How does cognitive behavior therapy for dissociative seizures work? A mediation analysis of the CODES trial.

BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Abolition of lifelong specific phobia: a novel therapeutic consequence of left mesial temporal lobectomy.

Numerous imaging studies have confirmed the amygdala as prominent within a neural network mediating specific phobia, including arachnophobia. We report the case of a patient in whom arachnophobia was abolished after left temporal mesial lobectomy, with unchanged fear responses to other stimuli. The phenomenon of abolition of specific phobia after amygdala removal has not, to our knowledge, been previously reported.

Moderators of cognitive behavioural therapy treatment effects and predictors of outcome in the CODES randomised controlled trial for adults with dissociative seizures.

OBJECTIVE: We explored moderators of cognitive behavioural therapy (CBT) treatment effects and predictors of outcome at 12-month follow-up in the CODES Trial (N = 368) comparing CBT plus standardised medical care (SMC) vs SMC-alone for dissociative seizures (DS). METHODS: We undertook moderator analyses of baseline characteristics to determine who had benefited from being offered CBT 12 months post-randomisation. Outcomes included: monthly DS frequency, psychosocial functioning (Work and Social Adjustment Scale - WSAS), and health-related quality of life (Mental Component Summary (MCS) and Physical Component Summary (PCS) SF-12v2 scores). When moderating effects were absent, we tested whether baseline variables predicted change irrespective of treatment allocation. RESULTS: Moderator analyses revealed greater benefits (p < 0.05) of CBT on DS frequency for participants with more (≥22) symptoms (Modified PHQ-15) or ≥ 1 current (M.I.N.I.-confirmed) comorbid psychiatric diagnosis at baseline. The effect of CBT on PCS scores was moderated by gender; women did better than men in the CBT + SMC group. Predictors of improved outcome included: not receiving disability benefits, lower anxiety and/or depression scores (PCS, MCS, WSAS); shorter duration, younger age at DS onset, employment, fewer symptoms and higher educational qualification (PCS, WSAS); stronger belief in the diagnosis and in CBT as a "logical" treatment (MCS). Some variables that clinically might be expected to moderate/predict outcome (e.g., maladaptive personality traits, confidence in treatment) were not shown to be relevant. CONCLUSION: Patient complexity interacted with treatment. CBT was more likely to reduce DS frequency in those with greater comorbidity. Other patient characteristics predicted outcome regardless of the received intervention.

Depersonalization disorder: thinking without feeling.

Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive-compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization--absent subjective experience of emotion--is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation.

Emotional memory and perception in temporal lobectomy patients with amygdala damage.

BACKGROUND: The human amygdala is implicated in the formation of emotional memories and the perception of emotional stimuli--particularly fear--across various modalities. OBJECTIVES: To discern the extent to which these functions are related. METHODS: 28 patients who had anterior temporal lobectomy (13 left and 15 right) for intractable epilepsy were recruited. Structural magnetic resonance imaging showed that three of them had atrophy of their remaining amygdala. All participants were given tests of affect perception from facial and vocal expressions and of emotional memory, using a standard narrative test and a novel test of word recognition. The results were standardised against matched healthy controls. RESULTS: Performance on all emotion tasks in patients with unilateral lobectomy ranged from unimpaired to moderately impaired. Perception of emotions in faces and voices was (with exceptions) significantly positively correlated, indicating multimodal emotional processing. However, there was no correlation between the subjects' performance on tests of emotional memory and perception. Several subjects showed strong emotional memory enhancement but poor fear perception. Patients with bilateral amygdala damage had greater impairment, particularly on the narrative test of emotional memory, one showing superior fear recognition but absent memory enhancement. CONCLUSIONS: Bilateral amygdala damage is particularly disruptive of emotional memory processes in comparison with unilateral temporal lobectomy. On a cognitive level, the pattern of results implies that perception of emotional expressions and emotional memory are supported by separate processing systems or streams.

Time courses of left and right amygdalar responses to fearful facial expressions.

Despite the many studies highlighting the role of the amygdala in fear perception, few have examined differences between right and left amygdalar responses. Using functional magnetic resonance imaging (fMRI), we examined neural responses in three groups of healthy volunteers (n = 18) to alternating blocks of fearful and neutral faces. Initial observation of extracted time series of both amygdalae to these stimuli indicated more rapid decreases of right than left amygdalar responses to fearful faces, and increasing magnitudes of right amygdalar responses to neutral faces with time. We compared right and left responses statistically by modeling each time series with (1) a stationary fit model (assuming a constant magnitude of amygdalar response to consecutive blocks of fearful faces) and (2) an adaptive model (no assumptions). Areas of significant sustained nonstationarity (time series points with significantly greater adaptive than stationary model fits) were demonstrated for both amygdalae. There was more significant nonstationarity of right than left amygdalar responses to neutral, and left than right amygdalar responses to fearful faces. These findings indicate significant variability over time of both right and left amygdalar responses to fearful and neutral facial expressions and are the first demonstration of specific differences in time courses of right and left amygdalar responses to these stimuli.