Four-Way Wada: SEEG-based mapping with electrical stimulation, high frequency activity, and phase amplitude coupling to complement traditional Wada and functional MRI prior to epilepsy surgery.

Presurgical evaluation of refractory epilepsy involves functional investigations to minimize postoperative deficit. Assessing language and memory is conventionally undertaken using Wada and fMRI, and occasionally supplemented by data from invasive intracranial electroencephalography, such as electrical stimulation, corticortical evoked potentials, mapping of high frequency activity and phase amplitude coupling. We describe the comparative and complementary role of these methods to inform surgical decision-making and functional prognostication. We used Wada paradigm to standardize testing across all modalities. Postoperative neuropsychological testing confirmed deficit predicted based on these methods.

Scoring sleep using respiration and movement-based features.

Rules derived from standard Rechtschaffen and Kales criteria were developed to accurately score rodent sleep into wake, rapid eye movement (REM) sleep, and non-REM sleep using movements detected by non-contact electric field (EF) sensors. • Using this method, rodent sleep can be scored using only respiratory and gross body movements as a validated, non-invasive alternative to electrode techniques. • The methodology and rules established for EF sensor-based sleep scoring were easily learned and implemented. • Examples of expert-scored files are included here to help novice scorers self-train to score sleep. Though validated in mice, sleep scoring using respiratory movements has the potential for application in other species and through other movement-based technologies beyond EF sensors.

Noninvasive three-state sleep-wake staging in mice using electric field sensors.

STUDY OBJECTIVE: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. METHODS: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were attached to the exterior of each chamber to record respiration and other movement simultaneously with EEG, EMG, and video. A sleep-wake scoring method based on EF sensor data was developed with reference to EEG/EMG and then validated by three expert scorers. Additionally, novice scorers without sleep-wake scoring experience were self-trained to score sleep using only the EF sensor data, and results were compared to those from expert scorers. Lastly, ability to capture three-state sleep-wake staging with EF sensors attached to traditional mouse home-cages was tested. RESULTS: EF sensors quantified wake, rapid eye movement (REM) sleep, and non-REM sleep with high agreement (>93%) and comparable inter- and intra-scorer error as EEG/EMG. Novice scorers successfully learned sleep-wake scoring using only EF sensor data and scoring criteria, and achieved high agreement with expert scorers (>91%). When applied to traditional home-cages, EF sensors enabled classification of three-state (wake, NREM and REM) sleep-wake independent of EEG/EMG. CONCLUSIONS: EF sensors score three-state sleep-wake architecture with high agreement to conventional EEG/EMG sleep-wake scoring 1) without invasive surgery, 2) from outside the home-cage, and 3) and without requiring specialized training or equipment. EF sensors provide an alternative method to assess rodent sleep for animal models and research laboratories in which EEG/EMG is not possible or where noninvasive approaches are preferred.

Enhanced Fos expression in glutamic acid decarboxylase immunoreactive neurons of the mouse periaqueductal grey during opioid withdrawal.

Previous studies using c-Fos immunohistochemistry suggest that a sub-population of neurons in the midbrain periaqueductal gray region is activated during opioid withdrawal. The neurochemical identity of these cells is unknown but cellular physiological studies have implicated GABAergic neurons. The present study investigated whether GABAergic neurons are activated in the mouse periaqueductal gray during opioid withdrawal using dual-antibody immunohistochemistry for Fos and glutamic acid decarboxylase. Both chronic opioid treatment and naloxone-precipitated opioid withdrawal increased Fos expression in the periaqueductal gray, with the greatest increase being four-fold in the caudal ventrolateral subdivision following withdrawal. Neurons stained for both Fos and glutamic acid decarboxylase were greatly enhanced in all subdivisions of the periaqueductal gray following withdrawal, particularly in the lateral and ventrolateral divisions where the increase was up to 70-fold. These results suggest that activation of a subpopulation of GABAergic interneurons in the periaqueductal gray plays a role in opioid withdrawal.

Clozapine reverses hyperthermia and sympathetically mediated cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (ecstasy) in rabbits and rats.

Life-threatening hyperthermia occurs in some individuals taking 3,4-methylenedioxymethamphetamine (MDMA, ecstasy). In rabbits, sympathetically mediated vasoconstriction in heat-exchanging cutaneous beds (ear pinnae) contributes to MDMA-elicited hyperthermia. We investigated whether MDMA-elicited cutaneous vasoconstriction and hyperthermia are reversed by clozapine and olanzapine, atypical antipsychotic agents. Ear pinna blood flow and body temperature were measured in conscious rabbits; MDMA (6 mg/kg, i.v.) was administered; and clozapine (0.1-5 mg/kg, i.v.) or olanzapine (0.5 mg/kg, i.v.) was administered 15 min later. One hour after MDMA, temperature was 38.7 +/- 0.5 degrees C in 5 mg/kg clozapine-treated rabbits and 39.0 +/- 0.2 degrees C in olanzapine-treated rabbits, less than untreated animals (41.5 +/- 0.3 degrees C) and unchanged from pre-MDMA values. Ear pinna blood flow increased from the MDMA-induced near zero level within 5 min of clozapine or olanzapine administration. Clozapine-induced temperature and flow responses were dose-dependent. In urethane-anesthetized rabbits, MDMA (6 mg/kg, i.v.) increased ear pinna postganglionic sympathetic nerve discharge to 217 +/- 33% of the pre-MDMA baseline. Five minutes after clozapine (1 mg/kg, i.v.) discharge was reduced to 10 +/- 4% of the MDMA-elicited level. In conscious rats made hyperthermic by MDMA (10 mg/kg, s.c.), body temperature 1 hr after clozapine (3 mg/kg, s.c.) was 36.9 +/- 0.5 degrees C, <38.6 +/- 0.3 degrees C (Ringer's solution-treated) and not different from the pre-MDMA level. One hour after clozapine, rat tail blood flow was 24 +/- 3 cm/sec, greater than both flow in Ringer's solution-treated rats (8 +/- 1 cm/sec) and the pre-MDMA level (17 +/- 1 cm/sec). Clozapine and olanzapine, by interactions with 5-HT receptors or by other mechanisms, could reverse potentially fatal hyperthermia and cutaneous vasoconstriction occurring in some humans after ingestion of MDMA.

Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits.

3,4-Methylenedioxymethamphetamine (MDMA; "Ecstasy") increases body temperature. This process could be associated with increased cutaneous blood flow, as normally occurs with exercise-induced hyperthermia. Alternatively, an MDMA-induced fall in cutaneous blood flow could contribute to the hyperthermia by diminishing normal heat transfer from the body to the environment. We investigated these possibilities by administering MDMA (1.5-6 mg/kg, i.v.) to conscious freely moving rabbits, determining effects on body temperature, cutaneous blood flow (measured by a Doppler ultrasonic probe that was chronically implanted around the ear pinna artery), and other cardiovascular parameters. MDMA caused a dose-dependent increase in body temperature (from 38.3 +/- 0.3 to 41.2 +/- 0.4 degrees C after 6 mg/kg; p < 0.01; n = 5), preceded and accompanied by a dose-dependent cutaneous vasoconstriction (from 29 +/- 6 to 5 +/- 1 cm/sec after 6 mg/kg; p < 0.01; n = 5). MDMA (3 mg/kg) did not change blood flow to the mesenteric vascular bed. Prior unilateral cervical sympathectomy reduced the increase in body temperature elicited by MDMA (6 mg/kg) from 2.0 +/- 0.2 to 1.3 +/- 0.2 degrees C (p < 0.01; n = 5). On the denervated side, ear pinna blood flow after MDMA injection was 13 +/- 3 cm/sec, compared with 3 +/- 1 cm/sec on the sympathetically intact side (p < 0.05; n = 5). Thus, sympathetically mediated cutaneous vasoconstriction is one mechanism whereby MDMA causes hyperthermia. Reversal of cutaneous vasoconstriction by appropriate pharmacological means could be of therapeutic benefit in humans suffering from life-threatening hyperthermia induced by MDMA.

Tail artery blood flow measured by chronically implanted Doppler ultrasonic probes in unrestrained conscious rats.

We describe a surgical procedure for chronically implanting a Doppler ultrasonic probe around the tail artery of the rat to measure phasic flow velocity in the tail artery of the unrestrained conscious rat. The phasic tail flow signal is highly correlated with the simultaneously recorded superior mesenteric flow signal (range 0.70-0.89 in seven rats) during vasoconstriction induced by exposure to formaldehyde vapour. In response to two quick alerting taps on the cage, tail flow velocity fell from 20+/-2 to 7+/-1 cm/s (P<0.01) and mesenteric flow fell from 30+/-5 to 25+/-4 cm/s (P<0.05), with the fall in tail flow being significantly greater than the fall in mesenteric flow (P<0.05, n=7 rats). In anesthetized rats, the phasic tail flow signal was highly correlated with phasic arterial pressure (range 0.71-0.83 in seven rats). The ability to reliably measure phasic arterial tail flow in the conscious unrestrained rat should facilitate experimental studies of brain pathways regulating flow to this principally cutaneous vascular bed in different physiological situations.

[Mammography--watch out for false negatives]. / Mammografi--husk de falskt negative.

Patients with breast tumours should be examined by a combination of physical examination, mammography and fine needle aspiration biopsy. The authors discuss the history of four patients with palpable breast lesions. All of these patients had tumours which had not been discovered by mammography. The diagnosis was delayed 2,11,12 and 12 months respectively. Patients with palpable lesions must not be referred to mammography performed under "screening conditions", but must be examined in a clinical context, preferably by the "triple-test".

A rat model of psychopathology for use in exercise science.

Exploratory behavior, defecation, urination, and a subjective psychophysical rating system were evaluated in a series of four experiments designed to assess rat psychopathology. In every case, individual rats were studied for 5-min periods in an open field consisting of 49 7.5-inch squares. We find that the open-field test can be scored in a highly objective manner (r = 0.93-0.98) by two observers. The reproducibility (r = 0.79-0.85) of the assessment using total squares traversed is not improved using any of the other parameters evaluated. Use of total squares alone was also found to be in agreement with a subjective behavioral rating procedure (r = 0.96-0.98). Fifty percent of overall variability occurs in a rat's first trial. Therefore, the average of total squares traversed on the second and third (not necessarily consecutive) days provides a reliable and objective index of a rat's emotional status. Using this criterion, we find that a random group of 30 adult, male Sprague-Dawley rats exhibit a range of psychopathologies. We propose that this method of assessment provides a rat model of emotionality which should theoretically be modifiable by experimental paradigms involving exercise and pharmacological or dietary intervention.