateral OFC and amygdala differed between the groups throughout the extinction process indicating a failure of frontolimbic regulatory mechanisms. doi:10.1016/j.clinph.2008.07.093
95. Quantitative CMAP shape analysis differentiates between uniform and non-uniform motor nerve conduction slowing—W. Schulte-Mattler, V. Busch (Universität Regensburg, Neurologie, Regensburg, Germany) Objective: Demyelination may cause a uniform reduction of the conduction velocity of all the fibres of a peripheral nerve segment, or may non-uniformly affect only some nerve fibres while sparing others. In the latter case, the routinely determined nerve conduction velocity (NCV) is normal while amplitude, duration, and shape of compound muscle action potentials (CMAPs) vary with the distance between the stimulus and the muscle. This study was done to determine if and to what extent the quantitative analysis of CMAP shapes has the potential to differentiate between uniform and non-uniform conduction slowing. Methods: Data of patients with early inflammatory demyelinating polyneuropathy (IDP, non-uniform demyelination, n = 20), hereditary neuropathy (CMT, uniform demyelination, n = 8), motor neuron disease (MND, axon loss, n = 20), and healthy controls (n = 20) were analyzed. NCV, amplitude and duration of CMAP, minimal F-wave latency (FMIN), and F-wave chronodispersion (FDISP) in
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tibial nerves were measured. The high frequency attenuation (HFA) method was used to compare the CMAP shapes. Results: NCV and HFA are best differentiated between IDP and CMT (Fig. 1), as NCV was reduced only in patients with CMT (100%) and HFA was abnormal only in patients with early IDP (35%). CMAP duration was found increased in patients with early IDP (15%) and in patients with MND (10%). FDISP was increased in patients with early IDP (30%) and in patients with MND (20%). FMIN was increased in patients with early IDP (10%) and in patients with MND (10%), and in all the patients with CMT in whom F-waves could be recorded. Conclusion: The results stress that an increased HFA specifically indicates non-uniform slowing of nerve conduction while a reduced NCV indicates a uniform slowing. With the help of HFA measurements, the diagnostic sensitivity of routine nerve conduction studies can be increased. doi:10.1016/j.clinph.2008.07.094
96. Influence of tDCS of the right DLPFC on verbal working memory and non-noxious and noxious thermal stimulation—V. Mylius 1, M. Jung 1, K. Hattemer 1, A. Haag 1, M. Teepker 1, M. Huber 2, W.H. Oertel 1, F. Rosenow 1 (1 Universität Marburg, Neurologie, Marburg, Germany, 2 Universität Marburg, Psychiatrie, Marburg, Germany) Objective: Experimentally induced pain can be decreased by 1Hz repetitive transcranial magnetic stimulation (rTMS) of the right Dorsolateral Prefrontal Cortex (DLPFC), presumably by effects on the emotional-cognitive component of pain. Anodal transcranial Direct Current Stimulation (tDCS) ameliorated chronic pain when applied over the motor cortex and increased working memory (WM) function in a letter-based 3-back task when applied over the left DLPFC. Thus, we investigated whether (tDCS) of the right DLPFC modulates thermal sensation or thermal pain addition to WM function. Methods: Warm and cold sensation thresholds (WSTs and CSTs) as well as heat and cold pain thresholds (HPTs and CPTs) were assessed by using contact thermodes on the contra lateral forearm before and after 20 min of 2 mA anodal, cathodal or sham tDCS of the right DLPFC (center F 4) in 18 healthy volunteers (balanced randomization). WM was assessed by using a two number-based 2-back task during the stimulation. Results: The 2-back task revealed a prolongation of reaction time and an increase in the omission rate for anodal tDCS compared to cathodal tDCS (T(16) = 2.293, P = 0.037; T(16) = 2.557, P = 0.020). Further, for anodal tDCS there was a tendency to increase CSTs and CPTs compared to sham tDCS (T(17) = 1.9; P = 0.07; T(17) = 1.7; P = 0.09). Conclusion: The increased cortical excitability – induced by anodal tDCS – may account for the prolonged reaction times and higher omission rates. This slight deterioration of WM for the stimulation of the right DLPFC is in contrast to the effects on the left DLPFC and is only present compared to cathodal but not to sham tDCS. An amelioration of anticipation or a worsening of WM function may lead to increased thresholds for cold sensation and cold pain. Thus, the present data suggest an association of the perception of thermal sensation and thermal pain with higher cortical function. doi:10.1016/j.clinph.2008.07.095
Fig. 1. Nerve conduction velocities (NCV, m/s) and high-frequency attenuation (HFA) in tibial nerves of controls, and of patients with early inflammatory demyleinating poly-neuropathy (IDP), amyotrophic lateral sclerosis (ALS), and Charcot–Marie-tooth polyneuropathy (CMT). Mean values and 95% standard errors.
97. Reduced precuneus deactivation during object naming in dementia—L. Frings 1, S. Abel 2, K. Dressel 2, D. Saur 3, D. Kümmerer 3, H. Mast 4, C. Weiller 3, M. Hüll 1 (1 Universitätsklinik für Psychiatrie & Psychosomatik, Abteilung für Psychiatrie &
Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88
93. Structural brain abnormalities in attention-deficit/hyperactivity disorder: A voxel-based MRI study in adult patients—A. Konrad 1, T.F. Dielentheis 1, M. Bayerl 1, D. El Masri 1, T. Bauermann 2, G. Vucurevic 2, P. Stoeter 2, G. Winterer 3 (1 Johannes Gutenberg-Universität, Klinik für Psychiatrie und Psychotherapie, Mainz, Germany, 2 Johannes Gutenberg-Universität Mainz, Institut für Neuroradiologie, Mainz, Germany, 3 Heinrich-HeineUniversität Düsseldorf, Klinik für Psychiatrie, Düsseldorf, Germany) Objective: Most structural neuroimaging studies of subjects with attention-deficit/hyperactivity disorder (ADHD) have been conducted in children. The most replicated findings in ADHD children include significantly smaller volumes in the prefrontal cortex, basal ganglia, corpus callosum and cerebellum. In this study, we investigated structural brain abnormalities in the adult subjects with ADHD using voxel-based morphometry (VBM). Methods: Twenty-five ADHD patients (14 males, mean age 32 years) and 25 age- and gender-matched healthy control subjects (Table 1) underwent a detailed clinical interview as well as neuropsychological investigation of intelligence, memory, attention, psychomotor performance and executive functioning. We acquired MPRAGE (Magnetization Prepared Rapid Gradient Echo)-sequences for high-resolution structural magnetic resonance imaging (MRI) on a 1.5 T scanner. The MRI data sets were first normalized to a standard template using SPM5 software. Images were segmented into gray matter (GM), white matter and cerebrospinal fluid (Fig. 1) and were smoothed with an 8 mm FWHM kernel. Voxel-wise comparisons were then performed between the groups with two contrasts (2 sample unpaired t-test) to test for significant differences of local brain tissue concentration and volume. Following the established procedures, contrast maps were thresholded at a P < 0.001 without correction for multiple comparisons and the extent threshold for significant clusters was set to 100 voxels. Results: Typical group differences in ADHD measures were found (Table 1). Voxel-based morphometry analysis revealed regional volume differences in the gray matter of the right cerebellum showing significantly smaller GM volume in ADHD patients (Fig. 2; peak voxel coordinates MNI 16,-60,-38; cluster extend 125 voxels).
Table 1
Gender (m/f) Age (years) IQ WURS BADDS TOVA
ADHD patients mean ± SD
Controls mean ± SD
P value
14/ 11 32.0 ± 10.5 109.4 ± 8.9 108.9 ± 26.2 74.6 ± 18.7 5.0 ± 6.7
14/ 11 32.1 ± 8.5 111.4 ± 7.8 51.4 ± 20.7 14.4 ± 16.8 1.3 ± 2.6
NS NS NS P < 0.001 P < 0.001 P < 0.001
Fig. 1.
Fig. 2.
Conclusion: Our results provide additional support for the role of cerebellar abnormalities in the pathophysiology of ADHD. Together with the previous findings, there is growing evidence for the impact of the cerebellar-prefrontal-striatal network in ADHD pathophysiology. References Ashburner J, Friston KJ. Neuroimage 2000;11:805–21. Seidman LJ et al. Biol Psychiatry 2005;57:1263–72. Seidman LJ et al. Biol Psychiatry 2006;60:1071–80. Valera EM et al. Biol Psychiatry 2007;61:1361–9. doi:10.1016/j.clinph.2008.07.092
94. Extinction of cognitively conditioned fear in borderline personality disorder—Kamphausen 1, Schroeder 1, Maier 1, Bader 1, Tebartz van Elst 1, Jacob 1, Lieb 2, Tüscher 3 (1 Department of Psychiatry and Psychotherapy, University of Freiburg, Germany, 2 Department of Psychiatry and Psychotherapy, University of Mainz, Germany, 3 Department of Neurology, University of Freiburg, Germany) Background: Despite the prominent role of emotion dysregulation in the theoretical accounts of BPD, so far only few imaging studies have examined emotion dysregulation in BPD. Learning to combine a previously neutral stimulus with a possible aversive event by means of verbal instruction is an everyday experience which humans encounter. Symbolically acquired fear results in physiological fear responses and functional neuroimaging data comparable to the responses in classical fear conditioning. This study aims to investigate the neural underpinnings of extinction learning in female borderline patients to test the hypothesis of different emotion regulation during the extinction process. Methods: We explored the neural mechanisms of fear extinction by means of an instructed fear conditioning task (Phelps et al. 2001). Prior to scanning, was determined in the participants the level of electrodermal stimulation said to be received during the scan session via a standardized dial-up procedure. The scanning session consisted of a ‘‘threat condition’’, about which subjects were told that an electrodermal stimulation could occur at any time and a ‘‘safety condition’’, during which participants knew that they would not receive any stimulation. Threat and safety were signified by the presentation of easily distinguishable coloured squares. The expression of fear responses was controlled by measuring the skin conductance response (SCR). As no stimulation was given at any time during the experiment, extinction processes were recorded throughout the scanning session. So
Society Proceedings / Clinical Neurophysiology 120 (2009) e9–e88
far, 14 female patients with borderline personality disorder and 14 matched healthy controls have been included. Results: In the debriefing, all the subjects indicated that they expected to receive a stimulation during the presentation of the threat stimulus until some point in time when their expectancy was started to decrease. Interaction analysis (group condition time) of brain regions (ROI) previously shown to be associated with extinction processes revealed stronger activation of the lateral amygdalae in the patient group compared to controls, regardless of stimulus type. In both the groups, the amygdala response to the threat stimulus was largest at the beginning of the scanning procedure, but, in the patient group, the decline of activation turned out to be less pronounced over the extinction period. As hypothesized, all the control subjects revealed a stronger activation of the (lateral) orbitofrontal cortex (OFC) during extinction, possibly indicating the change of stimulus value that is encoded. Patients did not show a comparable activity increase, indicating the failure of stimulus value reversal. Conclusion: Analyses confirmed a hyperactivity of the amygdala in the borderline patients suggesting a more general responsiveness to threat stimuli. Furthermore, activations of the lateral OFC and amygdala differed between the groups throughout the extinction process indicating a failure of frontolimbic regulatory mechanisms. doi:10.1016/j.clinph.2008.07.093
95. Quantitative CMAP shape analysis differentiates between uniform and non-uniform motor nerve conduction slowing—W. Schulte-Mattler, V. Busch (Universität Regensburg, Neurologie, Regensburg, Germany) Objective: Demyelination may cause a uniform reduction of the conduction velocity of all the fibres of a peripheral nerve segment, or may non-uniformly affect only some nerve fibres while sparing others. In the latter case, the routinely determined nerve conduction velocity (NCV) is normal while amplitude, duration, and shape of compound muscle action potentials (CMAPs) vary with the distance between the stimulus and the muscle. This study was done to determine if and to what extent the quantitative analysis of CMAP shapes has the potential to differentiate between uniform and non-uniform conduction slowing. Methods: Data of patients with early inflammatory demyelinating polyneuropathy (IDP, non-uniform demyelination, n = 20), hereditary neuropathy (CMT, uniform demyelination, n = 8), motor neuron disease (MND, axon loss, n = 20), and healthy controls (n = 20) were analyzed. NCV, amplitude and duration of CMAP, minimal F-wave latency (FMIN), and F-wave chronodispersion (FDISP) in
e41
tibial nerves were measured. The high frequency attenuation (HFA) method was used to compare the CMAP shapes. Results: NCV and HFA are best differentiated between IDP and CMT (Fig. 1), as NCV was reduced only in patients with CMT (100%) and HFA was abnormal only in patients with early IDP (35%). CMAP duration was found increased in patients with early IDP (15%) and in patients with MND (10%). FDISP was increased in patients with early IDP (30%) and in patients with MND (20%). FMIN was increased in patients with early IDP (10%) and in patients with MND (10%), and in all the patients with CMT in whom F-waves could be recorded. Conclusion: The results stress that an increased HFA specifically indicates non-uniform slowing of nerve conduction while a reduced NCV indicates a uniform slowing. With the help of HFA measurements, the diagnostic sensitivity of routine nerve conduction studies can be increased. doi:10.1016/j.clinph.2008.07.094
96. Influence of tDCS of the right DLPFC on verbal working memory and non-noxious and noxious thermal stimulation—V. Mylius 1, M. Jung 1, K. Hattemer 1, A. Haag 1, M. Teepker 1, M. Huber 2, W.H. Oertel 1, F. Rosenow 1 (1 Universität Marburg, Neurologie, Marburg, Germany, 2 Universität Marburg, Psychiatrie, Marburg, Germany) Objective: Experimentally induced pain can be decreased by 1Hz repetitive transcranial magnetic stimulation (rTMS) of the right Dorsolateral Prefrontal Cortex (DLPFC), presumably by effects on the emotional-cognitive component of pain. Anodal transcranial Direct Current Stimulation (tDCS) ameliorated chronic pain when applied over the motor cortex and increased working memory (WM) function in a letter-based 3-back task when applied over the left DLPFC. Thus, we investigated whether (tDCS) of the right DLPFC modulates thermal sensation or thermal pain addition to WM function. Methods: Warm and cold sensation thresholds (WSTs and CSTs) as well as heat and cold pain thresholds (HPTs and CPTs) were assessed by using contact thermodes on the contra lateral forearm before and after 20 min of 2 mA anodal, cathodal or sham tDCS of the right DLPFC (center F 4) in 18 healthy volunteers (balanced randomization). WM was assessed by using a two number-based 2-back task during the stimulation. Results: The 2-back task revealed a prolongation of reaction time and an increase in the omission rate for anodal tDCS compared to cathodal tDCS (T(16) = 2.293, P = 0.037; T(16) = 2.557, P = 0.020). Further, for anodal tDCS there was a tendency to increase CSTs and CPTs compared to sham tDCS (T(17) = 1.9; P = 0.07; T(17) = 1.7; P = 0.09). Conclusion: The increased cortical excitability – induced by anodal tDCS – may account for the prolonged reaction times and higher omission rates. This slight deterioration of WM for the stimulation of the right DLPFC is in contrast to the effects on the left DLPFC and is only present compared to cathodal but not to sham tDCS. An amelioration of anticipation or a worsening of WM function may lead to increased thresholds for cold sensation and cold pain. Thus, the present data suggest an association of the perception of thermal sensation and thermal pain with higher cortical function. doi:10.1016/j.clinph.2008.07.095
Fig. 1. Nerve conduction velocities (NCV, m/s) and high-frequency attenuation (HFA) in tibial nerves of controls, and of patients with early inflammatory demyleinating poly-neuropathy (IDP), amyotrophic lateral sclerosis (ALS), and Charcot–Marie-tooth polyneuropathy (CMT). Mean values and 95% standard errors.
97. Reduced precuneus deactivation during object naming in dementia—L. Frings 1, S. Abel 2, K. Dressel 2, D. Saur 3, D. Kümmerer 3, H. Mast 4, C. Weiller 3, M. Hüll 1 (1 Universitätsklinik für Psychiatrie & Psychosomatik, Abteilung für Psychiatrie &