Effects of feeding on thermoregulatory behaviours and gut blood flow in white sturgeon (Acipenser transmontanus) using biotelemetry in combination with standard techniques.

The effects of thermoregulatory behaviours on gut blood flow in white sturgeon Acipenser transmontanus before and after feeding was studied using a blood flow biotelemetry system in combination with a temperature preference chamber. This is the first study to look at cardiovascular responses to feeding in white sturgeon, and also the first time behavioural tests in fish have been combined with recordings of cardiac output, heart rate, cardiac stroke volume and gut blood flow. The results showed strong correlations between gut blood flow and temperature choice after feeding (R(2)=0.88+/-0.03, 6-8 h postprandially and R(2)=0.89+/-0.04, 8-10 h postprandially) but not prior to feeding (R(2)=0.11+/-0.05). Feeding did not affect the actual temperature preference (18.4+/-0.7 degrees C before feeding, 18.1+/-0.7 degrees C, 6-8 h postprandially and 17.5+/-0.5 degrees C, 8-10 h postprandially). Fish instrumented with a blood flow biotelemetry device, and allowed to move freely in the water, had a significantly lower resting heart rate (37.3+/-0.26 beats min(-1)) compared with the control group that was traditionally instrumented with transit-time blood flow probes and kept in a confined area in accordance with the standard procedure (43.2+/-2.1 beats min(-1)). This study shows, for the first time in fish, the correlation between body temperature and gut blood flow during behavioural thermoregulation.

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms.

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.

Primitive (developmental) reflexes, tardive dyskinesia and intellectual impairment in schizophrenia.

Primitive reflexes, also known as higher cerebral, developmental or release reflexes, are present in foetal and infant life, and are found in certain organic brain diseases. They are normally regarded as non-localising signs of cerebral immaturity or dysfunction which are uncommon in the normal population. The main aims of this study were to find out whether recent reports of an association between primitive reflexes and severity of cognitive impairment in dementia and between primitive reflexes and tardive dyskinesia in schizophrenia could be replicated in a younger population of schizophrenic patients. Forty-eight schizophrenic patients (mean age 51 years) were assessed for primitive reflexes, involuntary movements and cognitive function, and 58% exhibited at least one primitive reflex and 23% at least two. No association was found between primitive reflexes and cognitive impairment or between primitive reflexes and tardive dyskinesia. These results fail to support the hypothesis that the presence of primitive reflexes in some schizophrenic patients indicates a vulnerability to tardive dyskinesia and intellectual decline with advancing age, but long-term prospective studies would be required to test this hypothesis adequately. Nevertheless, these findings support the notion of neurodevelopmental or neurodegenerative brain disease in at least a proportion of patients with schizophrenia.

Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage.

Neuropsychological studies of patients with schizophrenia have consistently identified deficits on tests sensitive to frontal lobe function. One paradigm that has been widely used is that of attentional set-shifting using the Wisconsin Card Sorting Test (WCST). In the present study, patients with chronic schizophrenia and with frontal lobe lesions were assessed on a computerised set-shifting task that provides a componential analysis of the WCST by distinguishing between intra-dimensional and extra-dimensional set-shifting. Out of 51 patients with schizophrenia, those with high IQ (n =24) were compared with patients with lesions in prefrontal cortex (n = 22) and with normal control subjects (n= 18). These three groups were well matched for age, sex and National Adult Reading Test (NART) IQ. The schizophrenic group showed a significantly higher rate of attrition at the intra-dimensional shift stage of learning compared with the other two groups. At the extra-dimensional shift stage, both the schizophrenic and frontal lesioned groups showed greater attrition than controls. Further, patients with schizophrenia who were able to learn the intradimensional reversal stage required more trials and made significantly more errors at that stage than the other two groups. In comparison with high IQ patients with schizophrenia, those with low IQ performed at a lower level but showed a qualitatively similar pattern of performance, providing further evidence that the set-shifting deficits were not simply explained by any global intellectual decline. Patients with schizophrenia who dropped out at the extradimensional shift stage had higher negative symptom scores compared with patients dropping out at previous learning stages, while patients failing at the intra-dimensional shift stage had lower scores for bradyphrenia (slowness of thought). The results suggest that patients with chronic schizophrenia fail to 'learn set' and are impaired at both set-shifting and concept formation. The relevance of these findings to understanding the nature of prefrontal cortical deficits in chronic schizophrenia is discussed. The implication of these findings to the rehabilitation of these patients is considered.

A modified card sorting test sensitive to frontal lobe defects.

Milner's (1963) report of impaired performance on the Wisconsin Card Sorting Test (WCST) in a group of patients with frontal lobe lesions suggested that this test might be a useful one in the investigation of individual patients with suspected brain lesions. However, for many of our older hospital population the WCST was found to be too difficult and distressing, and also the inherent ambiguities associated with certain responses limited the test's usefulness for research purposes. Therefore, a simpler and less ambiguous modification was devised (MCS) and a new method of measuring perseverative errors proposed. In a group of 53 patients with unilateral cerebral lesions, those with frontal lobe lesions performed less well with the MCST and made a higher proportion of perseverative errors than those with lesions elsewhere: there were no laterality effects in either frontal or non-frontal groups. The usefulness of the MCST for detecting frontal lobe lesions in individual patients was established, and the use of cut-off scores briefly discussed.

Dementia: the estimation of premorbid intelligence levels using the New Adult Reading Test.

The NART is a new word-reading test which was specifically designed for use with adults: the 50 words were selected in order to assess familiarity with words rather than the ability to phonetically decode unfamilar words, i.e. for each word intelligent guesswork alone would not result in a correct response. The results from a group of patients with cortical atrophy and a control group demonstrated the superiority of the NART over the best previously available word list (the Schonell GWRT) in enabling higher and more accurate levels of intelligence to be predicted. The evidence implied that the reading of the NART words was not significantly affected by the dementing processes in the patients with cortical atrophy, and therefore that the NART reading score can provide an accurate estimate of premorbid intelligence levels in these patients.

Improved detection of cognitive impairment with the NART: an investigation employing hierarchical discriminant function analysis.

A series of discriminant function analyses was performed to examine the ability of the WAIS and NART to discriminate between healthy subjects and patients with dementia/cortical atrophy. Inclusion of NART estimated IQs in the analyses resulted in significantly greater discrimination than was achieved by WAIS IQs alone.

An investigation of memory functions in dyslexic children.

A detailed investigation of short-term memory storage, long-term memory storage and semantic memory associated with developmental dyslexia is reported. Fifty-one dyslexic and 28 control children were tested, and the following deficits were found amongst the dyslexic children. Short-term memory functions were impaired both with respect to storage capacity and rate of decrement. Long-term memory functions for visual material were normal but verbal long-term memory functions were impaired. There was evidence of difficulties in incorporating new material into semantic memory but the rate of accessing information from within this system appeared to be normal. The significance of the memory deficits is discussed in relation to the hypothesis that childhood dyslexia is a double deficit of the graphemic-phonemic and graphemic-semantic reading routes.

The use of current reading ability in the assessment of dementia.

Word-reading ability and general intelligence level were shown to be highly correlated in a group of normal adults; from this data a regression equation was obtained. Using this regression equation, IQ levels were predicted from reading scores in a group of dementing patients. The evidence strongly suggested that these predicted IQ levels provided close approximations to the premorbid IQ levels. Furthermore, the evidence implied that reading ability is potentially a better indicator of premorbid level of functioning than vocabulary level. The advantages and limitations of using the regression equation in the detection and evaluation of dementia in the individual patient are considered.

Is the concept of frontal-subcortical dementia relevant to schizophrenia?

A syndrome of subcortical dementia has been described in conditions predominantly affecting the basal ganglia or thalamus, structures that have also been implicated in the pathogenesis of schizophrenia. There are similarities between subcortical dementia and the type II syndrome of schizophrenia, in terms of clinical features, pattern of neuropsychological deficits, pathology, biochemistry and data from brain-imaging studies. These similarities raise the possibility that certain schizophrenic symptoms, particularly negative symptoms and disturbance of movement, may reflect subcortical pathology. Neuropsychological deficits of presumed frontal lobe origin have been reported in some schizophrenic subjects. The occurrence of such deficits in a condition in which frontal lobe pathology has not been clearly demonstrated may be explicable in terms of a subcortical deafferentation of the pre-frontal cortex.

Drug-induced changes of adenylate cyclase activity in cells from asthmatic and nonasthmatic subjects.

Monolayers of adherent mononuclear leukocytes prepared from normal subjects and asthmatic children whose bronchodilater therapy did not include sympathomimetic drugs, respond to relatively low concentrations of isoproterenol (ISO) and prostaglandin E1 with increased intracellular cyclic adenosine monophosphate (cAMP) levels. The magnitude of in vitro responses to ISO is decreased by previous contact of the cells with ISO or other, orally effective, adrenergic drugs. The desensitization is rapid, concentration- and time-dependent, and is readily reversible after removal of the desensitizing drug. The phenomenon exhibits pharmacologic specificity. Cells in which the response to restimulation with ISO was decreased exhibited full sensitivity to prostaglandin E1. No differences in these behaviors were detected in cells from normal or asthmatic subjects. The results suggest that earlier observations reporting decreased responses to beta adrenergic stimulation in asthmatics may have been due to the treatment of these patients with sympathomimetic agents and not caused by a disease-related beta adrenergic receptor dysfunction.

Cognitive function and duration of rooflessness in entrants to a hostel for homeless men.

BACKGROUND: Four previous studies of homeless adults have yielded conflicting results regarding the presence of cognitive impairment. METHOD: A consecutive series of 80 roofless entrants to a hostel for homeless men were sampled and 62 (76%) completed a range of assessments, including measures of mental state, cognitive functions and substance use. RESULTS: Estimated premorbid IQ (mean = 96), current IQ (mean = 84) and cognitive speed were significantly lower than the norm. There was a significant IQ drop in all diagnostic groups. IQ drop, but not current IQ, correlated with duration of rooflessness. Those with schizophrenia or alcohol problems were roofless for longest. Alcohol misuse did not correlate with IQ drop, excepting alcohol withdrawal symptoms in those with schizophrenia. CONCLUSION: The hypothesis that low IQ is a risk factor for rooflessness is supported. However, length of rooflessness was more closely related to IQ drop than to current IQ, suggesting that some third factor may be affecting both rooflessness and intellectual functioning. Roofless men with schizophrenia or alcohol problems may be especially at risk of long-term rooflessness.

Electrode effectiveness during transcutaneous motor stimulation.

Four types of electrodes were evaluated for clinical effectiveness in electrically stimulating the quadriceps muscles to gain knee extension for time periods lasting up to 4 days. These electrodes included self-adhering pregelled pads, solvent-activated conductive tape, carbonized conductive silicone rubber, and felt-covered metal plates. The electrodes were compared for ability to produce knee extension torque, electrical impedance, ease of application, durability, comfort, and skin reactivity. Felt-pad electrodes soaked in tap water or saline produced the highest mean torque and lowest electrical impedance, which made them excellent choices for single session stimulation. Carbon-rubber electrodes with either gel produced slightly less torque, slightly higher impedances, and only minor skin reactions. They were relatively easy to apply, and the majority remained intact for the duration of the study period. They were found to be most suitable for prolonged functional electrical stimulation of the quadriceps. Stimulation using pregelled electrodes produced the lowest torque, and they displayed consistently higher electrical impedance. Even though they were easiest to apply and survived better than the other electrodes, they also produced the most skin reactions. The torque and electrical impedance of the activated-tape electrodes were extremely variable and unpredictable, and the process of application was long and involved, making them clinically impractical for either long or short stimulation.

Cognitive functioning and symptomatology in chronic schizophrenia.

Chronic schizophrenic patients in a long stay hospital were found to have low levels of intelligence (mean IQ of 80), which was attributed to the effects of substantial intellectual deterioration on below average pre-morbid levels of functioning. Patients with the lowest IQ scores had the least severe positive symptoms but symptomatology was not related to age or extent of intellectual decline. Speed of functioning was relatively more impaired than level of intellectual functioning, with cognitive speed being more affected than motor speed. The severity of negative but not positive symptoms was significantly related to the severity of bradyphrenia (cognitive slowing), a result which would be consistent with the notion of a subcortical pathology in patients with Type II schizophrenia.

Frontal-striatal cognitive deficits in patients with chronic schizophrenia.

Spatial working memory and planning abilities were assessed in 36 hospitalized patients with chronic schizophrenia, using the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB), and compared with those of normal subjects and patients with neurological disorders (frontal lobe lesions; temporal lobe and amygdalohippocampal lesions; Parkinson's disease), matched for age, sex and National Adult Reading Test IQ. The patients in the group with temporal lobe lesions were unimpaired in their performance on these tasks. Patients with schizophrenia were impaired on visuo-spatial memory span compared with all the other groups, while severity of Parkinson's disease was correlated with the degree of impairment on this task. The patients with schizophrenia and those with frontal lobe lesions were impaired on a 'spatial working memory' task, with increased 'between-search errors'. Patients with Parkinson's disease performed this task poorly compared with the younger control subjects. Patients with schizophrenia were unable to develop a systematic strategy to complete this task, relying instead on a limited visuo-spatial memory span. Higher level planning ability was investigated using the CANTAB 'Tower of London'. All groups were equally able to complete the task. However, the groups of patients with schizophrenia and frontal lobe lesions made fewer perfect solutions and required more moves for completion. Movement times were significantly slower in the schizophrenia group, suggesting impairment in the sensorimotor requirements of the task. The patients with schizophrenia were not impaired in their 'initial thinking' (planning) latencies, but had significantly prolonged 'subsequent thinking' (execution) latencies. This pattern resembled that of the group with frontal lobe lesions and contrasted with the prolonged 'initial thinking' time seen in Parkinson's disease. The results of this study are indicative of an overall deficit of executive functioning in schizophrenia, even greater than that seen in patients with frontal lobe lesions. However, the pattern of results in schizophrenia resembled that seen in patients with lesions of the frontal lobe or with basal ganglia dysfunction, providing support for the notion of a disturbance of frontostriatal circuits in schizophrenia. Our findings also indicate that there is a loss of the normal relationships between different domains of executive function in schizophrenia, with implications for impaired functional connectivity between different regions of the neocortex.

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.