Diffusion kurtosis and quantitative susceptibility mapping MRI are sensitive to structural abnormalities in amyotrophic lateral sclerosis.

OBJECTIVE: To construct a clinical diagnostic biomarker using state-of-the-art microstructural MRI in the motor cortex of people with amyotrophic lateral sclerosis (ALS). METHODS: Clinical and MRI data were obtained from 21 ALS patients (aged 54 ±â€¯14 years, 33% female) and 63 age- and gender-matched controls (aged 48 ±â€¯18 years, 43% female). MRI was acquired at 3T and included T1-weighted scan (for volumetrics), arterial spin labelling (for cerebral blood flow), susceptibility-weighted angiography (for iron deposition) and multiband diffusion kurtosis imaging (for tissue microstructure). Group differences in imaging measures in the motor cortex were tested by general linear model and relationships to clinical variables by linear regression. RESULTS: The ALS group had mild-to-moderate impairment (disease duration: 1.8 ±â€¯0.8 years; ALS functional rating scale 40.2 ±â€¯6.0; forced vital capacity 83% ±â€¯22%). No age or gender differences were present between groups. We found significant group differences in diffusion kurtosis metrics (apparent, mean, radial and axial kurtosis: p < .01) and iron deposition in the motor cortex (p = .03). Within the ALS group, we found significant relationships between motor cortex volume, apparent diffusion and disease duration (adjusted R2 = 0.27, p = .011); and between the apparent and radial kurtosis metrics and ALS functional rating scale (adjusted R2 = 0.25, p = .033). A composite imaging biomarker comprising kurtosis and iron deposition measures yielded a maximal diagnostic accuracy of 83% (81% sensitivity, 85% specificity) and an area-under-the-curve of 0.86. CONCLUSION: Diffusion kurtosis is sensitive to early changes present in the motor region in ALS. We propose a composite imaging biomarker reflecting tissue microstructural changes in early ALS that may provide clinically valuable diagnostic information.

Revealing the Hippocampal Connectome through Super-Resolution 1150-Direction Diffusion MRI.

The hippocampus is a key component of emotional and memory circuits and is broadly connected throughout the brain. We tracked the whole-brain connections of white matter fibres from the hippocampus using ultra-high angular resolution diffusion MRI in both a single 1150-direction dataset and a large normal cohort (n = 94; 391-directions). Using a connectomic approach, we identified six dominant pathways in terms of strength, length and anatomy, and characterised them by their age and gender variation. The strongest individual connection was to the ipsilateral thalamus. There was a strong age dependence of hippocampal connectivity to medial occipital regions. Overall, our results concur with preclinical and ex-vivo data, confirming that meaningful in vivo characterisation of hippocampal connections is possible in an individual. Our findings extend the collective knowledge of hippocampal anatomy, highlighting the importance of the spinal-limbic pathway and the striking lack of hippocampal connectivity with motor and sensory cortices.

Regional brain volumes in body dysmorphic disorder compared to controls.

OBJECTIVES: Body dysmorphic disorder (BDD) is characterized by a preoccupation with a misperceived flaw in appearance, causing significant distress and disability. Neuropsychological research has revealed deficits in executive function and inhibitory control of emotional responses. The few previous structural neuroimaging studies have had inconclusive findings and we aimed to take this field of research forward by contributing high quality structural data. METHODS: To investigate regional brain volumes we compared 20 BDD participants and 20 matched controls using high-resolution structural T1-weighted magnetic resonance imaging (MRI). The MRI data was subjected to cortical reconstruction and volumetric segmentation using Freesurfer software. RESULTS: Results showed the right orbitofrontal cortex, bilateral thalamus, left anterior cingulate cortex, hippocampus and amygdala were significantly smaller in the BDD sample compared to controls. The most pronounced differences were in the right orbitofrontal cortex and left anterior cingulate cortex, as these areas were smaller in BDD participants independent of reduced global brain volumes. Duration of illness significantly negatively correlated with right orbitofrontal cortex volumes. CONCLUSIONS: This is the largest volumetric neuroimaging study in BDD to date and provides important data on volumetric differences that implicate fronto-limbic circuits.

GABA and cortical inhibition in motor and non-motor regions using combined TMS-EEG: a time analysis.

OBJECTIVE: The induction of long interval cortical inhibition (LICI) in motor cortex with paired pulse transcranial magnetic stimulation (ppTMS) is an established paradigm for the assessment of cortical inhibition, proposed to be related to GABA(B) receptor inhibitory neurotransmission. This study aimed to further evaluate recent methods of the assessment of LICI in non motor regions with ppTMS and electroencephalography (EEG). METHODS: ppTMS was applied using a single coil to the motor and dorsolateral prefrontal cortex (DLPFC) in 14 healthy subjects, and in the parietal lobe in 5 of those subjects. RESULTS: In the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250 ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250 ms in DLPFC, and between 50 and 175 ms in the parietal lobe. CONCLUSIONS: ppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABA(B) activity. SIGNIFICANCE: ppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABA(B) activity.