Functional connectivity and cognitive changes after donepezil treatment in healthy participants.

RATIONALE: Donepezil is a potent, noncompetitive, reversible, clinically effective acetylcholinesterase inhibitor. The effects of this drug on healthy brains have seldom been investigated. OBJECTIVES: The primary objective of the present study was to identify possible functional connectivity markers of the effect of donepezil in healthy young adult volunteers. METHODS: The study had a double-blind, randomized, crossover design. 30 healthy adult volunteers underwent resting-state MRI scans during 15 days of donepezil or placebo treatment, in accordance with the design. RESULTS: Results showed significant differences in intrinsic functional connectivity between donepezil and placebo, mainly in the right executive control network (RECN). More specifically, we found a decrease in the connectivity of the right inferior parietal node with other RECN nodes. Analysis using the cingulate cortex and parahippocampal regions as seeds also revealed complex modulation of functional connectivity in the donepezil condition. CONCLUSIONS: In conclusion, donepezil treatment for 15 days may result in reorganization of resting-state networks, compared with placebo.

[Biofeedback and drug-resistant epilepsy: back to an earlier treatment?]. / Biofeedback et épilepsie pharmacorésistante : le retour d'une thérapeutique ancienne ?

Biofeedback is a complementary non-pharmacological and non-surgical therapeutic developed over the last thirty years in the management of drug-resistant epilepsy. Biofeedback allows learning cognitive and behavioral strategies via a psychophysiological feedback loop. Firstly, this paper describes the different types of biofeedback protocols used for the treatment of drug-refractory epilepsy and their physiological justifications. Secondly, this paper analyzes the evidence of effectiveness, from a medical point of view, on reducing the numbers of seizures, and from a neurophysiological point of view, on the changing brain activity. Electroencephalography (EEG) biofeedback (neurofeedback) protocol on sensorimotor rhythms (SMR) has been investigated in many studies, the main limitation being small sample sizes and lack of control groups. The newer neurofeedback protocol on slow cortical potential (SCP) and galvanic skin response (GSR) biofeedback protocols have been used in a smaller number of studies. But, these studies are more rigorous with larger sized samples, matched control groups, and attempts to control the placebo effect. These protocols also open the way for innovative neurophysiological researches and may predict a renewal of biofeedback techniques. Biofeedback would have legitimacy in the field of clinical drug-resistant epilepsy at the interface between therapeutic and clinical neurophysiology.

Evaluation of symptomatic drug effects in Alzheimer's disease: strategies for prediction of efficacy in humans.

In chronic diseases such as Alzheimer's disease (AD), the arsenal of biomarkers available to determine the effectiveness of symptomatic treatment is very limited. Interpretation of the results provided in literature is cumbersome and it becomes difficult to predict their standardization to a larger patient population. Indeed, cognitive assessment alone does not appear to have sufficient predictive value of drug efficacy in early clinical development of AD treatment. In recent years, research has contributed to the emergence of new tools to assess brain activity relying on innovative technologies of imaging and electrophysiology. However, the relevance of the use of these newer markers in treatment response assessment is waiting for validation. This review shows how the early clinical assessment of symptomatic drugs could benefit from the inclusion of suitable pharmacodynamic markers. This review also emphasizes the importance of re-evaluating a step-by-step strategy in drug development.