Working memory brain activation following severe traumatic brain injury

Functional magnetic resonance imaging (fMRI) has shown that brain activation during performance of working memory (WM) tasks under high memory loads is altered in adults with severe traumatic brain injury (TBI) relative to uninjured subjects (Perlstein et al., 2004; Scheibel et al., 2003). Our study attempted to equate TBI patients and orthopedically injured (OI) subjects on performance of an N-Back task that used faces as stimuli. To minimize confusion in TBI patients that was revealed in pilot work, we presented the memory conditions in two separate tasks, 0- versus 1-back and 0- versus 2-back. In the 0- versus 1-back task, OI subjects activated bilateral frontal areas more extensively than TBI patients, and TBI patients activated posterior regions more extensively than OI subjects. In the 0- versus 2-back task, there were no significant differences between the groups. Analysis of changes in activation over time on 1-back disclosed that OI subjects had decreases in bilateral anterior and posterior regions, while TBI patients showed activation increases in those and other areas over time. In the 2-back condition, both groups showed decreases over time in fusiform and parahippocampal gyri, although the OI group also showed increases over time in frontal, parietal, and temporal areas not seen in the TBI patients. The greatest group differences were found in the 1-back condition, which places low demand on WM. Although the extent of activation in the 2-back condition did not differ between the two groups, deactivation in the 2-back condition was seen in the OI patients only, and both groups' patterns of activation over time varied, suggesting a dissociation between the TBI and OI patients in recruitment of neural areas mediating WM.     

Psychosis following traumatic brain injury

Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.     

Irritability following traumatic brain injury

This study was undertaken to identify the clinical and pathoanatomical correlates of irritability in patients with closed head injuries. A consecutive series of 66 patients was assessed in hospital and at 3, 6, 9, and 12-month follow-ups. Patients fulfilling criteria for irritability were divided into 2 groups based on the immediate or delayed onset of their irritability and compared with patients without irritability for background characteristics, impairment variables, and lesion characteristics. There were 12 patients (18.2%) with acute onset irritability and 10 (15.1%) with delayed onset irritability. Acute onset irritability patients had a higher frequency of left cortical lesions. Delayed onset irritability patients showed a strong association with poor social functioning and greater impairment in activities of daily living. The findings suggest that post-brain injury irritability may have different causes and treatment in the acute and chronic stages.     

Psychosis following traumatic brain injury

Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic, neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful selection and administration of treatment interventions.     

Cognitive impairment associated with major depression following mild and moderate traumatic brain injury

Traumatic brain injury (TBI) and major depression are neuropsychiatric conditions that have been associated with cognitive dysfunction. The aim of this study was to explore the relationship between major depression and cognitive impairment following mild and moderate TBI. Seventy-four TBI patients were assessed for the presence of major depression using the Structured Clinical Interview for the DSM-IV and completed a neurocognitive assessment battery. Subjects with major depression (28.4%), compared to those without, were found to have significantly lower scores on measures of working memory, processing speed, verbal memory and executive function. Potential mechanisms and implications for treatment are discussed.     

Recurrent hypersomnia following traumatic brain injury

BackgroundRecurrent hypersomnia (RH) following a traumatic brain injury (TBI) is a rare form of RH. According to the International Classification of Sleep Disorders, 2nd edition (ICSD-2), RH must be considered in the differential diagnosis as secondary to an organic insult of the central nervous system and not as the clinical subtype of RH, Kleine–Levin syndrome (KLS). The aim of our study was to investigate if cases of RH following TBI should be considered in the differential diagnosis of RH as indicated by the International Classification of Sleep Disorders, 2nd edition or as genuine, or indicated by ICSD-2, RH must cases of KLS.MethodsTwelve cases of RH developed after TBI were collected and analyzed for circumstance at onset, severity of TBI, delay between TBI and occurrence of first episode of RH, symptoms of RH, duration and cycle length of episodes of hypersomnia, physical signs, and brain morphological imaging at the time of hypersomnia episodes.ResultsFactors such as the delay between TBI and the first episode of RH, the presence of other triggering factors and potential genetic factors, the degree of the severity of TBI, the presence or absence of any consistent brain imaging abnormality, provided the following results: (1) two of the cases could be considered as symptomatic of the underlying pathological brain process, (2) eight of the cases could be considered as simply triggered by TBI in patients at risk for KLS, and (3) two cases could be considered neither symptomatic nor triggered by TBI, due to the long delay between TBI and occurrence of symptoms.ConclusionCases of RH following TBI do not present under a single mechanism. Clinical assessment and laboratory tests are necessary to correctly classify them.     

Persisting insomnia following traumatic brain injury

Persisting insomnia secondary to traumatic brain injury, rarely reported and documented, is described in an adult male following head injury. The neuronal mechanisms underlying this sleep disorder as well as the neuropsychological concomitants and therapeutic approaches are discussed.     

Mood disorders following traumatic brain injury

Mood disorders are a frequent complication of traumatic brain injury that exerts a deleterious effect on the recovery process and psychosocial outcome of brain injured patients. Prior psychiatric history and impaired social support have been consistently reported as risk factors for developing mood disorders after traumatic brain injury (TBI). In addition, biological factors such as the involvement of the prefrontal cortex and probably other limbic and paralimbic structures may play a significant role in the complex pathophysiology of these disorders. Preliminary studies have suggested that selective serotonin reuptake inhibitors such as sertraline, mood stabilizers such as sodium valproate, as well as stimulants and ECT may be useful in treating these disorders. Mood disorders occurring after TBI are clearly an area of neuropsychiatry in which further research in etiology as well as treatment is needed.     

Predictions of episodic memory following moderate to severe traumatic brain injury during inpatient rehabilitation

We examined memory self-awareness and memory self-monitoring abilities during inpatient rehabilitation in participants with moderate to severe traumatic brain injury (TBI). A total of 29 participants with moderate to severe TBI and 29 controls matched on age, gender, and education completed a performance prediction paradigm. To assess memory self-awareness, participants predicted the amount of information they would remember before completing list-learning tasks and visual-spatial memory tasks. Memory self-monitoring was assessed by participants' ability to increase accuracy of their predictions after experience with the tests. Although the TBI participants performed more poorly than controls on both episodic memory tasks, no significant group differences emerged in memory self-awareness or memory self-monitoring. The TBI participants predicted that their memory performances would be poorer than that of controls, accurately adjusted their predictions in accordance with the demands of the tasks, and successfully modified their predictions following experience with the tasks. The results indicate that moderate to severe TBI individuals in the early stages of recovery can competently assess the demands of externally driven metamemorial situations and utilize experience with task to accurately update their knowledge of memory abilities.     

Mood disorders following traumatic brain injury

Mood disorders are a frequent complication of traumatic brain injury that exerts a deleterious effect on the recovery process and psychosocial outcome of brain injured patients. Prior psychiatric history and impaired social support have been consistently reported as risk factors for developing mood disorders after traumatic brain injury (TBI). In addition, biological factors such as the involvement of the prefrontal cortex and probably other limbic and paralimbic structures may play a significant role in the complex pathophysiology of these disorders. Preliminary studies have suggested that selective serotonin reuptake inhibitors such as sertraline, mood stabilizers such as sodium valproate, as well as stimulants and ECT may be useful in treating these disorders. Mood disorders occurring after TBI are clearly an area of neuropsychiatry in which further research in etiology as well as treatment is needed.     

Major depression following traumatic brain injury

BACKGROUND: Major depression is a frequent psychiatric complication among patients with traumatic brain injury (TBI). To our knowledge, however, the clinical correlates of major depression have not been extensively studied. OBJECTIVE: To determine the clinical, neuropsychological, and structural neuroimaging correlates of major depression occurring after TBI. DESIGN: Prospective, case-controlled, surveillance study conducted during the first year after the traumatic episode occurred.Settings University hospital level I trauma center and a specialized rehabilitation unit. METHODS: The study group consisted of 91 patients with TBI. In addition, 27 patients with multiple traumas but without evidence of central nervous system injury constituted the control group. The patients' conditions were evaluated at baseline and at 3, 6, and 12 months after the traumatic episode. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing and quantitative magnetic resonance imaging were performed at the 3-month follow-up visit. RESULTS: Major depressive disorder was observed in 30 (33%) of 91 patients during the first year after sustaining a TBI. Major depressive disorder was significantly more frequent among patients with TBI than among the controls. Patients with TBI who had major depression were more likely to have a personal history of mood and anxiety disorders than patients who did not have major depression. Patients with major depression exhibited comorbid anxiety (76.7%) and aggressive behavior (56.7%). Patients with major depression had significantly greater impairment in executive functions than their nondepressed counterparts. Major depression was also associated with poorer social functioning at the 6-and 12-month follow-up, as well as significantly reduced left prefrontal gray matter volumes, particularly in the ventrolateral and dorsolateral regions. CONCLUSIONS: Major depression is a frequent complication of TBI that hinders a patient's recovery. It is associated with executive dysfunction, negative affect, and prominent anxiety symptoms. The neuropathological changes produced by TBI may lead to deactivation of lateral and dorsal prefrontal cortices and increased activation of ventral limbic and paralimbic structures including the amygdala.     

Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury

Memory impairment is one of the most significant residual deficits following traumatic brain injury (TBI) and is among the most frequent complaints heard from patients and their relatives. It has been reported that the hippocampus is particularly vulnerable to TBI, which results in hippocampus-dependent cognitive impairment. There are different regions in the hippocampus, and each region is composed of different cell types, which might respond differently to TBI. However, regional and cell type-specific neuronal death following TBI is not well described. Here, we examined the distribution of degenerating neurons in the hippocampus of the mouse brain following controlled cortical impact (CCI) and found that the majority of degenerating neurons observed were in the dentate gyrus after moderate (0.5 mm cortical deformation) CCI-TBI. In contrast, there were only a few degenerating neurons observed in the hilus, and we did not observe any degenerating neurons in the CA3 or CA1 regions. Among those degenerating cells in the dentate gyrus, about 80% of them were found in the inner granular neuron layer. Analysis with cell type-specific markers showed that most of the degenerating neurons in the inner granular neuron layer are newborn immature neurons. Further quantitative analysis shows that the number of newborn immature neurons in the dentate gyrus is dramatically decreased in the ipsilateral hemisphere compared with the contralateral side. Collectively, our data demonstrate the selective death of newborn immature neurons in the hippocampal dentate gyrus following moderate injury with CCI in mice. This selective vulnerability of newborn immature dentate neurons may contribute to the persistent impairment of learning and memory post-TBI and provide an innovative target for neuroprotective treatment strategies.     

Prospective evaluation of first and last memory reports following moderate to severe traumatic brain injury

Prospective monitoring of posttraumatic amnesia (PTA) status is recommended following traumatic brain injury (TBI). Use of patients’ subjective reports is, however, still common and necessary in some circumstances. It is therefore important to understand how patients’ self-reported first memories relate to prospective measures and how reliable these reports remain over time. In the present study, patients with moderate–severe TBI in PTA were asked about their first and last memories surrounding the injury daily and were administered the Westmead Post-Traumatic Amnesia Scale (WPTAS). Following PTA emergence, a semistructured interview was used to ascertain participants’ reports of return of continuous memory after the injury, as well as their last preinjury memory. This interview was repeated six months later, along with the Community Integration Questionnaire to measure functional outcome and the Rey Auditory Verbal Learning Test to measure anterograde memory. The temporal order of recovery of WPTAS variables and subjective reports was determined, and consistency of subjective reports over time was examined using bivariate correlation and intraclass correlation coefficients (ICCs). Findings suggested that patients’ reports of return of continuous memory aligned most closely with return of consistent orientation, and occurred significantly earlier than attainment of criterion on the WPTAS. Reported first memories were significantly later at follow-up (i.e., greater days post injury) and the ICC was not suggestive of adequate clinical reliability. Last memory reports were slightly more reliable, with 71% of cases remaining in the same band at follow-up. Demographic and injury-related variables were not significantly associated with the discrepancy between reports. The variability in patients’ reports over time highlights the importance and value of prospective PTA monitoring.     

盐酸多奈哌齐治疗轻、中型脑外伤后认知障碍的临床研究

目的探讨盐酸多奈哌齐对轻、中型脑外伤患者伤后认知障碍及临床预后的影响。方法本组轻、中型脑外伤合并认知障碍患者78例,随机分成治疗组和对照组,治疗组应用盐酸多奈哌齐,对照组应用吡拉西坦,两组的治疗周期为12周。治疗前及治疗后分别应用简明精神状态检测量表（MMSE）、国人修订成人韦氏智力量表（WAIS-RC）和格拉斯哥预后评分（GOS）评价疗效。结果两组治疗后12周MMSE和WAIS-RC评分均较治疗前提高（P〈0.05）。治疗组MMSE和WAIS-RC评分提高较对照组明显（P〈0.05）,治疗组GOS预后优良率优于对照组（P〈0.05）。结论盐酸多奈哌齐对轻、中型脑外伤后认知障碍有积极治疗作用,并能改善临床预后。