Response inhibition after traumatic brain injury (TBI) in children: impairment and recovery

Children who experience traumatic brain injury (TBI) often show cognitive impairments postinjury, some of which recover over time. We examined the recovery of motor response inhibition immediately following TBI and over 2 years. We assessed the role of injury severity, age at injury, and lesion characteristics on initial impairment and recovery while considering the role of pre-injury psychiatric disorder. Participants were 136 children with TBI aged 5-16 years. Latency of motor response inhibition was measured with the stop-signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. The performance of the TBI participants at each measurement occasion was standardized with 117 children of similar age, but without injury. Residualized latency scores were calculated. Growth curve analyses showed an initial impairment in response inhibition and improvement over the 2 years following injury. Younger TBI patients were initially more impaired although they exhibited greater recovery of response inhibition than did older TBI patients. Longer duration of coma, but not reactivity of pupils or Glasgow Coma Scale score, predicted initial deficit. Lesion characteristics or pre-injury attention deficit hyperactivity disorder did not predict initial impairment or recovery. Replication with longitudinal testing of a comparison group of children sustaining extracranial injury is necessary to confirm our findings.     

Response Inhibition After Traumatic Brain Injury (TBI) in Children: Impairment and Recovery

Children who experience traumatic brain injury (TBI) often show cognitive impairments postinjury, some of which recover over time. We examined the recovery of motor response inhibition immediately following TBI and over 2 years. We assessed the role of injury severity, age at injury, and lesion characteristics on initial impairment and recovery while considering the role of pre-injury psychiatric disorder. Participants were 136 children with TBI aged 5–16 years. Latency of motor response inhibition was measured with the stop-signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. The performance of the TBI participants at each measurement occasion was standardized with 117 children of similar age, but without injury. Residualized latency scores were calculated. Growth curve analyses showed an initial impairment in response inhibition and improvement over the 2 years following injury. Younger TBI patients were initially more impaired although they exhibited greater recovery of response inhibition than did older TBI patients. Longer duration of coma, but not reactivity of pupils or Glasgow Coma Scale score, predicted initial deficit. Lesion characteristics or pre-injury attention deficit hyperactivity disorder did not predict initial impairment or recovery. Replication with longitudinal testing of a comparison group of children sustaining extracranial injury is necessary to confirm our findings.     

Phenomenological comparisons of major depression following stroke, myocardial infarction or spinal cord lesions

Patients with major depression admitted to hospital with acute stroke (n = 44), acute myocardial infarction (n = 25), or acute spinal cord injury (n = 12) were examined for differences in their phenomenological presentation of major depression. Depressed stroke patients were found to have significantly higher scores on the syndrome clusters for generalized anxiety and ideas of reference than depressed cardiac or spinal cord injury patients. In addition, significantly more stroke patients met diagnostic criteria for generalized anxiety disorder compared with the other two groups. Although spinal cord injury patients were younger, more likely to be treated with benzodiazepines, and less likely to be treated with beta-blockers, none of these factors distinguished stroke patients with anxious depression from stroke patients with depression only. These findings are consistent with the hypothesis that the etiology of depression following stroke may be different from that associated with myocardial infarction or spinal cord injury.     

White Matter Integrity Following Traumatic Brain Injury: The Association with Severity of Injury and Cognitive Functioning

Traumatic brain injury (TBI) frequently results in impairments of memory, speed of information processing, and executive functions that may persist over many years. Diffuse axonal injury is one of the key pathologies following TBI, causing cognitive impairments due to the disruption of cortical white matter pathways. The current study examined the association between injury severity, cognition, and fractional anisotropy (FA) following TBI. Two diffusion tensor imaging techniques—region-of-interest tractography and tract-based spatial statistics—were used to assess the FA of white matter tracts. This study examined the comparability of these two approaches as they relate to injury severity and cognitive performance. Sixty-eight participants with mild-to-severe TBI, and 25 healthy controls, underwent diffusion tensor imaging analysis. A subsample of 36 individuals with TBI also completed cognitive assessment. Results showed reduction in FA values for those with moderate and severe TBI, compared to controls and individuals with mild TBI. Although FA tended to be lower for individuals with mild TBI no significant differences were found compared to controls. Information processing speed and executive abilities were most strongly associated with the FA of white matter tracts. The results highlight similarities and differences between region-of-interest tractography and tract-based spatial statistics approaches, and suggest that they may be used together to explore pathology following TBI.     

Deficits in predictive smooth pursuit after mild traumatic brain injury

Given that even mild traumatic brain injury (TBI) may produce extensive diffuse axonal injury (DAI), we hypothesized that mild TBI patients would show deficits in predictive smooth pursuit eye movements (SPEM), associated with impaired cognitive functions, as these processes are dependent on common white matter connectivity between multiple cerebral and cerebellar regions. The ability to predict target trajectories during SPEM was investigated in 21 mild TBI patients using a periodic sinusoidal paradigm. Compared to 26 control subjects, TBI patients demonstrated decreased target prediction. TBI patients also showed increased eye position error and variability of eye position, which correlated with decreased target prediction. In all subjects, average target prediction, eye position error and eye position variability correlated with scores related to attention and executive function on the California Verbal Learning Test (CVLT-II). However, there were no differences between TBI and control groups in average eye gain or intra-individual eye gain variability, or in performance on the Wechsler Abbreviated Scale of Intelligence (WASI), suggesting that the observed deficits did not result from general oculomotor impairment or reduced IQ. The correlation between SPEM performance and CVLT-II scores suggests that predictive SPEM may be a sensitive assay of cognitive functioning, including attention and executive function. This is the first report to our knowledge that TBI patients show impaired predictive SPEM and eye position variability, and that these impairments correlate with cognitive deficits.     

Neuropsychological deficits among patients with late-onset minor and major depression.

Cognitive ability of minor depressed patients (N=28), major depressed patients (N=26) and healthy elderly (N=38) was examined cross-sectionally to determine if cognitive abilities of patients with late-onset depression decrease with increasing severity of disease and if cognitive scores for minor depressed patients fall between those of healthy elderly and major depressed patients. A pooled within-group principal component analysis of cognitive test scores identified five components, three of which showed significant group differences. Verbal Recall and Maintenance of Set separated controls from major depressed patients and minor from major depressed patients. Executive Functioning separated controls from minor depressed patients, and Working Memory was borderline for separating controls from major depressed patients. The component representing Nonverbal Recognition was not statistically significant. Partial correlations controlling for age and education indicate that cognitive performance does decrease as severity of depression increases, and the magnitude of the change varies from a trend to a significant deficit depending on the cognitive domain. This decline in cognitive performance parallels a similar trend observed in neuroanatomical studies in which the volume of the frontal and temporal lobes decrease with increasing severity of depression.     

Morphine protects for head trauma induced cognitive deficits in mice

Victims of minor traumatic brain injury (mTBI) can show long lasting cognitive, emotional and concentration difficulties, amnesia, depression, apathy and anxiety. The symptoms are generally known as a post-concussive syndrome without clear morphological brain defects. Endogenous opiates are released after impact to the brain, suggesting they may play a role in TBI pathophysiology. Furthermore, the administration of opiates to the brain of injured animals has been shown to affect the injury, induce cellular changes and also have protective qualities for neurological impairments. Here, we examined the protective properties of the opiate morphine on cognitive performances following minimal brain injury in mice. For this purpose, we have used our non-invasive closed-head weight drop model in mice, which closely mimics real life mTBI and examined mice performance in the Morris water maze. Our procedure did not cause visible structural or neurological damage to the mice. A single morphine injection administrated immediately after the induction of minimal TBI protected the injured mice from cognitive impairment, checked 30, 60 and 90 days post injury. However, mice injected with morphine that were examined 7 days after the injury did not show better performance than the saline injected mice. Our results indicate that morphine has long but not short-term effects on the cognitive ability of brain-injured mice. Although the exact nature of opioid neuroprotection is still unknown, its elucidation may lead to the much-needed treatment for traumatic brain injury.     

Cognitive functioning ten years following traumatic brain injury and rehabilitation

Many previous studies investigating long-term cognitive impairments following traumatic brain injury (TBI) have focused on extremely severely injured patients, relied on subjective reports of change and failed to use demographically relevant control data. The aim of this study was to investigate cognitive impairments 10 years following TBI and their association with injury severity. Sixty TBI and 43 control participants were assessed on tests of attention, processing speed, memory, and executive function. The TBI group demonstrated significant cognitive impairment on measures of processing speed (Symbol Digit Modalities Test [SDMT], Smith, 1973; Digit Symbol Coding, Wechsler, 1997), memory (Rey Auditory Verbal Learning Test [RAVLT]; Rey, 1958; Lezak, 1976), Doors and People tests; Baddeley, Emslie & Nimmo-Smith, 1994) and executive function (Hayling C [Burgess & Shallice, 1997] and SART errors, Robertson, Manly, Andrade, Baddeley & Yiend, 1997). Logistic Regression analyses indicated that the SDMT, Rey AVLT and Hayling C and SART errors most strongly differentiated the groups in the domains of attention/processing speed, memory and executive function, respectively. Greater injury severity was significantly correlated with poorer test performances across all domains. This study shows that cognitive impairments are present many years following TBI and are associated with injury severity.     

Suicidal ideation among patients with acute life-threatening physical illness: patients with stroke, traumatic brain injury, myocardial infarction, and spinal cord injury.

Suicide is one of the leading causes of death in the community. The risk of suicide is greater among patients with physical illnesses than among the general population. This study was undertaken to evaluate the clinical characteristics and correlates of suicidal ideation in patients with acute life-threatening physical illnesses and to assess the duration of suicidal ideation. The study included a consecutive series of patients admitted with stroke, traumatic brain injury, myocardial infarction, or spinal cord injury (n=496). Study participants were administered a semistructured psychiatric interview as well as a series of standardized quantitative scales of mood, cognitive function, physical impairment, social ties, and social functioning. Follow-up evaluations of up to 24 months were also carried out. This study found that 36 (7.3%) patients with acute medical illness had clinically significant suicidal ideation. The suicidal ideation occurred mostly among patients with major depression and sometimes in those with minor depression. About 25% of patients with major depression and acute physical illnesses developed suicidal ideation. After the improvement of depressive disorders, suicidal ideations were ameliorated. These findings suggest that the detection and treatment of depressive disorders is the most important factor in preventing suicide among this patient population.     

Understanding predictors of functional recovery and outcome 30 months following early childhood head injury

Much is known about outcome following traumatic brain injury (TBI) in school-age children; however, recovery in early childhood is less well understood. Some argue that such injuries should lead to good outcome, because of the plasticity of the developing brain. Other purport that the young brain is vulnerable, with injury likely to result in a substantial impairment (H. G. Taylor & J. Alden, 1997). The aim of this study was to examine outcomes following TBI during early childhood, to plot recovery over the 30 months postinjury, and to identify predictors of outcome. The study compared 3 groups of children sustaining mild, moderate, and severe TBI, ages 2.0 to 6.11 years at injury, with healthy controls. Groups were comparable for preinjury adaptive and behavioral function, psychosocial characteristics, age, and gender. Results suggested a strong association between injury severity and outcomes across all domains. Further, 30-month outcome was predicted by injury severity, family factors, and preinjury levels of child function. In conclusion, children with more severe injuries and lower preinjury adaptive abilities, and whose families are coping poorly, are at greatest risk of long-term impairment in day-to-day skills, even several years postinjury.     

Metacognition Following Pediatric Traumatic Brain Injury: A Preliminary Study

Metacognition is one of the cognitive processes included under the general term executive functions. The executive functions are widely held to be under the control of the prefrontal cortex, an area often damaged after severe traumatic brain injury (TBI). We examined the metacognitive processing of a group of 9 children with TBI, and a group of 9 healthy, age-matched control children. Children with TBI showed significant impairments in their accuracy of prediction of the ease with which an item would be learned and their ability to predict recall of an item after a 2-hr delay. No significant differences in recall performance between the TBI and control groups were exhibited. The results are interpreted as suggesting an impairment in metacognitive processing resulting from frontal lobe damage after TBI in children. Additional research is necessary to confirm the relation of frontal lobe pathology and severity of injury to metacognitive impairments.     

Metacognition following pediatric traumatic brain injury: a preliminary study

Metacognition is one of the cognitive processes included under the general term executive functions. The executive functions are widely held to be under the control of the prefrontal cortex, an area often damaged after severe traumatic brain injury (TBI). We examined the metacognitive processing of a group of 9 children with TBI, and a group of 9 healthy, age-matched control children. Children with TBI showed significant impairments in their accuracy of prediction of the ease with which an item would be learned and their ability to predict recall of an item after a 2-hr delay. No significant differences in recall performance between the TBI and control groups were exhibited. The results are interpreted as suggesting an impairment in metacognitive processing resulting from frontal lobe damage after TBI in children. Additional research is necessary to confirm the relation of frontal lobe pathology and severity of injury to metacognitive impairments.     

The prevalence of depression in relation to cerebral atrophy and cognitive performance in 70- and 74-year-old women in Gothenburg. The Women's Health Study

BACKGROUND: Hospital-based studies report that depression in the elderly is associated with brain atrophy. This notion could not be confirmed in a population study on 85-year-olds. We aimed to assess depression in relation to brain atrophy and cognition in 70- and 74-year-old women. METHODS; A representative sample of 70- and 74-year-old women (N = 501) was examined with a psychiatric examination including the Mini-Mental State Examination (MMSE), measuring global cognitive function, and computerized tomography (CT) of the brain (N = 268). Depression was diagnosed according to DSM-III-R. Previous depression was diagnosed by history and by information from previous examinations in this 24-year longitudinal study. RESULTS: The prevalence of depression was 11.6%, including 8.4% with major depression (MDD). Among those who were currently mentally healthy, 43.0% had a history of previous depression. Women with current MDD had lower scores on the MMSE than the mentally healthy women. This association was only found in women with a lower level of education. Current depressives, previous depressives and mentally healthy women without a history of depression did not differ on CT with regard to brain atrophy or white matter lesions. The association between MDD and lower cognitive performance was independent of the association of cognitive performance with structural brain changes on CT. CONCLUSIONS: Brain atrophy on CT is not associated with depression in the general population, despite the fact that individuals with depression have a worse cognitive performance. The finding that cognitive performance was not decreased in individuals with previous depression suggests that cognitive dysfunction is a state phenomenon in depression.     

Depression and neuropsychological test performance in acute spinal cord injury patients: lack of correlation.

Factors which have been causally related to neuropsychological deficits in acute spinal cord injury (SCI) patients include advanced age, limited educational level, acute traumatic brain injury, alcohol and/or substance abuse. Concomitant depression may impair motivation, prolong reaction time, and produce fatigue during neuropsychological testing, resulting in impaired performance. To test the hypothesis that abnormal neuropsychologic test results may be associated with depression, the Zung Self-Rating Depression Scale (ZUNG) and a comprehensive, predominantly motor-free neuropsychological test battery were administered to 66 acute SCI patients approximately 8 weeks following injury. Spinal cord injury groups were dichotomized based on their ZUNG scores. Comparison of neuropsychological test scores between SCI groups failed to demonstrate any impairment in neuropsychological performance, within the limits of the test battery administered, suggesting that cognitive performance in this sample of acute SCI patients may not be influenced by the presence of depression.     

Anoxic encephalopathy: neuroradiological and neuropsychological findings.

The effects of anoxic brain injury are examined in 12 patients. Neuroradiological as well as neuropsychological findings are discussed and clinical guidelines offered. The most common neuropsychological profile associated with anoxic brain injury is one in which there is generalized cognitive impairment but with particular deficits in memory function. The common neuropathological findings are manifested by a pattern of diffuse cerebral atrophy as identified by neuroimaging techniques. A detailed case study is presented.     

Age at onset in geriatric depression: relationship to clinical variables

The significance of age at onset of first depressive episode was evaluated in an elderly depressed population. A prospective study of 71 consecutively admitted inpatients with a diagnosis of major unipolar depression examined the relationship between age at onset of illness and several clinical variables. Subjects divided into early-onset (EO) and late-onset (LO) groups, matched for current age, did not significantly differ in terms of symptomatology, cognitive impairment, physical illness, family history or treatment responsivity. These findings do not support a nosologic separation of EO and LO depression in geriatric patients.     

Altered structural networks and executive deficits in traumatic brain injury patients

Recent research on traumatic brain injury (TBI) has shown that impairments in cognitive and executive control functions are accompanied by a disrupted neural connectivity characterized by white matter damage. We constructed binary and weighted brain structural networks in 21 patients with chronic TBI and 17 healthy young adults utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. Executive function was assessed with the local global task and the trail making task, requiring inhibition, updating, and switching. The results revealed that TBI patients were less successful than controls on the executive tasks, as shown by the higher reaction times, higher switch costs, and lower accuracy rates. Moreover, both TBI patients and controls exhibited a small world topology in their white matter networks. More importantly, the TBI patients demonstrated increased shortest path length and decreased global efficiency of the structural network. These findings suggest that TBI patients have a weaker globally integrated structural brain network, resulting in a limited capacity to integrate information across brain regions. Furthermore, we showed that the white matter networks of both groups contained highly connected hub regions that were predominately located in the parietal cortex, frontal cortex, and basal ganglia. Finally, we showed significant correlations between switching performance and network property metrics within the TBI group. Specifically, lower scores on the switching tasks corresponded to a lower global efficiency. We conclude that analyzing the structural brain network connectivity provides new insights into understanding cognitive control changes following brain injury.     

Relationship Between Diffusion Tensor Imaging (DTI) Findings and Cognition Following Pediatric TBI: A Meta-Analytic Review

This study meta-analyzed research examining relationships between diffusion tensor imaging and cognition following pediatric traumatic brain injury (TBI). Data from 14 studies that correlated fractional anisotropy (FA) or apparent diffusion coefficient/mean diffusivity with cognition were analyzed. Short-term (<4 weeks post-TBI) findings were inconsistent, but, in the medium to long term, FA values for numerous large white matter tracts and the whole brain were related to cognition. However, the analyses were limited by the diversity of brain regions and cognitive outcomes that have been examined; all in relatively small samples. Moreover, additional data are needed to investigate the impact of age and injury severity on these findings.     

Life events and hippocampal volume in first-episode major depression

BACKGROUND: There are many studies on life events in depression and also several studies examining brain structural changes in the hippocampus of depressed patients. However, only few studies have focused on the association of life events and hippocampal volume in depression. The hypothesis of a significant negative association between life events and hippocampal volumes in first episode depression was examined. METHODS: 28 in-patients with a first episode of major depression were examined with high-resolution magnetic resonance imaging measuring hippocampal volumes. The precourse of depression was assessed with the Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses (IRAOS) and life events by using the Munich Interview for the Assessment of Life Events and Conditions (MEL). RESULTS: A significant negative correlation between major life events three month before the onset of depression and the left hippocampal volume was found for male patients. In female patients no significant association between major life events and hippocampal volumes could be found. CONCLUSIONS: The results support the hypothesis that the hippocampus plays a crucial role in the pathogenesis of major depression in the early phase of the disorder particularly for male patients.