Lateralisation of language functioning by the Wada procedure and divided visual field presentation of a verbal task

In cases of intractable epilepsy, language and memory functioning in the hemisphere contralateral to the lesion is determined prior to unilateral temporal surgery. Patients with unilateral temporal lobe lesions were assessed using the intracarotid sodium amytal (Wada) procedure to determine the lateralisation of language and memory functioning. They also performed a divided visual field task in which letters were presented in pairs for brief durations on a computer screen in a phonemic matching task. The results showed only moderate agreement between the two methods with regard to identification of the speech-dominant hemisphere, indicating the divided visual field matching paradigm to be unsuitable as a basis for surgical decision-making.     

Fear conditioned changes of heart rate in patients with medial cerebellar lesions

Fear conditioned changes of heart rate and skin conductance responses were investigated in patients with medial cerebellar lesions. A classical conditioning paradigm with a tone as the conditioned stimulus (CS) and an electrical shock as the unconditioned stimulus (US) was tested on five patients with medial cerebellar lesions due to surgery for astrocytoma and five controls. The CS preceded the US by 5900 ms and coterminated with the US. Changes in heart rate and skin conductance responses were obtained as measures for autonomic fear responses. Effects of conditioning were quantified by comparison of the habituation and extinction phases. Controls, but not cerebellar patients, showed a significant decrease of heart rate during fear conditioning. However, there were no significant fear conditioned changes in electrodermal responses in either group. In summary, the medial cerebellum seems to be involved in fear-conditioned bradycardia in humans.     

Eyeblink conditioning indicates cerebellar abnormality in dyslexia

There is increasing evidence that cerebellar deficit may be a causal factor in dyslexia. The cerebellum is considered to be the major structure involved in classical conditioning of the eyeblink response. In a direct test of cerebellar function in learning, 13 dyslexic participants (mean age 19.5 years) and 13 control participants matched for age and IQ undertook an eyeblink conditioning experiment in which for 60 acquisition trials an 800-ms auditory tone (conditioned stimulus, CS) was presented. On 70% of the trials an 80-ms corneal airpuff (unconditioned stimulus, US) was presented 720 ms after the tone onset. The cerebellar deficit hypothesis, uniquely of the causal hypotheses for dyslexia, predicts that the dyslexic participants would show abnormal performance in the incidence and/or timing of the conditioned response (CR) of an eyeblink in response to the tone (and before the US). Three of the dyslexic group showed no conditioning at all. Furthermore, the dyslexic group showed significantly worse "tuning" of the CR timing, together with significantly reduced habituation of the orienting response (OR) to the CS. Individual analyses indicated that 85% of the dyslexic group showed either no conditioning or abnormally poor CR tuning and/or abnormally low OR habituation. It is concluded that the findings provide further converging evidence of cerebellar abnormality in dyslexia and for the first time demonstrate that there are fundamental abnormalities in the way that dyslexic people learn. Equally important, the eye blink conditioning paradigm provides a method of investigating further both homogeneity and heterogeneity in the learning deficits underlying dyslexia and other developmental disorders.     

Effects of lesions of the dorsal noradrenergic bundle on conditioned suppression to a CS and to a contextual background stimulus

The aim of the experiment was to determine whether the dorsal noradrenergic bundle (DB) plays a role in conditioning to context. Rats received either bilateral lesions of the DB by local injection of 6-hydroxydopamine, vehicle injections only, or sham operations. All animals were then trained to barpress for food on a variable interval (VI) schedule. Two 5-min intrusion periods were superimposed on the VI baseline during each session. An 'envelope' stimulus (flashing light) was on throughout each intrusion period. In addition, embedded in the two intrusion periods of each session, there occurred 8 presentations of a 'punctate' conditioned stimulus (CS) (a 15-s clicker), and 8 presentations of a 0.5-s footshock. Within each surgical condition rats were randomly allocated to one of three conditioning groups, receiving 100%, 50% or 0% temporal association between CS and shock. Conditioning to the punctate CS and to the context provided by the envelope stimulus was assessed by the degree of suppression of the barpress response relative to the VI baseline. Responding was most suppressed in the punctate CS in the 100 and 50% conditions, and most suppressed in the envelope stimulus in the 0% condition. DB lesions released response suppression to the punctate CS, had no effect on suppression to the envelope stimulus, and reduced sensitivity to CS-shock probability as measured by response suppression during the punctate CS. These results confirm previous reports that DB lesions alleviate response suppression to shock-associated cues, identify some of the parameters that affect this phenomenon, but fail to support a role for the DB in contextual conditioning.     

Cholinergic system and memory in the rat: effects of chronic ethanol, embryonic basal forebrain brain transplants and excitotoxic lesions of cholinergic basal forebrain projection system

Oral administration of ethanol (20% v/v) to male Sprague-Dawley rats for different periods of time up to 28 weeks resulted in profound reductions of acetylcholine content, in vitro synthesis and release of acetylcholine, choline uptake, activities of choline acetyltransferase, acetylcholinesterase and pyruvate decarboxylase, content of noradrenaline, serotonin and, to a lesser extent, dopamine throughout the brain. Changes were fully and partially reversible by a 4 weeks' ethanol-free period following a treatment of 8 and 18 weeks, respectively. They remained persistent, however, after 28 weeks of treatment. Performance in an eight arm-radial maze revealed a severe impairment in both spatial and non-spatial reference and working memory. A similar pattern of memory impairment was obtained after ibotenate lesion of the cholinergic basal forebrain projection system. In order to test whether this memory impairment depends on cholinergic deafferentation of the cortex, cholinergic-rich fetal basal forebrain cell suspensions were transplanted into cortex, hippocampus or both these sites in ethanol treated rats. Cholinergic-rich transplants, but not cholinergic-poor transplants, were effective in ameliorating impaired memory function and measures of cholinergic activity in the basal forebrain projection system. The behavioural efficacy of the basal forebrain grafts was well correlated with measures of both transplant volume and the degree to which they restored acetylcholine content at the transplant site; these transplants had no effect, however, on brain monoamine levels. The effects of the cholinergic-rich transplants into cortical and hippocampal sites were additive in their amelioration of performance in the radial maze. Similarly, ibotenate lesions of the sites of origin of the cholinergic projections to neocortex (in the region of the nucleus basalis magnocellularis) and hippocampus (the medial septal areas and nucleus of the diagonal band), respectively, were additive in their deleterious effects on maze performance. There were no qualitative differences in the susceptibility of the four different types of memory performance measured (spatial and non-spatial reference and working memory) to the effects of ethanol, ibotenate lesions of the cholinergic projection system, or cholinergic-rich brain tissue transplants. Thus, overall, the results indicate that the forebrain cholinergic system acts as a whole, without major functional differences between the projections originating in the medial septal area/diagonal band complex and the basal nucleus, and that it discharges a very general function in cognitive processes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Polylactide Microparticles Prepared by Double Emulsion/Evaporation Technique. I. Effect of Primary Emulsion Stability

The process of microencapsulation of proteins by double emulsion/evaporation in a matrix of polylactide (PLA) can be divided into three successive steps: first, an aqueous solution of the active compound is emulsified into an organic solution of the hydrophobic coating polymer; second, this primary water-in-oil emulsion (w/o) is dispersed in water with formation of a double water-oil-water emulsion (w/o/w); third, the organic solvent is removed with formation of solid microparticles. This paper focuses on the effect of primary emulsion stability on the morphology and properties of polylactide microparticles loaded with bovine serum albumin (BSA) used as model drug. Depending on the stability of the primary emulsion, the internal structure of microparticles can be changed from a multivesicular to a matrix-like structure. Similarly, the average porosity can be controlled in a range from a few tenths of a micron to ca. 20 to 30 microns. This morphology control could find potential applications not only for the controlled drug delivery but also for the production of microporous particles intended for some specific applications, such as cell culture supports and chromatographic matrices. Although, the interplay of several processing parameters (polymer precipitation rate, polymer coprecipitation with interfacial compounds such as protein or surfactant, stirring rate, . . .) may not be disregarded, this study also indicated that a high loading of a hydrophilic drug can only be expected from a stable primary emulsion. When the stability of the primary emulsion is such as to prevent formation of macropores (>10 µm), the total pore volume is close to that of the originally dispersed aqueous drug solution.     

Memory training in alcoholics

Abstract

Attentional and memory training was administered to 14 alcoholic patients whose performance was compared to that of 15 waiting-list control patients in a residential care centre. Patients had been abstinent for at least 6 weeks. Treatment was carried out over 6 weeks and consisted of 12 training sessions and 6 memory-games sessions. Assessments were carried out before and after treatment and over an equivalent time-span in the control group. The treated groups showed a small but significant improvement in verbal memory, both immediate and delayed, as well as in reproduction of figures.     

Long-term retention of classical eyeblink conditioning in amnesia

The retention of classical eyeblink conditioning was investigated in amnesic patients 10 days and 2 months after original learning. During reacquisition, the first CR occurred earlier and the CR frequencies during the first 10 trials were higher than in the baseline session. The overall CR rates increased significantly across sessions during both acquisition and extinction. The amnesics did not differ from matched controls on any of these effects, although they did not recall previous conditioning sessions and did not become fully aware of CS-US contingencies. The smaller number of electrodermal responses to the CS tone during extinction in the amnesics may relate to their lack of insight into the change in the reinforcement schedule.     

Impaired procedural learning after damage to the left supplementary motor area (SMA).

Two paradigms of procedural learning, serial reaction time and tracking tasks, were given to a patient with damage to the supplementary motor area (SMA) of the left mesiofrontal cortex. This patient exhibited impaired procedural learning during the serial reaction time test and mirror reversed tracking. Unreversed tracking performance was normal. Therefore the SMA--as well as the cerebellum and the striatum--participate in the development of skills requiring internal elaboration of motor behaviour.     

Symptom-Specific Psychophysiological Responses in Chronic Pain Patients.

Symptom-specific psychophysiological responding was assessed in 20 chronic back pain patients, 20 patients suffering from temporomandibular pain and dysfunction, and 20 matched healthy controls. Surface EMG from the lower and upper back, the masseter, and the biceps muscles, and heart rate and skin conductance level were continuously recorded during adaptation, resting baseline, and stressful and neutral imagery phases. Univariate and multivariate analyses of variance were performed on raw data as well as data corrected for autocorrelation. The results showed significantly higher EMG reactivity which was lateralized to the left side at the patients' site of pain but not distal sites. This hyperreactivity was observed only during stressful imagery. The healthy controls displayed a significantly higher response in heart rate, but skin conductance level was not significantly different. The results are interpreted as indicative of idiosyncratic muscular response patterns to personally relevant situations at the site of pain in patients suffering from chronic muscular pain.