Deep Brain Stimulation in Animal Models of Fear, Anxiety, and Posttraumatic Stress Disorder

Abstract

Although medications and psychotherapy are often effective for the treatment of posttraumatic stress disorder (PTSD), 20-30% of patients do not respond to these conventional therapies. In psychiatry, DBS has been either approved or is currently under investigation for different disorders. At present, whether DBS may be used to treat PTSD remains unknown. Preclinical research may provide the scientific rationale for helping conceive and further improve such trials. Some of the animal models commonly used to date are more suitable for investigating mechanisms of anxiety and fear than the long-lasting behavior that characterized PTSD. That said, mechanisms and neurocircuits involved in paradigms such as fear conditioning and extinction share several common features with those of PTSD. In this article, we review preclinical studies in which electrical stimulation has been delivered to animal models of PTSD-like behavior. In those studies, commonly targeted regions were the basolateral amygdala, ventral striatum, hippocampus, and prefrontal cortex. Overall, stimulation delivered at high frequencies to most of these targets improved fear extinction and anxiety-like behavior. Though further research is certainly needed, promising findings from DBS studies in animals are encouraging and suggest a positive future perspective for the field.

Deep Brain Stimulation of the Ventromedial Prefrontal Cortex Disrupts Consolidation of Fear Memories

“…Although using DBS to manipulate fear memory is not novel (36)(37)(38)(39), few studies have systematically studied its effects on the individual stages of the memory process. Furthermore, most studies have focused on increasing extinction efficacy rather than directly affecting the original memory (36)(37)(38)40).…”

Enriched Environment Facilitates Anxiolytic Efficacy Driven by Deep-Brain Stimulation of Medial Prefrontal Cortex

“…It has been previously used as an effective treatment in movement disorders like Parkinson’s disease (Hickey and Stacy, 2016 ) and several psychiatric disorders like Tourette syndrome and obsessive-compulsive disorder (Alonso et al, 2015 ; Fraint and Pal, 2015 ). This success has led to suggestions that this technique can also be used in treatment-recalcitrant cases of other brain-centric pathologies like post-traumatic stress disorder (Reznikov et al, 2016 ) or major clinical depression (Torres-Sanchez et al, 2017 ).…”

Prefrontal Cortex Deep Brain Stimulation Improves Fear and Anxiety-Like Behavior and Reduces Basolateral Amygdala Activity in a Preclinical Model of Posttraumatic Stress Disorder

“…One of the consequences of applying short trains of stimulation to the rodent prefrontal cortex is the decrease in firing rate of basolateral amygdala (BLA) principal cells (Likhtik et al, 2005;Rosenkranz and Grace, 2001;Rosenkranz et al, 2003). This is of importance as enhanced BLA activity may facilitate the encoding of fear memories, impair fear extinction, and contribute to enhance anxiety (Maren, 2003;Maren and Quirk, 2004;Reznikov et al, 2016).…”