The purpose of the present study was to evaluate the effects of Behavioral Activation Therapy on prefrontal brain function in response to cognitive control stimuli presented in sad versus neutral contexts in outpatients with MDD. Time 1 data, reported previously (Dichter, Felder & Smoski 2009
) revealed that MDD outpatients recruited prefrontal brain regions to a greater extent to cognitive control stimuli presented in sad contexts than in neutral contexts. These pretreatment data are consistent with conceptualizations of the prefrontal cortex as a mediator of affect regulation in emotional contexts (Ochsner et al. 2004
) as well as empirical evidence that behavioral performance in the context of increased task demands requires greater compensatory prefrontal neuronal activity (Adler et al. 2001
). Thus, it appeared as though patient with MDD required relatively greater cognitive “effort” to disengage from sad stimuli to engage with cognitive control stimuli.
Primary hypotheses of the present study were that symptom remission due to psychotherapy in outpatients with MDD would be accompanied by a concomitant decrease in the magnitude of prefrontal activation required to successfully respond to cognitive control stimuli in sad contexts versus neutral contexts. Findings supported hypotheses. A number of prefrontal regions showed decreased activation in sad contexts after treatment in the MDD group, including the paracingulate gyrus, right orbital frontal cortex, right frontal pole, and left postcentral gyrus. These findings are consistent with other reports of increased prefrontal activity following antidepressant treatment in response to cognitive control stimuli presented within sad contexts in MDD (Benedetti et al. 2009
; Miskowiak et al. 2009
Decreased activation in the right paracingulate gyrus is noteworthy, given a large literature demonstrating that metabolism in this region predicts treatment response in an array of functional and metabolic imaging paradigms (e.g., Kennedy et al. 2007
; Konarski et al. 2007
; Ressler & Mayberg 2007
). The finding of decreased right orbital frontal cortex activation may be conceptualized within the role of this region to mediate emotional evaluations (Wright et al. 2008
) and known linkages between orbital frontal cortex dysfunction and MDD in a number of contexts (see Drevets, Price & Furey 2008
for a review). Finally, the right frontal pole is a mediator of executive control of cognitive operations (John et al. 2009
) and has been suggested to be a cognitive “gateway” that prioritizes information processing (Burgess, Dumontheil & Gilbert 2007
Covariate analyses within the MDD group revealed that pretreatment paracingulate gyrus activation to the [Targets within Sad Blocks] minus [Targets within Neutral Blocks] contrast predicted change in symptoms scores. The direction of this effect is consistent with the conceptualization that MDD is associated with relatively greater prefrontal activation to targets embedded within sad blocks that reflects greater cognitive “effort” to disengage from sad stimuli (Dichter, Felder & Smoski 2009
): those with greater pretreatment signal intensity showed less symptom changes, whereas those with smaller pretreatment signal intensity showed greater symptom changes. Though the post-hoc nature of these analyses warrants replication, these findings suggest that greater paracingulate gyrus activation in the present context may be a marker of treatment response.
Unexpectedly, the right pars triangularis showed increased activation in the MDD group after psychotherapy. This region was not indentified in Dichter et al (2009)
as a region that differentiated groups at baseline. This region is involved in language, motor function, and imitation of action in others (Molnar-Szakacs et al. 2005
), and change in activation in this region after psychotherapy in MDD bears replication.
This is the first study to date to evaluate the effects of psychotherapy on cognitive control in affective contexts in MDD. The central finding of reduced prefrontal activation after psychotherapy stands in contrast to some of the available data addressing the effects of psychopharmacologic intervention in MDD, where prefrontal activation increases are typically observed (Fales et al. 2009
; Fu et al. 2004
; Langenecker et al. 2007
; Norbury et al. 2007
) (see Benedetti et al. 2009
; Miskowiak et al. 2009
for exceptions). Although these studies utilized different tasks and samples, the effects of psychotherapy and psychopharmacologic antidepressants on regional brain function are often in opposite directions, despite equivalent degrees of symptom reduction (Brody, Saxena et al. 2001
; Goldapple et al. 2004
). It may be the case that various treatment modalities initially affect brain sites differentially, yet all may result in a net change in neural functioning that results in symptom remission. Clearly, a full test of this model would require multiple brain imaging assessments over time to track the chronometry of brain responses to different treatment modalities.
We note that a number of brain regions reactive to psychotherapy were clearly outside of emotion processing and cognitive control structures. Additionally, the present sample and design had a number of characteristics that limit interpretability. First, the present study did not include wait-list or placebo control groups, and thus functional brain changes in the MDD group may have been due to other variables, such as spontaneous improvement of symptoms over time instead of to the BATD intervention. Additionally, the addition of another form of antidepressant treatment would allow for isolation of effects to the BATD modality specifically. The relatively broader age range of the MDD group is an additional limitation of this study. Finally, post-hoc tests of the effects of BATD in the MDD group were not corrected for multiple comparisons, and findings regarding the effects of BATD warrant replication. Despite these limitations, the present study suggests that Behavioral Activation Therapy for depression may normalize neural functioning in cognitive control and affective contexts.