The cerebellum's role in reading: a functional MR imaging study

BACKGROUND AND PURPOSE: Long considered to have a role limited largely to motor-related functions, the cerebellum has recently been implicated as being involved in both perceptual and cognitive processes. Our purpose was to determine whether cerebellar activation occurs during cognitive tasks that differentially engage the component processes of word identification in reading. METHODS: Forty-two neurologically normal adults underwent functional MR imaging of the cerebellum with a gradient-echo echo-planar technique while performing tasks designed to study the cognitive processing used in reading. A standard levels-of-processing paradigm was used. Participants were asked to determine whether pairs of words were written in the same case (orthographic processing), whether pairs of words and non-words rhymed with each other, respectively (phonologic assembly), and whether pairs of words belonged to the same category (semantic processing). Composite maps were generated from a general linear model based on a randomization of statistical parametric maps. RESULTS: During phonologic assembly, cerebellar activation was observed in the middle and posterior aspects of the posterior superior fissure and adjacent simple lobule and semilunar lobule bilaterally and in posterior aspects of the simple lobule, superior semilunar lobule, and inferior semilunar lobule bilaterally. Semantic processing, however, resulted in activation in the deep nuclear region on the right and in the inferior vermis, in addition to posterior areas active in phonologic assembly, including the simple, superior semilunar, and inferior semilunar lobules. CONCLUSION: The cerebellum is engaged during reading and differentially activates in response to phonologic and semantic tasks. These results indicate that the cerebellum contributes to the cognitive processes integral to reading.     

Functional organization of surgically created visual circuits

Lesions of cerebral targets of the retina in newborn hamsters, when combined with transection of lemniscal pathways to the primary auditory or somatosensory thalamic nuclei or the secondary thalamic visual nucleus, can induce the formation of permanent retinal projections to the deafferented non-visual structures. These projections are retinotopically organized and form functional synapses. Consequently, neurons in the auditory or somatosensory cortices, which normally are not driven by visual stimuli, become visually responsive and have receptive field properties that ressemble, in several important ways, those of neurons in the visual cortex of normal animals. The surgically-induced retinothalamo-cortical pathways can mediate visually guided behaviors whose normal substrate, the pathway from the retina to the primary visual cortex via the thalamic dorsal lateral geniculate nucleus, is missing.     

Thermogenic effects of sibutramine and its metabolites

1. The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. 2. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg(-1) of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5-1.0 degrees C) in body temperature. 3. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). 4. Combined high, non-selective doses (20 mg kg(-1)) of the beta-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, beta1-adrenoceptor-selective (atenolol) or beta2-adrenoceptor-selective (ICI 118551) doses (1 mg kg(-1)). 5. The ganglionic blocking agent, chlorisondamine (15 mg kg(-1)), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the beta3-adrenoceptor-selective agonist BRL 35135. 6. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg(-1)) that had no effect on VO2 when injected individually. 7. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via beta3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent.     

Noise in the signal-averaged electrocardiogram and accuracy for identification of patients with sustained monomorphic ventricular tachycardia after myocardial infarction

Late potentials are detected at various noise levels in clinicalstudies. The aim of this study was, in a case-control design,to assess the effect of residual noise level on the identificationof patients with sustained monomorphic ventncular tachycardiaafter myocardial infarction. Electrocardiograms from 16 patientswith prior myocardial infarction and documented sustained monomorphicventricular tachycardia and 41 patients with prior myocardialinfarction and without ventncular tachycardia, were analysedby two signal averaging procedures to noise level 0·2and 0·4 µV Standard time domain parameters weremeasured. Two definitions of late potential were analysed: (1)if any two of the following criteria were present (signal-averagedQRS duration >120 ms, late potential duration >40 ms,and root-mean-square voltage of the terminal 40 ms of the filteredQRS <25µV); or (2) if the signal-averaged QRS duration120 ms. Overall the signal-averaged electrocardiogram performedbetter at noise level 0·4µV compared to noise level0·2µV with respect to identification of patientswith or without ventricular tachycardia after myocordial infarction.Reducing noise level from 0·4 to 0·2 µVincreased the sensitivity, but the consequence was a substantialdecrease in specificity. Our data indicate that when a highsensitivity is the goal, the definition based only on signal-averagedQRS duration 120 ms should be applied; sensitivity was 88% andspecificity 59% at noise level 0·4 µV. If a highspecificity is the goal, the definition should be based on thedefinition with two abnormal parameters; sensitivity was 69%and specificity 68% at noise level 0·4µV.     

Enteral nutrition in malnourished patients with hepatic cirrhosis and acute encephalopathy

Ten patients with histologically proven cirrhosis, admitted in grade I to II acute hepatic coma, received in addition to a standard dietary protein free "anticoma" regime, a continuous nasogastric infusion of a branched-chain amino acid enriched chemically defined enteral diet (Hepaticaid) containing an equivalent of 70 g protein/day for a mean of 7.3 days (range 3-23). No complications of therapy were observed and, specifically, the use of fine bore tubes did not provoke variceal hemorrhage. Overall positive nitrogen balance (4.3 +/- 1.7 g N/day) was observed in patients fed 7 or more days. Improvement to coma grade 0 was seen in all patients save one, who died from hepatorenal failure. While serum ammonia levels remained elevated during the study period, there was a significant increase in the branched-chain/aromatic ratio (p less than 0.01) as plasma branched-chain amino acids rose (p less than 0.05) and tyrosine levels fell (p less than 0.05).     

Immune-mediated arrest and reversal of established visceral metastases in athymic mice.

The metastasizing MDAY-D2 tumor of DBA/2 mice disseminates in BALB/c allogeneic athymic nude (nu/nu) mice in a manner identical to that observed in the syngeneic host. Both the kinetics and organ distribution pattern of metastases from s.c. implants of MDAY-D2 are routinely predictable at any given tumor dose. BALB/c heterozygote (nu/+) litter-mates reject MDAY-D2 grafts on the basis of the multiple minor histocompatibility differences that exist between DBA/2 and BALB/c mice. The in vitro cell-mediated cytotoxic response detected in tumor-bearing BALB/c nu/+ mice is "low grade" (isotope release is approximately 40 to 50% by 24-hr 111-indium-8-hydroxyquinoline assay and approximately 6 to 8% by 6-hr 51Cr assay) and yet correlates directly with tumor rejection. BALB/c nu/nu mice can be protected against MDAY-D2 by previous reconstitution with lymphoid cells from normal or MDAY-D2-sensitized BALB/c nu/+ mice. In addition, surgically documented, established visceral metastases in BALB/c nu/nu mice can be arrested and regressed by the adoptive transfer of MDAY-D2-sensitized BALB/c nu/+ spleen cells. This represents one of the few models where established metastases have been immunotherapeutically regressed. As such, the MDAY-D2 BALB/c nu/nu mouse model offers unique advantages for studying the role of the immune system in regulating the metastatic process.