Jane H. Powell

White Matter Damage and Cognitive Impairment after Traumatic Brain Injury.

White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to be complex. We applied a flexible technique—tract-based spatial statistics—to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute/chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions.

Motivational deficits after brain injury: effects of bromocriptine in 11 patients.

OBJECTIVE: To test the hypothesis that treatment with bromocriptine would ameliorate deficits in clinical motivation, responsiveness to reward, and frontal cognitive function after brain injury. METHOD: An open trial in six men and five women who had had either traumatic brain injury or subarachnoid haemorrhage between two months and five years previously. After repeated baseline assessments, bromocriptine was given in gradually increasing doses. Assessments were repeated at increasing doses, during maintenance, and after withdrawal. Novel structured instruments for quantifying motivation were developed; measures of anxiety and depression, and cognitive tests sensitive to motivation or frontal lobe involvement were also given. RESULTS: Bromocriptine treatment was followed by improved scores on all measures other than mood. Improvement was maintained after bromocriptine withdrawal in eight of the patients. CONCLUSION: Poor motivation in patients with brain injury may result from dysfunction in the mesolimbic/mesocortical dopaminergic circuitry, giving rise to associated deficiencies in reward responsiveness and frontal cognitive function.

Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis

Objectives: To investigate (1) the prevalence of various aspects of cognitive and psychosocial dysfunction, including post-traumatic stress symptoms, over nine months after subarachnoid haemorrhage (SAH); (2) whether SAH is preceded by increased life stress; (3) to what extent adverse outcomes may be predicted from preillness life stress, early neurological impairment, age, and sex; and (4) relations between emotional and functional outcomes. Methods: 52 patients with good neurological recovery after surgery for SAH were each matched for age, sex, and occupation with a healthy control participant. SAH patients were assessed three and nine months postdischarge on measures of cognitive functioning, mood, and social functioning. Objective stressors and subjective life change during the preceding year were rated retrospectively. Controls completed measures of mood and social functioning once only. Results: Compared with controls, SAH patients showed increased mood disturbance, subtle cognitive impairment, and abnormally low independence and participation on measures of social functioning. 60% showed clinically significant post-traumatic stress symptomatology (intrusive thoughts or avoidance of reminders) at three months and 30% at nine months. Independence in activities of daily living was greatly reduced in half to a third of the sample at both three and nine months. Productive employment was below the 10th percentile of the control group for 75% of patients at three months and for 56% at nine months; this outcome could not be predicted from selected demographic, premorbid, or clinical variables but dependence on others for organisational activities was predicted by impaired prose recall. Mood at nine months was strongly predicted by prior mental health problems, poor physical health, dysphasia, and impaired prose recall at three months. There was no evidence of an abnormally high level of stressful life events in the year before SAH, although patients rated their subjective level of stress in this period slightly more highly than did the control participants. Conclusions: These findings highlight the need for structured support and treatment after surgery for SAH to reduce persisting mood disturbance and increase independence and participation.

Psychosocial outcomes at 18 months after good neurological recovery from aneurysmal subarachnoid haemorrhage

Objectives: To evaluate functioning, 18 months after surgery, of 49 patients with good neurological recovery following aneurysmal subarachnoid haemorrhage (SAH), and to determine the extent of any improvements in disturbances of mood, cognitive functioning, and levels of activity and participation previously observed at 9 month follow up. Methods: SAH patients, matched for age, gender, and occupation with healthy control participants, completely quantitative measures of mood (HADS, FIES, BDI) and activity/participation (BICRO-39 scales), and a brief cognitive assessment battery (verbal fluency, digit span, prose recall). Controls completed the HADS and the BICRO-39. Results: Patients showed some recovery of cognitive functioning, though impairments of prose recall persisted. Anxiety and depression symptoms were higher in patients than in controls, but fewer than 20% scored in the clinical range on any questionnaires except for RIES-Intrusive thoughts (22%); only three showed signs of full blown post-traumatic stress disorder. Almost half showed elevated dependence on others for domestic activities and organisation and abnormally low levels of employment. Very little variance in outcome was predicted by demographic variables, neurological or cognitive impairment, prior life stress, or mood. However, levels of social activity and self-organisation were related to persisting fatigue. Conclusions: The observed decline in intrusive thoughts and avoidance over time is consistent with that seen after life threatening illness or trauma. The persistent reductions in independence and levels of employment may in some cases reflect considered lifestyle adjustments rather than adverse and unwanted changes but in others indicate a need for focused rehabilitation.

Quality of Life after Brain Injury (QOLIBRI): Scale Validity and Correlates of Quality of Life

The QOLIBRI (Quality of Life after Brain Injury) is a novel health-related quality-of-life (HRQoL) instrument specifically developed for traumatic brain injury (TBI). It provides a profile of HRQoL in six domains together with an overall score. Scale validity and factors associated with HRQoL were investigated in a multi-center international study. A total of 795 adults with brain injury were studied from 3 months to 15 years post-injury. The majority of participants (58%) had severe injuries as assessed by 24-h worst Glasgow Coma Scale (GCS) score. Systematic relationships were observed between the QOLIBRI and the Glasgow Outcome Scale-Extended (GOSE), Hospital Anxiety and Depression Scale (HADS), and SF-36. Within each scale patients with disability reported having low HRQoL in two to three times as many areas as those who had made a good recovery. The main correlates of the total QOLIBRI score were emotional state (HADS depression and anxiety), functional status (amount of help needed and outcome on the GOSE), and comorbid health conditions. Together these five variables accounted for 58% of the variance in total QOLIBRI scores. The QOLIBRI is the first tool developed to assess disease-specific HRQoL in brain injury, and it contains novel information not given by other currently available assessments.

A double-blind placebo controlled experimental study of nicotine: I-effects on incentive motivation

RationaleBrain reward pathways implicated in addiction appear to be less reactive in regular drug users; behavioural manifestations may include decreased sensitivity to natural reinforcers.ObjectivesThis study aimed to replicate earlier findings of abstinence-associated incentive motivation deficits in smokers and to determine whether these can be reversed with nicotine in the form of lozenge.MethodsOne hundred forty-five smokers were each tested twice, once after receiving nicotine, and once after receiving placebo lozenge in counterbalanced order. Participants completed various tests of incentive motivational functioning: a measure of subjective enjoyment, the Snaith–Hamilton pleasure scale (SHAPS); a simple card sorting task, the card arranging reward responsivity objective test (CARROT) with and without financial incentive; the modified emotional Stroop test; a cue-reactivity task; and a novel reaction time task to explore effects of signals of reward, the incentive motivational enhancement of response speed task.ResultsCompared with performance during abstinence (placebo condition), nicotine was associated with: higher self-reported pleasure expectations on the SHAPS; enhanced responsiveness to financial reward on the CARROT in smokers who smoked 15 or more cigarettes a day; and greater interference from appetitive words on the Stroop task.ConclusionsThese results are generally consistent with contemporary neurobiological theories of addiction and suggest that short-term smoking abstinence is associated with impaired reward motivation which can be reversed with nicotine.

Measuring progress and outcome in community rehabilitation after brain injury with a new assessment instrument—the BICRO-39 scales

OBJECTIVE Construction and validation of a new instrument, the Brain Injury Community Rehabilitation Outcome scales, to assess problems experienced by brain-injured patients living in the community. DESIGN Seventy-six items describing aspects of personal and social functioning were generated. Two hundred thirty-five patients and/or their carers (separately) rated the items on 6-point scales, and patients retrospectively rated their functioning before injury. Seven scales were derived from factor analysis; one was included a priori. Thirty-nine items with high factor loadings were retained. Test-retest reliability, interrater reliability, and construct validity were examined in subsamples. SETTING Patients were recruited from four centers: two community-based teams, a day-patient clinic, and an outpatient clinic. PATIENTS Of the patients, 127 had traumatic brain injury, 72 had cerebrovascular accidents, 15 had multiple sclerosis, and 21 had acquired brain injury of other origins. Mean time since brain injury was 2.6 years; mean age was 43 years; 164 were men and 71 were women. RESULTS All scales showed good test-retest reliability, and agreement between patient and carer ratings was moderate to high. They showed predicted moderate correlations with other relevant scales. Postinjury scores differed significantly from preinjury scores, and 6 of the 8 scales showed change over a period of recovery/rehabilitation. CONCLUSIONS The scales appear reliable and easy to complete. They may have utility as quantitative measures of outcome for clinical and treatment evaluations.

Quality of life after traumatic brain injury: The clinical use of the QOLIBRI, a novel disease-specific instrument

Objective: To report the clinical use of the QOLIBRI, a disease-specific measure of health-related quality-of-life (HRQoL) after traumatic brain injury (TBI). Methods: The QOLIBRI, with 37 items in six scales (cognition, self, daily life and autonomy, social relationships, emotions and physical problems) was completed by 795 patients in six languages (Finnish, German, Italian, French, English and Dutch). QOLIBRI scores were examined by variables likely to be influenced by rehabilitation interventions and included socio-demographic, functional outcome, health status and mental health variables. Results: The QOLIBRI was self-completed by 73% of participants and 27% completed it in interview. It was sensitive to areas of life amenable to intervention, such as accommodation, work participation, health status (including mental health) and functional outcome. Conclusion: The QOLIBRI provides information about patients subjective perception of his/her HRQoL which supplements clinical measures and measures of functional outcome. It can be applied across different populations and cultures. It allows the identification of personal needs, the prioritization of therapeutic goals and the evaluation of individual progress. It may also be useful in clinical trials and in longitudinal studies of TBI recovery.

A double-blind placebo-controlled experimental study of nicotine: II-Effects on response inhibition and executive functioning.

RationaleSmokers may show abnormal functioning in prefrontal cortex during acute abstinence, reflecting deficient activity in mesocorticolimbic circuitry. Cognitive correlates of this putatively include impaired response inhibition and other aspects of executive functioning.ObjectivesTo investigate whether inhibitory control and other executive functions in smokers are impaired during acute abstinence relative to post-nicotine.Methods145 smokers were tested twice after overnight abstinence—once after nicotine and once after placebo lozenges (order counterbalanced, double-blind)—on an antisaccade task, a continuous performance task (CPT), a delayed response spatial working memory task and a verbal fluency test.ResultsCompared with placebo, nicotine was associated with better inhibitory control on the antisaccade task and fewer impulsive responses to filler stimuli (motor errors) on the CPT; at the first assessment only, nicotine also reduced impulsive responses to ‘catch’ stimuli on the CPT. However, it did not affect CPT response bias (an index of impulsive vs cautious decision-making), spatial working memory, or verbal fluency.ConclusionsSmoking abstinence appears to be associated with a difficulty in inhibiting prepotent motor responses, and with nicotine to attenuate this difficulty. However, more ‘cognitive’ forms of inhibitory control (e.g. decision-making) and the other aspects of executive function tested here appear to be unaffected.

Can Opiate Addicts Tell Us About Their Relapse Risk?: Subjective Predictors Of Clinical Prognosis

Given the high relapse rate of opiate addicts following detoxification, it is pertinent to identify whether any subjective variables mediate outcome, since these may then be targets of treatment. The present study assessed personality, cue-elicited craving, outcome expectancies for drug use, and self-efficacy for resisting drug use, in 43 opiate addicts receiving inpatient detoxification in either a specialist drug-dependence unit or a behavioral/general psychiatric ward, within the context of a randomised, controlled-treatment trial. Subjects were followed-up at between 1 and 3 months and again at 6 months after discharge. Frequency of drug use was not predicted by any of the subjective variables at the first follow-up; but at 6 months, subjects with lower self-efficacy and higher positive outcome expectancies were found to be using less often. Latency to first lapse was greater in subjects with higher anxiety and neuroticism scores. Precipitants to the first lapse were identified, but none of the predicted relationships between subjective variables and circumstances of lapse emerged. It is suggested that greater awareness of personal vulnerability may promote effective coping strategies.