Verbal Recall and Recognition Following Traumatic Brain Injury: A [O-15]-Water Positron Emission Tomography Study

Although several studies exist which have examined static functional neuroimaging following traumatic brain injury (TBI), controlled cognitive activation studies of episodic memory in this population have not been published. The present investigation studied verbal recall using [O-15]-water positron emission tomography (PET) in 5 individuals who sustained severe TBI (M GCS=6.8; M years post-injury=3.18), and 4 non-injured control participants. Statistical image analysis demonstrated changes in frontoparietal regional cerebral blood flow (rCBF) in both groups, but there were interesting differences between groups and across conditions. Frontal lobe rCBF changes in TBI patients were reduced during free recall but enhanced during recognition, when compared to controls. Changes in cerebellar rCBF were observed in the control group during free recall, but not in the TBI sample. In both groups, bifrontal rCBF increases were noted on recognition tasks. The present findings provide evidence of alterations in specific substrates involved in verbal recall following brain injury.     

Spacing of repetitions improves learning and memory after moderate and severe TBI

Extensive research has determined that new learning in healthy individuals is significantly improved when trials are distributed over time (spaced presentation) compared to consecutive learning trials (massed presentation). This phenomenon known as the "spacing effect" (SE) has been shown to enhance verbal and nonverbal learning in healthy adults of different ages and in different memory paradigms (e.g., recognition, recall, etc.). The purpose of this study was to examine whether learning in adults with moderate and severe traumatic brain injury (TBI) is improved using a spacing-of-repetitions procedure. Using a within-groups design, participants with TBI (n = 20) were presented a list of 115 words that were presented either once (single condition), twice consecutively (massed condition), or twice with 11 words between presentations (spaced condition). Participants were required to rank each word from 1 to 10 according to their familiarity with the word; they were not asked to "memorize" words for a later test. Word list learning was measured with a free recall test immediately following list presentation and with free recall and recognition tests after a 30-min delay. Participants recalled and recognized significantly more spaced words than massed words during this word list learning task. These results strongly indicate that the spacing of repetitions improves learning and memory in individuals who have sustained moderate to severe TBI. Implications for rehabilitation are discussed.     

Neural substrate differences in language networks and associated language-related behavioral impairments in children with TBI: a preliminary fMRI investigation

The present study examined whether functional MRI (fMRI) can identify changes in the neural substrates of language in young children following traumatic brain injury (TBI). Eight children with TBI (F/M=3/5, age (Mean +/- SD)=7.98 +/- 1 years, range = 6-9 years) and a comparison group of nine children with orthopedic injuries (OI) (F/M=4/5, age (Mean +/- SD)=7.4 +/- 1 years, range=6-9 years) participated in an fMRI study of covert verb generation (VG). Results revealed significantly different BOLD signal activation in perisylvian language areas between the groups, after accounting for potential confounders such as verbal fluency and executive function. We also found significant associations between the BOLD signal activation and performance on language-specific neuropsychological tests (NEPSY verbal fluency score, Verbal IQ) and Glasgow Coma Scale (GCS) score. This study suggests that children with TBI have significantly different brain activation patterns in language circuitry compared to children with orthopedic injuries. Although we found clear differences in brain activation between the two groups, conventional MR images showed no evidence of structural abnormalities in five of eight children with TBI. Our study demonstrates the feasibility and potential utility of fMRI as a means of quantifying changes associated with language deficits in future pediatric TBI studies.     

Verbal Learning and Memory Deficits in Traumatic Brain Injury: Encoding,Consolidation, and Retrieval

The present study examined the nature of verbal memory deficits in individuals with traumatic brain injury (TBI) compared to healthy controls. The study was designed to control for methodological shortcomings of previous related research. Three groups of participants were used: (a) a head injured sample with moderate to severe traumatic brain injuries (N=55), (b) a control sample matched on age and initial performance on CVLT Trial 5 and Sum of Trials 1 to 5 (N=55), and (c) a control sample matched on age, education, and race, but not on initial CVLT learning performance (N=55). Current findings indicate that: (a) rate of learning was comparable across groups, consistent with no encoding differences, (b) TBI patients have a significantly more rapid rate of forgetting of new information than either acquisition-matched or demographic-matched controls, consistent with consolidation problems in TBI, (c) TBI patients have less proactive interference than demographic-matched control participants, consistent with a consolidation problem in the TBI group, (d) TBI patients and acquisition-matched controls have comparably low rates of proactive interference, consistent with impaired acquisition in both of these groups, and (e) TBI patients and controls do not differ in the benefit experienced from semantic or recognition retrieval cues, consistent with no differences in retrieval processes. These data support an impaired consolidation hypothesis, rather than encoding or retrieval deficits, as the primary deficit underlying memory impairment in TBI.     

Verbal learning and memory deficits in traumatic brain injury: encoding, consolidation, and retrieval

The present study examined the nature of verbal memory deficits in individuals with traumatic brain injury (TBI) compared to healthy controls. The study was designed to control for methodological shortcomings of previous related research. Three groups of participants were used: (a) a head injured sample with moderate to severe traumatic brain injuries (N=55), (b) a control sample matched on age and initial performance on CVLT Trial 5 and Sum of Trials 1 to 5 (N=55), and (c) a control sample matched on age, education, and race, but not on initial CVLT learning performance (N=55). Current findings indicate that: (a) rate of learning was comparable across groups, consistent with no encoding differences, (b) TBI patients have a significantly more rapid rate of forgetting of new information than either acquisition-matched or demographic-matched controls, consistent with consolidation problems in TBI, (c) TBI patients have less proactive interference than demographic-matched control participants, consistent with a consolidation problem in the TBI group, (d) TBI patients and acquisition-matched controls have comparably low rates of proactive interference, consistent with impaired acquisition in both of these groups, and (e) TBI patients and controls do not differ in the benefit experienced from semantic or recognition retrieval cues, consistent with no differences in retrieval processes. These data support an impaired consolidation hypothesis, rather than encoding or retrieval deficits, as the primary deficit underlying memory impairment in TBI.     

Encoding and recognition after traumatic brain injury: neuropsychological and functional magnetic resonance imaging findings

Although impairment of episodic memory is common after traumatic brain injury (TBI), the complex nature of human memory suggests the need to study more than recall alone. For this reason, we are presenting an extension with additional analyses of persons reported in a previous publication ( Russell, Arenth, Scanlon, Kessler, & Ricker, 2011 ). We examined both the encoding and recognition components of an episodic memory paradigm containing both word and letter string blocks using functional magnetic resonance imaging (fMRI) and neuropsychological testing. This paradigm was completed by 12 persons with complicated mild, moderate, or severe TBI and 12 matched uninjured controls. Comparisons were made between groups and stimulus types. While task behavioral performance was not significantly different between groups, imaging results showed greater activation for the TBI group during the encoding portion of the task, while the control group exhibited more activation on the recognition portion. Observed areas of activation suggest that the TBI group may have used a less effective, but more automatic verbal strategy for encoding the nonpronounceable letter strings, while controls may have opted for more of a recognition-focused strategy. Group differences in California Verbal Learning Test-Second Edition (CVLT-II) performance supported these ideas, and further neuropsychological testing also suggested limitations in executive functioning in the TBI group that may have influenced performance. Implications for intervention are discussed.     

Recovery of content and temporal order memory for performed activities following moderate to severe traumatic brain injury

Few studies have investigated the complex nature of everyday activity memory following traumatic brain injury (TBI). This study examined recovery of content and temporal order memory for performed activities during the first year in individuals who suffered moderate to severe TBI. TBI and control participants completed eight different cognitive activities at baseline (i.e., acutely following injury for TBI) and then again approximately one year later (follow-up). Participants' free recall of the activities provided a measure of content memory. Temporal order memory was assessed with a reconstruction task. Self-report and informant report of everyday memory problems at follow-up were used to examine the relationship between activity memory performances and everyday memory. TBI participants showed significant recovery in both content and temporal order memory for activities during the first year. Despite showing significant recovery, the TBI group's activity memory performances remained poorer than that of controls at follow-up. Greater self- and informant report of everyday memory difficulties was associated with poorer temporal order memory but not content memory for activities. These findings demonstrate recovery in multiple memory processes that support activity memory following moderate to severe TBI. The findings also suggest a stronger link between everyday memory abilities and temporal order memory for activities than activity memory content in a TBI population.     

Longitudinal aspects of emotion recognition in patients with traumatic brain injury

Changes in emotional and social behaviour are relatively common following traumatic brain injury (TBI). Impairments in recognising the emotional state of others may underlie some of the problems in social relationships that these patients experience. The few previous studies examining emotion recognition in TBI typically assessed patients once, long after the onset of brain injury, making it difficult to distinguish the direct effect of brain injury from the effects of environmental changes. This study examined 30 patients with TBI shortly after brain injury and 32 orthopaedic control patients on their recognition of emotions expressed in the face and the voice using discrimination and labelling tasks. These patients were followed up 1 year later to examine the longitudinal development of emotion recognition deficits. TBI patients were found to be impaired on emotion recognition compared to the control patients both early after injury and 1 year later. The fact that impairments in emotion recognition were evident early after TBI and no evidence of recovery over time was found, suggests a direct effect of brain injury.     

The effects of pediatric traumatic brain injury on verbal and visual-spatial working memory

The purpose of this study was to investigate the effects of pediatric traumatic brain injury (TBI) on verbal and visual-spatial working memory (WM). WM tasks examined memory span through recall of the last item of a series of stimuli. Additionally, both verbal and visual-spatial tests had a dual-task condition assessing the effect of increasing demands on the central executive (CE). Inhibitory control processes in verbal WM were examined through intrusion errors. The TBI group (n = 73) performed more poorly on verbal and visual-spatial WM tasks than orthopedic-injured children (n = 30) and non-injured children (n = 40). All groups performed more poorly on the dual-task conditions, reflecting an effect of increasing CE load. This effect was not greater for the TBI group. There were no group differences in intrusion errors on the verbal WM task, suggesting that problems in WM experienced by children with TBI were not primarily due to difficulties in inhibitory control. Finally, injury-related characteristics, namely days to follow commands, accounted for significant variance in WM performance, after controlling for relevant demographic variables. Findings suggest that WM impairments in TBI are general rather than modality-specific and that severity indices measured over time are better predictors of WM performance than those taken at a single time point.     

Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres

To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.1-2.4 atm) and rCBF values were determined (a) prior to injury and 15 min and 1 h following injury (n = 7); and (b) prior to injury and 30 min and 2 h following injury (n = 7). At 15 min post injury, there was a profound reduction of rCBF in all brain regions studied (p less than 0.01). Although rCBF in the hindbrain had recovered to near-normal by 30 min post injury, rCBF in both injured and contralateral (uninjured) forebrain areas remained significantly suppressed up to 1 h post injury. At 2 h post injury, recovery of rCBF to near-normal values was observed in all brain regions except the focal area of injury (left parietal cortex) where rCBF remained significantly depressed (p less than 0.01). This prolonged focal oligemia at the injury site was associated with the development of reproducible cystic necrosis in the left parietotemporal cortex at 4 weeks post injury. Our results demonstrate that acute changes in rCBF occur following experimental traumatic brain injury in rats and that rCBF remains significantly depressed up to 2 h post injury in the area circumscribing the trauma site.     

Monetary incentive effects on event-based prospective memory three months after traumatic brain injury in children

Information regarding the remediation of event-based prospective memory (EB-PM) impairments following pediatric traumatic brain injury (TBI) is scarce. Addressing this, two levels of monetary incentives were used to improve EB-PM in children ages 7 to 16 years with orthopedic injuries (OI, n = 51), or moderate (n = 25) and severe (n = 39) TBI at approximately 3 months postinjury. The EB-PM task consisted of the child giving a specific verbal response to a verbal cue from the examiner while performing a battery of neuropsychological measures (ongoing task). Significant effects were found for age-at-test, motivation condition, period, and group. Within-group analyses indicated that OI and moderate TBI groups performed significantly better under the high- than under the low-incentive condition, but the severe TBI group demonstrated no significant improvement. These results indicate that EB-PM can be significantly improved at 3 months postinjury in children with moderate, but not severe, TBI.     

An analysis of communication in conversation after severe traumatic brain injury

Background and objective: Communication disorders have been reported following severe traumatic brain injury. However, we have little information about patient behaviour during dyadic interaction. Here, we analyzed conversation at the rehabilitation and chronic phase post traumatic brain injury (TBI), to define the main mechanisms of verbal and non‐verbal communication disorders and relationship with other cognitive difficulties. Methods: Sixteen patients were evaluated at the rehabilitation phase (2–12 months) and 18 at the chronic phase (after 2 years) following severe TBI. They were compared with equivalent groups of matching (gender, age, education level) control subjects. We used the Lille Communication Test, which comprises three parts: participation to communication (greeting, attention, engagement), verbal communication (verbal comprehension, speech outflow, intelligibility, word production, syntax, verbal pragmatics, verbal feedback) and non‐verbal communication (understanding gestures, affective expressivity, producing gestures, pragmatics, non‐verbal feedback). We also investigated executive functions (Stroop test, trail‐making test, categorical evocation), language (Montreal‐Toulouse protocol) and behaviour (Neurobehavioural Rating Scale). Verbal communication disorders were relatively equivalent at the rehabilitation and chronic phases. Results: Patients were impaired (P ≤ 0.01) in their participation to communication, especially in greeting behaviour. Verbal communication was mostly affected by difficulties in producing fluent and intelligible language and using pragmatics (responding to open questions, presenting new information and introducing new themes, organizing discourse and adapting to interlocutor knowledge). Non‐verbal communication was impaired by difficulties in using pragmatics (mostly adapted prosody). Participation and verbal communication correlated with the executive functions, language and behavioural assessment. Conclusions: Disorders of social communication justify systematic assessment in patients with TBI.     

A high-resolution single photon emission computed tomography study of verbal recognition memory in Alzheimer's disease

BACKGROUND: In view of the recent technological advances and its ease of availability, we used single photon emission computed tomography (SPECT) to examine the performance of early Alzheimer's disease (AD) subjects on a verbal recognition memory task. METHODS: Eighteen early AD and 10 matched healthy control subjects underwent split-dose (99m)Tc-HMPAO (Ceretec) SPECT using a verbal recognition memory and control task. SPECT images co-registered with MRI scans were used to determine relative regional cerebral blood flow (rCBF) changes in regions of interest. RESULTS: In healthy control subjects, verbal recognition increased rCBF in the right occipital region, thalamus, left prefrontal pole, posterior parietal region and cerebellum, and decreased rCBF in the right hippocampus. AD subjects showed bilateral prefrontal, posterior parietal and occipital increases, unilateral increase in the left posterior temporal region, and bilateral reductions in the hippocampus. Although activation was significantly different between the two groups in the right thalamus and left medial prefrontal region, the verbal recognition task did not enhance discrimination between groups. CONCLUSIONS: Compared with controls, AD subjects activate a similar but more extensive bilateral network during verbal recognition, possibly reflecting an attempt to compensate for impaired processing.     

Theory of mind following traumatic brain injury: the role of emotion recognition and executive dysfunction

A number of studies have now documented that traumatic brain injury (TBI) is associated with deficits in the recognition of basic emotions, the capacity to infer mental states of others (theory of mind), as well as executive functioning. However, no study to date has investigated the relationship between these three constructs in the context of TBI. In the current study TBI participants (N=16) were compared with demographically matched healthy controls (N=17). It was found that TBI participants' recognition of basic emotions, as well as their capacity for mental state attribution, was significantly reduced relative to controls. Performance on both of these measures was strongly correlated in the healthy control, but not in the TBI sample. In contrast, in the TBI (but not the control) sample, theory of mind was substantially correlated with performance on phonemic fluency, a measure of executive functioning considered to impose particular demands upon cognitive flexibility and self-regulation. These results are consistent with other evidence indicating that deficits in some aspects of executive functioning may at least partially underlie deficits in social cognition following TBI, and thus help explain the prevalence of social dysfunction in TBI.     

Acute and late changes in N-acetyl-aspartate following diffuse axonal injury in rats: an MRI spectroscopy and microdialysis study

N-acetyl-aspartate (NAA) measured by proton nuclear magnetic resonance spectroscopy (1H-NMR) has been used as a marker of neuronal injury in many cerebral pathologies. Therefore, we evaluate the roles of microdialysis vs. 1H-NMR as techniques to assess NAA (NAAd; NAA/Creatine ratio) in the living brain, and compare the results with whole brain NAA (NAAw), analyzed by HPLC after diffuse traumatic brain injury (TBI). Acute (4 h post-injury survival) and late (48 h survival) changes were studied in a sham-operated group (Sham, n = 4), and two injured groups (TBI/4 h, n = 8; TBI/48 h, n = 7). Baseline NAAd was 8.17 +/- 1 microM, and there was no significant difference between groups. There was only a small (twice of control), but transient increase in NAAd in the TBI/4 h group after trauma. Baseline NAA/Cr ratio was 1.35 +/- 0.2, which did not change significantly between baseline, 1, 2, 3, 4 and 48 h or between groups after TBI. Whole brain NAAw (baseline 8.5 +/- 0.5 mmol kg-1 wet weight) did not differ significantly between groups before and after TBI. Diffuse TBI did not produce long-term changes in NAA, assessed by three different methods. These results may indicate that NAA is not a sensitive marker of the severity of diffuse axonal damage. However, further studies are needed to evaluate whether confounding factors such as microdialysis probe, voxel position and non-regional tissue homogenization might have influenced our data.     

Differential profiles of verbal learning in traumatic brain injury

Several recent investigations have utilized cluster analytic procedures to elucidate profiles of verbal learning on the California Verbal Learning Test following traumatic brain injury (TBI). Although the results of these studies have contributed to our understanding of verbal learning following TBI, limitations in sample composition and methodology render the results difficult to evaluate. The current study provides an analysis of verbal learning clusters in the most comprehensive sample (n = 160) of TBI patients reported thus far. Results obtained from multiple hierarchical agglomerative clustering procedures suggested the presence of two distinct clusters, the first consisting of performance patterns falling within normal limits and the second consisting of moderate-to-severe impairment. Two iterative partitioning analyses further suggested a reliable solution with better-than-chance agreement (kappa coefficients >.85, p <.001). Thus, it is concluded that a two-cluster classification solution provides a parsimonious understanding of verbal learning profiles after TBI.     

Delayed hemorrhagic hypotension exacerbates the hemodynamic and histopathologic consequences of traumatic brain injury in rats.

Alterations in cerebral autoregulation and cerebrovascular reactivity after traumatic brain injury (TBI) may increase the susceptibility of the brain to secondary insults, including arterial hypotension. The purpose of this study was to evaluate the consequences of mild hemorrhagic hypotension on hemodynamic and histopathologic outcome after TBI. Intubated, anesthetized male rats were subjected to moderate (1.94 to 2.18 atm) parasagittal fluid-percussion (FP) brain injury. After TBI, animals were exposed to either normotension (group 1: TBI alone, n = 6) or hypotension (group 2: TBI + hypotension, n = 6). Moderate hypotension (60 mm Hg/30 min) was induced 5 minutes after TBI or sham procedures by hemorrhage. Sham-operated controls (group 3, n = 7) underwent an induced hypotensive period, whereas normotensive controls (group 4, n = 4) did not. For measuring regional cerebral blood flow (rCBF), radiolabeled microspheres were injected before, 20 minutes after, and 60 minutes after TBI (n = 23). For quantitative histopathologic evaluation, separate groups of animals were perfusion-fixed 3 days after TBI (n = 22). At 20 minutes after TBI, rCBF was bilaterally reduced by 57% +/- 6% and 48% +/- 11% in cortical and subcortical brain regions, respectively, under normotensive conditions. Compared with normotensive TBI rats, hemodynamic depression was significantly greater with induced hypotension in the histopathologically vulnerable (P1) posterior parietal cortex (P < 0.01). Secondary hypotension also increased contusion area at specific bregma levels compared with normotensive TBI rats (P < 0.05), as well as overall contusion volume (0.96 +/- 0.46 mm(3) vs. 2.02 +/- 0.51 mm(3), mean +/- SD, P < 0.05). These findings demonstrate that mild hemorrhagic hypotension after FP injury worsens local histopathologic outcome, possibly through vascular mechanisms.     

高压氧预适应对大鼠高原颅脑损伤的作用研究

目的探讨高压氧（HBO）预适应对高原颅脑损伤（TBI）的神经保护作用。方法将78只SD大鼠随机分为平原组、高原组和高压氧预适应组，各组按Feeney自由落体撞击法制作TBI模型，并通过低压氧舱模拟高原环境。采用Longa评分法进行神经功能缺损评分，Moor DRT4激光多普勒血流监测仪和LICOX CMP组织氧分压监测仪分别监测伤区局部脑血流（rCBF）和局部脑组织氧分压（PbtiO2）变化，利用光镜观察伤区脑组织的病理学改变。结果伤后24h高原组较平原组神经功能缺损评分上升。rCBF和PbtiO2下降，病理损伤加重；高压氧预适应组较高原组神经功能缺损评分下降（P〈0.05），rCBF和PbtiO2升高（均为P〈0.05）病理损伤减轻。结论高压氧预适应可诱导对高原颅脑损伤的神经保护作用改善神经功能。     

Transplantation of GABAergic neurons but not astrocytes induces recovery of sensorimotor function in the traumatically injured brain

Embryonic stem (ES) cells have been investigated in many animal models of injury and disease. However, few studies have examined the ability of pre-differentiated ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to compare the effect of murine ES cells that were pre-differentiated into GABAergic neurons or astrocytes on functional recovery following TBI. Neural and astrocyte induction was achieved by co-culturing ES cells on a bone marrow stromal fibroblast (M2-10B4) feeder layer and incubating them with various mitogenic factors. Rats were initially prepared with a unilateral controlled cortical contusion injury of the sensorimotor cortex or sham procedure. Rats were transplanted 7 days following injury with approximately 100K GABAergic neurons, astrocytes, fibroblasts, or media. Animals were assessed on a battery of sensorimotor tasks following transplantation. The stromal fibroblast cells (M2-10B4), as a control cell line, did not differ significantly from media infusions. Transplantation of GABAergic neurons facilitated complete and total recovery on the vibrissae-forelimb placing test as opposed to all other groups, which failed to show any recovery. It was also found that GABAergic neurons reduced the magnitude of the initial impairment on the limb use test. Histological analysis revealed infiltration of host brain with transplanted neurons and astrocytes. The results of the present study suggest that transplantation of pre-differentiated GABAergic neurons significantly induces recovery of sensorimotor function; whereas, astrocytes do not.     

Differential Profiles of Verbal Learning in Traumatic Brain Injury

Several recent investigations have utilized cluster analytic procedures to elucidate profiles of verbal learning on the California Verbal Learning Test following traumatic brain injury (TBI). Although the results of these studies have contributed to our understanding of verbal learning following TBI, limitations in sample composition and methodology render the results difficult to evaluate. The current study provides an analysis of verbal learning clusters in the most comprehensive sample (n = 160) of TBI patients reported thus far. Results obtained from multiple hierarchical agglomerative clustering procedures suggested the presence of two distinct clusters, the first consisting of performance patterns falling within normal limits and the second consisting of moderate-to-severe impairment. Two iterative partitioning analyses further suggested a reliable solution with better-than-chance agreement (kappa coefficients &gt;.85, p &lt; .001). Thus, it is concluded that a two-cluster classification solution provides a parsimonious understanding of verbal learning profiles after TBI.