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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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This study aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.
The human brain has constant access to a multitude of complex signals, which it must simplify and organize in order to sustain the integrity of the organism. Many of these signals originate from outside of the body, such as lights, sounds, and smells, and much is known about how humans consciously perceive these 'exteroceptive' signals and how the human brain represents them. Comparatively little is known about how the human brain processes 'interoceptive' signals originating from inside of the body, despite the fact that the brain has access to far more of them (for instance, intestinal tension, bladder distension, breath, heartbeat, body temperature, blood pressure, serum osmolality, inflammation, proprioception etc.).
The current study study therefore aims to identify the brain regions responsible for encoding cardiorespiratory 'interoceptive' sensations and determine whether they are dysfunctional in individuals affected by eating disorders, anxiety, depression, or brain injury. Participants in this study will receive stimulation of the cardiorespiratory channel of the interoceptive system using bolus intravenous infusions of isoproterenol, a peripherally acting medication similar to adrenaline, and saline. Stimulation will occur during functional magnetic resonance imaging (fMRI) as well as outside of the fMRI scanner. After the scan participants will consume a meal. By evaluating the same interoceptive sensations across different human illnesses, the investigators hope to provide convergent evidence resulting in identification of core underlying neural processes, and to discern relative contributions in each condition.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anorexia nervosa | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
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| Generalized anxiety disorder | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
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| Panic disorder | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
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| Major depressive disorder | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
|
| Brain injury | Experimental | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isoproterenol | Drug | Intravenous infusions of isoproterenol, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in cardiorespiratory sensation intensity | Visual analogue rating of intensity of heartbeat and breathing sensations (scale: 0 to 10) through study completion (e.g., the day of testing). | Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Change in anxiety level | Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks. | Baseline |
| Generalized anxiety disorder severity (Generalized Anxiety Disorder 7 scale) |
| Measure | Description | Time Frame |
|---|---|---|
| Resting cardiac interoceptive sensitivity (heartbeat tapping task tap latencies (in milliseconds)) | subject taps with their finger their own perceived heart beat | Baseline |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sahib S Khalsa, MD, PhD | Laureate Institute for Brain Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Laureate Institute for Brain Research | Tulsa | Oklahoma | 74136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35107563 | Derived | Teed AR, Feinstein JS, Puhl M, Lapidus RC, Upshaw V, Kuplicki RT, Bodurka J, Ajijola OA, Kaye WH, Thompson WK, Paulus MP, Khalsa SS. Association of Generalized Anxiety Disorder With Autonomic Hypersensitivity and Blunted Ventromedial Prefrontal Cortex Activity During Peripheral Adrenergic Stimulation: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Apr 1;79(4):323-332. doi: 10.1001/jamapsychiatry.2021.4225. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Nov 2, 2017 | Nov 9, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D000856 | Anorexia Nervosa |
| D003865 | Depressive Disorder, Major |
| D000098647 | Generalized Anxiety Disorder |
| D016584 | Panic Disorder |
| D001930 | Brain Injuries |
| D053120 | Respiratory Aspiration |
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D001068 | Feeding and Eating Disorders |
| D001523 | Mental Disorders |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
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| ID | Term |
|---|---|
| D007545 | Isoproterenol |
| D000077330 | Saline Solution |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| Healthy comparison | Active Comparator | Intravenous bolus infusions of isoproterenol (up to 4 micrograms per infusion) and normal saline. |
|
|
| Normal saline | Drug | Intravenous infusions of normal saline, delivered in a randomized double blinded order, in each participant from each group. Participants will rate the experience of heartbeat and breathing sensations as well as anxiety induced by the infusion. |
|
|
7 questions on anxiety symptoms
| Baseline |
| Panic disorder severity (Panic Disorder Severity scale) | panic symptoms questionnaire | Baseline |
| Major depressive disorder severity (Patient Health Questionnaire-9 scale) | 9 questions on depression symptoms | Baseline |
| Eating disorder severity (Eating Disorder Examination scale) | questionnaire about eating disorder symptoms | Baseline |
blood pressure assessed |
| Baseline |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task. | blood pressure assessed | Baseline |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of mental arithmetic. | blood pressure assessed | Baseline |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic cold pressor task. | blood pressure assessed | Baseline |
| Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of breath holding). | blood pressure assessed | Baseline |
| Structural magnetic resonance imaging (cortical thickness in millimeters cubed). | Structural MRI measure: cortical thickness. | Baseline |
| Functional magnetic resonance imaging (Blood Oxygenation Level Dependent i.e. BOLD signal) | Functional MRI measure: task based activation change | Baseline |
| EEG (coherence in alpha, beta, theta, delta, gamma frequencies, in Hertz (Hz)) | EEG: global and local coherence. | Baseline |
| Change in heart rate | Average heart rate change versus pre-infusion baseline | Baseline |
| Change in breathing pattern | Average respiratory volume variability change versus pre-infusion baseline | Baseline |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000588 |
| Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |