Decoding sequence learning from single-trial intracranial EEG in humans.

We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG) after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM) that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep) in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT) using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep) or a later consolidated phase (day 2, after sleep), whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence). Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition) at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

Evidence for validity and reliability of a french version of the FAAM.

BACKGROUND: The Foot and Ankle Ability Measure (FAAM) is a self reported questionnaire for patients with foot and ankle disorders available in English, German, and Persian. This study plans to translate the FAAM from English to French (FAAM-F) and assess the validity and reliability of this new version.METHODS: The FAAM-F Activities of Daily Living (ADL) and sports subscales were completed by 105 French-speaking patients (average age 50.5 years) presenting various chronic foot and ankle disorders. Convergent and divergent validity was assessed by Pearson's correlation coefficients between the FAAM-F subscales and the SF-36 scales: Physical Functioning (PF), Physical Component Summary (PCS), Mental Health (MH) and Mental Component Summary (MCS). Internal consistency was calculated by Cronbach's Alpha (CA). To assess test re-test reliability, 22 patients filled out the questionnaire a second time to estimate minimal detectable changes (MDC) and intraclass correlation coefficients (ICC).RESULTS: Correlations for FAAM-F ADL subscale were 0.85 with PF, 0.81 with PCS, 0.26 with MH, 0.37 with MCS. Correlations for FAAM-F Sports subscale were 0.72 with PF, 0.72 with PCS, 0.21 with MH, 0.29 with MCS. CA estimates were 0.97 for both subscales. Respectively for the ADL and Sports subscales, ICC were 0.97 and 0.94, errors for a single measure were 8 and 10 points at 95% confidence and the MDC values at 95% confidence were 7 and 18 points.CONCLUSION: The FAAM-F is valid and reliable for the self-assessment of physical function in French-speaking patients with a wide range of chronic foot and ankle disorders.

Kernohan's notch and misdiagnosis of disorders of consciousness.

A 69-year-old man presented with a sudden headache followed by unconsciousness. There was no head injury. The Glasgow Coma Scale (GCS) score was 3/15 and there was a left mydriasis, unreactive to light. The CT-scan showed a left acute subdural haematoma causing a remarkable mass effect. A supratentorial hemispheric craniotomy was performed. Nevertheless, after several weeks at the intensive care unit (ICU), the patient was still unresponsive to external stimuli and did not show any motor activity. A comfort care attitude was decided on with the family and the patient was extubated. However, a few days later, the patient subsequently showed a surprisingly favourable course, with improved wakefulness. Indeed, the GCS score improved, and the treatment plan was modified so that the patient benefited from rehabilitation. The MRI showed a right cerebral peduncle lesion, consistent with a Kernohan-Woltman notch phenomenon (KWNP). Six months later, the patient was able to walk and live quite normally.

CO-EXPRESSION OF GCDH AND OAT1 IN NEURONS AND PROXIMAL TUBULE CELLS

Tissue-specific expression studies of Glutaryl-CoA dehydrogenase (Gcdh) in adult rats revealed expression in the whole rat brain, almost exclusively in neurons, and surprisingly high expression in the juxtamedullar cortex of the kidney. The organic anion transporter 1 (OAT1) mediates basolateral uptake of glutarate derivatives from proximal tubule cells and contributes to their renal clearance. In brain, OAT1 is expressed at the choroid plexus, in neurons of cortex and hippocampus. We hypothesized that Gcdh and Oat1 are co-expressed in the same cells in kidney and brain and analyzed their mRNA expression by in situ hybridization on cryosections of adult rat brain, kidney and liver. In brain, Gcdh and Oat1 were found co-expressed in most neurons. Only the Purkinje neurons of the cerebellum were found to be Oat1 negative. In the kidney Gcdh and Oat1 are widely co-expressed with a specific high expression in proximal tubule cells. In conclusion there seems to be a functional coupling of Gcdh and Oat1 on a renal and neuronal level. Further studies are ongoing to confirm these findings in human tissues.

Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement.

BACKGROUND: Measurement of plasma renin is important for the clinical assessment of hypertensive patients. The most common methods for measuring plasma renin are the plasma renin activity (PRA) assay and the renin immunoassay. The clinical application of renin inhibitor therapy has thrown into focus the differences in information provided by activity assays and immunoassays for renin and prorenin measurement and has drawn attention to the need for precautions to ensure their accurate measurement. CONTENT: Renin activity assays and immunoassays provide related but different information. Whereas activity assays measure only active renin, immunoassays measure both active and inhibited renin. Particular care must be taken in the collection and processing of blood samples and in the performance of these assays to avoid errors in renin measurement. Both activity assays and immunoassays are susceptible to renin overestimation due to prorenin activation. In addition, activity assays performed with peptidase inhibitors may overestimate the degree of inhibition of PRA by renin inhibitor therapy. Moreover, immunoassays may overestimate the reactive increase in plasma renin concentration in response to renin inhibitor therapy, owing to the inhibitor promoting conversion of prorenin to an open conformation that is recognized by renin immunoassays. CONCLUSIONS: The successful application of renin assays to patient care requires that the clinician and the clinical chemist understand the information provided by these assays and of the precautions necessary to ensure their accuracy.