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Auditory System Target Engagement During Plasticity-Based Interventions in Schizophrenia: A Focus on Modulation of N-Methyl-D-Aspartate-Type Glutamate Receptor Function.
Kantrowitz, JT, Swerdlow, NR, Dunn, W, Vinogradov, S
Biological psychiatry. Cognitive neuroscience and neuroimaging. 2018;(7):581-590
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Abstract
Cognitive deficits are predictive of long-term social and occupational functional deficits in schizophrenia but are currently without gold-standard treatments. In particular, augmentation of auditory cortical neuroplasticity may represent a rate-limiting first step before addressing higher-order cognitive deficits. We review the rationale for N-methyl-d-aspartate-type glutamate receptor (NMDAR) modulators as treatments for auditory plasticity deficits in schizophrenia, along with potential serum and electroencephalographic target engagement biomarkers for NMDAR function. Several recently published NMDAR-modulating treatment studies are covered, involving D-serine, memantine, and transcranial direct current stimulation. While all three interventions appear to modulate auditory plasticity, direct agonists (D-serine) appear to have the largest and most consistent effects on plasticity, at least acutely. We hypothesize that there may be synergistic effects of combining procognitive NMDAR-modulating approaches with auditory cortical neuroplasticity cognitive training interventions. Future studies should assess biomarkers for target engagement and patient stratification, along with head-to-head studies comparing putative interventions and potential long-term versus acute effects.
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Effects of Noninvasive Brain Stimulation on Food Cravings and Consumption: A Meta-Analytic Review.
Lowe, CJ, Vincent, C, Hall, PA
Psychosomatic medicine. 2017;(1):2-13
Abstract
OBJECTIVE The primary aim of this review was to evaluate the effectiveness of noninvasive brain stimulation to the dorsolateral prefrontal cortex (dlPFC) for modulating appetitive food cravings and consumption in laboratory (via meta-analysis) and therapeutic (via systematic review) contexts. METHODS Keyword searches of electronic databases (PubMed, Scopus, Web of Science, PsychoInfo, and EMBASE) and searches of previous quantitative reviews were used to identify studies (experimental [single-session] or randomized trials [multi-session]) that examined the effects of neuromodulation to the dlPFC on food cravings (n = 9) and/or consumption (n = 7). Random-effects models were employed to estimate the overall and method-specific (repetitive transcranial magnetic stimulation [rTMS] and transcranial direct current stimulation [tDCS]) effect sizes. Age and body mass index were examined as potential moderators. Two studies involving multisession therapeutic stimulation were considered in a separate systematic review. RESULTS Findings revealed a moderate-sized effect of modulation on cravings across studies (g, -0.516; p = .037); this effect was subject to significant heterogeneity (Q, 33.086; p < .001). Although no statistically significant moderators were identified, the stimulation effect on cravings was statistically significant for rTMS (g, -0.834; p = .008) but not tDCS (g, -0.252; p = .37). There was not sufficient evidence to support a causal effect of neuromodulation and consumption in experimental studies; therapeutic studies reported mixed findings. CONCLUSIONS Stimulation of the dlPFC modulates cravings for appetitive foods in single-session laboratory paradigms; when estimated separately, the effect size is only significant for rTMS protocols. Effects on consumption in laboratory contexts were not reliable across studies, but this may reflect methodological variability in delivery of stimulation and assessment of eating behavior. Additional single- and multi-session studies assessing eating behavior outcomes are needed.