Effect of rTMS on Anxiety

University of Pennsylvania

Status: Completed

Conditions: Fear; Anxiety and Fear; Anxiety

Treatments: Device: rTMS to the right dlPFC

Study type: Interventional

Funder types: Other

Identifiers

NCT03993509

833320

Details and patient eligibility

About

Given the overall lack of treatment adherence/efficacy, side effects of drugs, and the substantial burden of anxiety disorders on the individual and on the national healthcare system, there is a critical need for mechanistic research into the CNS mechanisms that underlie these disorders. Accordingly, the objective of this grant is to use noninvasive neuromodulation to causally identify the key neural mechanisms that mediate the cognitive symptoms of anxiety. This project is relevant to public health because it has the potential to lead to novel repetitive transcranial magnetic stimulation treatments for pathological anxiety.

Full description

Although extensive research has explored the involvement of subcortical structures in arousal, arousal symptoms are only one facet of the symptom profile shared across anxiety disorders. Much less is known about the cognitive symptoms (i.e. difficulty concentrating) experienced by anxiety patients. Accordingly, there is a critical need for mechanistic research into the CNS mechanisms that mediate the cognitive symptoms experienced by anxiety patients. Without such research, treatment development for these disorders will continue to make slow progress. The objective of this application is to determine the key neural mechanisms that mediate the cognitive symptoms of anxiety. The central hypothesis is that the right dorsolateral prefrontal cortex (dlPFC) regulates emotion through top-down inhibition of emotion-related regions. The approach will be to use repetitive transcranial magnetic stimulation (rTMS) to study the effect of right dlPFC activity on objective and subjective measures of induced anxiety, anxiety-related working memory deficits (WM), and TMS-evoked blood oxygenation-level dependent (BOLD) responses during simultaneous TMS/fMRI (i.e. target engagement). The rationale for this approach is that by experimentally manipulating right dlPFC activity using rTMS, this research will be able to causally demonstrate involvement of this region in anxiety regulation, which could translate to future targeted rTMS treatments for anxiety. The first aim will be to determine the effect of a 1-week course of rTMS treatment (1 Hz vs. 10 Hz; right dlPFC target) on anxiety using the threat of unpredictable shock paradigm. The second aim will be to determine the effect of a 1-week course of rTMS treatment (1 Hz vs. 10 Hz; right dlPFC target) on anxiety-related WM-deficits using the Sternberg WM paradigm during threat of shock. The third aim will be to demonstrate target engagement by measuring BOLD responses evoked by TMS pulses to the right dlPFC during threat of shock. The work is innovative because it will combine advanced neuromodulatory techniques (fMRI guidance, electric-field modelling, neuronavigation, active-sham control) with a translational threat of shock paradigm. PUBLIC HEALTH RELEVANCE: Once completed, this research should yield direct evidence for a causal role of the right dlPFC in anxiety regulation, complete with evidence of target engagement, and a novel application to anxiety.

Enrollment: 68 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Subjects must be 18-50 years old
• Able to give their consent
• Right-handed

Exclusion criteria

• Non-english speaking
• Any significant medical or neurological problems
• Current or past Axis I psychiatric disorder(s), active or history of active suicidal ideation
• Alcohol/drug problems in the past year or lifetime alcohol or drug dependence
• Medications that act on the central nervous system
• History of seizure
• History of epilepsy
• Increased risk of seizure for any reason
• Pregnancy, or positive pregnancy test
• IQ <80
• Any medical condition that increases risk for fMRI or TMS
• Any metal in their body which would make having an MRI scan unsafe
• Any sort of medical implants
• Hearing loss
• Claustrophobia

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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68 participants in 2 patient groups

1 Hz Arm

Experimental group

Description:

Subjects will receive a continuous train of 1 Hz stimulation until all 3000 pulses are delivered. Consistent with the 10 Hz condition, TMS will occur during the Sternberg WM paradigm.

Treatment:

Device: rTMS to the right dlPFC

10 Hz Arm

Experimental group

Description:

Subjects will receive 75, 4 second trains at 10 Hz, separated by a 36 second ITI. Stimulation will occur while subjects are doing the Sternberg WM paradigm. The timing of the Sternberg task will be jittered so that each rTMS train will be administered during the maintenance interval of a WM trial.

Treatment:

Device: rTMS to the right dlPFC