Presurgical diffusion metrics of the thalamus and thalamic nuclei in postoperative delirium: A prospective two-centre cohort study in older patients.

BACKGROUND: The thalamus seems to be important in the development of postoperative delirium (POD) as previously revealed by volumetric and diffusion magnetic resonance imaging. In this observational cohort study, we aimed to further investigate the impact of the microstructural integrity of the thalamus and thalamic nuclei on the incidence of POD by applying diffusion kurtosis imaging (DKI). METHODS: Older patients without dementia (≥65 years) who were scheduled for major elective surgery received preoperative DKI at two study centres. The DKI metrics fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and free water (FW) were calculated for the thalamus and - as secondary outcome - for eight predefined thalamic nuclei and regions. Low FA and MK and, conversely, high MD and FW, indicate aspects of microstructural abnormality. To assess patients' POD status, the Nursing Delirium Screening Scale (Nu-DESC), Richmond Agitation Sedation Scale (RASS), Confusion Assessment Method (CAM) and Confusion Assessment Method for the Intensive Care Unit score (CAM-ICU) and chart review were applied twice a day after surgery for the duration of seven days or until discharge. For each metric and each nucleus, logistic regression was performed to assess the risk of POD. RESULTS: This analysis included the diffusion scans of 325 patients, of whom 53 (16.3 %) developed POD. Independently of age, sex and study centre, thalamic MD was statistically significantly associated with POD [OR 1.65 per SD increment (95 %CI 1.17 - 2.34) p = 0.004]. FA (p = 0.84), MK (p = 0.41) and FW (p = 0.06) were not significantly associated with POD in the examined sample. Exploration of thalamic nuclei also indicated that only the MD in certain areas of the thalamus was associated with POD. MD was increased in bilateral hemispheres, pulvinar nuclei, mediodorsal nuclei and the left anterior nucleus. CONCLUSIONS: Microstructural abnormalities of the thalamus and thalamic nuclei, as reflected by increased MD, appear to predispose to POD. These findings affirm the thalamus as a region of interest in POD research.

Presurgical Thalamus Volume in Postoperative Delirium: A Longitudinal Observational Cohort Study in Older Patients.

BACKGROUND: Previous studies suggest a role of the thalamus in cognitive function, while others implicate it as a central effect site of anesthetics. Yet, its role in postoperative neurocognition in the aging brain remains uncertain. We used presurgical thalamic volume as a functional indicator and determined its association with postoperative delirium (POD). METHODS: For this study, 301 older adults (aged ≥65) without dementia and scheduled for surgery were enrolled. Before surgery, participants underwent magnetic resonance imaging (MRI). Thalamus volume was segmented using Freesurfer (Version 5.3.). Participants were screened for POD twice a day until discharge or for a maximum of 7 days. POD was defined as a positive screening on ≥1 of 4 validated instruments: Richmond Agitation Sedation Scale (RASS), Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score. A logistic regression associated thalamus volume with POD with adjustment for age, global brain atrophy, and physical status according to the American Society of Anesthesiologists (ASA) classification. RESULTS: In this cohort, 44 participants (14.6%) were diagnosed with POD. Independently of age, global brain atrophy, and physical status score, a higher preoperative thalamus volume was associated with a reduced odds of POD (odds ratio per 1-cm3 increment; 0.73 [95% confidence interval (CI), 0.58-0.92]; P = .008). CONCLUSIONS: A larger thalamus volume was associated with reduced odds of POD. Thus, the thalamus marks a region of interest in POD in the aging brain. These findings may help to understand the neuronal basis of POD.

Stimulation-history effects on the M100 revealed by its differential dependence on the stimulus onset interval.

The amplitudes of the most prominent component of auditory evoked magnetic fields and electrical potentials, the M100 and N100, recorded from the human scalp depend on the duration of the stimulus onset interval (SOI). Here, we show, using magnetoencephalography, that the SOI dependence of the M100 amplitude strongly depends upon whether stimuli with different SOIs are presented in a conventional block design or in a random manner. This differential dependence reveals that the M100 is affected not only by the stimulus evoking it and by its predecessor, but by a longer-term history of stimulation. We provide a parsimonious model that accounts for our findings with both designs in a quantitative manner. It assumes a transient, temporally asymmetric reduction in the excitability of a fraction of potentially excitable neurons. A rather stereotyped response function may therefore underlie the stimulation-history effects in the human auditory cortex.

The M100 component of evoked magnetic fields differs by scaling factors: implications for signal averaging.

MEG and EEG studies of event-related responses often involve comparisons of grand averages, requiring homogeneity of the variances. Here, we examine the possibility, implied by the nature of neural sources and the measuring principles involved, that the M100 component of auditory-evoked magnetic fields of different subjects, hemispheres, to different stimuli, and at different sensors differs by scaling factors. Such a multiplicative model predicts a linear increase in the standard deviation with the mean, and thus would have important implications for averaging and comparing such data. Our analyses, at the sensor and the source level, clearly show that the multiplicative model applies. We therefore propose geometric, rather than arithmetic, averaging of the M100 component across subjects and suggest a novel and superior normalization procedure. Our results question the justification of the common practice of subtracting arithmetic grand averages.