CentralCentral Inhibition: The Inhibition: The ““GatingGating”” System for the Brain System for the Brain

Neuroanatomy of the Frontal Corticesand Basal Ganglia System

*The basal ganglia is a system made of several major sub-structures: The Striatum (Caudate, Putamen andAccumbens) and the Globus Pallidum. Many scientific camps also include: parts of the Cortex, Thalamus,and Brainstem (e.g., substantia nigra which makes dopamine)

Cortex -> Striatum ->Pallidum -> Thalamus:The anatomy the direct pathways of the frontal-subcortical circuits

Thalamus

(MD)

Thalamus

(VA and MD)Thalamus

(VA and MD)

Globus pallidus

(Rostrolateral)

Globus pallidus

(Medial dorsomedial)Globus pallidus

(Lateral dorsomedial)

Nucleus

Accumbens

Caudate

(Ventromedial)Caudate

(Dorsolateral)

Anterior Cingulate

Cortex

Lateral Orbital

Cortex

Prefrontal

CortexC->C->

S->S->

P->P->

T->T->

C ---------> S ---------> P --->TC ---------> S ---------> P --->T

Glutamate is excitatory, GABA is inhibitory

HDHD NormalNormalOCDOCD

OCD: Resting Brain Metabolism (FDG-PET)

DSM-IV OCD Field Trial (N = 425)

Primary Obsessions

Contamination 37.8%Fear of Harm 23.6Symmetry 10.0Somatic 7.2Religious 5.9Sexual 5.5Hoarding 4.8Unacceptable Urge 4.3Miscellaneous 1.0

Primary Compulsions

Checking 28.2%Cleaning/washing 26.8Miscellaneous 11.8Repeating 11.1Mental Rituals 10.9Ordering 5.7Hoarding/collecting 3.5Counting 2.1

Clinical Summary: OCD and TSClinical Summary: OCD and TSOCD TS

Prevalence 1.5-2.5% 0.05-1.0%M-F 1:1 4:1Age Onset 18 7First Symptoms 13 7Lag Between SX and DX 7 7Course Chronic, waxing and waning

Considerable variabilityStress sensitivityShifting SX and clustersTics decline with age in about 50% TS pts

Comorbid TS/OCD 7% 10%Comorbid TICS/OCS 20% 50%MZ Concordance 65-85% 75-90+%(Include. OCS and TICS)Associated conditions Panic, phobias ADHD, Rage, SIB

Major depression

“Primary” RX SRI DA AntagCBT Habit Reversal

Quality of Life with OCD

Relationships92% lowered self-esteem73% interfered with family relationships62% fewer friends or difficulty in maintaining friendships

Education58% lowered academic achievements

Work66% lowered career aspirations47% interfered with work40% unable to work; average loss of 2 years

Suicide Attempts13% suicide attempts secondary to OCD symptoms

The diagnostic criteria for PANDAS (Swedo et al, 1997) are:

1. The diagnosis of OCD and/or a tic disorder2. Symptom onset between ages 3 years and puberty;3. Episodic course of illness characterized by an abrupt onset of symptoms orfrequent, dramatic exacerbations;4. Symptom exacerbations are associated with GABHS infection;5. Presence of neurological abnormalities such as motor hyperactivity oradventitious movements, including choreiform movements (not chorea) or tics.

““Definite TSDefinite TS”” (or (or TouretteTourette’’s s Disorder)*Disorder)*(tic: sudden, rapid, recurrent, nonrhythmic, stereotyped movement or vocalization)A. Multiple motor and > 1 vocal tic at some timeB. Tics occur many times per day, nearly every day, or intermittently for 1 year (with no

tic-free period > 3 months)Tics change over time(C. Marked distress or functional impairment)D. Onset < 21 (18)E. Exclusion CriteriaWitnessed live or taped by a reliable examiner

*TSA Classification Study Group vs. (DSM-IV)