How a transdiagnostic approach can improve the treatment of emotional disorders: Insights from clinical psychology and neuroimaging.

Multiple psychological treatments for emotional disorders have been developed and implemented, improving the quality of life of individuals. Nevertheless, relapse and poor response to psychotherapy are common. This article argues that a greater understanding of both the psychological and neurobiological mechanisms of change in psychotherapy is essential to improve treatment for emotional disorders. It aims to demonstrate how an understanding of these mechanisms provides a basis for (i) reconceptualizing some mental disorders, (ii) refining and establishing the evidence for existing therapeutic techniques and (iii) designing new techniques that precisely target the processes that maintain these disorders. Possible future directions for researchers and practitioners working at the intersection of neuropsychology and clinical psychology are discussed.

Cathodal transcranial direct current stimulation on the prefrontal cortex applied after reactivation attenuates fear memories and prevent reinstatement after extinction.

BACKGROUND: In the last decade, pharmacological strategies targeting reconsolidation after memory retrieval have shown promising efforts to attenuate persistent memories and overcome fear recovery. However, most reconsolidation inhibiting agents have not been approved for human testing. While non-invasive neuromodulation can be considered an alternative approach to pharmacological treatments, there is a lack of evidence about the efficacy of these technologies when modifying memory traces via reactivation/reconsolidation mechanism. OBJECTIVE: In this study, we evaluate the effect of cathodal (c-tDCS) and anodal (a-DCS) transcranial direct current stimulation applied after memory reactivation and extinction in rats. METHODS: Male Wistar rats were randomly assigned into three groups: one sham group, one anodal tDCS group, and one cathodal tDCS group (500 µA, 20 min). Reconsolidation and extinction of fear memories were evaluated using a contextual fear conditioning. RESULTS: Our results showed that c-tDCS and a-tDCS after memory reactivation can attenuate mild fear memories. However, only c-tDCS stimulation prevented both fear expression under strong fear learning and fear recovery after a reinstatement protocol without modification of learning rate or extinction retrieval. Nevertheless, the remote memories were resistant to modification through this type of neuromodulation. Our results are discussed considering the interaction between intrinsic excitability promoted by learning and memory retrieval and the electric field applied during tDCS. CONCLUSION: These results point out some of the boundary conditions influencing the efficacy of tDCS in fear attenuation and open new ways for the development of noninvasive interventions aimed to control fear-related disorders via reconsolidation.

Medial orbitofrontal cortex lesion prevents facilitatory effects of d-cycloserine during fear extinction.

Animal models of fear extinction have an important clinical relevance to pharmacological and exposure-based therapies for anxiety disorders. Lesions of prefrontal structures impair fear extinction. On the other hand, d-cycloserine is able to enhance this process. We hypothesize that the integrity of cortical structures involved in inhibitory control of emotional responses is crucial for the facilitatory effects of d-cycloserine. Here, we showed that medial orbitofrontal cortex lesion prevents d-cycloserine enhancement of fear extinction. These preliminary results suggest that effects of pharmacological treatments could be dependent on cortical activity state to promote fear memory reduction.

Reconsolidation may incorporate state-dependency into previously consolidated memories.

Some memories enter into a labile state after retrieval, requiring reconsolidation in order to persist. One functional role of memory reconsolidation is the updating of existing memories. There are reports suggesting that reconsolidation can be modulated by a particular endogenous process taking place concomitantly to its natural course, such as water or sleep deprivation. Here, we investigated whether an endogenous process activated during a natural/physiological experience, or a pharmacological intervention, can also contribute to memory content updating. Using the contextual fear conditioning paradigm in rats, we found that the endogenous content of an aversive memory can be updated during its reconsolidation incorporating consequences of natural events such as water deprivation, transforming a previously stored memory into a state-dependent one. This updating seems to be mediated by the activation of angiotensin AT1 receptors in the dorsal hippocampus and local infusion of human angiotensin II (ANGII) was shown to mimic the water deprivation effects on memory reconsolidation. Systemic morphine injection was also able to turn a previously acquired experience into a state-dependent memory, reproducing the very same effects obtained by water deprivation or local angiotensin II infusion, and suggesting that other state-dependent-inducing protocols would also be able to contribute to memory updating. These findings trigger new insights about the influence of ordinary daily life events upon memory in its continuing reconstruction, adding the realm of reconsolidation to the classical view of endogenous modulation of consolidation.