Progressive Neurodegeneration Across Chronic Stages of Severe Traumatic Brain Injury.

OBJECTIVE: To examine the trajectory of structural gray matter changes across 2 chronic periods of recovery in individuals who have sustained severe traumatic brain injury (TBI), adding to the growing literature indicating that neurodegenerative processes occur in the months to years postinjury. PARTICIPANTS: Patients who experienced posttraumatic amnesia of 1 hour or more, and/or scored 12 or less on the Glasgow Coma Scale at the emergency department or the scene of the accident, and/or had positive brain imaging findings were recruited while receiving inpatient care, resulting in 51 patients with severe TBI. METHODS: Secondary analyses of gray matter changes across approximately 5 months, 1 year, and 2.5 years postinjury were undertaken, using an automated segmentation protocol with improved accuracy in populations with morphological anomalies. We compared patients and matched controls on regions implicated in poorer long-term clinical outcome (accumbens, amygdala, brainstem, hippocampus, thalamus). To model brain-wide patterns of change, we then conducted an exploratory principal component analysis (PCA) on the linear slopes of all regional volumes across the 3 time points. Finally, we assessed nonlinear trends across earlier (5 months-1 year) versus later (1-2.5 years) time-windows with PCA to compare degeneration rates across time. Chronic degeneration was predicted cortically and subcortically brain-wide, and within specific regions of interest. RESULTS: (1) From 5 months to 1 year, patients showed significant degeneration in the accumbens, and marginal degeneration in the amygdala, brainstem, thalamus, and the left hippocampus when examined unilaterally, compared with controls. (2) PCA components representing subcortical and temporal regions, and regions from the basal ganglia, significantly differed from controls in the first time-window. (3) Progression occurred at the same rate across both time-windows, suggesting neither escalation nor attenuation of degeneration across time. CONCLUSION: Localized yet progressive decline emphasizes the necessity of developing interventions to offset degeneration and improve long-term functioning.

Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI.

BACKGROUND: A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI). However, the progress toward clinical translation of these techniques has not been established. METHODS: A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were identified for final inclusion (97% from the initial database search). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing an increased number of publications in recent years. The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls. However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent. CONCLUSIONS: State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.

Visual-spatial ability and fMRI cortical activation in surgery residents.

BACKGROUND: We previously reported that a particular type of visual-spatial ability, mental rotation of visual forms, correlates with surgical performance in residents. In the current study, we used functional magnetic resonance imaging (fMRI) to identify patterns of cortical activation associated with mental rotation ability in those same residents. METHODS: Seventeen surgery residents underwent fMRI scan while performing a mental rotations test (MRT) and a perceptual matching task as a control (CON) for nonimagery components, such as visual attention. A contrast analysis (MRT greater than CON) revealed cortical regions engaged during mental rotation by all participants, and parametric statistical analysis identified regions having the strongest association with MRT performance. RESULTS: Significant bilateral (left greater than right) activation was seen in all participants for rotation-versus-perceptual CON contrast. Better MRT performance was associated with greater activation in several cortical regions related to visual imagery and motion processing. COMMENTS: Surgery residents represent a unique population in which to study individual differences in visual-spatial abilities and associated neural substrates because they may relate to technical skills. These findings suggest that variation in performance on spatially complex tasks involving imagery may reflect different spatial problem-solving strategies in surgery students.

Neural correlates of the prolonged salience of painful stimulation.

Pain is a unique class of sensory experience from the perspective of salience. Nonpainful somatosensory stimuli usually require behavioral relevance or voluntary attention to maintain salience. In contrast, painful stimuli tend to have sustained salience even without explicit behavioral relevance or voluntary attention. We have previously identified a frontal-parietal-cingulate network of regions responding transiently to nonpainful sensory events. This network is sensitive to the task relevance and novelty of sensory events and likely represents the salience of events in the sensory environment. Since pain can remain salient for a prolonged period, we hypothesized that this network should show transient responses to the onset or offset of a nonpainful stimulus, but sustained responses throughout the duration of a painful stimulus. To test this hypothesis, we used functional MRI to examine the response of these regions to sustained (60-s) periods of painful and nonpainful transcutaneous electrical nerve stimulation. As predicted, the temporoparietal, inferior frontal, and anterior cingulate cortex showed only transient responses to the onset or offset of nonpainful stimulation, but a sustained response throughout the duration of painful stimulation. These regions therefore show tonic responses to stimuli with tonic salience, supporting a general role for these areas in representing stimulus salience. The thalamus and putamen also responded tonically throughout painful but not nonpainful stimulation. Previous studies have implicated the basal ganglia in supporting voluntary sustained attention. Our findings suggest that the basal ganglia may play a more general role in supporting sustained salience, whether through voluntary or involuntary mechanisms.

Localization of clinically effective stimulating electrodes in the human subthalamic nucleus on magnetic resonance imaging.

OBJECT: The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD). METHODS: Fifty-four DBS electrodes were localized in and adjacent to the subthalamic nucleus (STN) postoperatively by using magnetic resonance (MR) imaging in a series of 29 patients in whom electrodes were implanted for the treatment of medically refractory PD, and for whom quantitative clinical assessments were available both pre- and postoperatively. A novel MR imaging sequence was developed that optimized visualization of the STN. The coordinates of the tips of these electrodes were calculated three dimensionally and the results were normalized and corrected for individual differences by using intraoperative neurophysiological data (mean 5.13 mm caudal to the midcommissural point [MCP], 8.46 mm inferior to the anterior commissure-posterior commissure [AC-PC], and 10.2 mm lateral to the midline). Despite reported concerns about distortion on the MR image, reconstructions provided consistent data for the localization of electrodes. The neurosurgical procedures used, which were guided by combined neuroimaging and neurophysiological methods, resulted in the consistent placement of DBS electrodes in the subthalamus and mesencephalon such that the electrode contacts passed through the STN and dorsally adjacent fields of Forel (FF) and zona incerta (ZI). The mean location of the clinically effective contacts was in the anterodorsal STN (mean 1.62 mm posterior to the MCP, 2.47 mm inferior to the AC-PC, and 11.72 mm lateral to the midline). Clinically effective stimulation was most commonly directed at the anterodorsal STN, with the current spreading into the dorsally adjacent FF and ZI. CONCLUSIONS: The anatomical localization of clinically effective electrode contacts provided in this study yields useful information for the postoperative programming of DBS electrodes.

A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities.

Stimulus salience depends both on behavioral context and on other factors such as novelty and frequency of occurrence. The temporo-parietal junction (TPJ) responds preferentially to behaviorally relevant stimuli and is thought to play a general role in detecting salient stimuli. If so, it should respond preferentially to novel or infrequent events, even in a neutral behavioral context. To test this hypothesis, we used event-related functional magnetic resonance imaging (fMRI) to identify brain regions sensitive to the novelty of visual, auditory, and tactile stimuli during passive observation. Cortical regions with a greater response to novel than familiar stimuli across all modalities were identified at two sites in the TPJ region: the supramarginal gyrus (SMG) and superior temporal gyrus. The right inferior frontal gyrus (IFG), right anterior insula, left anterior cingulate cortex (ACC), and left inferior temporal gyrus also showed sensitivity to novelty. The novelty-sensitive TPJ activation in SMG overlaps a region previously identified as sensitive behavioral context. This region may play a general role in identifying salient stimuli, whether the salience is due to the current behavioral context or not. The IFG activation overlaps regions previously identified as responsive to nonnovel sensory events regardless of behavioral context. The IFG may therefore play a general role in stimulus evaluation rather than a specific role in identifying novel stimuli. The ACC activation lies in a region active during complex response-selection tasks, suggesting a general role in detecting and/or planning responses to salient events. A frontal-parietal-cingulate network may serve to identify and evaluate salient sensory stimuli in general.