- Email: [email protected]
385. Amygdala-Neurofeedback Reduces Traumatic Stress Vulnerability
Biological Psychiatry
Friday Abstracts
Methods: This study used 810nm, 10Hz pulsed, light-emitting diode (LED) devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN – e.g., mesial prefrontal, precuneus, angular gyri (transcranial PBM); and hippocampus (intranasal PBM). Five patients with mild to moderately-severe dementia, MCI or AD were entered into 12 weeks of active treatment followed by a 4-week, no treatment period. Patients were assessed with MMSE and Alzheimer’s Disease Assessment Scale–cognitive (ADAS-cog) tests. The protocol involved weekly, in-clinic use of a transcranial plus intranasal PBM device; and daily at-home use of a separate, intranasal-only PBM device. Results: There was significant cognitive improvement after 12 weeks of PBM (MMSE, p,0.003; ADAS-cog, p,0.023). Fewer angry outbursts, better sleep, better daily functioning, less anxiety and wandering were reported. There were no negative side effects. Precipitous declines were observed during the 4week, no treatment period, a possible problem for future studies. Here, following their completion of study participation each case was given his/her own PBM devices to keep. This case series is the first completed PBM case series to report significant, cognitive improvement in mild to moderately-severe dementia cases post-PBM. Conclusions: Results suggest that larger, controlled studies are warranted. PBM shows potential for home treatment of patients with dementia, MCI, AD. Supported By: Vielight Inc. Keywords: Transcranial and intranasal photobiomodulation
younger children exhibit more positive connectivity between the regions during emotion regulation tasks. Methods: In the current study, we use real-time functional magnetic resonance imaging-based neurofeedback to explore the relationship between plasticity in emotion regulation circuits and anxiety in development. Specifically, we taught a group of pre-clinically high-anxious girls aged 14-16 years to change functional connectivity between the vmPFC and the amygdala. Results: We found that over neurofeedback 4 runs, participants learned to increase the negative functional connectivity between the two regions. We also found that changes in the connectivity between the two regions were driven by changes in vmPFC activation (in 2/3 of the trials), rather than changes in amygdala activation. Conclusions: Our findings support the notion that neurofeedback can be used to change in functional connectivity patterns during development. They also shed some light on the underlying mechanisms, i.e., the relative contribution of the underlying brain regions. Supported By: EC-FP7 No. 602186 Keywords: Adolescence, Anxiety, real-time fMRI neurofeedback, Emotion Regulation
385. Amygdala-Neurofeedback Reduces Traumatic Stress Vulnerability Jackob Keynan1 and Talma Hendler2 1
Tel Aviv Center for Brain Function, Tel Aviv Sourasky Medical Center, 2Tel Aviv Sourasky Medical Center
SYMPOSIUM Training Limbic Activity Modulation with Neurofeedback Friday, May 19, 2017 - 12:30 PM - 2:30 PM Aqua EF Chair: Christian Schmahl 384. Using Functional-Connectivity Neurofeedback to Change Emotion Regulation Networks in Pre-Clinically Anxious Adolescents Kathrin Cohen Kadosh1, Catharina Zich1, Stephen Lisk2, and Jennifer Lau2 1
University of Oxford, Department Psychology, 2King's College London
of
Experimental
Background: Approximately 1 in 4 children exhibit increased levels of worries and anxiety as they enter adolescence, yet current frontline treatments for paediatric anxiety are only effective in about half of the cases. It has been suggested that early difficulties with emotion regulation go along with an increased risk for developing anxiety, and there is some evidence that the functional coupling between two key emotion regulation regions, the ventro-medial prefrontal cortex (vmPFC) and the amygdala changes during adolescence. Specifically, whereas the mature brain exhibits top-down vmPFC regulation of amygdala reactivity, this specific relationship is only established during late adolescence with research showing that
Background: Amygdala hyper-activation among a-priori healthy individuals, was previously found to predict more post-traumatic symptoms following exposure. Pharmacological and behavioral approaches however do not specifically target the amygdala, possibly explaining the low efficacy of existing therapeutics. The current work tested whether amygdala targeted neurofeedback prior to- or immediately after- traumatic exposure may facilitate emotion-regulation and reduce stress vulnerability. We present results from a large scale (n5160) field study conducted with apriori healthy Israeli soldiers and preliminary results from a clinical trial conducted with recent trauma survivors. Methods: To enable home stationed training we used a recently developed fMRI-Inspired EEG model of amygdala activity: "The amygdala-electrical-fingerprint” (amyg-EFP). 160 soldiers of combative units were randomly assigned to three groups: (1) Amyg-EFP group training amyg-EFP down-regulation, (2) A/T group training down-regulation of alpha/theta ratio, and (3) No-treatment group continuing military training without neurofeedback. Additional civilian group of recent trauma survivors underwent either amyg-EFP or A/T neurofeedback. Participants underwent six neurofeedback sessions including clinical, neural and psychological outcome measures. Results: Relative to the control groups, following training the amyg-EFP group exhibited improved emotion-regulation and lower stress vulnerability as indicated by self-report questionnaires and an emotional-stroop task. Post-training fMRI revealed that the amyg-EFP group also exhibited lower amygdala reactivity in response to threat cues and higher functional connectivity of the amygdala with the mPFC.
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
S157
Biological Psychiatry
Friday Abstracts
Preliminary results further indicated that amyg-EFP neurofeedback may alleviate stress symptoms among recent trauma survivors. Conclusions: These results demonstrate the promising potential of amygdala targeted neurofeedback as a preventive or early intervention of traumatic stress. Supported By: US DOD, EU Seventh Framework Keywords: fMRI, EEG, PTSD, Emotion-Regulation, Clinical-Trial
386. Plastic Modulation of Intrinsic Neural Networks in PTSD through Amygdala Downregulation via Real-Time fMRI Neurofeedback Ruth Lanius1, Andrew A Nicholson1, Daniela Rabellino1, Maria Densmore1, Paul Frewen1, Christian Paret2, Rosemarie Kluetsch2, Christian Schmahl2, Jean Theberge3, Richard W.J. Neufeld1, Margaret McKinnon4, Jeffrey Reiss1, and Jetly Rakesh5 Western University of Canada, 2Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, 3Lawson Health Research Institute, 4McMaster University, 5National DefenseDefense Res & Dev Brch- Ottawa 1
Background: Large scale neural networks, such as the default mode network (DMN), salience network (SN), and central executive (CE) network, have been shown to be altered in patients with posttraumatic stress disorder (PTSD), where electroencephalography neurofeedback has been shown to plastically modulate these networks. Using real-time fMRI neurofeedback, downregulation of the amygdala during PTSD symptom provocation has been shown to increase amygdala connectivity with prefrontal executive functioning regions. However, changes in large scale neural network intrinsic connectivity during amygdala downregulation has not yet been investigated in PTSD. Methods: Patients (n515) completed 3 sessions of real-time fMRI neurofeedback, with the instruction to downregulate the amygdala while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting a) regulate trials, with b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run without neurofeedback. Independent component analyses were used to explore functional connectivity within the SN, CE, and DMN. Results: PTSD patients were successfully able to downregulate their amygdala, displaying both increased connectivity within the SN and CE and decreased connectivity within the DMN. Changes in the intrinsic functional connectivity of these networks were negatively correlated to PTSD symptoms. Conclusions: This is the first demonstration that amygdala downregulation using real-time fMRI neurofeedback results in network connectivity changes within PTSD patients. This suggests that amygdala downregulation is targeting neural networks that may be related to a spectrum of clinical symptoms observed in PTSD, including cognitive dysfunction (CE), arousal/ interoception (SN), and an altered sense of self (DMN). Supported By: Canadian Institutes for Veterans and Military Health #W7714-125624/001/SV Keywords: Posttraumatic Stress Disorder, real-time fMRI neurofeedback
S158
387. Training Amygdala-Prefrontal Networks with Neurofeedback in Borderline Personality Disorder Christian Paret1, Gabriele Ende2, Jenny Zähringer1, Matthias Ruf2, and Christian Schmahl1 1
Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, 2Department Neuroimaging, Central Institute of Mental Health Background: With functional magnetic resonance imaging neurofeedback (NF), amygdala activity is visualized in real time. The neural circuitry of emotion dysregulation can be targeted with this technique. Limbic hyper-responsiveness is characteristic for conditions with heightened affective lability, such as Borderline Personality Disorder (BPD). Training patients to down-regulate limbic brain activity with NF directly involves dysregulated networks and may be beneficial in future treatment. Methods: Data from two completed and two ongoing experiments will be reported. Participants with BPD and participants without a psychiatric diagnosis were presented with amygdala NF while viewing emotional pictures. Feedback was given by a thermometer presented besides the pictures. The instruction was to downregulation the amplitude of the thermometer display. Results: Patients and healthy controls were successful in downregulating their amygdala response. Prefrontal-limbic connectivity was increased with neurofeedback. Patients with BPD reported a decrease in dissociation and increase in emotional awareness over the course of four sessions. New results will be reported, aiming to give a broader understanding of the neural mechanisms behind brain self-regulation with amygdala NF. Conclusions: NF is instrumental in understanding neural mechanisms of emotion and brain self-regulation. In line with others, our findings are in accord with a potential therapeutic benefit. Ongoing studies try to establish transfer effects of amygdala NF on different measures of emotion processing and regulation. Supported By: German Research Foundation (DFG) Keywords: Borderline Personality Disorder, real-time fMRI neurofeedback, Amygdala, Emotion Regulation
ORAL SESSION Neuroimaging and Related Methods in Mood Disorders Friday, May 19, 2017 - 12:30 PM - 2:30 PM Aqua 311 AB Chair: Jorge Almeida 388. A Complex Networks Approach to the Symptomatology of Mood Disorders Baktash Babadi1, Ji Hyun Baek2, and Andrew Nierenberg2 1
Harvard Medical School/McLean Hospital, 2Massachusetts General Hospital Background: Conventional psychiatric diagnosis, based on criteria such as DSM-IV, might come short of providing a full picture of the disorders due to methodological limitations.
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
Friday Abstracts
Methods: This study used 810nm, 10Hz pulsed, light-emitting diode (LED) devices combining transcranial plus intranasal PBM to treat the cortical nodes of the DMN – e.g., mesial prefrontal, precuneus, angular gyri (transcranial PBM); and hippocampus (intranasal PBM). Five patients with mild to moderately-severe dementia, MCI or AD were entered into 12 weeks of active treatment followed by a 4-week, no treatment period. Patients were assessed with MMSE and Alzheimer’s Disease Assessment Scale–cognitive (ADAS-cog) tests. The protocol involved weekly, in-clinic use of a transcranial plus intranasal PBM device; and daily at-home use of a separate, intranasal-only PBM device. Results: There was significant cognitive improvement after 12 weeks of PBM (MMSE, p,0.003; ADAS-cog, p,0.023). Fewer angry outbursts, better sleep, better daily functioning, less anxiety and wandering were reported. There were no negative side effects. Precipitous declines were observed during the 4week, no treatment period, a possible problem for future studies. Here, following their completion of study participation each case was given his/her own PBM devices to keep. This case series is the first completed PBM case series to report significant, cognitive improvement in mild to moderately-severe dementia cases post-PBM. Conclusions: Results suggest that larger, controlled studies are warranted. PBM shows potential for home treatment of patients with dementia, MCI, AD. Supported By: Vielight Inc. Keywords: Transcranial and intranasal photobiomodulation
younger children exhibit more positive connectivity between the regions during emotion regulation tasks. Methods: In the current study, we use real-time functional magnetic resonance imaging-based neurofeedback to explore the relationship between plasticity in emotion regulation circuits and anxiety in development. Specifically, we taught a group of pre-clinically high-anxious girls aged 14-16 years to change functional connectivity between the vmPFC and the amygdala. Results: We found that over neurofeedback 4 runs, participants learned to increase the negative functional connectivity between the two regions. We also found that changes in the connectivity between the two regions were driven by changes in vmPFC activation (in 2/3 of the trials), rather than changes in amygdala activation. Conclusions: Our findings support the notion that neurofeedback can be used to change in functional connectivity patterns during development. They also shed some light on the underlying mechanisms, i.e., the relative contribution of the underlying brain regions. Supported By: EC-FP7 No. 602186 Keywords: Adolescence, Anxiety, real-time fMRI neurofeedback, Emotion Regulation
385. Amygdala-Neurofeedback Reduces Traumatic Stress Vulnerability Jackob Keynan1 and Talma Hendler2 1
Tel Aviv Center for Brain Function, Tel Aviv Sourasky Medical Center, 2Tel Aviv Sourasky Medical Center
SYMPOSIUM Training Limbic Activity Modulation with Neurofeedback Friday, May 19, 2017 - 12:30 PM - 2:30 PM Aqua EF Chair: Christian Schmahl 384. Using Functional-Connectivity Neurofeedback to Change Emotion Regulation Networks in Pre-Clinically Anxious Adolescents Kathrin Cohen Kadosh1, Catharina Zich1, Stephen Lisk2, and Jennifer Lau2 1
University of Oxford, Department Psychology, 2King's College London
of
Experimental
Background: Approximately 1 in 4 children exhibit increased levels of worries and anxiety as they enter adolescence, yet current frontline treatments for paediatric anxiety are only effective in about half of the cases. It has been suggested that early difficulties with emotion regulation go along with an increased risk for developing anxiety, and there is some evidence that the functional coupling between two key emotion regulation regions, the ventro-medial prefrontal cortex (vmPFC) and the amygdala changes during adolescence. Specifically, whereas the mature brain exhibits top-down vmPFC regulation of amygdala reactivity, this specific relationship is only established during late adolescence with research showing that
Background: Amygdala hyper-activation among a-priori healthy individuals, was previously found to predict more post-traumatic symptoms following exposure. Pharmacological and behavioral approaches however do not specifically target the amygdala, possibly explaining the low efficacy of existing therapeutics. The current work tested whether amygdala targeted neurofeedback prior to- or immediately after- traumatic exposure may facilitate emotion-regulation and reduce stress vulnerability. We present results from a large scale (n5160) field study conducted with apriori healthy Israeli soldiers and preliminary results from a clinical trial conducted with recent trauma survivors. Methods: To enable home stationed training we used a recently developed fMRI-Inspired EEG model of amygdala activity: "The amygdala-electrical-fingerprint” (amyg-EFP). 160 soldiers of combative units were randomly assigned to three groups: (1) Amyg-EFP group training amyg-EFP down-regulation, (2) A/T group training down-regulation of alpha/theta ratio, and (3) No-treatment group continuing military training without neurofeedback. Additional civilian group of recent trauma survivors underwent either amyg-EFP or A/T neurofeedback. Participants underwent six neurofeedback sessions including clinical, neural and psychological outcome measures. Results: Relative to the control groups, following training the amyg-EFP group exhibited improved emotion-regulation and lower stress vulnerability as indicated by self-report questionnaires and an emotional-stroop task. Post-training fMRI revealed that the amyg-EFP group also exhibited lower amygdala reactivity in response to threat cues and higher functional connectivity of the amygdala with the mPFC.
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal
S157
Biological Psychiatry
Friday Abstracts
Preliminary results further indicated that amyg-EFP neurofeedback may alleviate stress symptoms among recent trauma survivors. Conclusions: These results demonstrate the promising potential of amygdala targeted neurofeedback as a preventive or early intervention of traumatic stress. Supported By: US DOD, EU Seventh Framework Keywords: fMRI, EEG, PTSD, Emotion-Regulation, Clinical-Trial
386. Plastic Modulation of Intrinsic Neural Networks in PTSD through Amygdala Downregulation via Real-Time fMRI Neurofeedback Ruth Lanius1, Andrew A Nicholson1, Daniela Rabellino1, Maria Densmore1, Paul Frewen1, Christian Paret2, Rosemarie Kluetsch2, Christian Schmahl2, Jean Theberge3, Richard W.J. Neufeld1, Margaret McKinnon4, Jeffrey Reiss1, and Jetly Rakesh5 Western University of Canada, 2Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, 3Lawson Health Research Institute, 4McMaster University, 5National DefenseDefense Res & Dev Brch- Ottawa 1
Background: Large scale neural networks, such as the default mode network (DMN), salience network (SN), and central executive (CE) network, have been shown to be altered in patients with posttraumatic stress disorder (PTSD), where electroencephalography neurofeedback has been shown to plastically modulate these networks. Using real-time fMRI neurofeedback, downregulation of the amygdala during PTSD symptom provocation has been shown to increase amygdala connectivity with prefrontal executive functioning regions. However, changes in large scale neural network intrinsic connectivity during amygdala downregulation has not yet been investigated in PTSD. Methods: Patients (n515) completed 3 sessions of real-time fMRI neurofeedback, with the instruction to downregulate the amygdala while viewing personalized trauma words. Amygdala downregulation was assessed by contrasting a) regulate trials, with b) viewing trauma words and not attempting to regulate. Training was followed by one transfer run without neurofeedback. Independent component analyses were used to explore functional connectivity within the SN, CE, and DMN. Results: PTSD patients were successfully able to downregulate their amygdala, displaying both increased connectivity within the SN and CE and decreased connectivity within the DMN. Changes in the intrinsic functional connectivity of these networks were negatively correlated to PTSD symptoms. Conclusions: This is the first demonstration that amygdala downregulation using real-time fMRI neurofeedback results in network connectivity changes within PTSD patients. This suggests that amygdala downregulation is targeting neural networks that may be related to a spectrum of clinical symptoms observed in PTSD, including cognitive dysfunction (CE), arousal/ interoception (SN), and an altered sense of self (DMN). Supported By: Canadian Institutes for Veterans and Military Health #W7714-125624/001/SV Keywords: Posttraumatic Stress Disorder, real-time fMRI neurofeedback
S158
387. Training Amygdala-Prefrontal Networks with Neurofeedback in Borderline Personality Disorder Christian Paret1, Gabriele Ende2, Jenny Zähringer1, Matthias Ruf2, and Christian Schmahl1 1
Department of Psychosomatic Medicine and Psychotherapy, Central Institute of Mental Health, 2Department Neuroimaging, Central Institute of Mental Health Background: With functional magnetic resonance imaging neurofeedback (NF), amygdala activity is visualized in real time. The neural circuitry of emotion dysregulation can be targeted with this technique. Limbic hyper-responsiveness is characteristic for conditions with heightened affective lability, such as Borderline Personality Disorder (BPD). Training patients to down-regulate limbic brain activity with NF directly involves dysregulated networks and may be beneficial in future treatment. Methods: Data from two completed and two ongoing experiments will be reported. Participants with BPD and participants without a psychiatric diagnosis were presented with amygdala NF while viewing emotional pictures. Feedback was given by a thermometer presented besides the pictures. The instruction was to downregulation the amplitude of the thermometer display. Results: Patients and healthy controls were successful in downregulating their amygdala response. Prefrontal-limbic connectivity was increased with neurofeedback. Patients with BPD reported a decrease in dissociation and increase in emotional awareness over the course of four sessions. New results will be reported, aiming to give a broader understanding of the neural mechanisms behind brain self-regulation with amygdala NF. Conclusions: NF is instrumental in understanding neural mechanisms of emotion and brain self-regulation. In line with others, our findings are in accord with a potential therapeutic benefit. Ongoing studies try to establish transfer effects of amygdala NF on different measures of emotion processing and regulation. Supported By: German Research Foundation (DFG) Keywords: Borderline Personality Disorder, real-time fMRI neurofeedback, Amygdala, Emotion Regulation
ORAL SESSION Neuroimaging and Related Methods in Mood Disorders Friday, May 19, 2017 - 12:30 PM - 2:30 PM Aqua 311 AB Chair: Jorge Almeida 388. A Complex Networks Approach to the Symptomatology of Mood Disorders Baktash Babadi1, Ji Hyun Baek2, and Andrew Nierenberg2 1
Harvard Medical School/McLean Hospital, 2Massachusetts General Hospital Background: Conventional psychiatric diagnosis, based on criteria such as DSM-IV, might come short of providing a full picture of the disorders due to methodological limitations.
Biological Psychiatry May 15, 2017; 81:S140–S276 www.sobp.org/journal