Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury

We investigated residual brain damage in subjects who suffered severe traumatic brain injury (TBI) in childhood, and its relationship with declarative memory impairment. Magnetic resonance imaging (MRI) volumetric data and memory performance were compared between 16 adolescents with antecedents of severe TBI and 16 matched normal controls. Volumes of grey matter, white matter, cerebrospinal fluid (CSF), hippocampus, and caudate nuclei were measured. Verbal memory was assessed by the Rey's Auditory Verbal Learning test and visual memory by the Rey's Complex Figure. TBI patients performed significantly worse than controls in both verbal and visual memory. Patients presented decreased white matter volume and increased CSF. The hippocampus was reduced, but not the caudate nuclei. Memory performance correlated with CSF. Plasticity is incomplete for structural and functional deficits in children with TBI. Hippocampal atrophy, white matter loss, and memory impairment remain until adolescence. Memory sequelae are related more to diffuse brain injury, as reflected by MRI findings of increased CSF, than to hippocampal injury.     

Verbal working memory impairments following traumatic brain injury: an fNIRS investigation

The construct of working memory and its reliance on dorsolateral prefrontal cortex (DLPFC) have been the focus of many studies in healthy subjects and in clinical populations. However, transfer of knowledge gained from cognitive science studies to clinical applications can be a challenging goal. This scarce cross-dissemination may be partially due to the use of ‘tools’ that are limited in their ability to generate meaningful information about impairments in clinical groups. To this end, this paper investigates the use of functional near-infrared spectroscopy (fNIRS), which offers unique opportunities for recording neuroactivation. Specifically, we examine measures of the DLPFC hemodynamic response during a working memory task in adults with traumatic brain injury (TBI) and healthy controls. Analysis of hemodynamic measures showed significant differences between the two groups, even without differences in behavioral performance. Additional subtle disparities were linked to levels of performance in TBI and healthy subjects. fNIRS hemodynamic measures may therefore provide novel information to existing theories and knowledge of the working memory construct. Future studies may further define these subtle differences captured by fNIRS to help identify which components affect inter-individual variations in performance and could play a contributing role in the choice and planning of neurorehabilitation interventions targeting working memory.     

Brain activation during working memory after traumatic brain injury in children

Eight children with moderate to severe traumatic brain injury (TBI) and eight matched, uninjured control children underwent fMRI during an N-back task to test effects of TBI on working memory performance and brain activation. Two patterns in the TBI group were observed. Patients whose criterion performance was reached at lower memory loads than control children demonstrated less extensive frontal and extrafrontal brain activation than controls. Patients who performed the same, highest (3-back) memory load as controls demonstrated more frontal and extrafrontal activation than controls. Our findings of performance and brain activation changes in children after TBI await longitudinal investigation.     

Functional magnetic resonance imaging of working memory impairment after traumatic brain injury

OBJECTIVES: To examine patterns of brain activation while performing a working memory task in persons with moderate to severe traumatic brain injury (TBI) and healthy controls. It is well established that working memory is an area of cognition that is especially vulnerable to disruption after TBI. Although much has been learned about the system of cerebral representation of working memory in healthy people, little is known about how this system is disrupted by TBI. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory task (a modified version of the paced auditory serial addition test) in nine patients with TBI and seven healthy controls. RESULTS: Patients with TBI were able to perform the task, but made significantly more errors than healthy controls. Cerebral activation in both groups was found in similar regions of the frontal, parietal, and temporal lobes, and resembled patterns of activation found in previous neuroimaging studies of working memory in healthy persons. However, compared with the healthy controls, the TBI group displayed a pattern of cerebral activation that was more regionally dispersed and more lateralised to the right hemisphere. Differences in lateralisation were particularly evident in the frontal lobes. CONCLUSIONS: Impairment of working memory in TBI seems to be associated with alterations in functional cerebral activity.     

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.     

Administration of raloxifene reduces sensorimotor and working memory deficits following traumatic brain injury

Hormonal differences between males and females have surfaced as a crucial component in the search for effective treatments after experimental models of traumatic brain injury (TBI). Recent findings have shown that selective estrogen receptor modulators (SERMs) may have therapeutic benefit. The present study examined the effects of raloxifene, a SERM, on functional recovery after bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received injections of raloxifene (3.0 mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min, 24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both sensorimotor (bilateral tactile removal and locomotor placing tests) and cognitive tests (reference and working memory in the Morris water maze). Raloxifene-treated animals showed a significant reduction in the initial magnitude of the deficit and facilitated the rate of recovery for the bilateral tactile removal test, compared to vehicle-treated animals. The raloxifene-treated animals also showed a significant improvement in the acquisition of working memory compared to vehicle-treated animals. However, raloxifene did not significantly improve the acquisition of reference memory or locomotor placing ability. Raloxifene treatment also did not result in a significant reduction in the size of the lesion cavity. Thus, the task-dependent improvements seen following raloxifene treatment do not appear to be the result of cortical neuroprotection. However, these results suggest that raloxifene improves functional outcome following bCCI and may present an interesting avenue for future research.     

The neural correlates of visuo-spatial working memory in children with autism spectrum disorder: effects of cognitive load

Background

Research on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI).

Methods

We used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7–13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load.

Results

Performance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends.

Conclusions

Children with ASD showed differences in activation in the frontal and parietal lobes—both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level processing, whereas controls showed activity in frontal lobes related to the classic WM network. Findings will help guide future work by localizing areas of vulnerability to developmental disturbances.     

Working memory after severe traumatic brain injury.

The aim of the present study was to assess the functioning of the different subsystems of working memory after severe traumatic brain injury (TBI). A total of 30 patients with severe chronic TBI and 28 controls received a comprehensive assessment of working memory addressing the phonological loop (forward and backward digit span; word length and phonological similarity effects), the visuospatial sketchpad (forward and backward visual spans), and the central executive (tasks requiring simultaneous storage and processing of information, dual-task processing, working memory updating). Results showed that there were only marginal group differences regarding the functioning of the two slave systems, whereas patients with severe TBI performed significantly poorer than controls on most central executive tasks, particularly on those requiring a high level of controlled processing. These results suggest that severe TBI is associated with an impairment of executive aspects of working memory. The anatomic substrate of this impairment remains to be elucidated. It might be related to a defective activation of a distributed network, including the dorsolateral prefrontal cortex.     

Pediatric traumatic brain injury and procedural memory

This study investigated the effects of pediatric Traumatic brain injury (TBI) on procedural memory. Fifteen children with moderate to severe TBI and 15 matched controls were compared on two procedural-memory tasks: motor-perceptual (rotary pursuit) and cognitive (mirror reading). Explicit-memory tasks were also completed: recall or recognition of rotary-pursuit items and mirror-reading words. On both procedural tasks, the TBI group learned at a similar rate and retained equally well as the controls. On the explicit-memory tasks, however, the TBI group recalled and recognized fewer test items than the controls. These results are consistent with those reported in the adult TBI literature and suggest that procedural memory, a type of implicit memory, is preserved in children with TBI. Implications of these findings for the management and rehabilitation of children with TBI were discussed.     

Patterns of verbal learning and memory in traumatic brain injury.

CVLT and WMS-R Digit Span variables were used to calculate indexes of seven specific short- and long-term memory processes: working memory span and central executive functions, and long-term memory encoding, consolidation, retention, retrieval, control abilities. Scores on these indexes were then cluster-analyzed to determine whether subtypes of memory performance exist that correspond to deficits in these theoretical memory constructs. Parallel analyses were conducted with two large samples (N = 150 and N = 151) of individuals who had sustained a traumatic brain injury (TBI). Findings showed that TBI results in subgroups of memory disorders with specific deficits in consolidation, retention, and retrieval processes. Control problems (keeping track of list versus non-list items) only appeared in conjunction with retrieval deficits. Working memory span and central executive functioning (i.e., the ability to manipulate information in working memory) do not appear to be deficits characteristic of TBI as no such clusters emerged in the analyses. By using specific indexes of memory processes, and in contrast to previous studies, patterns of memory dysfunction were found that correspond to deficits in theoretically meaningful memory constructs.     

Neuroimaging correlates of anxiety after pediatric traumatic brain injury.

BACKGROUND: Anxiety disorders are common after traumatic brain injury (TBI). Data on the neural correlates of these conditions are lacking. This study examines the relationship between brain damage, particularly to the orbitofrontal cortex (OFC) and temporal lobe, and anxiety symptoms and disorders. METHODS: Ninety-five children and adolescents were followed for one year postinjury. Preinjury and one-year postinjury anxiety status were obtained from the parent. Magnetic resonance imaging was performed to evaluate brain lesions. The primary analysis used regression models to determine relationships between brain lesions and anxiety outcomes. As a secondary analysis, previously reported posttraumatic stress disorder (PTSD) data were reanalyzed using similar methods for purposes of comparison. RESULTS: The primary analysis showed that greater volume and number of OFC lesions correlated with decreased risk for anxiety, whereas lesions in other brain areas did not correlate with anxiety. Consistent with prior data, the secondary analysis showed an inverse correlation between OFC damage and PTSD; temporal lobe damage was positively correlated with PTSD. CONCLUSIONS: After pediatric TBI, greater damage to the OFC is associated with decreased risk for anxiety outcomes. Similar to adult data, these findings implicate OFC dysfunction in childhood anxiety. Temporal lobe damage did not correlate with anxiety, in contrast to the findings for PTSD.     

Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study.

OBJECTIVE: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). BACKGROUND: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. METHODS: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. RESULTS: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. CONCLUSION: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.     

Implicit and explicit memory in children with traumatic brain injury.

This study aimed to investigate whether implicit memory is preserved in children with traumatic brain injury (TBI). A fragmented picture-completion procedure (Snodgrass, Smith, Feenan, & Corwin, 1987) was used to compare implicit and explicit memory of 12 children with severe long-term TBI and 12 controls, matched for age and gender. On the implicit memory task, both the TBI and control groups were found to show significant priming. In addition, the extent of priming for the two groups was not found to be different. On the explicit memory task, however, the TBI group was found to perform significantly more poorly than the control group. These results are consistent with those reported in the adult TBI literature and have implications for understanding and rehabilitating memory impairments in children with TBI.     

Double dissociation in neural correlates of visual working memory: a PET study

Using positron emission tomography (PET), we investigated the organisation of spatial versus object-based visual working memory in 11 normal human subjects. The paradigm involved a conditional colour-response association task embedded within two visual working memory tasks. The subject had to remember a position (spatial) or shape (object-based) and then use this to recover the colour of the matching element for the conditional association. Activation of the nucleus accumbens and the anterior cingulate cortex was observed during the conditional associative task, indicating a possible role of these limbic structures in associative memory. When the 2 memory tasks were contrasted, we observed activation of 2 distinct cortical networks: (1) The spatial task activated a dorsal stream network distributed in the right hemisphere in the parieto-occipital cortex and the dorsal prefrontal cortex, and (2) The non spatial task activated a ventral stream network distributed in the left hemisphere in the temporo- occipital cortex, the ventral prefrontal cortex and the striatum. These results support the existence of a domain-specific dissociation with dorsal and ventral cortical systems involved respectively in spatial and non spatial working memory functions.     

Reduced contribution of executive functions in impaired working memory performance in mild traumatic brain injury patients

Aim

Mild traumatic brain injury (MTBI) is associated with often selective impairment of both working memory (WM) and the executive functions (EFs). Research indicates that one of the commonest deficits present in MTBI patients falls in the domain of WM. We aimed to investigate the role of EFs in WM impairment following MTBI.

Methods

Performance on the tests of EFs and the verbal and visuo-spatial WM of 30 consecutive MTBI patients were compared with age/education/IQ matched 30 normal healthy control participants. Correlation between EFs and WM was studied separately for the MTBI and the control group.

Results

The MTBI and control group were tested on a range of EF tests and WM. The MTBI group was demonstrated impairment on verbal and visuo-spatial WM and category fluency tests only. Furthermore, the MTBI group had fewer significant correlations between the WM and EFs (5 out of 54 possible correlations) than in the control group (13 out of 54 possible correlations).

Conclusions

We suggest that MTBI may lead to WM deficits as the contribution of executive processes to support the WM is diminished following MTBI. Such an understanding of the poor WM performance in MTBI patients will be helpful when planning appropriate strategies for cognitive rehabilitation.     

Working memory after traumatic brain injury in children

To investigate the effects of traumatic brain injury on working memory in children, we administered semantic (letter identity) and phonological (letter rhyme) N-back tasks to children who were on average 5 years post-mild (n = 54) or -severe (n = 26) traumatic brain injury and 44 typically developing children who were comparable in age. The correct detection of targets and false alarms were measured for each task. Memory load (which varied from 0 to 3 letters back) and age significantly affected the detection of targets and false alarms in both tasks. The severity of traumatic brain injury affected the correct detection of letters on the identity task and false alarms on the rhyme task. Traumatic brain injury severity also interacted with memory load in its effect on false alarms on the rhyme task. Traumatic brain injury results in impaired working memory and diminished inhibition in children. The N-back working memory task is feasible for administration to brain-injured children and potentially could be useful for studying brain activation associated with working memory and effects of drug therapy in this group of patients.     

Recovery of memory and learning functions following traumatic brain injury.

Twenty-four traumatically brain-injured males, of whom eight had sustained right-sided, eight left-sided, and eight bilateral or diffuse closed head injuries, took a battery of neuropsychological tests within the first six months, the second six months, the second year and the third year post injury. Performances on WAIS Digits Forward and Backward and Rey's Auditory-Verbal Learning Test were classified as within or below normal range. Comparisons were made (1) between time periods and tests and (2) between subgroups formed by severity, site of lesion, and age. The findings give an overall picture of wide performance variability with consistent improvement in immediate memory span and learning. Recovery varied with the specific nature of the tested function, task complexity, and severity of injury. Neither age, site of injury, not recency were associated with improvement.     

Self-regulation and social and behavioral functioning following childhood traumatic brain injury.

This study examined the impact of childhood traumatic brain injury (TBI) on self-regulation and social and behavioral functioning, and the role of self-regulation as a predictor of children's social and behavioral functioning. Participants included 65 children with moderate to severe TBI and 65 children without TBI, all between 6 and 11 years of age. Self-regulation and social and behavioral functioning were assessed 2 to 5 years following injury. Children with TBI displayed deficits in self-regulation and social and behavioral functioning, after controlling for socioeconomic status (SES), although the magnitude of the deficits was not related to injury severity. Self-regulation accounted for significant variance in children's social and behavioral functioning, after controlling for SES and group membership. Self-regulation may be an important determinant of children's social and behavioral functioning following TBI.