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The Neural Underpinnings of OCD

Obsessive–compulsive disorder (OCD) is a common anxiety condition characterised
by recurring, upsetting thoughts (obsessions) that are typically along themes of
contamination, doubts, the need to order things, impending doom, or aggression, just
to name a few. These obsessions are managed by ritualistic actions (compulsions)
such as hand washing, checking, ordering, counting, praying, and other sequences of
action or thought. People who suffer from OCD feel driven to perform specific
compulsions to mitigate the anxiety generated by the obsessive thoughts. One of the
more common OCD experiences is that of feeling contaminated and being compelled
to wash the hands or the entire body to be clean again. The feeling of being clean
either never happens or is fleeting, despite excessive efforts to wash. Another typical
example is persistent doubt upon leaving the house that the house is locked and
windows closed or that the oven has been turned off, and such persistent thoughts
lead to compulsive checking of things (like the locks and windows)—a distressing
state that intrudes on the harmonious flow of life and torments the sufferer when
they are not in a position to do the checking.

What do we know about the neurobiological underpinnings of OCD? As brain
imaging technology becomes more sophisticated, we are starting to see specific brain
structures that are implicated in OCD and some of the neurochemicals involved in
modulating the OCD response. This month we will consider the circuits involved in
OCD and the treatment ramifications.
At a Parisian hospital in 1967, Jean Talairach and his team were trying to find the
origins of seizures in epileptic patients when they discovered that the stimulation of
the cingulum resulted in compulsive behaviours. The cingulum, located directly
above the corpus callosum in the cingulate gyrus, is involved in complex repetitive
movements and is implicated in a bigger circuit involved in OCD. This more elaborate
neural circuit has become known as the OCD loop (Modell, Mountz, Curtis, & Greden,
1989) that includes the orbitofrontal cortex (OFC), striatum, and thalamus.

The OFC is involved with the cognitive processing of decision making and
expectation. It is an emotionally attuned part of the frontal cortex that is sensitive to
threatening situations. Connected to the OFC is information from the striatum, a
major part of the basal ganglia involved in reward and habit formation. It is the
striatum that allows us to multitask by running automatic behaviour in the
background, like the student who plays with her hair while listening to a challenging
lecture. Part of the striatum, the caudate nucleus, working with the putamen, acts
rather like an entrance or gate within the basal ganglia to activate or attenuate
automatic responses. Part of what is believed to be happening in OCD is that when
the striatum is not doing its gatekeeping job properly (i.e., the “entrance” is open),
obsessive thoughts and compulsions can flood the OFC uninhibited. There may be a
“warning” from the amygdala about germs, for example, that prompts thoughts of
washing hands. The OFC responds to such incoming information by reinforcing
compulsive behaviours (such as hand washing) to “make things right”. But a single
action doesn’t satisfy the OFC, because there is an open loop happening that recycles
the “warning” signal (that there is still contamination, for example) back to the OFC.
This hyperactivity of the OFC and the lack of inhibition by the dorsolateral prefrontal
cortex (DLPFC) of the striatum could be one of the main causes of OCD.

The OFC receives messages from the amygdala that are sent back to the lateral
amygdala. This fear circuit is mediated by the HPA-axis (discussed in Part 2), and is
further activated when people suffering OCD do not engage in the compulsive
behaviour—in other words, when they consciously stop the compulsive behaviour but
the obsessive thoughts are still feeding back to the amygdala, letting the system know
that “things are still not OK”. When there is engagement in the compulsive behaviour,
there is some temporary relief, as the fear circuits are down-regulated. This
management of fear and anxiety can lead to even more obsessive thinking and
compulsive behaviours to avoid the uncomfortable consequences of an anxiety
Normally there is a balance between the OFC, basal ganglia, and thalamus that gives
us flexibility as we activate or inhibit, in a situationally appropriate way, responses to
thoughts and the environment. When the balance breaks down and there is less
inhibition, as in the case of Tourette’s syndrome, automatic behaviours become very
difficult to inhibit. An OFC flooded with input from the basal ganglia needs help in
inhibiting the automatic behaviour that is trying to “make things right”. This help can
come from the DLPFC—the part of the frontal cortex involved in positive, goal-
orientated, reflective, and rational behaviour—which can assist the more emotionally
driven OFC in putting the brakes on the obsessive–compulsive loop. This is achieved
by strengthening the control the OFC has over the amygdala to shut down the fear
network. The DLPFC can strengthen attentional skills (such as presence focus,
reframing, tolerance, and acceptance) and override the automatic and habitual flow
from the OFC, in effect distracting the OFC from autopilot and training it to engage
something more beneficial than the habitual OCD response. As clients in therapy
learn to ignore the compulsive urges and see the behaviour as non-functional, they
can establish stronger connections from the OFC to the amygdala and regain control
over what was an uninhibited autopilot of fear.

There is theory that postulates a delayed maturation of the frontal cortex–striatum
circuitry, where the maturation of the cingulate is a causal factor in OCD (Rosenberg
& Keshavan, 1998). Neuroimaging studies have shown higher activity in the OFC,
ACC, and striatum in OCD patients than non-OCD subjects.

A closer look at the loop

The OFC and anterior cingulate cortex
(ACC) connect to the basal ganglia and the
thalamus in what is known as the cortico–
basal ganglia–thalamocortical (CBGTC)
loop (Alexander, DeLong, & Strick, 1986).
There are “direct” and “indirect” pathways
through the basal ganglia that create an
equilibrium of response to situations. This
figure shows both pathways. The direct
pathway is an excitatory one, whereas the
indirect pathway is inhibitory. So it may be
that relatively excessive activity in the direct pathway in these loops could result in
positive feedback loops leading to OCD (Saxena & Rauch, 2000).

Direct pathways run from the cortex to the striatum, then to the globus pallidus
internal segment (GPi) and substantia nigra pars reticulate (SNr), then to the
thalamus, and finally back to the cortex. The glutamatergic pathways are in red,
dopaminergic in magenta, and GABA in blue. The indirect pathways run from the
cortex to the striatum, then to the globus pallidus external segment (GPe), the
subthalamic nucleus (STN), the GPi and SNr, then to the thalamus, and finally back
to the cortex.

(Image created by Andrew Gillies from Wikimedia

Neurochemistry of OCD
The limbic component of the striatum is the nucleus accumbent, also referred to as
the “pleasure centre” of the brain. This area, rich in dopaminergic neurons, plays a
central role in reward behaviour. Engaging in OCD behaviour to down-regulate the
stress response and resolve internal anxiety is also inherently rewarding, as it
increases the dopaminergic activity in the brain. Other neurotransmitters that seem
to be important in the OCD loop are glutamate and GABA activity between the OFC
and caudate nucleus, the globus pallidus, and the thalamus. Dopamine modulates the
activity of the caudate nucleus, and serotonin modulates the activity of the globus
pallidus. Although there have been no prevailing serotonin deficits observed in OCD
patients, when they are placed on serotonin reuptake inhibitors (SRIs) they can show
improvements (anywhere from 40–60% of patients can show improvements of
symptoms). Similarly, when people are given a dopamine antagonist, it can be
effective in reducing motor tics, indicating dopamine as a possible modulator of
behavioural compulsions in OCD.

Psychopharmacological therapy today revolves around the use of SRIs/SSRIs, even
though there is not a good explanation as to why increasing serotonin levels improves
OCD symptoms. Clomipramine (Anafranil) was the first SRI to demonstrate
improvement in some cases of OCD. It blocks 5-HT (serotonin) and norepinephrine
uptake and has some dopamine receptor-blocking function. This class of SRI has
more side effects than more recent SSRIs such as fluoxetine (Prozac), sertraline
(Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox). Sometimes anxiolytics like
benzodiazepines are used as well to combat the anxiety associated with OCD. It is
difficult to judge how effective these pharmacological therapies are, and most
approaches are a combination of chemical intervention and some form of cognitive
behavioural therapy.

Therapeutic Intervention
As stated above, the DLPFC is the brain region that can be utilised to break the OCD
loop by reorientation of the OFC away from its obsessive–compulsive drive. By
activating the DLPFC (in conjunction with the hippocampus) to take executive
control over thoughts and behaviour, recognising that OCD behaviour is not adaptive,
and laying down new neural traces that are more adaptive, the OFC can be retrained.
The most common approach to this is through CBT techniques such as exposure and
response prevention (ERP), first developed in the 1970s. By exposing clients
gradually and systematically, with careful cognitive processing, the abnormal portico-
ganglia circuit can be rewired to function in a much more adaptable and flexible way.
Research has indicated that OCD patients who engage in such CBT therapy do have
decreased metabolism in the right caudate nucleus in the basal ganglia, a decrease in
thalamus activity, and an increase in right-side ACC activity (Linden, 2006; Saxena et
al., 2009). A practical and up-to-date workbook for clients is Brain Based Therapy for
OCD: A Workbook for Clinicians and Clients, by John Arden.