Midazolam and Ketamine Produce Distinct Neural Changes in Memory, Pain, and Fear Networks during Pain

Background Despite the well-known clinical effects of midazolam and ketamine, including sedation and memory impairment, the neural mechanisms of these distinct drugs in humans are incompletely understood. The authors hypothesized that both drugs would decrease recollection memory, task-related brain activity, and long-range connectivity between components of the brain systems for memory encoding, pain processing, and fear learning. Methods In this randomized within-subject crossover study of 26 healthy adults, the authors used behavioral measures and functional magnetic resonance imaging to study these two anesthetics, at sedative doses, in an experimental memory paradigm using periodic pain. The primary outcome, recollection memory performance, was quantified with d′ (a difference of z scores between successful recognition versus false identifications). Secondary outcomes were familiarity memory performance, serial task response times, task-related brain responses, and underlying brain connectivity from 17 preselected anatomical seed regions. All measures were determined under saline and steady-state concentrations of the drugs. Results Recollection memory was reduced under midazolam (median [95% CI], d′ = 0.73 [0.43 to 1.02]) compared with saline (d′ = 1.78 [1.61 to 1.96]) and ketamine (d′ = 1.55 [1.12 to 1.97]; P < 0.0001). Task-related brain activity was detected under saline in areas involved in memory, pain, and fear, particularly the hippocampus, insula, and amygdala. Compared with saline, midazolam increased functional connectivity to 20 brain areas and decreased to 8, from seed regions in the precuneus, posterior cingulate, and left insula. Compared with saline, ketamine decreased connectivity to 17 brain areas and increased to 2, from 8 seed regions including the hippocampus, parahippocampus, amygdala, and anterior and primary somatosensory cortex. Conclusions Painful stimulation during light sedation with midazolam, but not ketamine, can be accompanied by increased coherence in brain connectivity, even though details are less likely to be recollected as explicit memories. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

The Scope of Planning Serial Actions during Typing

Human activities consisting of multiple component actions require the generation of ordered sequences. This study investigated the scope of response planning in highly serial task, typing, by means of ERPs indexing motor response preparation. Specifically, we compared motor-related ERPs yielded by words typed using a single hand against words that had all keystrokes typed with a single hand, except for a deviant one, typed with the opposite hand. The deviant keystroke occurred either early in the typed sequence, corresponding to the second or third letters, or late, corresponding to the penultimate or last letter. Motor-related ERPs detected before response onset were affected only by deviant keystrokes located at the beginning of the sequence, whereas deviant keystrokes located at the end yielded ERPs that were undistinguishable from unimanual responses. These results impose some constraints on the notion of parallel processing of component actions.

Advances in the Application of the Divide-and-Conquer Algorithm to Multibody System Dynamics

This paper summarizes the various recent advancements achieved by utilizing the divide-and-conquer algorithm (DCA) to reduce the computational burden associated with many aspects of modeling, designing, and simulating articulated multibody systems. This basic algorithm provides a framework to realize O(n) computational complexity for serial task scheduling. Furthermore, the framework of this algorithm easily accommodates parallel task scheduling, which results in coarse-grain O(log n) computational complexity. This is a significant increase in efficiency over forming and solving the Newton–Euler equations directly. A survey of the notable previous work accomplished, though not all inclusive, is provided to give a more complete understanding of how this algorithm has been used in this context. These advances include applying the DCA to constrained systems, flexible bodies, sensitivity analysis, contact, and hybridization with other methods. This work reproduces the basic mathematical framework for applying the DCA in each of these applications. The reader is referred to the original work for the details of the discussed methods.

Effects of relative frequency and delay interval of knowledge of results (KR) in the acquisition of motor skills

The purpose of the present study was to identify the effects of relative frequency and delay interval of Knowledge of Results (KR) in the acquisition of a serial motor skill. Sixty students were randomly distributed in 2 experiments, with three groups in each experiment (n = 10). The Experiment 1 investigated the effects of the KR frequency without KR delay interval and the Experiment 2 investigated the effects of the KR frequency with KR delay interval (3 seconds) in the acquisition of a serial motor skill. The serial task consisted of putting a tennis ball into six holes, positioned in a wood platform in a previously determined target time. In both experiments, the subjects performed 60 trials in target time of 2,700 ms, in the acquisition phase. In the Experiment 1, the results showed superiority of G33 in relation to the other groups, during the tests. In the Experiment 2, the results did not show any difference among the groups. These results are discussed with respect to the effect of KR delay interval, showing the role of combination of the variables.