Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Developmental onset distinguishes three types of spontaneous recognition memory in mice.

Spontaneous recognition memory tasks build on an animal's natural preference for novelty to assess the what, where and when components of episodic memory. Their simplicity, ethological relevance and cross-species adaptability make them extremely useful to study the physiology and pathology of memory. Recognition memory deficits are common in rodent models of neurodevelopmental disorders, and yet very little is known about the expression of spontaneous recognition memory in young rodents. This is exacerbated by the paucity of data on the developmental onset of recognition memory in mice, a major animal model of disease. To address this, we characterized the ontogeny of three types of spontaneous recognition memory in mice: object location, novel object recognition and temporal order recognition. We found that object location is the first to emerge, at postnatal day (P)21. This was followed by novel object recognition (24 h delay), at P25. Temporal order recognition was the last to emerge, at P28. Elucidating the developmental expression of recognition memory in mice is critical to improving our understanding of the ontogeny of episodic memory, and establishes a necessary blueprint to apply these tasks to probe cognitive deficits at clinically relevant time points in animal models of developmental disorders.

Diffusion Tensor Imaging Findings in Post-Concussion Syndrome Patients after Mild Traumatic Brain Injury: A Systematic Review.

OBJECTIVES: To review the evidence for the use of diffusion tensor imaging (DTI) parameters in the human brain as a diagnostic tool for and predictor of post-concussion syndrome (PCS) after a mild traumatic brain injury (mTBI). DESIGN: Systematic review. DATA SOURCES: All relevant studies in AMED, Embase, MEDLINE, Ovid, PubMed, Scopus, and Web of Science through 20 May, 2016. STUDY SELECTION: Studies that analyze traditional DTI measures [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD)] and the severity of PCS symptoms or the development of PCS in humans after an mTBI. DATA EXTRACTION: Population studied, patient source, mTBI diagnosis method, PCS diagnosis method, DTI values measured, significant findings, and correlation between DTI findings and PCS. DATA SYNTHESIS: Ten studies investigated correlations between DTI values and PCS symptom severity or between DTI values and the development of PCS in mTBI patients. Decreased FA and increased MD and RD were associated with the development and severity of PCS. AD was not found to change significantly. Brain regions found to have significant changes in DTI parameters varied from study to study, although the corpus callosum was most frequently cited as having abnormal DTI parameters in PCS patients. CONCLUSION: DTI abnormalities correlate with PCS incidence and symptom severity, as well as indicate an increased risk of developing PCS after mTBI. Abnormal DTI findings should prompt investigation of the syndrome to ensure optimal symptom management at the earliest stages. Currently, there is no consensus in the literature about the use of one DTI parameter in a specific region of the brain as a biomarker for PCS because no definite trends for DTI parameters in PCS subjects have been identified. Further research is required to establish a standard biomarker for PCS.