Microstructural changes in the thalamus after mild traumatic brain injury: A longitudinal diffusion and mean kurtosis tensor MRI study.

PRIMARY OBJECTIVE: The primary aim of this study was to assess microstructural changes in the thalamus, hippocampus and corpus callosum with a fast mean kurtosis tensor (MKT) technique, in the acute and sub-acute phase after mTBI. It was hypothesized that MKT would differ between baseline and follow-up in patients. The secondary aim was to relate diffusion measures to symptoms of mTBI. RESEARCH DESIGN: A longitudinal case-control study. METHODS AND PROCEDURES: Twenty-seven patients with mTBI and 27 age- and gender-matched healthy controls were enrolled in the study. Patients were scanned within 2 weeks and 3 months after mTBI, while the controls were scanned once. MAIN OUTCOMES AND RESULTS: MKT decreased significantly (p = 0.02) from baseline to follow-up in the thalamus in patients. Compared to healthy subjects, thalamic MKT values were significantly larger in patients at baseline (p = 0.048). Secondary analysis revealed a significant decrease (p = 0.01) in fractional anisotropy in the splenium of corpus callosum from baseline to follow-up. CONCLUSIONS: The current study indicates microstructural changes in the thalamus and corpus callosum from within 14 days to 3 months after mTBI and suggests MKT as a potential biomarker after mTBI.

Automatic thalamus and hippocampus segmentation from MP2RAGE: comparison of publicly available methods and implications for DTI quantification.

PURPOSE: In both structural and functional MRI, there is a need for accurate and reliable automatic segmentation of brain regions. Inconsistent segmentation reduces sensitivity and may bias results in clinical studies. The current study compares the performance of publicly available segmentation tools and their impact on diffusion quantification, emphasizing the importance of using recently developed segmentation algorithms and imaging techniques. METHODS: Four publicly available, automatic segmentation methods (volBrain, FSL, FreeSurfer and SPM) are compared to manual segmentation of the thalamus and hippocampus imaged with a recently proposed T1-weighted MRI sequence (MP2RAGE). We evaluate morphometric accuracy on 22 healthy subjects and impact on diffusivity measurements obtained from aligned diffusion-weighted images on a subset of 10 subjects. RESULTS: Compared to manual segmentation, the highest Dice similarity index of the thalamus is obtained with volBrain using a local library ([Formula: see text], [Formula: see text]) followed by volBrain using an external library ([Formula: see text], [Formula: see text]), FSL ([Formula: see text], [Formula: see text]), FreeSurfer ([Formula: see text], [Formula: see text]) and SPM ([Formula: see text], [Formula: see text]). The same order is found for hippocampus with volBrain local ([Formula: see text], [Formula: see text]), volBrain external ([Formula: see text], [Formula: see text]), FSL ([Formula: see text], [Formula: see text]), FreeSurfer ([Formula: see text], [Formula: see text]) and SPM ([Formula: see text], [Formula: see text]). For diffusivity measurements, volBrain provides values closest to those obtained from manual segmentations. volBrain is the only method where FA values do not differ significantly from manual segmentation of the thalamus. CONCLUSIONS: Overall we find that volBrain is superior in thalamus and hippocampus segmentation compared to FSL, FreeSurfer and SPM. Furthermore, the choice of segmentation technique and training library affects quantitative results from diffusivity measures in thalamus and hippocampus.

GABA levels are decreased after stroke and GABA changes during rehabilitation correlate with motor improvement.

BACKGROUND AND OBJECTIVE: γ-Aminobutyric acid (GABA) is the dominant inhibitory neurotransmitter in the brain and is important in motor learning. We aimed to measure GABA content in primary motor cortex poststroke (using GABA-edited magnetic resonance spectroscopy [MRS]) and in relation to motor recovery during 2 weeks of constraint-induced movement therapy (CIMT). METHODS: Twenty-one patients (3-12 months poststroke) and 20 healthy subjects were recruited. Magnetic resonance imaging structural T1 and GABA-edited MRS were performed at baseline and after CIMT, and once in healthy subjects. GABA:creatine (GABA:Cr) ratio was measured by GABA-edited MRS. Motor function was measured using Wolf Motor Function Test (WMFT). RESULTS: Baseline comparison between stroke patients (n = 19) and healthy subjects showed a significantly lower GABA:Cr ratio in stroke patients (P < .001) even after correcting for gray matter content in the voxel (P < .01) and when expressing GABA relative to N-acetylaspartic acid (NAA; P = .03). After 2 weeks of CIMT patients improved significantly on WMFT, but no consistent change across the group was observed for the GABA:Cr ratio (n = 17). However, the extent of improvement on WMFT correlated significantly with the magnitude of GABA:Cr changes (P < .01), with decreases in GABA:Cr ratio being associated with better improvements in motor function. CONCLUSIONS: In patients 3 to 12 months poststroke, GABA levels are lower in the primary motor cortex than in healthy subjects. The observed association between GABA and recovery warrants further studies on the potential use of GABA MRS as a biomarker in poststroke recovery.

Predicting behavioural response to TDCS in chronic motor stroke.

Transcranial direct current stimulation (TDCS) of primary motor cortex (M1) can transiently improve paretic hand function in chronic stroke. However, responses are variable so there is incentive to try to improve efficacy and or to predict response in individual patients. Both excitatory (Anodal) stimulation of ipsilesional M1 and inhibitory (Cathodal) stimulation of contralesional M1 can speed simple reaction time. Here we tested whether combining these two effects simultaneously, by using a bilateral M1-M1 electrode montage, would improve efficacy. We tested the physiological efficacy of Bilateral, Anodal or Cathodal TDCS in changing motor evoked potentials (MEPs) in the healthy brain and their behavioural efficacy in changing reaction times with the paretic hand in chronic stroke. In addition, we aimed to identify clinical or neurochemical predictors of patients' behavioural response to TDCS. There were three main findings: 1) unlike Anodal and Cathodal TDCS, Bilateral M1-M1 TDCS (1 mA, 20 min) had no significant effect on MEPs in the healthy brain or on reaction time with the paretic hand in chronic stroke patients; 2) GABA levels in ipsilesional M1 predicted patients' behavioural gains from Anodal TDCS; and 3) although patients were in the chronic phase, time since stroke (and its combination with Fugl-Meyer score) was a positive predictor of behavioural gain from Cathodal TDCS. These findings indicate the superiority of Anodal or Cathodal over Bilateral TDCS in changing motor cortico-spinal excitability in the healthy brain and in speeding reaction time in chronic stroke. The identified clinical and neurochemical markers of behavioural response should help to inform the optimization of TDCS delivery and to predict patient outcome variability in future TDCS intervention studies in chronic motor stroke.