Detection of nonlinear interactions of EEG alpha waves in the brain by a new coherence measure and its application to epilepsy and anti-epileptic drug therapy.

EEG and field potential rhythms established in the cortex and thalamus may accommodate the propagation of seizures. This article describes the interaction between thalamus and cortex during pentylenetetrazol (PTZ) seizures in rats with and without prior treatment with ethosuximide (ESM), a well-known antiepileptic drug (AED) that raises the threshold for seizures, was given before PTZ. The AED was given before PTZ convulsant administration. We track this thalamo-cortical association with a novel measure we have called the cross-bicoherence gain, or BISCOH. This quantity allows us to measure the spectral coherence in a purely higher order spectralmethodology. BISCOH is able to track the formation of nonlinearities at specific frequencies in the recorded EEG. BISCOH showed a strong increase in low alpha wave harmonic generationat 10 and 12.5 Hz after ESM treatment (p < 0.02 and p < 0.007, respectively). Conventional coherence failed to show distinctive and significant changes in thalamo-cortical coupling after ESM treatment at those frequencies and instead showed changes at 5 Hz. This rise in cortical rhythms is evidence of harmonic generation or new frequency formation in the thalamo-cortical system withAED therapy. BISCOH could become a powerful tool in unraveling changes in coherence due to neuroelectric modulation resulting from drug treatment or electrical stimulation.

Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus.

OBJECTIVE: Anterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS. METHODS: Anesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS. RESULTS: Latency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control. CONCLUSION: Increased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

Relationship between direct-to-consumer advertising and physician diagnosing and prescribing.

The relationships between direct-to-consumer advertising expenditures and the monthly frequencies of diagnoses and prescriptions written associated with the products advertised are examined. The analyses utilized quasi-experimental time-series techniques. Data from the National Ambulatory Medical Care Survey and Competitive Media Reporting were used to calculate monthly levels of the dependent and independent variables. The dependent variables included monthly frequencies of diagnoses for the products' FDA-approved indications, medications prescribed within the advertised pharmaceutical class, and medications prescribed for the specific advertised agent. The independent variables included monthly expenditures for advertising each pharmaceutical class and each specific agent. Several significant monthly relationships were found. The diagnoses of hyperlipidemia (p = 0.008) and the number of prescriptions written for antilipemics (p = 0.003) were positively associated with the advertising expenditure for antilipemics. The number of prescriptions written for Claritin (p = 0.004) and Zocor (p < 0.001) was positively related to the advertising expenditure for their respective pharmaceutical classes; the amount of prescriptions written for Hismanal (p = 0.007), Seldane (p < 0.001), and Zantac (p = 0.004) was negatively related to the advertising expenditure for their respective pharmaceutical classes. The number of prescriptions written for Claritin (p = 0.005) and Zocor (p < 0.001) was positively related to the advertising expenditure for each specific product; the amount of prescriptions written for Hismanal (p = 0.049) was negatively associated with the amount of money spent specifically advertising the agent. No significant associations were found in antihypertensive drugs and drugs to treat benign prostatic hypertrophy. The results of the analyses suggest that the direct-to-consumer advertising expenditure is associated with physician diagnosing and physician prescribing for certain drugs and drug classes.