Reporting Guidelines and Issues to Consider for Using Intracranial Brain Stimulation in Studies of Human Declarative Memory

Recent decades have witnessed tremendous advances in the neuroscience of emotion, learning and memory, and in animal models for understanding depression and anxiety. This review focuses on new rationally designed psychiatric treatments derived from preclinical human and animal studies. Nonpharmacological treatments that affect disrupted emotion circuits include vagal nerve stimulation, rapid transcranial magnetic stimulation and deep brain stimulation, all borrowed from neurological interventions that attempt to target known pathological foci. Other approaches include drugs that are given in relation to specific learning events to enhance or disrupt endogenous emotional learning processes. Imaging data suggest that common regions of brain activation are targeted with pharmacological and somatic treatments as well as with the emotional learning in psychotherapy. Although many of these approaches are experimental, the rapidly developing understanding of emotional circuit regulation is likely to provide exciting and powerful future treatments for debilitating mood and anxiety disorders.

Short, high frequency stimulation bursts (4 pulses at 100 Hz) were applied to Schaffer/commissural projections to the CA1 field of rat hippocampal slices at 0.1, 0.2, 1.0 or 2.0-s intervals to assess their efficacy in eliciting long-term potentiation (LTP). Bursts repeated at 2-s intervals induced very little LTP; shorter repetition intervals reliably elicited LTP, with the 200-ms repetition interval producing the greatest potentiation. A short-term potentiation effect, which was maximal 20 s after the last burst and decayed within 10 min, was affected differently by the stimulation parameters than was LTP, suggesting that the two phenomena are due to different processes. The results indicate that patterns of stimulation resembling spike discharge patterns of hippocampal neurons in animals in exploratory situations are effective in inducing LTP and suggest temporal constraints on the mechanisms involved in triggering synaptic plasticity.

Subcallosal cingulate white matter (SCC) deep brain stimulation (DBS) is an evolving investigational treatment for depression. Mechanisms of action are hypothesized to involve modulation of activity within a structurally defined network of brain regions involved in mood regulation. Diffusion tensor imaging was used to model white matter connections within this network to identify those critical for successful antidepressant response. Preoperative high-resolution magnetic resonance imaging data, including diffusion tensor imaging, were acquired in 16 patients with treatment-resistant depression, who then received SCC DBS. Computerized tomography was used postoperatively to locate DBS contacts. The activation volume around the contacts used for chronic stimulation was modeled for each patient retrospectively. Probabilistic tractography was used to delineate the white matter tracts traveling through each activation volume. Patient-specific tract maps were calculated using whole-brain analysis. Clinical evaluations of therapeutic outcome from SCC DBS were defined at 6 months and 2 years. Whole-brain activation volume tractography demonstrated that all DBS responders at 6 months (n = 6) and 2 years (n = 12) shared bilateral pathways from their activation volumes to 1) medial frontal cortex via forceps minor and uncinate fasciculus; 2) rostral and dorsal cingulate cortex via the cingulum bundle; and 3) subcortical nuclei. Nonresponders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from nonresponders. Patient-specific activation volume tractography modeling may identify critical tracts that mediate SCC DBS antidepressant response. This suggests a novel method for patient-specific target and stimulation parameter selection. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.