Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).     

Combined tool approach is 100% successful for emergency football face mask removal.

OBJECTIVE: To compare effectiveness of two techniques for removing football face masks: cutting loop straps [cutting tool: FMXtractor (FMX)] or removing screws with a cordless screwdriver and using the FMXtractor as needed for failed removals [combined tool (CT)]. Null hypotheses: no differences in face mask removal success, removal time or difficulty between techniques or helmet characteristics. DESIGN: Retrospective, cross-sectional. SETTING: NOCSAE-certified helmet reconditioning plants. PARTICIPANTS: 600 used high school helmets. INTERVENTIONS: Face mask removal attempted with two techniques. MAIN OUTCOME MEASUREMENTS: Success, removal time, rating of perceived exertion (RPE). RESULTS: Both techniques were effective [CT 100% (300/300); FMX 99.4% (298/300)]. Use of the backup FMXtractor in CT trials was required in 19% of trials. There was significantly (P<0.001) less call for the backup tool in helmets with silver screws (6%) than in helmets with other screws (31%). Mean removal time was 44.51+/-18.79s (CT: 37.84+/-15.37s, FMX: 51.21+/-19.54s; P<0.001). RPE was different between techniques (CT: 1.83+/-1.20, FMX: 3.11+/-1.27; P<0.001). Removal from helmets with silver screws was faster (Silver=33.38+/-11.03, Others=42.18+/-17.64; P<0.001) and easier (Silver=1.42+/-0.89, Other=2.23+/-1.33; P<0.001). CONCLUSIONS: CT was faster and easier than FMX. Most CT trials were completed with the screwdriver alone; helmets with silver screws had 94% screwdriver success. Clinically, these findings are important because this and other research shows that compared to removal with cutting tools, screwdriver removal decreases time, difficulty and helmet movement (reducing potential for iatrogenic injury). The combined-tool approach captures benefits of the screwdriver while offering a contingency for screw removal failure. Teams should use degradation-resistant screws. CLINICAL RELEVANCE: Sports medicine professionals must be prepared with appropriate tools and techniques to efficiently remove the face mask from an injured football player's helmet.     

Gender-specific response to isoflurane preconditioning in focal cerebral ischemia.

Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1(+/+) and Akt1(-/-) mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.     

Does an oral appliance reduce palatal flutter and tongue base snoring?

OBJECTIVES: Oral appliances are designed to treat snoring and sleep apnea by advancing the mandible and tongue. We test the hypothesis that an oral appliance affects palatal snoring as well as tongue base obstruction. METHODS: Prospective observational cohort study. Sixty patients with a chief complaint of snoring with or without apnea were enrolled. Each patient underwent a home sleep test followed by 3 weeks sleeping with an oral appliance. Each patient then underwent a repeat home sleep test while using the device. RESULTS: There was a statistically significant improvement in the snores per hour (P = 0.0005), the maximum snoring loudness (P = 0.0001), average snoring loudness (P = 0.00001), and the percentage of palatal snoring (P = 0.0007). There was also a significant decrease in oxygen desaturation events (P = 0.003). CONCLUSIONS: This study suggests oral appliances may be effective treatment for both palatal and tongue base snoring.     

Band-pass response properties of rat SI neurons

Rats typically employ 4- to 12-Hz "whisking" movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates /=3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0-35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (>15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5-10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.     

Behavioural strategies used by the hookworms Necator americanus and Ancylostoma duodenale to find, recognize and invade the human host

The infective third-stage larvae of the hookworms Necator americanus and Ancylostoma duodenale infect their human hosts by active skin invasion, but A. duodenale is in addition capable of oral infection. The behaviour of the larvae when crawling on surfaces has already been described. Here we analyse in various in vitro systems the other behavioural invasion phases: activation, penetration, and orientation within the host. The larvae normally remained in a motionless, energy-saving, resting posture. An activation to sinusoidal locomotion was stimulated in both species by similar cues such as touch, vibration, water currents, heat, light, and chemicals. Human breath in addition stimulated searching and waving (nictating) behaviour, which facilitates a change-over to the host. Activating cues in air streams were warmth and moisture; CO₂ activated only in combination with warmth and/or moisture. Penetration behaviour in both species was stimulated by warmth and skin extracts. The stimulating components of skin extracts were fatty acids, but their stimulating characteristics differed from those inducing schistosome cercarial skin penetration. After penetration into agar substrates, both species showed thermo-orientation, but only A. duodenale followed gradients of serum. The directing serum cues were not amino acids and glucose (the supposed cues for schistosome blood vessel localization), but Ringers solution attracted the larvae. The host-finding and host-invasion behaviour of both hookworm species is well adapted to the invasion of the human skin, and there seems to be no particular adaptation of A. duodenale behaviour to the oral infection mode. Hookworm host-finding behaviour is not as complex as that of schistosome cercariae but seems well adapted to the ecological conditions in the transmission sites.     

Improving delivery of hydrophobic drugs from hydrogels through cyclodextrins

A simple and effective technique of improving delivery of hydrophobic drugs from swellable systems is presented. Conventional methods of drug loading in hydrogel systems are limited by the characteristics of the pharmacological agent. The approach we present uses complexants to modulate drug release. Crosslinked poly(ethylene glycol) (PEG) hydrogels were synthesized, characterized, and used for vascular applications. The release of cyclosporine (CyA) from PEG hydrogels is significantly altered by the sterilization techniques. It was hypothesized that the release of CyA from PEG hydrogels can be modulated by using complexants. A cyclodextrin-CyA complex solution was prepared and used for drug loading. The sterilized PEG hydrogels that were loaded using the cyclodextrin-CyA complex solution had favorable release characteristics compared with the release from PEG hydrogels that were loaded using the conventional technique. Hence, drug release from swellable systems can be tailored by the application of this strategy.