THE INHIBITORY HYPOTHESIS AND THE ASSESSMENT OF SEVERERESISTANT OCD WITH TRANSCRANIAL MAGNETIC STIMULATION (TMS)

Jeremy Potterfield

CRASH COURSE IN OCD

OCD is an anxiety disorder characterized by intrusive thoughts and repetitive behaviors aimed at reducing the anxiety of having the thoughts. OCD is most commonly treated with
Medication (SSRIs/Tricyclic Antidepressants) Cognitive Behavioral Therapy Combined Approach

30 60% of patients are either unable to tolerate medication side ef fects or respond to medication. Severe Resistant OCD: a clinical category defined by a lack of response to at least one adequate trial of an SSRI and/or CBT,

NON-PHARMACOLOGICAL TREATMENTS
Deep-brain stimulation Neurosurgery/ablation Transcranial magnetic stimulation
Use magnetic field to stimulate neurons noninvasively

BRIEF OVERVIEW OF TRANS-CRANIAL MAGNETIC STIMULATION (TMS)

Generation of Magnetic Field Repeated trains of pulses ( rTMS) delivered to localized areas of the brain Stimulus frequency
Low frequency <= 1Hz (inhibitory) High frequency > 1Hz (excitatory)

Safety
Some patients have light headaches, some scalp and neck pain.

TMS IN PRACTICE

OCD CIRCUITRY
Inhibitory Hypothesis of OCD
Cortico-striato-pallido -thalamic circuit (CSPT)
Prefrontal Cortex Dorsolateral prefrontal cortex Orbitofrontal cortex

Supplementar y Motor Area Insula

SPECIFIC AIM #1: OPTIMAL CONFIGURATION FOR TREATING SEVERE-RESISTANT OCD

Stimulating areas strengthens deficits in circuitry

No consensus on best region

Compare efficacy of four brain regions
Novel region: Insula

SPECIFIC AIM #1: OPTIMAL CONFIGURATION FOR TREATING SEVERE-RESISTANT OCD (CONT.)
Five Groups of Severe Resistant cases (right handed)
Four receiving TMS (each of the four receiving TMS in different neuroanatomical region: DLPFC, OFC, SMA, Insula) Control group receiving sham

Treatment
40-60mins of low-freq TMS (1Hz) (increase inhibition) 5 days per week, for six weeks.

Yale-Brown Obsessive Compulsive Scale

Pre/Post

Cognitive self-reporting
Beck Depression Inventory (BDI), Thought-Action Fusion Scale (TAFS), Metacognitions, Questionnaire (MCQ-30), and White Bear Suppression Inventory (WBSI).

Brain functional connectivity

Use pre/post fMRI to gauge changes in circuitry strength
Compare pre-post treatment Compare against sham group

SPECIFIC AIMS #2: USE OF TMS TO ASSESS CORTICAL INHIBITION IN S E V E R E - R E S I S TA N T O C D W I T H C O R T I C A L S I L E N T P E R I O D ( C S P ) , S H O R T I N T E R VA L C O R T I C A L I N H I B I T I O N ( S I C I ) M O D E L S .

C o r t i c al S i l e n t Pe r i o d ( C S P ) a n d S h o r t - I n te r va l C o r t i ca l I n h i b i t io n ( S I C I )
Models of Cortical Inhibition Inhibitory Hypothesis predicts that these are both decreased in severe -resistant OCD CSP indexes GABAa receptor-mediated inhibition/SICI to GABAb activity Use of electromyography; detects electrical output of muscle cells

CSP
Transcranial stimulation of motor cortex Interruption of electromyography (EMG)/Silence of motor activity Time it takes to resume motor activity Duration of CSP is indicator of cortical inhibition (shorter duration means less inhibition/more impulsive)

SICI
SICI consists of a subthreshold conditioning pulse followed by a suprathreshold test pulse (1-5ms apart . Motor-evoked potential (MEP) response is inhibited by 50 90%

SPECIFIC AIMS #2: USE OF TMS TO ASSESS CORTICAL INHIBITION IN S E V E R E - R E S I S TA N T O C D W I T H C O R T I C A L S I L E N T P E R I O D ( C S P ) , S H O R T I N T E R VA L C O R T I C A L I N H I B I T I O N ( S I C I ) M O D E L S . ( C O N T. )

C o m p a r is o n s CSP and SICI Pre-TMS/Post-TMS Therapy Non-Severe Resistant OCD, Non-OCD control Te s t i n g Stimulation of motor cortex with TMS Surface electromyography (EMG) will be recorded from the right abductor pollicis brevis (APB) muscle. (flat of palm near thumb) Twice; Pre-TMS/Post-TMS (50-75 trials each) P r e d i c t io n s Severe-Resistant will have shorter CSP and SICI pre -TMS than post-TMS (TMS will strengthen circuits and improve inhibition) Shorter CSP and SICI than controls (decreased inhibition is characteristic of severe resistant

LIMITATIONS
Severe-Resistant Population
Depression Comorbidity (difficult to control for the alleviation of depression)
Concomitant pharmaceutical treatment Control for severity risks narrowing an already narrow group