Background. The clinical Global Impression Scale (CGI) is commonly used as a primary outcome measure in studies evaluating the efficacy of treatments for anxiety disorders. The current study evaluated the psychometric properties and predictors of clinicians' ratings on an adapted version of the CGI among individuals with social anxiety disorders.

Method. An independent assessor administered the CGI Severity of Illness and Improvement ratings to 123 patients at baseline and the subset of treated patients again mid- and post-treatment.

Results. Improvement ratings were strongly related to both concurrent Severity of Illness and changes in Severity of Illness ratings from baseline. Additionally, both CGI ratings were positively correlated with both self-report and clinician-administered measures of social anxiety, depression, impairment and quality of life. Measures of social anxiety symptoms accounted for a large portion of the variance in Severity of Illness ratings, with significant additional variance accounted for by measures of impairment and depression. Changes in social anxiety symptoms from baseline accounted for significant variance in Improvement ratings, but no significant additional variance was accounted for by changes in impairment and depressive symptoms.

Conclusions. Our findings support the utility of the CGI as an index of global severity and symptom-specific improvement among individuals with social anxiety disorder.

Background. The paper describes a randomized controlled trial of targeting cognitive behavioural therapy (CBT) during prodromal or early signs of relapse in schizophrenia. We hypothesized that CBT would result in reduced admission and relapse, reduced positive and negative symptoms, and improved social functioning.

Method. A total of 144 participants with schizophrenia or a related disorder were randomized to receive either treatment as usual (TAU) (N=72) or CBT+TAU (N=72). Participants were prospectively followed up between entry and 12 months.

Results. At 12 months, 11 (15·3%) participants in the CBT group were admitted to hospital compared to 19 (26·4%) of the TAU group (hazard ratio=0·53, P=0·10, 95% CI 0·25, 1·10). A total of 13 (18·1%) participants in CBT relapsed compared to 25 (34·7%) in TAU (hazard ratio=0·47, P<0·05, 95% CI 0·24, 0·92). In addition, the CBT group showed significantly greater improvement in positive symptoms, negative symptoms, global psychopathology, performance of independent functions and prosocial activities.

Conclusions. The study provides evidence for the feasibility and effectiveness for targeting CBT on the appearance of early signs of relapse in schizophrenia. The results are discussed in context of the study's methodological limitations.

Background. Dieting in healthy women results in a decrease in the availability of tryptophan (TRP), the amino-acid precursor of serotonin (5-HT), for brain 5-HT synthesis. This is associated with increases in the prolactin response to 5-HT drug challenge suggesting a ‘supersensitivity’ of 5-HT neuroendocrine responses. The aim of the study was to assess whether increased TRP intake during dieting would prevent the changes in TRP availability and 5-HT neuroendocrine function.

Method. Fifty female subjects underwent a 1000 kcal daily diet for 3 weeks. In the final week of the diet subjects were randomly allocated to receive either nutritionally-sourced TRP (1·8 g daily) or placebo in a double-blind, parallel group, design.

Results. TRP supplementation failed to modify the dieting-induced reduction in fasting TRP availability to the brain. However, in contrast to placebo-treated subjects, subjects receiving additional TRP did not show enhanced prolactin responses to intravenous TRP challenge.

Conclusions. The decrease in TRP availability produced by dieting may be due to increased TRP metabolism rather than decreased TRP intake. While TRP treatment did not increase fasting TRP availability it may have modified the effect of dieting on brain 5-HT function. Further studies will be needed to see if this effect of TRP has consequences for the effectiveness of dieting as means of weight control.

Background. It is unclear whether there is an interaction of ageing on the association between major life events and onset of depression.

Method. This was a population-based nested case–control study with linkage of the Danish Psychiatric Central Research Register and the Integrated Database for Longitudinal Labour Market Research. The study includes data on all admissions at psychiatric wards in Denmark from 1981 to 1998 and data on sociodemographic variables and death/suicide of first-degree relatives.

Results. A total of 13006 patients who received a diagnosis of depression at the first ever admission at a psychiatric ward and a gender- and age-matched control group of 260108 subjects were identified. A recent divorce and recent unemployment and suicide of a relative (mother, father, sibling, child, spouse) were associated with increased risk of being admitted for the first time ever at a psychiatric ward with a diagnosis of depression whereas death of a relative by causes other than suicide years had no significant effect. In general, no interaction was found with age with any of the variables, totally, or for men or women, separately.

Conclusions. The susceptibility to major life stressors does not seem to change throughout life.

Background. Trends in deliberate self-harm (DSH) are important because they have implications for hospital services, may indicate levels of psychopathology in the community and future trends in suicide, and can assist in identification of means of suicide prevention.

Method. We have investigated trends in DSH and characteristics of DSH patients between 1990 and 2000 based on data collected through the Oxford Monitoring System for Attempted Suicide.

Results. During the 11-year study period 8590 individuals presented following 13858 DSH episodes. The annual numbers of persons and episodes increased overall by 36·3% and 63·1% respectively. Rates (Oxford City) declined, however, in the final 3 years. There were gender- and age-specific changes, with a rise in DSH rates in males aged [ges ]55 years and in females overall and those aged 15–24 years and 35–54 years. Repetition of DSH increased markedly during the study period. Antidepressant overdoses, especially of SSRIs, increased substantially. Paracetamol overdoses declined towards the end of the study period. Alcohol abuse, use of alcohol in association with DSH, and violence increased, especially in females, and the proportion of patients in current psychiatric care and misusing drugs also rose.

Conclusions. While overall rates of DSH did not increase markedly between 1990 and 2000, substantial changes in the characteristics of the DSH population and a rise in repetition suggest that the challenges facing clinical services in the management of DSH patients have grown.

Background. The General Health Questionnaire (GHQ) is the most popular screening instrument for detecting psychiatric disorders in community samples. Using longitudinal data of a large sample of UK twin pairs, we explored (i) heritabilities of the four scales and the total score; (ii) the genetic stability over time; and (iii) the existence of differential heritable influences at the high (ill) and low (healthy) tail of the distribution.

Method. At baseline we assessed the GHQ in 627 MZ and 1323 DZ female pairs and at a second occasion (3·5 years later) for a small subsample (90 MZ and 270 DZ pairs). Liability threshold models and raw ordinal maximum likelihood were used to estimate twin correlations and to fit longitudinal genetic models. We estimated extreme group heritabilities of the GHQ distribution by using a model-fitting implementation of the DeFries–Fulker regression method for selected twin data.

Results. Heritabilities for Somatic Symptoms, Anxiety, Social Dysfunction, Depression and total score were 0·37, 0·40, 0·20, 0·42 and 0·44, respectively. The contribution of shared genetic factors to the correlations between time points is substantial for the total score (73%). Group heritabilities of 0·48 and 0·43 were estimated for the top and bottom 10% of the total GHQ score distribution, respectively.

Conclusion. The overall heritability of the GHQ as a measure of psychosocial distress was substantial (44%), with all scales having significant additive genetic influences that persisted across time periods. Extreme group analyses suggest that the genetic control of resilience is as important as the genetic control of vulnerability.

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.

Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.

Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.

Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

Background. Counsellors have been employed in general practice with little evidence of effectiveness. This study examined the effectiveness and cost-effectiveness of short-term counselling in general practice for patients with chronic depression either alone or combined with anxiety.

Method. A randomized controlled trial with an economic evaluation was carried out in Derbyshire. One hundred and forty-five patients were recruited at seven GP practices by screening using the Beck Depression Inventory. Both the experimental and control group received routine GP treatment but the experimental group were also referred to the practice counsellor. Depression, anxiety and other mental health symptoms, social and interpersonal functioning and social support were measured at baseline, 6 months and 12 months. Comprehensive costs were also estimated.

Results. There was an overall significant improvement in the actual scores over time, but there were no significant differences between the two groups on any of the measures at either 6 or 12 months. However fewer experimental group patients were still ‘cases’ on the BDI than controls at 12 months. There were no significant differences in the mean total costs, aggregate costs of services, or any service-group costs except for primary care, between the experimental and control groups over time.

Conclusions. This trial demonstrates only very limited evidence of improved outcomes in those referred to counselling and increased primary care treatment costs in the short-term. Stricter referral criteria to exclude the more severely depressed in the group (BDI[ges ]24) might have yielded more conclusive results.

Background. Good communication is a crucial clinical skill. Previous research demonstrated better clinical outcomes when practitioners and patients agree about the nature of patients' core presenting complaints. We investigated the nature of this agreement and its impact on outcome among depressed primary care patients.

Method. We compared presenting problem formulations completed by patients, GPs and therapists in a primary care randomized controlled trial of cognitive-behavioural therapy and non-directive counselling for depression. Participants compiled formulations from a list of 13 potential problems of self-completed questionnaires. Subjects scored at least 14 on the Beck Depression Inventory (BDI) at baseline. Outcome measure for this study included BDI at 4 and 12 months, failure to attend for therapy when referred, dropout from therapy and patient satisfaction.

Results. Among 464 trial patients, 395 received therapy. Patient baseline problem formulations included significantly more items than GPs, who identified significantly more items than therapists. Agreement levels varied according to a range of patient and professional variables. While patients in complete agreement with their therapists about their main problem after assessment had lower average BDI scores at 12 months (9·7 v. 12·8, P=0·03); we found no other significant associations between the extent of agreement and clinical outcome. There were significant (but relatively weak) associations between agreement and aspects of patient satisfaction.

Conclusion. Our results suggest that detailed mutual understanding of the presenting complaints may be less important than agreement that the core problem is psychological, and that referral for psychological therapy is appropriate.

Background. Ghrelin and leptin are endogenous peripheral proteins involved in the regulation of eating behaviour. In particular, ghrelin stimulates hunger and promotes food ingestion, whereas leptin increases satiety and reduces food consumption. Therefore, alterations in the physiology of these peptides may play a role in the pathogenesis of eating disorders such as bulimia nervosa. In the present study, we investigated ghrelin and leptin responses to food ingestion in patients with bulimia nervosa.

Method. Nine symptomatic drug-free bulimic women and 12 age-matched healthy women ingested a meal of 1207 kcal (60% carbohydrates, 23% fat and 17% proteins) at 12.00 a.m. and underwent blood sample collection before and 45, 60, 90, 120 and 180 min after the meal. Plasma levels of ghrelin, leptin, insulin and glucose were measured.

Results. In healthy women, circulating ghrelin exhibited a drastic decrease after the food intake whereas, in bulimic patients, this response was significantly blunted. No difference between the two subjects groups was observed in post-prandial profiles of plasma leptin, insulin and glucose.

Conclusions. The lack of a leptin response to food ingestion, in both bulimic and healthy women, is compatible with the role of this peptide as long-term rather than short-term modulator of eating behaviour. The blunted ghrelin response to food ingestion may support the occurrence in bulimic subjects of an impaired suppression of the drive to eat following a meal. This may have implications for binge-eating.

Background. Because neurocognitive impairments of schizophrenia appear to be ‘rate limiting’ in the acquisition of skills for community functioning, it is important to develop efficacious rehabilitative interventions that can compensate for these impairments. Procedures based on errorless learning may facilitate work rehabilitation because they effectively automate training of work and other skills, thereby reducing the cognitive burden on persons with schizophrenia.

Method. The present study examined the ability of a training method based on errorless learning to compensate for neurocognitive deficits in teaching two entry-level job tasks (index card filing and toilet-tank assembly) to a sample of 54 unemployed, clinically stable schizophrenic and schizoaffective disorder out-patients. Participants were randomly assigned to one of two training groups, errorless learning v. conventional trial-and-error type instruction. Prior to randomization, all subjects were administered a neurocognitive battery. Job task performance was assessed by percentage accuracy scores immediately after training.

Results. For three of the six inter-relationships among neurocognitive functioning and training condition, the pattern was the same: the errorless learning group scored high in job task performance regardless of neurocognitive impairment, whereas the conventional instruction group showed a close correspondence between job task performance and degree of neurocognitive impairment.

Conclusions. These findings support errorless learning as a technique that can compensate for neurocognitive deficits as they relate to the acquisition of new skills and abilities in the work rehabilitation of persons with schizophrenia.

Background. High and low frequency repetititve transcranial magnetic stimulation (rTMS) are both effective in treating depression but have contrary effects on motor cortical activity. This study aimed to understand further the mechanisms of action of high and low frequency rTMS by examining their acute effects on regional cerebral blood flow (rCBF) in depressed patients.

Method. Eighteen depressed subjects underwent brain single photon emission computerized tomography (SPECT) scanning using split-dose 99mTc-HMPAO, and were examined during sham and active rTMS to the left prefrontal cortex, at 15 Hz or 1 Hz (N=9 each). Relative rCBF changes were examined by statistical parametric mapping and by regions of interest analysis.

Results. High (15 Hz) frequency rTMS resulted in relative rCBF increases in the inferior frontal cortices, right dorsomedial frontal cortex, posterior cingulate and parahippocampus. Decreases occurred in the right orbital cortex and subcallosal gyrus, and left uncus. Low (1 Hz) frequency rTMS led to increased relative rCBF in the right anterior cingulate, bilateral parietal cortices and insula and left cerebellum. High frequency rTMS led to an overall increase, whereas low frequency rTMS produced a slight decrease, in the mean relative rCBF in the left dorsolateral prefrontal cortex.

Conclusions. High (15 Hz) and low (1 Hz) frequency rTMS led to different frontal and remote relative rCBF changes, which suggests different neurophysiological and possibly neuropsychiatric consequences of a change in frequency of rTMS.

Background. Individuals with bulimia nervosa report significant symptom fluctuation, and some studies have suggested a premenstrual exacerbation of binge frequency. The purpose of this study is to explore the hormonal correlates of symptom fluctuation in bulimia nervosa.

Method. For five consecutive weeks (one full menstrual cycle), eight women with bulimia nervosa and eight non-eating-disordered control women collected morning saliva samples and recorded several mood characteristics; the bulimic women also recorded binge and purge episodes. Subsequently, salivary cortisol and androgen levels were determined by radioimmunoassay.

Results. Bulimic symptoms were exacerbated in both the mid-luteal and premenstrual phases, when compared with the follicular and ovulatory phases (F(3,21)=3·76, P=0·026; contrast analysis t(7)=3·47, P<0·01). Fluctuation in cortisol was closely correlated with fluctuation of bulimic symptoms, with elevated cortisol secretion following symptom exacerbation (r(24)=0·64, P=0·001).

Conclusions. Bulimic symptom fluctuation appears to be related to two hormonal phenomena – phase of the menstrual cycle and cortisol secretion – with menstrual-cycle phase influencing bulimic symptom severity, and bulimic symptom severity effecting increases in cortisol secretion. Improved understanding of the hormonal causes and consequences of symptom fluctuation may lead to improved psychological and pharmacological treatments for bulimia nervosa.

Background. The role of stress in the onset of chronic fatigue syndrome is unclear. Our objectives in this study were first, to determine the relation between the onset of chronic fatigue syndrome and stressful life events and difficulties. Secondly, we examined the role of a particular type of problem, dilemmas, in the onset of chronic fatigue syndrome.

Method. We used a case–control design with 64 consecutive referrals from an Infectious Diseases/Liaison Psychiatry Fatigue clinic and 64 age- and sex-matched controls from a general practice population control group in Leeds. We had two main outcome measures; the odds ratios of the risk of developing chronic fatigue syndrome after experiencing a severe life event, severe difficulties or both in the year and 3 months preceding onset; and the proportion of subjects in each group who experienced a dilemma prior to onset.

Results. Patients with chronic fatigue syndrome were more likely to experience severe events and difficulties in the 3 months (OR=9, 95% CI 3·2 to 25·1) and year (OR=4·3, 95% CI 1·8 to 10·2) prior to onset of their illness than population controls. In the 3 months prior to onset 19 of the 64 patients (30%) experienced a dilemma compared to none of the controls.

Conclusions. Chronic fatigue syndrome is associated with stressful events and difficulties prior to onset. Those events and difficulties characterized as being dilemmas seem to be particularly important.

Background. Previous twin studies investigating the heritability of schizotypy have often had limited power and have failed to measure the disorganization/social anxiety component.

Method. Seven hundred and thirty-three female twin pairs, drawn from the Institute of Psychiatry Volunteer Twin Register, completed the Oxford–Liverpool Inventory of Feelings and Experiences and the Peters et al. Delusions Inventory. Structural equation modelling was carried out on scores for MZ and DZ twin pairs.

Results. The best fitting models for all scales comprised additive genetic and unique environmental effects. Heritability was estimated at approximately 50% for most scales, although it was lower at 37% for the PDI scale. Multivariate structural equation model fitting revealed a best-fitting model in which additive genetic and unique environmental influences act through a single common pathway for Cognitive Disorganization, Unusual Experiences and the PDI, and through a separate common pathway for Cognitive Disorganization and Introvertive Anhedonia.

Conclusions. The various components of schizotypy are moderately heritable. Multivariate model fitting indicates that at least two latent factor structures are required to account for the covariation between the various components of schizotypy. The positive and negative components of schizotypy are relatively genetically independent, although each in turn may be related to Cognitive Disorganization.

Background. The development and validation of the Social Phobia Diagnostic Questionnaire (SPDQ), a new self-report diagnostic instrument for social phobia is described in three separate studies.

Study 1. The participants were 125 undergraduates seeking help for an anxiety disorder of whom 60 had social phobia. Receiver operating characteristics (ROC) analysis was conducted comparing SPDQ diagnoses and clinician-based Anxiety Disorder Interview Schedule-IV (ADIS-IV) diagnoses of social phobia. Diagnoses made by the SPDQ showed an 85% specificity, an 82% sensitivity and kappa agreement with the ADIS-IV of 0·66.

Study 2. The participants were 462 undergraduates who completed the SPDQ and a battery of additional questionnaires. The SPDQ had good internal consistency (α=0·95), good split-half reliability (r=0·90) and strong convergent and discriminant validity.

Study 3. The participants were 145 undergraduates who completed the SPDQ at two time points separated by 2 weeks as well as several additional questionnaires. Scores on the SAD, FNE and SISST of SPDQ categorized undergraduates were also compared to scores on these measures from 35 clinical community participants to determine the clinical validity of the SPDQ. The SPDQ had strong 2-week test–retest reliability and good convergent and discriminant validity. Undergraduates diagnosed with social phobia by the SPDQ were not significantly different on the SAD, FNE and SISST from the socially phobic community sample, but both groups had significantly higher scores than undergraduates identified by the SPDQ as not meeting criteria for social phobia, demonstrating clinical validity of the SPDQ.

Conclusions. These three studies provide preliminary evidence of the strong psychometric properties of the SPDQ as a measure to identify socially phobic participants.

Background. Chronic fatigue and chronic fatigue syndrome are most often encountered in primary care settings. Given the disabling nature of chronic fatigue it may have a substantial impact on service use and costs as well as on employment. This study estimates this impact.

Method. Patients presenting to general practitioners with unexplained chronic fatigue were recruited to the study. Service use over a 3 month period was measured and lost employment recorded. These data were used to estimate economic costs. Patients with chronic fatigue syndrome were compared to patients with only chronic fatigue using a multiple regression model with sample differences controlled.

Results. The mean total cost of services and lost employment across the sample was £1906 for the 3-month period with formal services accounting for 9·3% of this figure. Service use was higher for patients with chronic fatigue syndrome compared to those with chronic fatigue alone. Total 3-month costs were on average higher for chronic fatigue syndrome (£3515 v. £1176) but when sample differences were taken account of the mean difference was reduced to £1406 (P=0·086). Over 90% of the cost was accounted for by care provided by friends and family members and by lost employment. Patients with dependants had significantly higher costs than those with none and costs were also significantly higher for greater levels of functional impairment.

Conclusion. Chronic fatigue imposes substantial economic costs on society, mainly in the form of informal care and lost employment. Treatments need to be developed which recognize these impacts.

Background. While psychiatric epidemiology often focuses on the causal relationship between environmental adversity and the individual (e.g. environment to person), individuals probably make important contributions to the quality of their environments (person to environment).

Method. In a population based sample of >7000 male and female adult twins, we examined the relationship between the personality trait of neuroticism (N) and the occurrence of stressful life events (SLEs) and the quality of interpersonal relationships (IPR). We compared the magnitude of the prediction of twin 1's self-reported SLEs and IPR from: (i) twin 1's self-reported N; (ii) twin 2's report of twin 1's N; and (iii) twin 2's report of twin 2's N in monozygotic pairs.

Results. In our entire sample, self-report N significantly predicted the occurrence of most SLEs and all dimensions of IPR. Using the co-twin's report of N produced associations that were of the same magnitude for SLEs and modestly weaker for IPR. In monozygotic pairs, the level of N in one twin predicted SLEs and IPR in the co-twin at levels similar to those found for the co-twin's report of N. Repeating these analyses with a prospective subsample produced similar results.

Conclusion. An individual's personality in adulthood plays a significant role in influencing exposure to some forms of environmental adversity and this association is not the result of reporting bias. Furthermore, this relationship is largely mediated by a common set of familial factors that predispose both to a ‘difficult’ temperament and to environmental adversity. Developmental models of psychiatric illness should adopt an interactionist view of individuals and their environment (person and environment).

Background. We aimed to examine factors that influence vulnerability/resiliency of depressed young people to suicidal ideation and suicide attempt.

Method. Data were gathered during a 21-year longitudinal study of a birth cohort of 1265 New Zealand young people. Measures included: suicide attempt; suicidal ideation; major depression; childhood, family, individual and peer factors.

Results. Young people who developed major depression had increased rates of suicidal ideation (OR=5·4; 95% CI 4·5–6·6) and suicide attempt (OR=12·1; 95% CI 7·9–18·5). However, the majority of depressed young people did not develop suicidal ideation or make suicide attempts, suggesting that additional factors influence vulnerability or resiliency to suicidal responses. Factors influencing resiliency/vulnerability to suicidal responses included: family history of suicide; childhood sexual abuse; neuroticism; novelty seeking; self-esteem; peer affiliations; and school achievement. These factors operated in the same way to influence vulnerability/resiliency among those depressed and those not depressed.

Conclusions. Vulnerability/resiliency to suicidal responses among those depressed (and those not depressed) is influenced by an accumulation of factors including: family history of suicide, childhood sexual abuse, personality factors, peer affiliations and school success. Positive configurations of these factors confer increased resiliency, whereas negative configurations increase vulnerability.

Background. There is considerable variability between patients in their expression of the diverse range of symptoms encompassed by the syndrome of schizophrenia, which may modulate functional activation to cognitive processing.

Method. Here we investigate associations between schizophrenic subsyndrome scores, identified by factor analysis, and experimentally controlled brain activation. Five factors were defined by rotated principal components analysis of PANSS rating scale measurements in 100 patients with schizophrenia. A subsample of 30 patients and a group of 27 comparison subjects were studied using functional magnetic resonance imaging (fMRI) during the performance of two periodically designed cognitive activation experiments: verbal working memory and psychomotor sequencing.

Results. Factor analysis replicated the five dimensions consistently reported. Within the patient group, power of activation by working memory was negatively associated with global symptom severity in left lingual and temporo-parietal cortices; negatively associated with positive subsyndrome scores in left inferior frontal and superior temporal cortices and basal ganglia; and positively associated with negative subsyndrome scores in lateral and medial premotor cortex. No relationship was observed between subsyndrome scores and functional activation during the motor task. Between-group comparisons demonstrated reduced power of response to the working memory task by patients in bilateral dorsolateral prefrontal and left pre- and post-central cortices.

Conclusions. In this study we observed task-specific modulation of functional response associated with symptom expression in schizophrenia. Our findings are compatible with previous empirical findings and theoretical conceptualization of human brain function, in terms of capacity constraints on activation in the face of competing demands from pathological and task-related cognitive activity.