Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis.

Complex bimanual motor learning causes specific changes in activation across brain regions. However, there is little information on how motor learning changes the functional connectivity between these regions, and whether this is influenced by different sensory feedback modalities. We applied graph-theoretical network analysis (GTNA) to examine functional networks based on motor-task-related fMRI activations. Two groups learned a complex 90° out-of-phase bimanual coordination pattern, receiving either visual or auditory feedback. 3T fMRI scanning occurred before (day 0) and after (day 5) training. In both groups, improved motor performance coincided with increased functional network connectivity (increased clustering coefficients, higher number of network connections and increased connection strength, and shorter communication distances). Day×feedback interactions were absent but, when examining network metrics across all examined brain regions, the visual group had a marginally better connectivity, higher connection strength, and more direct communication pathways. Removal of feedback had no acute effect on the functional connectivity of the trained networks. Hub analyses showed an importance of specific brain regions not apparent in the standard fMRI analyses. These findings indicate that GTNA can make unique contributions to the examination of functional brain connectivity in motor learning.

Correlations of interictal FDG-PET metabolism and ictal SPECT perfusion changes in human temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: The pathophysiological role of the extensive interictal cerebral hypometabolism in complex partial seizures (CPS) in refractory mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is poorly understood. Our aim was to study ictal-interictal SPECT perfusion versus interictal fluorodeoxyglucose (FDG)-PET metabolic patterns. METHODS: Eleven adults with refractory unilateral mTLE-HS, who were rendered seizure free after epilepsy surgery, were included. All had an interictal FDG-PET and an interictal and ictal perfusion SPECT scan. FDG-PET data were reconstructed using an anatomy-based reconstruction algorithm, which corrected for partial volume effects, and analyzed semi-quantitatively after normalization to white matter activity. Using Statistical Parametric Mapping (SPM), we compared interictal metabolism of the patient group with a control group. We correlated metabolic with ictal perfusion changes in the patient group. RESULTS: Global cerebral grey matter glucose metabolism in patients was decreased 10-25% compared with control subjects. Interictal PET hypometabolism and ictal SPECT hypoperfusion were maximal in the ipsilateral frontal lobe. Ictal frontal lobe hypoperfusion was associated with crossed cerebellar diaschisis. The ipsilateral temporal lobe showed maximal ictal hyperperfusion and interictal hypometabolism, which was relatively mild compared with the degree of hypometabolism affecting the frontal lobes. CONCLUSION: Interictal hypometabolism in mTLE-HS was greatest in the ipsilateral frontal lobe and represented a seizure-related dynamic process in view of further ictal decreases. Crossed cerebellar diaschisis suggested that there is a strong ipsilateral frontal lobe inhibition during CPS. We speculate that surround inhibition in the frontal lobe is a dynamic defense mechanism against seizure propagation, and may be responsible for functional deficits observed in mTLE.

[Low-level resistance to fluoroquinolones conferred by efflux overproduction in Pseudomonas aeruginosa: clinical significance and routine detection]. / Résistance de bas niveau aux fluoroquinolones par surexpression de l'efflux chez Pseudomonas aeruginosa: conséquences thérapeutiques et détection au laboratoire.

The aim of this study was (i) to assess the impact of stable overproduction of efflux systems MexAB-OprM and MexXY-OprM on the bacteriostatic activities of fluoroquinolones in clinical Pseudomonas aeruginosa strains and (ii) to find a convenient test for screening isolates with a low level resistance to fluoroquinolones. The minimal inhibitory concentrations (MICs) of ciprofloxacin and levofloxacin were determined for clinical isolates of P. aeruginosa overexpressing MexAB-OprM or MexXY-OprM. Efflux pumps derepression was associated with a modest two- to fourfold increase in resistance to the tested fluoroquinolones. Clinical significance of low level resistance conferred by the efflux mechanism was evaluated with a Monte Carlo simulation with various fluoroquinolone regimens. With this model, low levels of resistance to ciprofloxacin (MIC > or =0.25 mg/L) or levofloxacin (MIC > or =1 mg/L) such as those due to overproduced MexAB-OprM or MexXY-OprM were predicted to result in poor clinical outcomes. Altogether these data strongly suggest that when derepressed MexAB-OprM or MexXY-OprM provides P. aeruginosa with a resistance that may be sufficient to impair the efficacy of single therapy with highly potent fluoroquinolones such as ciprofloxacin and levofloxacin. Routine detection of clinical strains that displayed low-level resistance to fluoroquinolones with a Mueller Hinton agar containing 0.20 mg/L of ciprofloxacin will help clinician in his therapeutical choice.

Cerebral regions processing first- and higher-order motion in an opposed-direction discrimination task.

Using PET, we studied the processing of different types of motion in an opposed-direction discrimination task. We used first-order motion and two types of higher-order motion (presented as moving gratings with stripes defined by flickering texture and kinetic boundaries, respectively). In these experiments, we found that all types of motion activate a common set of cortical regions when comparing a direction discrimination task to a detection of the dimming of the fixation point. This set includes left hV3A, bilateral hMT/V5+ and regions in the middle occipital gyrus, bilateral activations in the posterior and anterior parts of the intraparietal sulcus, bilateral precentral gyrus, medial frontal cortex and regions in the cerebellum. No significant differences were observed between different types of motion, even at low statistical thresholds. From this we conclude that, under our experimental conditions, the same cerebral regions are involved in the processing of first-order and higher-order motion in an opposed-direction discrimination task.

Near-fatal gamma-butyrolactone intoxication--first report in the UK.

Gamma-hydroxybutyrate (GHB) is a compound used in the treatment of alcohol withdrawal, narcolepsy, and for induction of anaesthesia. It is also contained in many products illegally marketed as "dietary supplements" and is increasingly being recognised as a potential drug of abuse. We report the case of a 44-year-old man who suffered coma and life-threatening respiratory depression following an accidental overdose of the GHB prodrug, gamma-butyrolactone (GBL), contained in a "health drink". He made a full recovery following appropriate supportive treatment. GHB toxicity should be included in the differential diagnosis of patients with altered mental state, particularly where there is a history of recreational drug abuse.

Human brain regions involved in direction discrimination.

To obtain further evidence for the functional specialization and task-dependent processing in the human visual system, we used positron emission tomography to compare regional cerebral blood flow in two direction discrimination tasks and four control tasks. The stimulus configuration, which was identical in all tasks, included the motion of a random dot pattern, dimming of a fixation point, and a tone burst. The discrimination tasks comprised the identification of motion direction and successive direction discrimination. The control tasks were motion detection, dimming detection, tone detection, and passive viewing. There was little difference in the activation patterns evoked by the three detection tasks except for decreased activity in the parietal cortex during the detection of a tone. Thus attention to a nonvisual stimulus modulated different visual cortical regions nonuniformly. Comparison of successive discrimination with motion detection yielded significant activation in the right fusiform gyrus, right lingual gyrus, right frontal operculum, left inferior frontal gyrus, and right thalamus. The fusiform and opercular activation sites persisted even after subtracting direction identification from successive discrimination, indicating their involvement in temporal comparison. Functional magnetic resonance imaging (fMRI) experiments confirmed the weak nature of the activation of human MT/V5 by successive direction discrimination but also indicated the involvement of an inferior satellite of human MT/V5. The fMRI experiments moreover confirmed the involvement of human V3A, lingual, and parietal regions in successive discrimination. Our results provide further evidence for the functional specialization of the human visual system because the cortical regions involved in direction discrimination partially differ from those involved in orientation discrimination. They also support the principle of task-dependent visual processing and indicate that the right fusiform gyrus participates in temporal comparison, irrespective of the stimulus attribute.

Effect of a low-protein diet on chemiluminescence production by leukocytes from uremic patients.

Chemiluminescence (CL) emission from leukocytes was studied in 20 uremic patients after ingestion of opsonized zymosan. CL production was impaired when compared with control groups. Six months after a low-protein, low-phosphorus diet supplemented with essential amino acids and ketoanalogues (SD) was started, a significant improvement in CL production was observed. SD may be expected to decrease the susceptibility of uremic patients to bacterial infections.

[Long-term side-effects of diuretics in the treatment of hypertension (author's transl)]. / Effets secondaires à long terme des diurétiques employés comme hypotenseurs.

The clinical and biochemical side-effects of diuretics administered without potassium supplement were monitored during one year in 58 hypertensive out-patients. The only changes observed were a moderate rise in triglycerides (correlated with weight increase) and in blood glucose. Blood urea, creatinine, potassium, calcium, uric acid and cholesterol remained unchanged. The objections raised against the use of diuretics as anti-hypertensive agents, such as the need for close surveillance of biochemical values and the fear that the beneficial effects on blood pressure would be upset by an increase in other cardiovascular risk factors (some of which are still highly controversial), therefore appear to be unfounded.