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1.
N Engl J Med ; 380(26): 2497-2505, 2019 06 27.
Article in English | MEDLINE | ID: mdl-31242361

ABSTRACT

BACKGROUND: Brain activation in response to spoken motor commands can be detected by electroencephalography (EEG) in clinically unresponsive patients. The prevalence and prognostic importance of a dissociation between commanded motor behavior and brain activation in the first few days after brain injury are not well understood. METHODS: We studied a prospective, consecutive series of patients in a single intensive care unit who had acute brain injury from a variety of causes and who were unresponsive to spoken commands, including some patients with the ability to localize painful stimuli or to fixate on or track visual stimuli. Machine learning was applied to EEG recordings to detect brain activation in response to commands that patients move their hands. The functional outcome at 12 months was determined with the Glasgow Outcome Scale-Extended (GOS-E; levels range from 1 to 8, with higher levels indicating better outcomes). RESULTS: A total of 16 of 104 unresponsive patients (15%) had brain activation detected by EEG at a median of 4 days after injury. The condition in 8 of these 16 patients (50%) and in 23 of 88 patients (26%) without brain activation improved such that they were able to follow commands before discharge. At 12 months, 7 of 16 patients (44%) with brain activation and 12 of 84 patients (14%) without brain activation had a GOS-E level of 4 or higher, denoting the ability to function independently for 8 hours (odds ratio, 4.6; 95% confidence interval, 1.2 to 17.1). CONCLUSIONS: A dissociation between the absence of behavioral responses to motor commands and the evidence of brain activation in response to these commands in EEG recordings was found in 15% of patients in a consecutive series of patients with acute brain injury. (Supported by the Dana Foundation and the James S. McDonnell Foundation.).


Subject(s)
Brain Injuries/physiopathology , Brain/physiopathology , Cognition/physiology , Electroencephalography , Motor Activity/physiology , Support Vector Machine , Adult , Aged , Area Under Curve , Brain Injuries/psychology , Female , Glasgow Coma Scale , Glasgow Outcome Scale , Humans , Intensive Care Units , Male , Middle Aged , Neurologic Examination , Prognosis , Prospective Studies , Reference Values , Unconsciousness/physiopathology
2.
Article in English | MEDLINE | ID: mdl-15610921

ABSTRACT

Two experiments were designed to evaluate the effects of pairings of ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on ethanol sipper CS-directed drinking in rats. In both experiments, rats were deprived of neither food nor water, and initiation of drinking of unsweetened 3% ethanol was evaluated, as were the effects of increasing the concentration of unsweetened ethanol (3-10%) across sessions. In Experiment 1, Group Paired (n=8) received 35 trials per session wherein the ethanol sipper CS was presented for 10 s immediately prior to 15 s of social opportunity US. All rats initiated sipper CS-directed drinking of 3% ethanol. Increasing the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8%, 10% (vol./vol.)] across sessions induced escalation of daily g/kg ethanol intake. To evaluate the hypothesis that the drinking in Group Paired was due to autoshaping, Experiment 2 included a pseudoconditioning control that received sipper CS and social opportunity US randomly with respect to one another. All rats in Group Paired (n=6) and in Group Random (n=6) initiated sipper CS-directed drinking of 3% ethanol and daily mean g/kg ethanol intake in the two groups was comparable. Also comparable was daily g/kg ethanol intake, which increased for both groups with the availability of higher concentrations of ethanol in the sipper CS, up to a maximum of approximately 0.8 g/kg ethanol intake of 10% ethanol. Results indicate that random presentations of ethanol sipper CS and social opportunity US induced reliable initiation and escalation of ethanol intake, and close temporally contiguous presentations of CS and US did not induce still additional ethanol intake. This may indicate that autoshaping CR performance is not induced by these procedures, or that high levels of ethanol intake induced by factors related to pseudoconditioning produces a ceiling effect. Implications for ethanol drinking in humans are discussed.


Subject(s)
Alcohol Drinking/psychology , Social Environment , Animals , Central Nervous System Depressants/blood , Central Nervous System Depressants/pharmacology , Conditioning, Operant/drug effects , Ethanol/blood , Ethanol/pharmacology , Male , Rats , Rats, Long-Evans , Reinforcement, Psychology , Solutions
3.
Alcohol Alcohol ; 39(3): 197-202, 2004.
Article in English | MEDLINE | ID: mdl-15082456

ABSTRACT

AIMS: The present study evaluates the effects of pairing ethanol sipper conditioned stimulus (CS) with social opportunity unconditioned stimulus (US) on CS-directed ethanol drinking in rats. Subjects were Long-Evans male rats (n = 32) deprived of neither food nor water, and the concentration of unsweetened ethanol (3 to 16%) in the sipper CS was increased across sessions. METHODS: Group Paired/Ethanol (n = 12) received the ethanol sipper CS for 10 s immediately prior to 15 s of social opportunity US. Control groups received water rather than ethanol in the sipper CS (Paired/Water), or ethanol sipper CS and US presentations randomly (Random/Ethanol), or ethanol sipper CS but no social opportunity US (Sipper Only). RESULTS: Mean ethanol intake in the Paired/Ethanol and Random/Ethanol groups exceeded 1.0 g/kg when the sipper CS contained 12%, 14% and 16% ethanol, and higher fluid intakes were observed in the Paired/Ethanol and Random/Ethanol groups than in the Paired/Water and Sipper Only groups. CONCLUSIONS: Social opportunity increased ethanol drinking, and more so than water drinking; however, autoshaping did not induce additional ethanol drinking beyond that observed in random controls.


Subject(s)
Alcohol Drinking/psychology , Conditioning, Operant/drug effects , Ethanol/administration & dosage , Social Environment , Animals , Conditioning, Operant/physiology , Male , Rats , Rats, Long-Evans , Self Administration
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