Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

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.

Anorexia Nervosa, Major Depressive Disorder, Generalized Anxiety Disorder, Panic Disorder, Brain Injury

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.

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.

Visual analogue rating of intensity of heartbeat and breathing sensations (scale: 0 to 10) through study completion (e.g., the day of testing).

Visual analog rating of level of anxiety (scale: 0 to 10) through study completion, an average of 2 weeks.

Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of the valsalva maneuver

Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic handgrip task.

Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of mental arithmetic.

Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic cold pressor task.

Systolic and diastolic blood pressure (millimeters of mercury; mmHg) during the autonomic task of breath holding).

Inclusion Criteria: Diagnostic and Statistical Manual 5 (DSM 5) criteria for anorexia nervosa and age 18 to 40, or generalized anxiety disorder, or panic disorder, or major depressive disorder, or brain injury caused either by herpes simplex encephalitis or Urbach-Wiethe disease. Exclusion Criteria: DSM 5 diagnosis with any of the following: Schizophrenia spectrum and other psychotic disorders, bipolar and related disorders, antisocial personality disorder, active suicidal ideation with intent or plan Current cardiac arrhythmia Current respiratory disease Seizure disorder MRI contraindications including: cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/ wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60-120 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.

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. Erratum In: JAMA Psychiatry. 2022 Apr 1;79(4):382.