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We investigate the characteristics of injury of four portions of the Papez circuit in patients with diffuse axonal injury (DAI), using diffusion tensor tractography (DTT). Thirty-four consecutive patients with DAI and 30 normal control subjects were recruited. Four portions of the Papez circuit were reconstructed: the fornix, cingulum, thalamocingulate tract, and mammillothalamic tract. Analysis of DTT parameters [fractional anisotropy (FA) and tract volume (TV)] and configuration (narrowing, discontinuation, or non-reconstruction) was performed for each portion of the Papez circuit. The Memory Assessment Scale (MAS) was used for the estimation of cognitive function. In the group analysis, decreased fractional anisotropy and tract volume of the entire Papez circuit were observed in the patient group compared with the control group (p < 0.05). In the individual analysis, all four portions of the Papez circuit were injured in terms of DTT parameters or configuration. Positive correlation was observed between TV of the fornix and short-term memory on MAS r = 0.618, p < 0.05), and between FA of the fornix and total memory on MAS (r = 0.613, p < 0.05). We found that all four portions of the Papez circuit in the patient group were vulnerable to DAI, and among four portions of the Papez circuit, the fornix was the most vulnerable portion in terms of injury incidence and severity., (© 2020. Belgian Neurological Society.)

A 39-year-old man with a diffuse axonal injury self-presented to the cognitive function clinic of the Ashikaga Red Cross Hospital complaining of behavioral errors in his daily life, such as scooping hot rice into a glass instead of a bowl or forgetting to turn off the gas stove after cooking. This type of error has been referred to as an action slip-a form of unintentional behavioral error that occurs when an individual attempts to perform an automatic and/or familiar task. In this case, action slips occurred nine times a day on average and had a serious and long-term impact on the man's daily quality of life. To reduce the impact of action slips, we created a one-on-one cognitive intervention that used a combination of mnemonic strategies, such as verbalizing his actions as he carried them out, and external aids, including a waist pouch, a voice-controlled artificial intelligence (AI) speaker, and an AI key finder. After 3 years of intervention, the man reported some improvement in his daily activities and a reduction in the number of action slips. Thus, intervention strategies for individuals with a diffuse axonal injury may benefit from targeting action slips. To our knowledge, this is the first detailed description of action slips in an individual with a diffuse axonal injury.

Traumatic brain injury is a calamity of various causes, pathologies, and extremely varied and often complex clinical presentations. Because of its predilection for brain systems underlying cognitive and complex behavioral operations, it may cause chronic and severe psychiatric illness that requires expert management. This is more so for the modern epidemic of athletic and military brain injuries which are dominated by psychiatric symptoms. Past medical, including psychiatric, history, and comorbidities are important and relevant for formulation and management. Traumatic brain injury is a model for other neuropsychiatric disorders and may serve as an incubator of new ideas for neurodegenerative disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and significantly contributes to cognitive deficits. The mechanisms that underlie these cognitive deficits are often associated with complex molecular alterations. α7nAChR, one of the abundant and widespread nicotinic acetylcholine receptors (nAChRs) in the brain, plays important physiological functions in the central nervous system. However, the relationship between temporospatial alterations in the α7nAChR and DAI-related learning and memory dysfunction are not completely understood. Our study detected temporospatial alterations of α7nAChR in vulnerable areas (hippocampus, internal capsule, corpus callosum and brain stem) of DAI rats and evaluated the development and progression of learning and memory dysfunction via the Morris water maze (MWM). We determined that α7nAChR expression in vulnerable areas was mainly reduced at the recovery of DAI in rats. Moreover, the escape latency of the injured group increased significantly and the percentages of the distance travelled and time spent in the target quadrant were significantly decreased after DAI. Furthermore, α7nAChR expression in the vulnerable area was significantly positively correlated with MWM performance after DAI according to regression analysis. In addition, we determined that a selective α7nAChR agonist significantly improved learning and memory dysfunction. Rats in the α7nAChR agonist group showed better learning and memory performance than those in the antagonist group. These results demonstrate that microstructural injury-induced alterations of α7nAChR in the vulnerable area are significantly correlated with learning and memory dysfunctions after DAI and that augmentation of the α7nAChR level by its agonist contributes to the improvement of learning and memory function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine whether high-frequency repetitive transcranial magnetic stimulation (rTMS) improves cognition in patients with severe traumatic brain injury., Methods: A single-center, randomized, double-blind, placebo-controlled study of rTMS was conducted in patients aged 18-60 years with chronic (>12 months postinjury) diffuse axonal injury (DAI). Patients were randomized to either a sham or real group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Neuropsychological assessments were performed at 3 time points: at baseline, after the 10th rTMS session, and 90 days after intervention. The primary outcome was change in executive function evaluated using the Trail Making Test Part B., Results: Thirty patients with chronic DAI met the study criteria. Between-group comparisons of performance on TMT Part B at baseline and after the 10th rTMS session did not differ between groups ( p = 0.680 and p = 0.341, respectively). No significant differences were observed on other neuropsychological tests. No differences in adverse events between treatment groups were observed., Conclusions: Cognitive function in individuals with chronic DAI is not improved by high-frequency rTMS over the left DLPFC, though it appears safe and well-tolerated in this population., Clinicaltrialsgov Identifier: NCT02167971., Classification of Evidence: This study provides Class II evidence that for individuals with chronic DAI, high-frequency rTMS over the left DLPFC does not significantly improve cognition., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Traumatic brain injury (TBI) is the major public health problem worldwide, particularly in the Middle East. Diffuse axonal injury (DAI) is commonly found in TBI. Although DAI can lead to physical and psychosocial disabilities, its prognostic value is still a matter of debate. Magnetic Resonance (MR) is more sensitive for detecting DAI lesions., Objective: To identify the radiological and clinical factors associated with the functional capacity one year after the traumatic brain injury., Methods: The study included 251 patients with severe head trauma for whom Brain MRI was done within one month after injury. Demographic, clinical, and radiological data were collected during hospitalization. Neurocognitive and psychiatric evaluation were done one year thereafter., Results: DAI was more frequent in our patients. Psychiatric disorders, cognitive impairment, and poor functional outcome were more common in patients with DAI especially those with cerebral hemisphere and brain stem lesion, and mixed lesions. Duration of post traumatic amnesia (DPTA), lost consciousness and hospital stay (DHS) as well as the volume of diffuse axonal injury (DAI) were associated with poor neurocognitive outcome. DPTA, and DAIV may be considered independent factors that could predict the neurocognitive outcome., Conclusion: MRI following traumatic brain injury yields important prognostic information, with several lesion patterns significantly associated with poor long-term neurocognitive and psychiatric outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800-900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients., Methods/design: This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm 2 , 10 J/cm 2 ) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation., Discussion: This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials., Trial Registration: ClinicalTrials.gov, NCT03281759 . Registered on 13 September 2017.

Patients with diffuse axonal injury (DAI) may initially present with prominent physical impairments, but their cognitive dysfunctions are more persistent and are attributable to later unemployment. In this study, we analyzed how the findings of early and delayed neuropsychological assessments correlated with employment outcome of patients with DAI. A total of 56 patients with DAI without motor or visual dysfunction were included in this study. The neuropsychological battery consisted of the Wechsler Adult Intelligent Scale - Revised (WAIS-R), Wechsler Memory Scale - Revised (WMS-R), Trail Making Test (TMT), Wisconsin Card Sorting Test (WCST), and Word Fluency Test (WFT). This battery of tests was administered twice in early stage after injury and in later stage. The results of all of the neuropsychological tests improved significantly (P <0.001) between the early and later assessments. All scores other than TMT part A and B improved to the normal range (Z-score ≥ 2). The patient characteristics (age, gender, initial Glasgow Coma Scale, and duration of posttraumatic amnesia) had no relationship to the outcome. The results of TMT part B, however, were significantly correlated with employment outcome in both the early and later assessments (P = 0.01, 0.04). Given that TMT evaluates visual attention, we surmise that a lack of attention may be the core symptom of the cognitive deficit and cause the re-employment failure in patients with DAI. TMT part B in both early and later assessments has the potential to accurately predict chronic functional outcome.

Objective: Diffuse axonal injury (DAI) is prevalent in traumatic brain injury (TBI), and is often associated with poor outcomes and cognitive impairment, including memory deficits. Few studies have explored visual memory after TBI and its relationship to executive functioning. Executive functioning is crucial for remembering an object's location, operating devices, driving, and route finding. We compared visual memory performance via the Rey-Osterrieth Complex Figure (ROCF) test 6 and 12 months after DAI., Method: In total, 40 patients (mean age 28.7 years; 87.5% male) with moderate-to-severe DAI following a road traffic accident completed the 1-year follow-up. There was a three-phase prospective assessment. In phase 1 (1-3 months after trauma), patients completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). In phases 2 (6 months) and 3 (12 months), they completed the BDI, STAI, and a neuropsychological battery [ROCF copy and recall, digit span forward/backward, Grooved Pegboard test, intelligence quotient (IQ) by Wechsler Adult Intelligence Scale-III (WAIS-III)]., Results: There was an improvement in ROCF recall over time (p=0.013), but not ROCF copy (p=0.657).There was no change in executive function (Savage scores) copy (p=0.230) or recall (p=0.155). Age, years of education, severity of the trauma, and IQ did not influence ROCF recall improvement., Conclusion: There are time-dependent improvements in visual memory in patients with DAI. Neuroplasticity in the 1st months after trauma provides an opportunity for visuospatial memory learning. The present findings may be useful to formulate management plans for long-term TBI rehabilitation.

Objective: Facial emotion recognition impairment has been well documented in patients with traumatic brain injury. Studies exploring the neural substrates involved in such deficits have implicated specific grey matter structures (e.g. orbitofrontal regions), as well as diffuse white matter damage. Our study aims to clarify whether different types of injuries (i.e. focal vs. diffuse) will lead to different types of impairments on facial emotion recognition tasks, as no study has directly compared these patients., Methods: The present study examined performance and response patterns on a facial emotion recognition task in 14 participants with diffuse axonal injury (DAI), 14 with focal injury (FI) and 22 healthy controls., Results: We found that, overall, participants with FI and DAI performed more poorly than controls on the facial emotion recognition task. Further, we observed comparable emotion recognition performance in participants with FI and DAI, despite differences in the nature and distribution of their lesions. However, the rating response pattern between the patient groups was different., Conclusion: This is the first study to show that pure DAI, without gross focal lesions, can independently lead to facial emotion recognition deficits and that rating patterns differ depending on the type and location of trauma.

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) has been proposed as a new tool in neurological rehabilitation of victims of traumatic brain injury (TBI). However, its usefulness to treat this condition has never been tested rigorously. The primary goal is to conduct a study protocol to determine whether rTMS used to cognitive rehabilitation of victims of TBI with diffuse axonal injury (DAI) is a safe instrument and if it enhances cognitive function recovery., Methods: Double-blind randomized controlled trial of patients with diffuse axonal injury. Thirty-six patients will be randomized to either an active coil group or sham group in a 1:1 ratio. rTMS protocol: 10 sessions of high-frequency rTMS (10 Hz) over the left dorsolateral prefrontal cortex (DLPFC). Cortical Excitability measures will be obtained. Neuropsychological evaluations will be performed 1 week before, 1 week and 3 months after rTMS. There are 2 study hypotheses: (1) rTMS over the left DLPFC in patients with DAI will improve cognitive function and (2) whether rTMS is safe in TBI patients., Discussion: This study evaluates the immediate and delayed effects of rTMS over the DLPFC on the cognitive domain of patients with DAI following TBI. rTMS has shown good results in treating major depression and may be promising for patients with TBI. As such, the results of this study can greatly modify the cognitive rehabilitation strategies., Trial Registration: This trial was registered in clinicaltrials.gov ( NCT02167971 ) on 17 June 2014.

A 15-year-old male was treated secondary to sustaining a moderate traumatic brain injury (moderate TBI). Symptom self-report, and computerized and paper-and-pencil-based neurocognitive, vestibular/ocular motor, and imaging data were used throughout to document impairment and recovery. The patient demonstrated persistent emotional lability concurrent with vestibular impairment. In addition to clinical evaluation and management, the patient also underwent susceptibility-weighted imaging, which revealed axonal shearing across the corpus callosum and areas innervating the prefrontal cortex. Paper-and-pencil neurocognitive measures revealed persisting deficits, despite normal-appearing computerized test results. Implications of this case underline the importance of an integrative evaluation process including clinical interview, neurocognitive and vestibular/ocular physical therapy, and advanced neuroimaging, especially in cases with atypical presentation.

The velocity of impact between an object and the human head is a critical factor influencing brain injury outcomes but has not been explored in any detail in animal models. Here we provide a comprehensive overview of the interplay between impact velocity and injury severity in a well-established weight-drop impact acceleration (WDIA) model of diffuse brain injury in rodents. We modified the standard WDIA model to produce impact velocities of 5.4, 5.85 and 6.15 m/s while keeping constant the weight and the drop height. Gradations in impact velocity produced progressive degrees of injury severity measured behaviourally, electrophysiologically and anatomically, with the former two methods showing greater sensitivity to changes in impact velocity. There were impact velocity-dependent reductions in sensorimotor performance and in cortical depth-related depression of sensory cortex responses; however axonal injury (demonstrated by immunohistochemistry for β-amyloid precursor protein and neurofilament heavy-chain) was discernible only at the highest impact velocity. We conclude that the WDIA model is capable of producing graded axonal injury in a repeatable manner, and as such will prove useful in the study of the biomechanics, pathophysiology and potential treatment of diffuse axonal injury., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe fatigue and its relationship to cognition, psychosocial adjustment, quality of life (QoL), work status and relative's experiences 12 months after suspected traumatic axonal injury (TAI)., Methods: Eighteen patients were assessed with the Daily Fatigue Impact Scale (D-FIS), the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), the European Questionnaire 5 Dimensions health-related quality of life, the Glasgow Coma Outcome Scale Extended, and the European Brain Injury Questionnaire (EBIQ) (patient and relative). Return to work was registered., Results: At 1 year, fatigue still caused great problems in daily life. Although fatigue and cognition (BNIS) did not correlate, the more fatigued patients subjectively experienced significantly more cognitive dysfunction. Although D-FIS and QoL did not correlate, most patients reported that feelings of tiredness and dullness related to having lower QoL. However, lower QoL was associated with cognitive and attention disability (BNIS), subjective perception of executive dysfunction, lack of motivation, and mood disturbances (EBIQ). Neither fatigue nor cognition associated with return to work. The general consequences of TAI showed good agreement between patients' and relatives' experiences., Conclusion: The patient's subjective experience of the impact of TAI seems to be most essential, as it is the objective reality that the patient responds to, and this should therefore be assessed and treated.

Background: Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the central fluid percussion injury (cFPI) TAI model in mice, the neuroinflammatory and astroglial response and behavioral changes are unknown., Methods: Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data)., Results: At all post-injury time points, β-amyloid precursor protein (β-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood-brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P<0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls., Conclusions: Traumatic axonal injury TAI resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting TAI.

Objective: Axonal injury (AI) after traumatic brain injury (TBI) is often overlooked as an explanation for cognitive complaints when no damage is detected by computed tomography. The purpose was to assess cognition during the 12 months following a TBI and suspected traumatic axonal injury (TAI)., Methods: The sample included 17 patients younger than 65 years old, however one died. In the acute phase and at 6 and 12 months, cognition, reaction time, psychomotor performance and finger tapping speed were assessed. Working memory and work status were added at 12 months. Acute MRI findings were recorded., Results: After 1 year, all patients still showed cognitive dysfunction. A recovery had been noted at 6 months, but a cognitive decline was indicated for the majority at 12 months. The sick-listed patients had TAI located in the corpus callosum and the brainstem. They were cognitively more impaired and in more areas than the four patients who had returned to work., Conclusion: Cognitive screening can identify the long-term impact of TAI identified by conventional MRI, used as a routine clinical technique. For rehabilitation and for insurance-related matters, these injuries must be taken seriously, as a deterioration over time might occur. Further research is needed.

Diffuse axonal injury (DAI) is the predominant effect of severe traumatic brain injury and contributes significantly to cognitive deficits. The mechanisms underlying these cognitive deficits are often associated with complex metabolic alterations. However, the relationships between temporospatial alterations in cerebral glucose metabolism and the pathophysiology of DAI-related learning and memory dysfunction are not yet completely understood. We used a small animal positron emission tomography (PET) scanner with 2-[F-18]-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) as a molecular probe to evaluate temporospatial glucose metabolism in vulnerable areas of rats with DAI. The Morris water maze (MWM) was used to evaluate the development and progression of learning and memory dysfunction. Compared to the sham-treated group, PET-MRI fusion images showed that glucose metabolism was reduced in animals with DAI. In addition, the standardized uptake value (SUV) of ¹⁸F-FDG was significantly decreased in the sensorimotor cortex, hippocampus, corpus callosum, caudate putamen, brain stem, and cerebellum at days 1, 3, and 7 after injury. SUV returned to baseline levels by 30 days after injury. The escape latency of the injured group was significantly increased, and the percentages of distance travelled and time spent in the target quadrant were significantly decreased 1 month after injury. These effects persisted for 3 months. SUVs in the hippocampus at the acute stage were significantly correlated with MWM performance during the recovery stage of DAI. These results demonstrate that microstructural injury-induced hypometabolism in the hippocampus at the acute stage are all significantly correlated with learning and memory dysfunctions during the recovery stage of DAI.

Primary Objective: To establish whether the budgeting task of the Instrumental Activities of Daily Living (IADL) Profile discriminates individuals with a traumatic brain injury (TBI) from healthy controls and to identify the nature of the observed difficulties., Method: This study tested 27 adults with moderate or severe TBI and 27 controls matched for age, sex and education on the budgeting task of the IADL Profile. The budgeting task is a complex real-world problem involving the preparation of a yearly budget for an individual living on a fixed income with the goal of saving money to purchase a car., Main Results: The results showed that TBI subjects, the majority of whom had documented frontal lesions and/or diffuse axonal injury based on CT scan reports, were more likely than control subjects to experience difficulties on all task-related operations (planning, carrying out and verifying attainment of goal), with planning being particularly affected. These deficits were shown to impact on financial abilities, an issue of particular concern for TBI individuals reporting full responsibility of their finances., Conclusions: The budgeting task of the IADL Profile discriminates TBI subjects from controls. Planning was shown to be the most significant difficulty underlying reduced independence in the task.

Higher cortical dysfunction after traumatic brain injury(TBI) is one of the most important aspects for rehabilitation. Main etiology is traffic accidents and classification after TBI is diffuse axonal injury, cerebral contusion, etc. Though Wechsler Intelligence Scale for Children-III, Kaufman assessment battery for children, Trail Making Test, etc. are used for assessing higher cortical dysfunction in children, the most important evaluation method is to get information precisely from his/her families and teachers. Memory disturbance, attention deficit and dyscontrol of feeling are the top 3 symptoms of higher cortical dysfunction in children with TBI. Support for re-entrance to schools should be begun as fast as possible with cooperation among hospitals, schools and homes. As many problems are observed in the aspects of study, behavior, communication, etc, a lot of support from the professional staffs is necessary. After the school age, support should be continued by stuffs for adult cases.

Objective: To investigate the influence of Chinese medicine Huishen granule (HG) containing ginseng, grassleaved sweet flag rhizome, pilose deer antler, etc, on learning and memory functions in diffuse axonal injury (DAI) and the mechanisms thereof., Methods: Impact acceleration method was used to establish DAI Wistar rat models. Twenty model rats were randomly divided into 2 equal groups, the DAI+HG group treated with gastric perfusion of HG 3 times a day since 24 h after the establishment of model for 14 days, and the DAI group without treatment. Ten rats underwent sham operation as controls. Fourteen days after the injury, Morris water maze (MWM) test was used to detect the rat's abilities of learning and memory for continuous 5 days. The changes of escape latency in acquisition of the task, the percentage of time spent in target quadrant, and the number of crossing the point of original platform in probe test were recorded. At day 20 after the-operation, the rats were subjected to long-term potentiation (LTP) recording in hippocampus to measure the percentage of slope and baseline of excitatory post-synaptic potential (EPSP). Two rats from each group were killed 24 h, 14 d, and 20 d after the operation with their brains taken out, HE and immunohistochemical staining were employed to exam the brain lesion at 24 h, day 14 and 20 post-injury., Results: The escape latency of the DAI group was (32.8+/-4.6) s, significantly longer than those of the DAI+HG and sham operation groups [(20.3+/-0.7) and (16.8+/-0.8) s respectively, both P<0.05]. The target quadrant staying time percentage and number of platform location crossings of the DAI group were (36.4+/-3.2)% and 4.5+/-0.6 respectively, both significantly less than those of the DAI+HG and sham operation groups [(46.0+/-2.4)% and 6.8+/-0.8, and (46.9+/-2.1)% and 8.1+/-0.8 respectively, all P<0.05]. The LTP level of the DAI group was (101.4+/-3.3)%, significantly lower than those of the DAI+HG and sham operation groups [(116.3+/-6.7)% and (117.9+/-2.8)% respectively, both P<0.05]. No significant differences in the parameters were found between the DAI+HG and sham operation groups (all P>0.05). Classical pathological changes of DAI occurred in the brains of the DAI and DAI+HG groups at the time point of 24 h, and mitigated partly at the time points of day 14 and 20., Conclusion: The learning and memory impairment of DAI was ameliorated significantly with the treatment of Chinese medicine HG, owing to the recuperation of synaptic plasticity in hippocampal area.

Background: Deficits in working memory are commonly observed after traumatic brain injury (TBI), with executive control processes preferentially impacted relative to storage and rehearsal. Previous activation functional neuroimaging investigations of working memory in patients with TBI have reported altered functional recruitment, but methodologic issues including sample heterogeneity (e.g., variability in injury mechanism, severity, neuropathology or chronicity), underspecified definitions of "working memory," and behavioral differences between TBI and control groups have hindered interpretation of these changes., Methods: Executive control processing in working memory was explicitly engaged during fMRI in a sample of carefully selected chronic-stage, moderate-to-severe TBI patients with diffuse axonal injury (DAI) but without focal lesions., Results: Despite equivalent task performance, we observed a pattern of greater recruitment of interhemispheric and intrahemispheric regions of prefrontal cortex (PFC) and posterior cortices in our DAI sample. Enhanced activations were recorded in the left dorsolateral PFC (middle frontal gyrus), right ventrolateral PFC (inferior frontal gyrus), bilateral posterior parietal cortices, and left temporo-occipital junction. Region-of-interest analyses confirmed that these effects were robust across individual patients and could not be attributed to load factors or slowed speed of processing., Conclusions: Augmented functional recruitment in the context of normal behavioral performance may be a neural marker of capacity or efficiency limits that can affect functional outcome after traumatic brain injury with diffuse injury.

It is well known that traumatic brain injury particularly affects the frontal lobes. Consequently, patients often suffer from executive dysfunction and behavioral disturbances. Accordingly, our study aimed at investigating patients after traumatic brain injury with two tasks involving different functional processes and structural networks supported by the frontal lobes. Two paradigms were applied: the Stroop color-word task and a task in which subjects had to inhibit imitative response tendencies. We selected a patient group solely with diffuse axonal injury, as this type of injury is homogenous and is correlated with cognitive dysfunction more than focal contusions. To evaluate long-term effects most relevant for rehabilitation, we selected a patient group whose brain injuries dated back several years. Our results show that patients with diffuse axonal injury inhibited imitative responses more successfully than control subjects, whereas executive processes examined with the Stroop task were unaltered. Interestingly, impairments were tightly correlated both with the length of the post-traumatic amnesia predicting outcome in traumatic brain injury and with behavioral disturbances. Impairments in the imitation-inhibition task may indicate alterations in an anterior frontomedian neural network even years after traumatic brain injury.

To evaluate the utility of easy Z-score imaging system (eZIS) in 27 diffuse axonal injury (DAI) cases. Twenty-seven DAI patients were examined with an magnetic resonance imaging (MRI) T2* sequence and with eZIS (seven women, 20 men; age range, 19-35 years; median age: 26.6 years). In this investigation, we excluded patients who exhibited complications such as acute subdural hematoma, acute epidural hematoma, intracerebral hematoma, or brain contusion. We examined the neuropsychological tests and correlated with findings from MRI/eZIS. Furthermore, we evaluated the degree of ventricular enlargement in the bifrontal cerebroventricular index (CVI). Patients were divided into two groups: the enlargement group (bifrontal CVI > 35%, 12 patients) and the non-enlargement group (bifrontal CVI < 35%, 15 patients). All of the patients showed cognitive deficits as observed from the neuropsychological test results. Fifteen out of 27 patients by MRI T1/T2 weighted images and fluid attenuated inversion recovery (FLAIR), 22 out of 27 patients by MRI T2* weighted images and 24 out of 27 patients by eZIS showed abnormal findings. In MRI T2* weighted imaging, the white matter from the frontal lobe, corpus callosum, and brainstem showed abnormal findings. With eZIS, 22 patients (81.5%) showed blood flow degradation in the frontal lobe, and 12 patients (44.4%) in cingulate gyrus. In the enlargement group, Functional Independence Measure, Mini-Mental State Examination, Verbal IQ (VIQ)/Full Scale IQ (FIQ), Trail Making Test-B (TMT-B), and Non-paired of Miyake Paired Test were significantly lower. Amongst 12 patients without ventricular enlargement who had no abnormal findings in MRI T1/T2 weighted images and FLAIR, abnormal findings were detectable in seven patients with MRI T2* weighted imaging and to 10 patients with eZIS. Results of the MRI examination alone cannot fully explain DAI frontal lobe dysfunction. However, addition of the eZIS-assisted analysis derived from the single photon emission computed tomography (SPECT) data enabled us to understand regions where blood flow was decreased, i.e., where neuronal functions conceivably might be reduced.

Patients with Diffuse axonal injury (DAI) frequently exhibit cognitive disorders chronically. Radiologic recognition of DAI can help understand the clinical syndrome and to make treatment decisions. However, CT and conventional MRI are often normal or demonstrate lesions that are poorly related to the cognitive disorders. Recently, diffusion tensor imaging (DTI) fiber tractography has been shown to be useful in detecting various types of white matter damage. The aim of this study was to evaluate the feasibility of using DTI fiber tractography to detect lesions in DAI patients, and to correlate the DAI lesions with the cognitive disorders. We investigated two patients with chronic DAI. Both had impaired intelligence, as well as attention and memory disorders that restricted their activities of daily living. In both patients, DTI fiber tractography revealed interruption of the white matter fibers in the corpus collosum and the fornix, while no lesions were found on conventional MRI. The interruption of the fornix which involves the circuit of Papez potentially correlates with the memory disorder. Therefore, DTI fiber tractography may be a useful technique for the evaluation of DAI patients with cognitive disorders.

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.

Psychomotor slowing in patients with diffuse brain injury frequently underlies impaired cognitive performance on neuropsychological tests, for example, the Stroop Colored Word test. The aim of the present study was to determine the neural basis associated with performance on the Stroop interference subtask in patients with diffuse brain injury. We hypothesized that patients would be slower than healthy controls, and that this would be associated with brain activations other than those seen in healthy subjects. Brain perfusion, using a split-dose activation paradigm with single photon emission tomography (SPECT) and the Stroop test, was assessed in 9 patients with diffuse brain injury. The Stroop interference score was calculated as a behavioral parameter, and functional imaging data were analyzed with statistical parametrical mapping (SPM99) to determine significant voxel-wise differences of activation between the control and the activation condition. Patients were impaired on the interference subtask of the Stroop test. Comparison of the SPECT data obtained during the activation condition with those obtained during the control condition by means of SPM showed significant activations in the left inferior parietal lobe, the right anterior cingulate extending into the right middle frontal gyrus and the right caudate, and the left posterior cingulate cortex. Patients with diffuse brain injury were slower than healthy controls on the interference subtask of the Stroop test, suggesting difficulty with resistance to distractions. This finding was associated with activation effects in posterior (mainly parietal) brain areas in addition with activation of previously observed anterior (mainly anterior cingulate) brain regions., (Copyright 2004 Mary Ann Liebert, Inc.)

Severe diffuse traumatic brain injury (TBI) may impair the performance of daily-life complex activities. The aim of the present study was to assess whether these difficulties are related to a representational impairment of action knowledge. Two tasks requiring the manipulation of scripts were used. The first (script reconstitution) required subjects to sort cards describing actions belonging to 4 different scripts, presented in a random order. The second (script generation) required subjects to generate actions belonging to a given script. The results showed that TBI patients had preserved access to goal representation and action knowledge. However, they demonstrated (1) significant impairments when they had to deal with simultaneous competing sources of information and (2) a lack of inhibitory control on routine overlearned skills. Patients' performance was significantly correlated with behavioral modifications in everyday life. These data suggest that action impairment in severe TBI patients cannot be attributed to an impairment of action knowledge per se. As previously suggested by Schwartz et al., a restriction of limited-capacity processing resources may account for the observed deficits.

This study used a semantic-category visual search task to investigate skill acquisition and automatic process development in a severe closed-head injured (CHI) population. Eighteen severe CHI participants (> I year post injury) and 18 matched controls completed over 3600 trials of training in both consistent mapping (CM) and varied mapping (VM) training situations. Transfer conditions were also used to test for development of an automatic attention response (AAR) that was independent of general, task-related learning. For both the severe CHI and control group, CM training, where individuals always responded in the same way to a specific class of stimuli, resulted in dramatic performance improvements and the development of an AAR. In the VM training condition, where individuals could not respond in the same way to a class of stimuli from one stimulus exposure to the next, there was little performance improvement and continued reliance on controlled processes. The visual search rates of the CHI participants also remained slower than those of controls following extended VM but not extended CM practice. These results indicate that skill acquisition training guidelines can be used to teach severe CHI patients to develop a new automatic skill.

This investigation evaluated the neuropsychological symptoms in the early posttraumatic period following blunt head injury and their correlation to routine imaging data in a consecutive series of TBI patients (Magdeburg Neurotrauma Databank). Of 135 consecutive patients, 68 could be assessed neuropsychologically 8-21 days after trauma. In 61 patients, routine clinical CT data were sufficient for neuroradiological analysis focusing on the presence or absence of CT signs of diffuse axonal injury (DAI) or focal traumatic injury. In these patients, the initial GCS score was significantly correlated with the presence of DAI but not with focal pathology. The presence of DAI was correlated with behavioral and cognitive symptoms of frontal lobe dysfunction, especially in interference tasks (Go/NoGO and Stroop reaction times) and semantic fluency. The presence of local frontal or temporal traumatic lesions was associated with deficits in concept formation, fluency tasks and behavioral symptoms, but not with increased interference. Patients with frontal contusions were impaired in a task of visuomotor planning and performance (Block design). Our data indicate that both traumatic DAI and focal lesions result in frontal lobe symptoms. We conclude that, even in clinically "mild" TBI, brain imaging should be used to identify patients with substantial brain damage. These should be assessed neuropsychologically for possible posttraumatic cognitive or behavioral impairment. In consideration of its easy accessibility, the refined use of the CT is considered a promising and valid tool for patient stratification. The application of MRI and biochemical markers may further improve prognostic predictions.

The performance of 80 pediatric patients with traumatic head injury (THI) on the Wisconsin Card Sorting Test (WCST; Heaton, Chelune, Talley, Kay, & Curtiss, 1993) was examined to determine the underlying latent structure. Exploratory factor analysis with oblique rotation identified three factors: response accuracy, failure to self-monitor, and learning. The response accuracy factor was directly affected by both age and length of coma. Level of performance on this factor also covaried with post-injury psychometric intelligence. It is concluded that interpretation of the WCST results of children with THI should consider the multifactorial nature of the instrument in combination with injury severity characteristics and demographic variables.

We investigated the functional prognosis after traumatic diffuse axonal injury in children. We evaluated the status of the acute stage, as well as the functional independence measure (FIM) and intelligence quotient (IQ) at 4, 12, and 24 months after the injury. Physical disabilities persisted in all but 1 case, but 5 cases could walk by themselves after 1 year. IQ at 2 years after the injury was 64 in one case, but between 81 and 100 in others. Concerning the higher cortical function, all cases showed memory disturbance. None developed epilepsy. All cases showed abnormalities on cerebral MRI. Five of the 7 cases showed EEG abnormalities. As to the course of recovery scaled by FIM and IQ, marked improvement was seen in 4 cases during the first 4 months, 3 cases during the first 1 year. After 1 year, the degree of improvement became slower in all. All cases showed learning disability at school.