Continuous Three-Dimensional Control of a Virtual Helicopter Using a Motor Imagery Based Brain-Computer Interface

Brain-computer interfaces (BCIs) allow a user to interact with a computer system using thought. However, only recently have devices capable of providing sophisticated multi-dimensional control been achieved non-invasively. A major goal for non-invasive BCI systems has been to provide continuous, intuitive, and accurate control, while retaining a high level of user autonomy. By employing electroencephalography (EEG) to record and decode sensorimotor rhythms (SMRs) induced from motor imaginations, a consistent, user-specific control signal may be characterized. Utilizing a novel method of interactive and continuous control, we trained three normal subjects to modulate their SMRs to achieve three-dimensional movement of a virtual helicopter that is fast, accurate, and continuous. In this system, the virtual helicopter's forward-backward translation and elevation controls were actuated through the modulation of sensorimotor rhythms that were converted to forces applied to the virtual helicopter at every simulation time step, and the helicopter's angle of left or right rotation was linearly mapped, with higher resolution, from sensorimotor rhythms associated with other motor imaginations. These different resolutions of control allow for interplay between general intent actuation and fine control as is seen in the gross and fine movements of the arm and hand. Subjects controlled the helicopter with the goal of flying through rings (targets) randomly positioned and oriented in a three-dimensional space. The subjects flew through rings continuously, acquiring as many as 11 consecutive rings within a five-minute period. In total, the study group successfully acquired over 85% of presented targets. These results affirm the effective, three-dimensional control of our motor imagery based BCI system, and suggest its potential applications in biological navigation, neuroprosthetics, and other applications

Interruption of continuous opioid exposure exacerbates drug-evoked adaptations in the mesolimbic dopamine system

Drug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may, therefore, represent a strategy to minimize iatrogenic effects on brain reward circuits

Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration

<div><p>To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.</p></div

Prepulse Inhibition of the Acoustic Startle Reflex in fbΔBMPRII Mice.

<p>The fbΔBMPRII mutants (red) and control littermates (white) showed similar levels of prepulse inhibition of the acoustic startle across three different intensities of the prepulse stimulus. Thus, the mutant mice did not show deficits in sensorimotor gating.</p

Western Blot Analysis of BMPRII Protein in the Brain.

<p>Western blot analysis of tissues from the hippocampus (HP), Cerebellum (Cb), and cortex (Cx) in BMPRII flox/flox controls (cn) and BMPRII flox/flox; CaMKIIα-Cre (ko) mice. At 2 months old, fbΔBMPRII mutant mice show a great reduction of BMPRII protein in the hippocampus and cortex, but show similar levels of BMPRII protein in the cerebellum.</p

Loss of BMPRII Modulates Anxiety-Related Behavior in the Elevated Plus Maze.

<p>In the Elevated Plus Maze (A) the fbΔBMPRII mutant mice (red) spent a significantly increased proportion of time exploring the open-arms compared to control littermates (white), and (B) had a significantly increased duration of time on the open-arms, (C) but there was no significant difference in open-arm entries. When closed-arm exploration was examined, (D) the fbΔBMPRII mutant mice spent a significantly reduced proportion of time on the closed-arms, and (E) had a significantly reduced duration of time on the closed-arms, (F) but there was no significant difference in closed-arm entries. Results reported as mean ± S.E.M. Asterisk indicates *p<0.05 or **p<0.005.</p

Floating Behavior in the Water Maze and Immobility of BMPRII Mice in the Porsolt Swim Test.

<p>(A) The fbΔBMPRII mutant mice (red) had significantly more trials with floating behavior during the water maze compared to control littermates, (B) and significantly more trials with floating across days, which impacted the average swimming speed of the mice, as well as the latency to find the hidden platform. (C) When tested in the PST, the fbΔBMPRII mutants did not have any differences in immobility compared to littermate controls, (D) and did not have any differences in the latency to first bout of immobility. Results reported as mean ± S.E.M. Asterisk indicates *p<0.05, **p<0.005.</p

Loss of Smad4 Modulates Anxiety-Related Behavior in the Elevated Plus Maze.

<p>In the Elevated Plus Maze (A) the fbΔSmad4 mutant mice (blue) spent a significantly increased proportion of time exploring the open-arms, (B) had a significantly increased duration of time on the open-arms, (C) and made significantly more entries onto the open-arms compared to control littermates (white). When closed-arm exploration was examined, (D) the fbΔSmad4 mutant mice spent a significantly reduced proportion of time on the closed-arms, but (E) there was no significant difference in duration of time on the closed-arms, however, (F) the number of closed-arm entries was significantly reduced. Results reported as mean ± S.E.M. Asterisk indicates *p<0.05.</p