Blunted midbrain reward activation during smoking withdrawal: a preliminary study.

Introduction: Tobacco smoking is the leading preventable cause of death, causing more than six million deaths annually worldwide, mainly due to cardiovascular disease and cancer. Many habitual smokers try to stop smoking but only about 7% are successful, despite widespread knowledge of the risks. Development of addiction to a range of substances is associated with progressive blunting of brain reward responses and sensitisation of stress responses, as described by the allostasis theory of addiction. There is pre-clinical evidence from rodents for a dramatic decrease in brain reward function during nicotine withdrawal. Methods: Here we tested the hypothesis that habitual smokers would also exhibit blunted reward function during nicotine withdrawal using a decision-making task and fMRI. Results: Our findings supported this hypothesis, with midbrain reward-related responses particularly blunted. We also tested the hypothesis that smokers with a longer duration of smoking would have more pronounced abnormalities. Contrary to expectations, we found that a shorter duration of smoking in younger smokers was associated with the most marked abnormalities, with blunted midbrain reward related activation including the dopaminergic ventral tegmental area. Discussion: Given the substantial mortality associated with smoking, and the small percent of people who manage to achieve sustained abstinence, further translational studies on nicotine addiction mechanisms are indicated.

Abnormal reward valuation and event-related connectivity in unmedicated major depressive disorder.

BACKGROUND: Experience of emotion is closely linked to valuation. Mood can be viewed as a bias to experience positive or negative emotions and abnormally biased subjective reward valuation and cognitions are core characteristics of major depression. METHODS: Thirty-four unmedicated subjects with major depressive disorder and controls estimated the probability that fractal stimuli were associated with reward, based on passive observations, so they could subsequently choose the higher of either their estimated fractal value or an explicitly presented reward probability. Using model-based functional magnetic resonance imaging, we estimated each subject's internal value estimation, with psychophysiological interaction analysis used to examine event-related connectivity, testing hypotheses of abnormal reward valuation and cingulate connectivity in depression. RESULTS: Reward value encoding in the hippocampus and rostral anterior cingulate was abnormal in depression. In addition, abnormal decision-making in depression was associated with increased anterior mid-cingulate activity and a signal in this region encoded the difference between the values of the two options. This localised decision-making and its impairment to the anterior mid-cingulate cortex (aMCC) consistent with theories of cognitive control. Notably, subjects with depression had significantly decreased event-related connectivity between the aMCC and rostral cingulate regions during decision-making, implying impaired communication between the neural substrates of expected value estimation and decision-making in depression. CONCLUSIONS: Our findings support the theory that abnormal neural reward valuation plays a central role in major depressive disorder (MDD). To the extent that emotion reflects valuation, abnormal valuation could explain abnormal emotional experience in MDD, reflect a core pathophysiological process and be a target of treatment.

Severity of negative mood and anxiety symptoms occurring during acute abstinence from tobacco: A systematic review and meta-analysis.

This review was conducted with the following goals: To quantify the severity of mood and anxiety symptoms emerging during acute abstinence from tobacco (1). To explore sex differences related to the experience of specific symptoms (2). To investigate the early time course of symptoms (3). A meta-analysis was performed from 28 studies assessing mood and anxiety symptoms during the earliest phases of tobacco abstinence (up to 24 hrs post-quit) conducted from 1999 to 2019. Results revealed a significant (p < 0.0001) increase in 'anxiety', 'anger/irritability', 'depressed mood /sadness', and composite negative affect ('NA') in the 24 hours following smoking cessation. The largest effect size was detected for 'anxiety' (0.63). A qualitative analysis was performed to investigate sex differences and the time course of the specific symptoms. Results indicated that female smokers may experience worse mood symptoms compared to male smokers and that these symptoms may emerge within 3 hrs post-quit. Smoking cessation programs should implement sex-tailored interventions in order to improve their effectiveness, while future research should focus on alternative methods of nicotine administration.

Chronic tobacco smoking and neuropsychological impairments: A systematic review and meta-analysis.

The link between neuropsychological impairments and chronic tobacco smoking is not clear and in the current literature there is a lack of robust analyses investigating this association. A systematic review of the literature was conducted in order to identify relevant longitudinal and cross-sectional studies conducted from 1946 to 2017. A meta-analysis was performed from 24 studies testing the performance of chronic tobacco smokers compared with non-smokers on neuropsychological tests related to eight different neuropsychological domains. The results revealed a cross-sectional association between neuropsychological impairments and chronic tobacco smoking in cognitive impulsivity, non-planning impulsivity, attention, intelligence, short term memory, long term memory, and cognitive flexibility, with the largest effect size being related to cognitive impulsivity (SDM = 0.881, p <0.005), and the smallest effect size being related to intelligence (SDM = 0.164, p < 0.05) according to Cohen's benchmark criteria. No association was found between chronic smoking and motor impulsivity (SDM = 0.105, p = 0.248). Future research is needed to investigate further this association by focusing on better methodologies and alternative methods for nicotine administration.

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence.

BACKGROUND: Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. METHOD: The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). RESULTS: Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. CONCLUSIONS: Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Neural correlates of social exchanges during the Prisoner's Dilemma game in depression.

BACKGROUND: Depression is a disabling disorder that significantly impacts on the interpersonal functioning of individuals. However, little is known about the neural substrates of such difficulties. In the last few years neuroeconomics, which combines imaging with multiplayer behavioural economic paradigms, has been used to study the neural substrates of normal and abnormal interpersonal interactions. METHOD: This study used functional magnetic resonance imaging to investigate neural activity in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic game, the Prisoner's Dilemma. In this game, the participant and a co-player independently choose either to cooperate or not cooperate with each other. RESULTS: Depressed participants reported higher levels of negative feelings (betrayal, guilt) during the game than did controls. Neural activation was compared between 'imbalanced' events [when one of the players cooperated and the other defected ('CD' and 'DC')] and 'draw' events [when both players either cooperated or defected ('CC' and 'DD')]. Participants preferentially activated the anterior insula and the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and regulation of emotions. Importantly, compared to controls depressed participants showed reduced activation in the left DLPFC, with the extent of signal reduction correlating with increased self-report feelings of guilt associated with DC outcomes. CONCLUSIONS: Our findings suggest that depression is associated with reduced activation of the DLPFC during social events that involve unreciprocated cooperation. This abnormality may underlie anomalies in cognitive control and top-down regulation of emotions during challenging social exchanges.

Abnormal brain responses to social fairness in depression: an fMRI study using the Ultimatum Game.

BACKGROUND: Depression is a prevalent disorder that significantly affects the social functioning and interpersonal relationships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social difficulties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroimaging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates. METHOD: We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players. RESULTS: In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe. CONCLUSIONS: Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie abnormalities in processing information linked to the fairness and rewarding aspects of other people's decisions.

Predictive classification of individual magnetic resonance imaging scans from children and adolescents.

Neuroimaging techniques are increasingly being explored as potential tools for clinical prediction in psychiatry. There are a wide range of approaches which can be applied to make individual predictions for various aspects of disorders such as diagnostic status, symptom severity scores, identification of patients at risk of developing disorders and estimation of the likelihood of response to treatment. This selective review highlights a popular group of pattern recognition techniques, support vector machines (SVMs) for use with structural magnetic resonance imaging scans. First, however, we outline various practical issues, limitations and techniques which need to be considered before SVM's can be applied. We begin with a discussion on the practicalities of scanning children and adolescent participants and the importance of acquiring high quality images. Scan processing required for inter-subject comparisons is then discussed. We then briefly discuss feature selection and other considerations when applying pattern recognition techniques. Finally, SVMs are described and various studies highlighted to indicate the potential of these techniques for child and adolescent psychiatric research.

Connecting the brain and new drug targets for schizophrenia.

One thing we know for certain after decades of functional imaging in schizophrenia is that it is not a disorder that can simply be attributed to circumscribed lesions in the brain. It is, in other words, a disorder of the connectivity of the brain. In this overview, we will consider the power of connectivity analyses of functional MRI (and PET) data as tools for translational neuroscience. We describe the patterns of functional and effective disconnectivity seen in schizophrenia and particular psychotic symptoms, those that appear to be attributable to genetic and/or environmental risk factors for psychosis, the potential of these disconnectivities as trait and state biomarkers, and their sensitivity to drug effects. We conclude that substantial work needs to be done on standardising connectivity analyses across laboratories and that disconnectivity studies should be an integral part of drug discovery programmes.

Abnormal temporal difference reward-learning signals in major depression.

Anhedonia is a core symptom of major depressive disorder (MDD), long thought to be associated with reduced dopaminergic function. However, most antidepressants do not act directly on the dopamine system and all antidepressants have a delayed full therapeutic effect. Recently, it has been proposed that antidepressants fail to alter dopamine function in antidepressant unresponsive MDD. There is compelling evidence that dopamine neurons code a specific phasic (short duration) reward-learning signal, described by temporal difference (TD) theory. There is no current evidence for other neurons coding a TD reward-learning signal, although such evidence may be found in time. The neuronal substrates of the TD signal were not explored in this study. Phasic signals are believed to have quite different properties to tonic (long duration) signals. No studies have investigated phasic reward-learning signals in MDD. Therefore, adults with MDD receiving long-term antidepressant medication, and comparison controls both unmedicated and acutely medicated with the antidepressant citalopram, were scanned using fMRI during a reward-learning task. Three hypotheses were tested: first, patients with MDD have blunted TD reward-learning signals; second, controls given an antidepressant acutely have blunted TD reward-learning signals; third, the extent of alteration in TD signals in major depression correlates with illness severity ratings. The results supported the hypotheses. Patients with MDD had significantly reduced reward-learning signals in many non-brainstem regions: ventral striatum (VS), rostral and dorsal anterior cingulate, retrosplenial cortex (RC), midbrain and hippocampus. However, the TD signal was increased in the brainstem of patients. As predicted, acute antidepressant administration to controls was associated with a blunted TD signal, and the brainstem TD signal was not increased by acute citalopram administration. In a number of regions, the magnitude of the abnormal signals in MDD correlated with illness severity ratings. The findings highlight the importance of phasic reward-learning signals, and are consistent with the hypothesis that antidepressants fail to normalize reward-learning function in antidepressant-unresponsive MDD. Whilst there is evidence that some antidepressants acutely suppress dopamine function, the long-term action of virtually all antidepressants is enhanced dopamine agonist responsiveness. This distinction might help to elucidate the delayed action of antidepressants. Finally, analogous to recent work in schizophrenia, the finding of abnormal phasic reward-learning signals in MDD implies that an integrated understanding of symptoms and treatment mechanisms is possible, spanning physiology, phenomenology and pharmacology.

Blunted response to feedback information in depressive illness.

Depressive illness is associated with sustained widespread cognitive deficits, in addition to repeated experience of distressing emotions. An accepted theory, which broadly accounts for features of the syndrome, and its delayed response to antidepressant medication, is lacking. One possibility, which has received considerable attention, is that depressive illness is associated with a specific underlying deficit: a blunted or impaired ability to respond to feedback information. Unlike healthy controls, if patients with a depressive illness commit an error, they can be at increased risk of committing a subsequent error, possibly due to a failure to adjust performance in order to reduce the risk of error. In some speeded tasks, performance adjustment in humans is reliably associated with trial-to-trial change in reaction times (RTs), such as 'post-error slowing'. Previous studies of abnormal response to feedback have not investigated RT change in any detail. We used a combination of quantitative modelling of RTs and fMRI in 15 patients and 14 matched controls to test the hypothesis that depressive illness was associated with a blunted behavioural and neural response to feedback information during a gambling task. The results supported the hypothesis. Controls responded to negative ('lose') feedback by an increase in RT and activation of the anterior cingulate, the extent of which correlated with RT change. Patients did not significantly increase their RTs, nor activate the anterior cingulate. Controls responded to positive ('win') feedback by a reduction in RT and activation of the ventral striatum, the extent of which correlated with RT change. Patients neither reduced their RT nor activated the ventral striatum. RT adjustment correlated with self-reported anhedonia for both patients and controls. This behavioural deficit, together with its associated pattern of abnormal neural activity, implies that the anterior midline cortical substrate for error correction, which includes projections from the monoamine systems, is dysfunctional in depressive illness. Many studies have reported abnormalities of the medial frontal cortex in depressive illness; however, the mechanism by which antidepressant medication acts via the monoamine systems remains elusive. Our results suggest a direct link between the core subjective symptom of anhedonia, replicated neuropsychological deficits, electrophysiological and imaging abnormalities, and hypothesized dysfunction of the error correction system.

Possible structural abnormality of the brainstem in unipolar depressive illness: a transcranial ultrasound and diffusion tensor magnetic resonance imaging study.

BACKGROUND: Most empirically derived antidepressants increase monoamine levels. The nuclei of cells synthesising these monoamines are located in the brainstem, and projection tracts such as the medial forebrain bundle reach virtually all other brain areas. Two studies of unipolar depressive illness using transcranial ultrasound have reported reduced echogenicity of the brainstem midline in unipolar depressed patients. This may be consistent with disruption of white matter tracts, including the medial forebrain bundle, and it has been suggested that the effect of such disruption could be reversed by antidepressants. OBJECTIVE: To replicate these findings in a group of unipolar depressed patients and controls. METHODS: Fifteen unipolar depressed patients and 15 controls were studied using transcranial ultrasound imaging and diffusion tensor magnetic resonance imaging (DT-MRI). RESULTS: No difference in echogenicity of the brainstem midline of unipolar depressed patients was found. A possible trend (Cohen's d = 0.39) in the direction of previous studies was found. Although the echogenicity of the brainstem midline of the control group was found to be similar to previous reports, there was no reduction in the patient group. Additionally, no structural abnormality of the brainstem was identified using DT-MRI. CONCLUSIONS: While these data do not replicate the findings of previous studies reporting a significant reduction in the echogenicity of the brainstem midline in unipolar depressed patients, the ultrasound investigation indicated that there may be a trend in this direction. Given the importance of identifying the causes of depressive illness, it is important that other groups attempt similar studies.

Neural predictive error signal correlates with depressive illness severity in a game paradigm.

Considerable experimental evidence supports the existence of predictive error signals in various brain regions during associative learning in animals and humans. These regions include the prefrontal cortex, temporal lobe, cerebellum and monoamine systems. Various quantitative theories have been developed to describe behaviour during learning, including Rescorla-Wagner, Temporal Difference and Kalman filter models. These theories may also account for neural error signals. Reviews of imaging studies of depressive illness have consistently implicated the prefrontal and temporal lobes as having abnormal function, and sometimes structure, whilst the monoamine systems are directly influenced by antidepressant medication. It was hypothesised that such abnormalities may be associated with a dysfunction of associative learning that would be reflected by different predictive error signals in depressed patients when compared with healthy controls. This was tested with 30 subjects, 15 with a major depressive illness, using a gambling paradigm and fMRI. Consistent with the hypothesis, depressed patients differed from controls in having an increased error signal. Additionally, for some brain regions, the magnitude of the error signal correlated with Hamilton depression rating of illness severity. Structural equation modelling was used to investigate hypothesised change in effective connectivity between prespecified regions of interest in the limbic and paralimbic system. Again, differences were found that in some cases correlated with illness severity. These results are discussed in the context of quantitative theories of brain function, clinical features of depressive illness and treatments.

Segregation of cognitive and emotional function in the prefrontal cortex: a stereotactic meta-analysis.

Imaging studies of major depressive disorder and schizophrenia strongly implicate the prefrontal cortex. Interpretation of such studies is hindered by the limited knowledge of normal functional segregation. Different anatomical regions may be functionally specialised. Elucidating such specialisation may assist design and interpretation of patient studies. In this meta-analysis, 330 emotion induction and cognitive task studies of normal subjects published over the past decade reporting prefrontal activation have been examined. It was hypothesised that emotion induction would result in inferior medial activation and cognitive tasks dorsolateral activation. A significant difference in the pattern of reported activations was found in keeping with this hypothesis. Estimates of most likely reported activation loci for emotion induction and cognitive task studies have been made. In Montreal Neurological Institute (MNI) stereotactic space, these comprise of +/-5, 46, 18 and +/-5, 28, 31 for the medial prefrontal cortex, and +/-42, 28, -16 and +/-54, 28, 18 for the lateral prefrontal cortex, respectively. Additionally, estimates of the boundaries between emotional and cognitive-processing regions have been made. We restricted the effects of various potential sources of bias on the above estimates by attempting to include all relevant studies and independent selection by both authors of at most two activation loci from each study according to prespecified criteria. Such estimates of most likely reported activation loci may allow improved planning, analysis, and interpretation of imaging studies of psychiatric disorder and of normal function.

Impacts of swine manure pits on groundwater quality.

Manure deep-pits are commonly used to store manure at confined animal feeding operations. However, previous to this study little information had been collected on the impacts of deep-pits on groundwater quality to provide science-based guidance in formulating regulations and waste management strategies that address risks to human health and the environment. Groundwater quality has been monitored since January 1999 at two hog finishing facilities in Illinois that use deep-pit systems for manure storage. Groundwater samples were collected on a monthly basis and analyzed for inorganic and bacteriological constituent concentrations. The two sites are located in areas with geologic environments representing different vulnerabilities for local groundwater contamination. One site is underlain by more than 6 m of clayey silt, and 7-36 m of shale. Concentrations of chloride, ammonium, phosphate, and potassium indicated that local groundwater quality had not been significantly impacted by pit leakage from this facility. Nitrate concentrations were elevated near the pit, often exceeding the 10 mg N/l drinking water standard. Isotopic nitrate signatures suggested that the nitrate was likely derived from soil organic matter and fertilizer applied to adjacent crop fields. At the other site, sandstone is located 4.6-6.1 m below land surface. Chloride concentrations and delta15N and delta15O values of dissolved nitrate indicated that this facility may have limited and localized impacts on groundwater. Other constituents, including ammonia, potassium, phosphate, and sodium were generally at or less than background concentrations. Trace- and heavy-metal concentrations in groundwater samples collected from both facilities were at concentrations less than drinking water standards. The concentration of inorganic constituents in the groundwater would not likely impact human health. Fecal streptococcus bacteria were detected at least once in groundwater from all monitoring wells at both sites. Fecal streptococcus was more common and at greater concentrations than fecal coliform. The microbiological data suggest that filtration of bacteria by soils may not be as effective as commonly assumed. The presence of fecal bacteria in the shallow groundwater may pose a significant threat to human health if the ground water is used for drinking. Both facilities are less than 4 years old and the short-term impacts of these manure storage facilities on groundwater quality have been limited. Continued monitoring of these facilities will determine if they have a long-term impact on groundwater resources.

The NRPB PADC neutron personal dosimetry service.

The UK National Radiological Protection Board has been operating a successful contract neutron personal dosimetry service based on poly-allyl diglycol carbonate (PADC, also known by the trade name CR-39) since 1986, covering about 1500 workers and serving major nuclear sites in the UK and abroad. In that time approximately 100,000 dosemeters have been issued. Since the service was launched, a number of aspects have undergone evolution and it is therefore worthwhile to give an updated summary of how the service operates and performs today. The description covers the choice of plastic and of etching technique, the design of the dosemeter, the features of the automated image analysis, and the characteristics of the control software. Also described are the approaches to calibration and traceability and to compensation for energy and angle dependence, with particular mention of the ability of the service to estimate the quantity Hp(10) in accordance with the requirements of the European Council Directive 96/29/Euratom.

Measurements of the high energy neutron component of cosmic radiation fields in aircraft using etched track dosemeters.

Measurements of the complex cosmic radiation field in aircraft at altitude are made with a passive survey meter comprising routine-use thermoluminescent detectors and etched track detectors. The energy dependence of response of the etched track detectors used to determine the neutron component has been characterized, partly, up to a neutron energy of 180 MeV. The neutron detectors are routinely calibrated in the CERN/EC Reference Field. The 15% determination level for total dose equivalent is 100 microSv. The evidence is that the passive survey meter provides a reliable determination of route dose.

Increased cortical inhibition in depression: a prolonged silent period with transcranial magnetic stimulation (TMS).

BACKGROUND: Motor slowing in depression may be associated with a relative dopaminergic (DA) deficit. Bradykinesia in Parkinson's syndrome is associated with an abnormally short silent period (SP) using transcranial magnetic stimulation (TMS). We hypothesized that depression would also be associated with a short SP. METHODS: Sixteen patients with DSM-IV depression and 19 matched controls participated. SPs were elicited by exercising the contralateral abductor policis brevis (APB) during TMS. RESULTS: The SP was significantly increased in the patient group. No correlation was found between SP and depression score. CONCLUSION: A long SP suggests increased motor cortical inhibition in depression. This finding is inconsistent with the hypothesis of behavioural motor slowing in depression being associated with Parkinsonian-like mechanisms including the dopaminergic deficit. There is a need for studies incorporating larger patient groups to investigate potential correlations between SP and depression indices.

Cognitive brain potentials and regional cerebral blood flow equivalents during two- and three-sound auditory "oddball tasks".

Ten healthy volunteers were examined with single photon emission tomography and 99mTc-exametazime. They were studied on 2 occasions, during a 2- and a 3-sound auditory discrimination (oddball) task. Twenty healthy volunteers were used as controls, studied once at rest. During the 2-tone task there was a bilateral posterior (occipito-) temporal and medial frontal activation, a left pericentral increase, and posterior cingulate suppression. During the 3-sound task activation was again found in posterior (occipito-) temporal, medial frontal cortex, left pericentral, with a small non-significant reduction in posterior cingulate uptake. Compared with the 2-tone task, there was a trend towards higher activity in left medial frontal, right posterior temporal and posterior cingulate cortex in the 3-sound task. P3b amplitudes were negatively correlated with posterior cingulate tracer uptake during both tasks. Positive correlations with P3b amplitudes were found in various frontal and temporal regions. These results are consistent with more invasive localisation studies of P3b. Posterior cingulate cortex appears to be inhibited during the oddball tasks, the more so, the more restricted the range of stimuli, and the greater the task-related recruitment of neurones (P3b amplitude). As expected from its more frontal distribution, P3a amplitude was positively correlated with anterior cingulate tracer uptake, and negatively correlated with temporal cortical activity.

Hand skin temperature changes in patients with chronic liver disease.

Previous studies have shown that changes in the peripheral circulation occur in patients with liver disease. We have investigated the temperature of the hands of 26 patients and 13 controls using a liquid crystal contact thermography system. Significant differences in resting hand temperature and appearance were observed when the patients were categorised according to Child's score. The appearance depended upon the severity of liver disease; Child's A patients have warm hands of normal thermographic appearance; Child's B patients have cold hands with an abnormal thermographic appearance; whilst Child's C patients have warm hands with an abnormal thermographic appearance. After right-hand ice-cold water immersion, right-hand recovery was abnormally slow in Child's B & C groups compared with Child's A patients and controls. In addition, there was left-hand reflex vasoconstriction during the right-hand warm-up period in those with severe liver disease. With regard to autonomic function, no significant difference in right-hand temperature, thermographic appearance or warm-up rate was detected between those with and those without autonomic neuropathy. These results indicate that autonomic nervous system dysfunction is not the predominant cause of these changes.