- Email: [email protected]
TMS improves anxious aggressive behaviour in dogs: A case study
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3rd European Conference on Brain Stimulation in Psychiatry / L’Encéphale 45S2 (2019) S68–S83
nary results using fronto-cerebellar tDCS in a sample of children with ASD. Methods Twenty patients (16 M, 4F) with ASD, aged 9 to 14 years, were randomized to receive either active or sham tDCS. Active treatment consisted in 20 daily sessions of 20 minutes/1.0 mA (age ≤ 10) or 1.5 mA (age > 11) tDCS. Sham was identical to active treatment except that the stimulation was stopped after 1 minute. The anode was placed in F3 and the cathode in the occipital region corresponding to the right cerebellum. During the treatment, no changes were made to the pharmacological and rehabilitative therapies in progress. Behavioral symptoms (Aberrant Behavior Checklist - ABC), effect of treatment (Autism Treatment Evaluation Checklist - ATEC), and parental stress (Parental Stress Index–PSI) were assessed just before and 1 week after the completion of the treatment. Results Seven patients in the active and 9 in the sham group completed the treatment. ABC and ATEC scores significantly decreased in the active group, while no change was observed in the sham group. Conclusion Our findings suggest that fronto-cerebellar tDCS may have a role for the treatment of children with ASD. Disclosure of interest The authors have not supplied their declaration of competing interest.
ferences were found for Theta. VAS for attention was significantly increased (z = −2.197; P = .030), whereas VAS for anxiety was statistically decreased (z = −2.265; P = .023). Conclusion Neurofeedback can be regarded as a promising therapeutic technique at reducing anxiety symptoms and attention deficits in adolescents. However, future research should be conducted in order to investigate the effectiveness of Neurofeedback in alleviating anxiety and attention deficits in adolescents by recruiting a larger number of individuals and over a longer period of time. Disclosure of interest The authors have not supplied their declaration of competing interest.
https://doi.org/10.1016/j.encep.2019.04.040
Posttraumatic stress disorder (PTSD) is associated with brain changes that commonly involve the fear network including the prefrontal cortex (PFC), hippocampus and amygdala. Neurostimulation can been recommended as an adjunct to psychotherapy in order to facilitate extinction of fear in PTSD. Repetitive transcranial magnetic stimulation (rTMS) can thus target the PFC to provide promising treatment responses. However, preclinical rodent-based studies need to be performed to enhance the comprehension and empirical-driven efficacy of rTMS. We used a focal 40-mm coil to apply a high frequency/intensity rTMS pattern (5 daily sessions) to the ventromedial PFC (vmPFC) in a mouse model of PTSD. This procedure was assessed against fluoxetine (SSRI treatment). Through spatially precise stereotaxic framing, one session of rTMS (750 pulses) was able to focally increase c-Fos functional maps in the vmPFC immediately after stimulation. When used as a chronic treatment (5 daily sessions for 3750 pulses) in a foot-shock PTSD model, rTMS counteracted PTSD-related behavioural deficit in the object recognition task 6 days after the last treatment session and enhanced extinction dynamics in a reexposure task (4 days afterward) compared to sham treatment. Reexposure-associated c-Fos activity was found increased in the infralimbic cortex, the basolateral amygdala and the CA1 of ventral hippocampus of mice exposed to the trauma and treated with rTMS. In conclusion, chronic rTMS treatment reversed PTSD-induced impairments by acting on distributed networks of fear neurocircuitry that self-sustained 10 days post-treatment in the infralimbic cortex, the basolateral amygdala and the ventral CA1. Disclosure of interest The authors have not supplied their declaration of competing interest.
Other NIBS, animals, combination studies PO29
Effective Neurofeedback applications in anxiety and attention symptomatology in adolescents Marianna Tsatali 1,2,∗ , Stathis Sidiropoulos 1,2 , Panagiotis Bamidis 1,2 1 Neuroscience of Cognition and Affection Group (NCA), Laboratory of Medical Physics, Medical School, Aristotle University of Thessaloniki, Greece 2 Northern Greece Neurofeedback Centre, Thessaloniki, Greece ∗ Corresponding author. E-mail address: [email protected] (M. Tsatali) Objectives It is expected that Alpha and SMR activity would be enhanced (Vernon et al., 2003), whereas Theta activity would be diminished (Hammond, 2005) in adolescents in line with previous studies on this population. Methods Ten adolescents from 11 to 18 years old came to the Northern Greece Neurofeedback Centre because they had problems about their self-reported attention, as well as having anxiety symptoms, including daydreaming, loss of concentration during reading, and thoughts of worry. Neurofeedback training consisted of 10 sessions, 20 minutes each. Participants’ EEG records were evaluated pre and post the Neurofeedback training in eyes-opened resting-state by Nexus-10. In continuation, they were trained on Alpha, Theta and Beta bands through specific protocols. The active electrode was placed to the Cz point with frequency rate two times/week. Additionally, individuals completed two Visual Analogue Scales (VAS), scored from 0–100, before each Neurofeedback session regarding to whether they felt anxiety and felt absentminded during the previous days. Results Non parametric Wilcoxon signed-rank test was used in order to identify possible differences between the post amplitude of the EEG brain rhythms, especially Alpha, Theta and SMR. After attending the Neurofeedback sessions, participants’ Alpha and SMR bands were enhanced. Specifically, significant differences were found in Alpha mean amplitude (z = − 2.366; P = .018), as well as SMR activity (z = −2.666; P = .008). Furthermore, no significant dif-
https://doi.org/10.1016/j.encep.2019.04.041 PO30
Efficacy of rTMS in a mouse model of posttraumatic stress disorder Wissam El-Hage 1,2,∗ , Marc Legrand 1 , Catherine Belzung 1 UMR 1253, iBrain, Université de Tours, Inserm, Tours, France 2 Clinique Psychiatrique Universitaire, CIC 1415, CHRU de Tours, Inserm, Tours, France ∗ Corresponding author. E-mail address: [email protected] (W. El-Hage)
1
https://doi.org/10.1016/j.encep.2019.04.042 PO31
TMS improves anxious aggressive behaviour in dogs: A case study Robrecht Dockx 1,∗ , Kathelijne Peremans 2 , Ilse Smolders 3 , Ann Van Eeckhaut 3 , Lise Vlerick 4 , Ingeborgh Polis 4 , Jimmy H. Saunders 2 , Chris Baeken 1 1 Department of Psychiatry and Medical Psychology, Ghent Experimental Psychiatry (GHEP) lab, Ghent University, Ghent, East Flanders, Belgium 2 Department of Veterinary medical imaging and small animal orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
3rd European Conference on Brain Stimulation in Psychiatry / L’Encéphale 45S2 (2019) S68–S83 3
Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research group Experimental Pharmacology, Center for Neurosciences (C4 N), Vrije Universiteit Brussel, Brussels, Belgium 4 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium ∗ Corresponding author. E-mail address: [email protected] (R. Dockx) Background Accelerated high frequency repetitive transcranial magnetic stimulation (aHF-rTMS) has proven to produce fast clinical effects in humans suffering from psychiatric illnesses. Although dogs also frequently present behavioural symptoms similar to mental illness, nothing is known about the clinical influence in this species. A 5-year-old neutered male Belgian shepherd dog was presented with anxious aggressive behaviour. Hypothesis It was hypothesized that an aHF-rTMS treatment over the frontal cortex would improve the dogs’ behaviour and alter its regional cerebral blood flow (rCBF) and monoamines. Methodology An aHF-rTMS protocol was applied twice (3 weeks separated) over the left frontal cortex (5 sessions, 20 Hz, 110% CMT). Each protocol was preceded and followed by a behaviour assessment and a [99mTc]HMPAO-SPECT scan. A Z-score for each VOI at each time point was obtained, a |Z|-score > 3.09 (P-value of 0.001) indicated significant differences. Cerebrospinal fluid (CSF) and serum was analysed for the detection of monoamines. Results An improvement of the dogs’ aggressive behaviour was detected. At baseline, only a decreased rCBF of the left frontal cortex was noticeable (Z-score = −3.87). Twenty-four hours after the first protocol, the perfusion in the left frontal cortex was normalized but decreased in subcortical region (Z-score = −6.97). Twenty-four hours after the second protocol, only the subcortical region was hypo-perfused (Z-score = −6.88). Three weeks after each stimulation protocol, no deviations in the rCBF were found. Parallel changes (over time) of 3,4-Dihydroxyphenylacetic acid (DOPAC) concentrations in the serum and CSF were present (Table 1). Conclusion This case study demonstrates that a single day aHFrTMS treatment reduces a dogs’ anxious/aggressive behaviour. This was accompanied by immediate and long-lasting alterations in the rCBF and DOPAC concentration. Thereby, this study confirms the interaction between the frontal cortex and the subcortical region in behaviour in dogs and puts DOPAC forward as possible biomarker. Table 1 Concentrations (ng/100 L) of 7 monoamines measured with HPLC.
NAD: norepinephrine; AD: epinephrine; DOPAC: 3,4Dihydroxyphenylacetic acid; HVA: homovanillic acid; 5-HT: serotonin; 5-HIAA: 5-Hydroxyindoleacetic acid; Na: missing data.
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Disclosure of interest The authors have not supplied their declaration of competing interest. https://doi.org/10.1016/j.encep.2019.04.043 PO32
Interest of non-invasive brain stimulation techniques in the treatment of Substance Use Disorders
Noomane Bouaziz ∗ , Charles Laidi , René Benadhira , Dominique Januel URC, Pôle 93G03, EPS Ville Evrard, France ∗ Corresponding author. E-mail address: [email protected] (N. Bouaziz) Substance Use Disorders are a public health problem and a leading cause of disability worldwide. The pharmacological and psychotherapeutic treatments currently available have little or no effect for a significant number of patients. Recently, there has been an accumulation of preclinical and clinical evidence on the potential therapeutic benefits of Non-Invasive Brain Stimulation (NIBS) techniques: repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) in the treatment of addictive disorders. This work aims to show the rationale behind the use of NIBS in addictive disorders, and highlight the main animal and clinical studies on this promising therapeutic tool. Disclosure of interest The authors have not supplied their declaration of competing interest. https://doi.org/10.1016/j.encep.2019.04.044 PO33
Improved functional brain anomalies after personalized rTMS relative to classical rTMS and tDCS in resistant depression Jack R. Foucher 1,2,∗ , A. Robert 1 , C. de Billy 1,2 , S. Weibel 3,4 , G. Bertschy 3,4 , Olivier Mainberger 1,2 , P.L. de Sousa 1 1 ICube–CNRS UMR 7357, Neurophysiology, FMTS, University of Strasbourg, France 2 CEMNIS–Noninvasive Neuromodulation Center, University Hospital Strasbourg, France 3 Physiopathologie et Psychopathologie Cognitive de la Schizophrénie–Inserm 1114, FMTS, University of Strasbourg, France 4 Pôle de Psychiatrie, Santé Mentale et Addictologie, University Hospital Strasbourg, France ∗ Corresponding author. E-mail address: [email protected] (J.R. Foucher) Introduction The iADAPT study - Imagery guided Anti-Depressive Adaptive Personalized TMS (NCT02863380) - is a double-blind randomized cross-over study designed to assess the feasibility and efficiency of personalizing rTMS protocol, based on the functional imaging of single subjects, relative to classical rTMS and tDCS. Method Brain imaging included two kinds of ASL sequences, converted in rCBF, repeated in three different sessions, using different functional paradigms and contrasted to 38 normal controls. The tDCS protocol used an F3 anodal positioning (20 min, 2 mA). Classical rTMS used F3 positioning (3000 pulses, 120%, 10 Hz). Last personalized rTMS was designed to correct the rCBF anomalies. Thirty bilateral targets were planned to cover the reachable parts of the complex regions with abnormal perfusion. Coil positioning used a robotic neuronavigated device. In case of hypo-perfusion, targets were stimulated using the same protocol than HF-rTMS. There were 2 sessions per day for 10 days in each of the 3 conditions (personalized rTMS, classical rTMS, tDCS) Changes in brain perfusion were assessed on rCBF-ASL imaging and changes in connectivity were assessed on the BOLD signal.
3rd European Conference on Brain Stimulation in Psychiatry / L’Encéphale 45S2 (2019) S68–S83
nary results using fronto-cerebellar tDCS in a sample of children with ASD. Methods Twenty patients (16 M, 4F) with ASD, aged 9 to 14 years, were randomized to receive either active or sham tDCS. Active treatment consisted in 20 daily sessions of 20 minutes/1.0 mA (age ≤ 10) or 1.5 mA (age > 11) tDCS. Sham was identical to active treatment except that the stimulation was stopped after 1 minute. The anode was placed in F3 and the cathode in the occipital region corresponding to the right cerebellum. During the treatment, no changes were made to the pharmacological and rehabilitative therapies in progress. Behavioral symptoms (Aberrant Behavior Checklist - ABC), effect of treatment (Autism Treatment Evaluation Checklist - ATEC), and parental stress (Parental Stress Index–PSI) were assessed just before and 1 week after the completion of the treatment. Results Seven patients in the active and 9 in the sham group completed the treatment. ABC and ATEC scores significantly decreased in the active group, while no change was observed in the sham group. Conclusion Our findings suggest that fronto-cerebellar tDCS may have a role for the treatment of children with ASD. Disclosure of interest The authors have not supplied their declaration of competing interest.
ferences were found for Theta. VAS for attention was significantly increased (z = −2.197; P = .030), whereas VAS for anxiety was statistically decreased (z = −2.265; P = .023). Conclusion Neurofeedback can be regarded as a promising therapeutic technique at reducing anxiety symptoms and attention deficits in adolescents. However, future research should be conducted in order to investigate the effectiveness of Neurofeedback in alleviating anxiety and attention deficits in adolescents by recruiting a larger number of individuals and over a longer period of time. Disclosure of interest The authors have not supplied their declaration of competing interest.
https://doi.org/10.1016/j.encep.2019.04.040
Posttraumatic stress disorder (PTSD) is associated with brain changes that commonly involve the fear network including the prefrontal cortex (PFC), hippocampus and amygdala. Neurostimulation can been recommended as an adjunct to psychotherapy in order to facilitate extinction of fear in PTSD. Repetitive transcranial magnetic stimulation (rTMS) can thus target the PFC to provide promising treatment responses. However, preclinical rodent-based studies need to be performed to enhance the comprehension and empirical-driven efficacy of rTMS. We used a focal 40-mm coil to apply a high frequency/intensity rTMS pattern (5 daily sessions) to the ventromedial PFC (vmPFC) in a mouse model of PTSD. This procedure was assessed against fluoxetine (SSRI treatment). Through spatially precise stereotaxic framing, one session of rTMS (750 pulses) was able to focally increase c-Fos functional maps in the vmPFC immediately after stimulation. When used as a chronic treatment (5 daily sessions for 3750 pulses) in a foot-shock PTSD model, rTMS counteracted PTSD-related behavioural deficit in the object recognition task 6 days after the last treatment session and enhanced extinction dynamics in a reexposure task (4 days afterward) compared to sham treatment. Reexposure-associated c-Fos activity was found increased in the infralimbic cortex, the basolateral amygdala and the CA1 of ventral hippocampus of mice exposed to the trauma and treated with rTMS. In conclusion, chronic rTMS treatment reversed PTSD-induced impairments by acting on distributed networks of fear neurocircuitry that self-sustained 10 days post-treatment in the infralimbic cortex, the basolateral amygdala and the ventral CA1. Disclosure of interest The authors have not supplied their declaration of competing interest.
Other NIBS, animals, combination studies PO29
Effective Neurofeedback applications in anxiety and attention symptomatology in adolescents Marianna Tsatali 1,2,∗ , Stathis Sidiropoulos 1,2 , Panagiotis Bamidis 1,2 1 Neuroscience of Cognition and Affection Group (NCA), Laboratory of Medical Physics, Medical School, Aristotle University of Thessaloniki, Greece 2 Northern Greece Neurofeedback Centre, Thessaloniki, Greece ∗ Corresponding author. E-mail address: [email protected] (M. Tsatali) Objectives It is expected that Alpha and SMR activity would be enhanced (Vernon et al., 2003), whereas Theta activity would be diminished (Hammond, 2005) in adolescents in line with previous studies on this population. Methods Ten adolescents from 11 to 18 years old came to the Northern Greece Neurofeedback Centre because they had problems about their self-reported attention, as well as having anxiety symptoms, including daydreaming, loss of concentration during reading, and thoughts of worry. Neurofeedback training consisted of 10 sessions, 20 minutes each. Participants’ EEG records were evaluated pre and post the Neurofeedback training in eyes-opened resting-state by Nexus-10. In continuation, they were trained on Alpha, Theta and Beta bands through specific protocols. The active electrode was placed to the Cz point with frequency rate two times/week. Additionally, individuals completed two Visual Analogue Scales (VAS), scored from 0–100, before each Neurofeedback session regarding to whether they felt anxiety and felt absentminded during the previous days. Results Non parametric Wilcoxon signed-rank test was used in order to identify possible differences between the post amplitude of the EEG brain rhythms, especially Alpha, Theta and SMR. After attending the Neurofeedback sessions, participants’ Alpha and SMR bands were enhanced. Specifically, significant differences were found in Alpha mean amplitude (z = − 2.366; P = .018), as well as SMR activity (z = −2.666; P = .008). Furthermore, no significant dif-
https://doi.org/10.1016/j.encep.2019.04.041 PO30
Efficacy of rTMS in a mouse model of posttraumatic stress disorder Wissam El-Hage 1,2,∗ , Marc Legrand 1 , Catherine Belzung 1 UMR 1253, iBrain, Université de Tours, Inserm, Tours, France 2 Clinique Psychiatrique Universitaire, CIC 1415, CHRU de Tours, Inserm, Tours, France ∗ Corresponding author. E-mail address: [email protected] (W. El-Hage)
1
https://doi.org/10.1016/j.encep.2019.04.042 PO31
TMS improves anxious aggressive behaviour in dogs: A case study Robrecht Dockx 1,∗ , Kathelijne Peremans 2 , Ilse Smolders 3 , Ann Van Eeckhaut 3 , Lise Vlerick 4 , Ingeborgh Polis 4 , Jimmy H. Saunders 2 , Chris Baeken 1 1 Department of Psychiatry and Medical Psychology, Ghent Experimental Psychiatry (GHEP) lab, Ghent University, Ghent, East Flanders, Belgium 2 Department of Veterinary medical imaging and small animal orthopaedics, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium
3rd European Conference on Brain Stimulation in Psychiatry / L’Encéphale 45S2 (2019) S68–S83 3
Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research group Experimental Pharmacology, Center for Neurosciences (C4 N), Vrije Universiteit Brussel, Brussels, Belgium 4 Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, East Flanders, Belgium ∗ Corresponding author. E-mail address: [email protected] (R. Dockx) Background Accelerated high frequency repetitive transcranial magnetic stimulation (aHF-rTMS) has proven to produce fast clinical effects in humans suffering from psychiatric illnesses. Although dogs also frequently present behavioural symptoms similar to mental illness, nothing is known about the clinical influence in this species. A 5-year-old neutered male Belgian shepherd dog was presented with anxious aggressive behaviour. Hypothesis It was hypothesized that an aHF-rTMS treatment over the frontal cortex would improve the dogs’ behaviour and alter its regional cerebral blood flow (rCBF) and monoamines. Methodology An aHF-rTMS protocol was applied twice (3 weeks separated) over the left frontal cortex (5 sessions, 20 Hz, 110% CMT). Each protocol was preceded and followed by a behaviour assessment and a [99mTc]HMPAO-SPECT scan. A Z-score for each VOI at each time point was obtained, a |Z|-score > 3.09 (P-value of 0.001) indicated significant differences. Cerebrospinal fluid (CSF) and serum was analysed for the detection of monoamines. Results An improvement of the dogs’ aggressive behaviour was detected. At baseline, only a decreased rCBF of the left frontal cortex was noticeable (Z-score = −3.87). Twenty-four hours after the first protocol, the perfusion in the left frontal cortex was normalized but decreased in subcortical region (Z-score = −6.97). Twenty-four hours after the second protocol, only the subcortical region was hypo-perfused (Z-score = −6.88). Three weeks after each stimulation protocol, no deviations in the rCBF were found. Parallel changes (over time) of 3,4-Dihydroxyphenylacetic acid (DOPAC) concentrations in the serum and CSF were present (Table 1). Conclusion This case study demonstrates that a single day aHFrTMS treatment reduces a dogs’ anxious/aggressive behaviour. This was accompanied by immediate and long-lasting alterations in the rCBF and DOPAC concentration. Thereby, this study confirms the interaction between the frontal cortex and the subcortical region in behaviour in dogs and puts DOPAC forward as possible biomarker. Table 1 Concentrations (ng/100 L) of 7 monoamines measured with HPLC.
NAD: norepinephrine; AD: epinephrine; DOPAC: 3,4Dihydroxyphenylacetic acid; HVA: homovanillic acid; 5-HT: serotonin; 5-HIAA: 5-Hydroxyindoleacetic acid; Na: missing data.
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Disclosure of interest The authors have not supplied their declaration of competing interest. https://doi.org/10.1016/j.encep.2019.04.043 PO32
Interest of non-invasive brain stimulation techniques in the treatment of Substance Use Disorders
Noomane Bouaziz ∗ , Charles Laidi , René Benadhira , Dominique Januel URC, Pôle 93G03, EPS Ville Evrard, France ∗ Corresponding author. E-mail address: [email protected] (N. Bouaziz) Substance Use Disorders are a public health problem and a leading cause of disability worldwide. The pharmacological and psychotherapeutic treatments currently available have little or no effect for a significant number of patients. Recently, there has been an accumulation of preclinical and clinical evidence on the potential therapeutic benefits of Non-Invasive Brain Stimulation (NIBS) techniques: repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) in the treatment of addictive disorders. This work aims to show the rationale behind the use of NIBS in addictive disorders, and highlight the main animal and clinical studies on this promising therapeutic tool. Disclosure of interest The authors have not supplied their declaration of competing interest. https://doi.org/10.1016/j.encep.2019.04.044 PO33
Improved functional brain anomalies after personalized rTMS relative to classical rTMS and tDCS in resistant depression Jack R. Foucher 1,2,∗ , A. Robert 1 , C. de Billy 1,2 , S. Weibel 3,4 , G. Bertschy 3,4 , Olivier Mainberger 1,2 , P.L. de Sousa 1 1 ICube–CNRS UMR 7357, Neurophysiology, FMTS, University of Strasbourg, France 2 CEMNIS–Noninvasive Neuromodulation Center, University Hospital Strasbourg, France 3 Physiopathologie et Psychopathologie Cognitive de la Schizophrénie–Inserm 1114, FMTS, University of Strasbourg, France 4 Pôle de Psychiatrie, Santé Mentale et Addictologie, University Hospital Strasbourg, France ∗ Corresponding author. E-mail address: [email protected] (J.R. Foucher) Introduction The iADAPT study - Imagery guided Anti-Depressive Adaptive Personalized TMS (NCT02863380) - is a double-blind randomized cross-over study designed to assess the feasibility and efficiency of personalizing rTMS protocol, based on the functional imaging of single subjects, relative to classical rTMS and tDCS. Method Brain imaging included two kinds of ASL sequences, converted in rCBF, repeated in three different sessions, using different functional paradigms and contrasted to 38 normal controls. The tDCS protocol used an F3 anodal positioning (20 min, 2 mA). Classical rTMS used F3 positioning (3000 pulses, 120%, 10 Hz). Last personalized rTMS was designed to correct the rCBF anomalies. Thirty bilateral targets were planned to cover the reachable parts of the complex regions with abnormal perfusion. Coil positioning used a robotic neuronavigated device. In case of hypo-perfusion, targets were stimulated using the same protocol than HF-rTMS. There were 2 sessions per day for 10 days in each of the 3 conditions (personalized rTMS, classical rTMS, tDCS) Changes in brain perfusion were assessed on rCBF-ASL imaging and changes in connectivity were assessed on the BOLD signal.