A thalamocortical mechanism for the absence of overt motor behavior in covertly aware patients:Thalamocortical Mechanism for the Absence of Overt Motor Behavior

Importance It is well accepted that a significant number of patients in a vegetative state are covertly aware and capable of following commands by modulating their neural responses in motor imagery tasks despite remaining nonresponsive behaviorally. To date, there have been few attempts to explain this dissociation between preserved covert motor behavior and absent overt motor behavior. Objectives To investigate the differential neural substrates of overt and covert motor behavior and assess the structural integrity of the underlying networks in behaviorally nonresponsive patients. Design, Setting, and Participants A case-control study was conducted at an academic center between February 7, 2012, and November 6, 2014. Data analysis was performed between March 2014 and June 2015. Participants included a convenience sample of 2 patients with severe brain injury: a paradigmatic patient who fulfilled all clinical criteria for the vegetative state but produced repeated evidence of covert awareness (patient 1) and, as a control case, a patient with similar clinical variables but capable of behavioral command following (patient 2). Fifteen volunteers participated in the study as a healthy control group. Main Outcomes and Measures We used dynamic causal modeling of functional magnetic resonance imaging to compare voluntary motor imagery and motor execution. We then used fiber tractography to assess the structural integrity of the fibers that our functional magnetic resonance imaging study revealed as essential for successful motor execution. Results The functional magnetic resonance imaging study revealed that, in contrast to mental imagery, motor execution was associated with an excitatory coupling between the thalamus and primary motor cortex (Bayesian model selection; winning model Bayes factors >17). Moreover, we detected a selective structural disruption in the fibers connecting these 2 regions in patient 1 (fractional anisotropy, 0.294; P = .047) but not in patient 2 (fractional anisotropy, 0.413; P = .35). Conclusions and Relevance These results suggest a possible biomarker for the absence of intentional movement in covertly aware patients (ie, specific damage to motor thalamocortical fibers), highlight the importance of the thalamus for the execution of intentional movements, and may provide a target for restorative therapies in behaviorally nonresponsive patients

Diffusion tensor imaging and white matter abnormalities in patients with disorders of consciousness.

Progress in neuroimaging has yielded new powerful tools which, potentially, can be applied to clinical populations, improve the diagnosis of neurological disorders and predict outcome. At present, the diagnosis of consciousness disorders is limited to subjective assessment and objective measurements of behavior, with an emerging role for neuroimaging techniques. In this review we focus on white matter alterations measured using Diffusion Tensor Imaging on patients with consciousness disorders, examining the most common diffusion imaging acquisition protocols and considering the main issues related to diffusion imaging analyses. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps and the potential role of neuroimaging in understanding the pathogenesis and clinical features of disorders of consciousness

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness. Methods fMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits. Results fMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus. Conclusions These results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.Published versio

Diffusion tensor imaging differences relate to memory deficits in diffuse traumatic brain injury

BACKGROUND: Memory is one of the most impaired functions after traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to determine the structural basis of memory deficit. We correlated fractional anisotropy (FA) of the fasciculi connecting the main cerebral regions that are involved in declarative and working memory functions. METHODS: Fifteen patients with severe and diffuse TBI and sixteen healthy controls matched by age and years of education were scanned. The neuropsychological assessment included: Letter-number sequencing test (LNS), 2-back task, digit span (forwards and backwards) and the Rivermead profilet. DTI was analyzed by a tract-based spatial statics (TBSS) approach. RESULTS: Whole brain DTI analysis showed a global decrease in FA values that correlated with the 2-back d-prime index, but not with the Rivermead profile. ROI analysis revealed positive correlations between working memory performance assessed by 2-back d-prime and superior longitudinal fasciculi, corpus callosum, arcuate fasciculi and fornix. Declarative memory assessed by the Rivermead profile scores correlated with the fornix and the corpus callosum. CONCLUSIONS: Diffuse TBI is associated with a general decrease of white matter integrity. Nevertheless deficits in specific memory domains are related to different patterns of white matter damage

Long-term declarative memory deficits in diffuse TBI:correlations with cortical thickness, white matter integrity and hippocampal volume

We investigated structural brain damage in subjects who had suffered severe and diffuse traumatic brain injury (TBI), and examined its relationship with declarative memory impairment. Cortical thickness, diffusion tensor imaging (DTI), and volumetric and shape data of the hippocampus were assessed in a group of 26 adults with severe TBI in the chronic stage and 22 healthy matched controls. Declarative memory was evaluated by Rey’s Auditory Verbal Learning Test (RAVLT). TBI patients performed significantly worse than controls on all RAVLT measures. The group comparison for cortical thickness and DTI revealed a pattern of widespread atrophy in TBI patients. In the TBI group DTI measures correlated with cortical thickness in the prefrontal and parietal regions, including the precuneus. Declarative memory correlated with both cortical thickness and DTI measures. However, although hippocampal volume was significantly decreased in TBI patients, no correlations were found. Multiple regression analysis of all the structural measures revealed that decreases in Fractional anisotropy (FA) and thinning of the left parietal region were the best predictors of memory impairment. In conclusion, cortical thickness reductions in the left hemisphere and a lack of white matter integrity are the main contributors to long-term impairment in declarative memory among patients suffering from severe and diffuse TBI. In this study the hippocampus did not make a significant contribution to memory dysfunctions, suggesting that damage to this structure is compensated for by other regions, with the definitive sequelae being mainly explained by alterations in corticosubcortical connectivityMedicin

Diffusion tensor imaging differences relate to memory deficits in diffuse traumatic brain injury

Abstract Background Memory is one of the most impaired functions after traumatic brain injury (TBI). We used diffusion tensor imaging (DTI) to determine the structural basis of memory deficit. We correlated fractional anisotropy (FA) of the fasciculi connecting the main cerebral regions that are involved in declarative and working memory functions. Methods Fifteen patients with severe and diffuse TBI and sixteen healthy controls matched by age and years of education were scanned. The neuropsychological assessment included: Letter-number sequencing test (LNS), 2-back task, digit span (forwards and backwards) and the Rivermead profilet. DTI was analyzed by a tract-based spatial statics (TBSS) approach. Results Whole brain DTI analysis showed a global decrease in FA values that correlated with the 2-back d-prime index, but not with the Rivermead profile. ROI analysis revealed positive correlations between working memory performance assessed by 2-back d-prime and superior longitudinal fasciculi, corpus callosum, arcuate fasciculi and fornix. Declarative memory assessed by the Rivermead profile scores correlated with the fornix and the corpus callosum. Conclusions Diffuse TBI is associated with a general decrease of white matter integrity. Nevertheless deficits in specific memory domains are related to different patterns of white matter damage.</p

A longitudinal fMRI study of working memory in severe TBI patients with diffuse axonal injury

AbstractTraumatic brain injury (TBI) patients have working memory deficits and altered patterns of brain activation during this function. The evolution of the impairment has not been examined to date. This study investigated longitudinal changes in brain activation during a working memory task. Twelve patients with severe and diffuse TBI and ten healthy matched controls were fMRI scanned twice at a 6-month interval during an n-back task (0-, 2- and 3-back). All the TBI patients selected presented signs of diffuse axonal injury on CT but had no evidence of focal lesions on MRI clinical examination. Significant changes in brain activation over time were observed in patients, but not in controls. During the first examination, though both groups engaged bilateral fronto-parietal regions known to be involved in working memory, activation of the right superior frontal gyrus was low in the TBI group. However, the difference between TBI and controls had decreased significantly after 6 months. A factor analysis confirmed the greater increase in activation in the right superior frontal cortex in the TBI group than in healthy controls, leading to normalization of the brain activation pattern. In conclusion, this longitudinal study provides evidence of a progressive normalization of the working memory activation pattern after diffuse axonal injury in severe TBI, coinciding with an improvement in performance on this function