Functional connectivity between the habenula and default mode network and its association with the antidepressant effect of ketamine.

BACKGROUND: Recently, an animal model for depression has shown that ketamine, an N-methyl- d-aspartate receptor (NMDAR) antagonist, elicits a rapid-acting antidepressant effect by blocking NMDAR-dependent bursting in the lateral habenula (Hb). However, evidence from human studies remains scarce. METHODS: This study explored the changes of resting-state functional connectivity (FC) of the Hb in responders and nonresponders who was diagnosed with unipolar or bipolar depression before and after ketamine treatment. The response was defined as a ≥50% reduction in the total MADRS score at Day 13 (24 h following the sixth infusion) in comparison with the baseline score. Correlation analyses were performed to identify an association between symptom improvement and the signals of the significantly different brain regions detected in the above imaging analysis. RESULTS: In the post-hoc region-of-interest analysis, an enhanced baseline FC between Hb and several hubs of the default mode network (including angulate cortex, precuneus, medial prefrontal cortex, and middle temporal cortex) was observed in responders (≥50% decrease in the Montgomery-Asberg Scale at 2 weeks) compared with nonresponders. CONCLUSIONS: These pilot findings may suggest a potential neural mechanism by which ketamine exerts its robust antidepressant efficacy via downregulation of aberrant habenular FC with parts of the default mode network.

Sleep improvement is associated with the antidepressant efficacy of repeated-dose ketamine and serum BDNF levels: a post-hoc analysis.

RATIONALE: Recently, the effects of ketamine on the circadian rhythm have suggested that ketamine's rapid antidepressant effects are associated with and without sleep disturbance improvement. OBJECTIVES: Here, we evaluated the antidepressant efficacy of repeated ketamine infusions in patients with sleep disturbances. METHODS: This study included 127 patients with major depressive disorder or bipolar disorder who received ketamine treatments during a 12-day period. Sleep quality was assessed by the 17-item Hamilton Depression Rating Scale sleep disturbance factor (SDF) (items 4, 5 and 6). Serum brain-derived neurotrophic factor (BDNF) was measured at baseline, day 13 and day 26. This study was a post-hoc analysis. RESULTS: Significant differences were found in the HAMD-17 score at 13 post-infusion time points compared to baseline, as well as the scores in SDF score at each of the 7 post-infusion (4 h after each infusion excluded) time points among all patients. Logistic regression and linear correlation analyses revealed that a greater reduction in the SDF after 24 h of the first ketamine infusion resulted in a better antidepressant effect in the last two follow-up visits. Moreover, BDNF levels were significantly higher in sleep responders than in non-responders. CONCLUSIONS: In the 127 patients, six ketamine infusions induced better therapeutic effects in sleep responders than in sleep non-responders and patients without sleep disturbances. The sleep response after repeated ketamine infusions was positively associated with high serum BDNF levels. Early sleep disturbance improvement (as early as 24 h after the first ketamine injection) may predict the antidepressant effect of repeated-dose ketamine.

Infrared Thermography for Measuring Elevated Body Temperature: Clinical Accuracy, Calibration, and Evaluation.

Infrared thermographs (IRTs) implemented according to standardized best practices have shown strong potential for detecting elevated body temperatures (EBT), which may be useful in clinical settings and during infectious disease epidemics. However, optimal IRT calibration methods have not been established and the clinical performance of these devices relative to the more common non-contact infrared thermometers (NCITs) remains unclear. In addition to confirming the findings of our preliminary analysis of clinical study results, the primary intent of this study was to compare methods for IRT calibration and identify best practices for assessing the performance of IRTs intended to detect EBT. A key secondary aim was to compare IRT clinical accuracy to that of NCITs. We performed a clinical thermographic imaging study of more than 1000 subjects, acquiring temperature data from several facial locations that, along with reference oral temperatures, were used to calibrate two IRT systems based on seven different regression methods. Oral temperatures imputed from facial data were used to evaluate IRT clinical accuracy based on metrics such as clinical bias (Δcb), repeatability, root-mean-square difference, and sensitivity/specificity. We proposed several calibration approaches designed to account for the non-uniform data density across the temperature range and a constant offset approach tended to show better ability to detect EBT. As in our prior study, inner canthi or full-face maximum temperatures provided the highest clinical accuracy. With an optimal calibration approach, these methods achieved a Δcb between ±0.03 °C with standard deviation (σΔcb) less than 0.3 °C, and sensitivity/specificity between 84% and 94%. Results of forehead-center measurements with NCITs or IRTs indicated reduced performance. An analysis of the complete clinical data set confirms the essential findings of our preliminary evaluation, with minor differences. Our findings provide novel insights into methods and metrics for the clinical accuracy assessment of IRTs. Furthermore, our results indicate that calibration approaches providing the highest clinical accuracy in the 37-38.5 °C range may be most effective for measuring EBT. While device performance depends on many factors, IRTs can provide superior performance to NCITs.

Clinical evaluation of fever-screening thermography: impact of consensus guidelines and facial measurement location.

SIGNIFICANCE: Infrared thermographs (IRTs) have been used for fever screening during infectious disease epidemics, including severe acute respiratory syndrome, Ebola virus disease, and coronavirus disease 2019 (COVID-19). Although IRTs have significant potential for human body temperature measurement, the literature indicates inconsistent diagnostic performance, possibly due to wide variations in implemented methodology. A standardized method for IRT fever screening was recently published, but there is a lack of clinical data demonstrating its impact on IRT performance. AIM: Perform a clinical study to assess the diagnostic effectiveness of standardized IRT-based fever screening and evaluate the effect of facial measurement location. APPROACH: We performed a clinical study of 596 subjects. Temperatures from 17 facial locations were extracted from thermal images and compared with oral thermometry. Statistical analyses included calculation of receiver operating characteristic (ROC) curves and area under the curve (AUC) values for detection of febrile subjects. RESULTS: Pearson correlation coefficients for IRT-based and reference (oral) temperatures were found to vary strongly with measurement location. Approaches based on maximum temperatures in either inner canthi or full-face regions indicated stronger discrimination ability than maximum forehead temperature (AUC values of 0.95 to 0.97 versus 0.86 to 0.87, respectively) and other specific facial locations. These values are markedly better than the vast majority of results found in prior human studies of IRT-based fever screening. CONCLUSION: Our findings provide clinical confirmation of the utility of consensus approaches for fever screening, including the use of inner canthi temperatures, while also indicating that full-face maximum temperatures may provide an effective alternate approach.