12 - Neuropsychological effects of cognitive behavioral therapy

CBT for OCD

Attend “just to the bare facts of a perception as presented either through the five physical senses or through the mind…without reacting to them by deed, speech or by mental comment”

This means learning to experience an OCD symptom without reacting emotionally, learning to realize that the feeling that something is amiss is just the manifestation of overactivity in the OCD circuit

Patients reported that obsessive thoughts no longer controlled them

client with OCD is taught to

Relabel: identify what’s real and what isn’t and refuse to be misled by obsessive thoughts

Reattribute: you understand that those thoughts and urges are merely false messages being sent from your brain

Refocus: turn your attention to more constructive behavior, knowing that by doing so, you are actually changing the way your brain works in an extremely healthy and wholesome way

Revalue: you come to see compulsions and obsessive thoughts as the useless garbage they really are as soon as they arise

Research has indicated that OCD is characterized by hyperactivity in two

regions:

Orbitofrontal: serves to identify when something is amiss

Striatum, in particular, the caudate nucleus: involved in execution of motor

behavior with inputs from the orbitofrontal, as well as the amygdala

Together, these areas form what has been called the “worry circuit”

In people with OCD this circuit is buzzing with activity

Early PET studies found that, after course of CBT in patients with OCD

Metabolic activity of a caudate–orbital–thalamic brain circuit fell dramatically

Degree of alteration was associated with a positive treatment response to CBT

Effect was similar to that produced by pharmacotherapy (with SSRI)

consistent findings among studies of patients participating in CBT or IPT

therapy outcomes were primarily associated, during an awake state at rest, with altered functioning in:

Dorsolateral prefrontal cortex

Important in executive function, working memory, and cognitive flexibility

Altered function may reflect improved problem-solving (more effective coping with life stress) or reduction in worrying and associated negative affect

Ventrolateral prefrontal regions, particularly within the right hemisphere;

anterior and posterior cingulate; and medial prefrontal regions

May reflect improved affect regulation and self-perception

interpersonal therapy

focuses on improving people’s current relationships

PET analysis of MDD patients participating in 15-20 sessions of CBT

Decreased activation in dorsal, ventral, and medial frontal cortex

Increased activation in hippocampus and dorsal cingulate

Patients reported that they ruminated less and no longer felt emotionally dead inside

studies with patients treated with Paxil (SSRI) showed

Increased activation in prefrontal

Decreased activation in hippocampus and subgenual cingulate

 Both types of treatments (CBT & SSRI) result in a net change in critical prefrontal-hippocampal pathways, but the changes were in opposite directions

Proposed explanation is that it is the overall modulation of this complex system rather than any one focal regional change that may be most critical for disease remission

depression is associated with

exaggerated activity in the medial prefrontal

Reduction in medial frontal activity may be associated with reduction in rumination

Reduction in activity in these regions may reflect a reduced bias toward the processing of negative information in the recovered state, with implications for future relapse risk

CBT treatment alone more effectively prevents relapse than

antidepressant medication alone

Effects of placebos on brain activity

Interestingly though, the brain changes associated with placebos tend to directly shadow the true drug-response pattern

Fluoxetine (Prozac) treatment for depression is associated with

− Increased activity in the frontal cortex

− Decreased activity in the subgenual cingulate

CBT for PTSD

Relative to controls, CBT-treated patients had significantly increased connectivity of the amygdala with the fronto-parietal network following CBT

CBT in PTSD patients:

• Increased hippocampal volume

• Decreased amygdala activation

• Increased dorsolateral prefrontal activation

Tailoring treatment based on neuroimaging data for OCD

PET study on OCD:

Those who responded to behavioral therapy showed higher metabolism in left frontal orbital cortex before treatment

On the other hand, lower metabolic activity in left frontal orbital cortex was associated with better response to fluoxetine (Prozac) treatment

Tailoring treatment based on neuroimaging data for social anxiety

Differences in brain structure and neural connectivity among different regions predicted how well CBT reduced symptoms of those with social anxiety disorder

Estimates of treatment outcome were five times more accurate than estimates using a behavioral assessment tool alone

Participants with social anxiety disorder were asked to identify letters behind which occasionally lurked pictures of angry faces

Those who struggled most to avoid being distracted by the threatening stimuli—indicated by more activity in dorsal anterior cingulate cortex—showed the most symptom improvement when treated with CBT 

new research aims to treat MDD by optogentically reactivating neurons associated with positive memories

Male mice were exposed to a pleasurable experience (spending time with female mice)

Cells in the hippocampus that encoded the memory engram were labeled using optogenetics

Researchers then induced depression-like symptoms in the mice by exposing them to chronic stress

Mice showed symptoms that mimic those of human sufferers of depression, such as giving up easily when faced with a difficult situation and failing to take pleasure in activities that are normally enjoyable

When cells in dentate gyrus of hippocampus that were previously active during the positive experience were reactivated, symptoms improved dramatically— but only for as long as the pleasant memory stayed activated

Challenges with optogenetics in humans

highly invasive

follow up study on optogentic mice

Pleasant memory was reactivated 15 minutes, twice a day, for five days

This time, though the memories were not reactivated during the behavioral tests for depression, the mice

− Behaved like mice that had never been depressed (!)

− Experienced an increase in neurogenesis

Glutamatergic activity in the hippocampus-amygdala-nucleus accumbens pathway was identified as a probable circuit supporting improvement

researchers found that allowing the mice to engage in pleasurable experiences after becoming depressed did not improve their symptoms nearly as much as reactivating an old memory