Glutamate and GABA concentrations following mild traumatic brain injury: a pilot study.

Animal models of mild traumatic brain injury (mTBI) suggest that metabolic changes in the brain occur immediately after a mechanical injury to the head. Proton magnetic resonance spectroscopy (1H-MRS) can be used to determine relative concentrations of metabolites in vivo in the human brain. The purpose of this study was to determine concentrations of glutamate and GABA in the brain acutely after mTBI and throughout 2 mo of recovery. Concentrations of glutamate and GABA were obtained using 1H-MRS in nine individuals who had suffered an mTBI and nine control individuals in two brain regions of interest: the primary motor cortex (M1), and the dorsolateral prefrontal cortex (DLPFC), and at three different time points postinjury: 72 h, 2 wk, and 2 mo postinjury. There were no differences between groups in concentrations of glutamate or GABA, or the ratio of glutamate to GABA, in M1. In the DLPFC, glutamate concentration was lower in the mTBI group compared with controls at 72 h postinjury (d = 1.02), and GABA concentration was lower in the mTBI group at 72 h and 2 wk postinjury (d = 0.81 and d = 1.21, respectively). The ratio of glutamate to GABA in the DLPFC was higher in the mTBI group at 2 wk postinjury (d = 1.63). These results suggest that changes in glutamate and GABA concentrations in the brain may be region-specific and may depend on the amount of time that has elapsed postinjury. NEW & NOTEWORTHY To our knowledge, this is the first study to examine neurotransmitter concentrations in vivo at multiple time points throughout recovery from mild traumatic brain injury in humans.

Reorganization of sensorimotor representations of the intact limb after upper but not lower limb traumatic amputation.

It is becoming increasingly clear that limb loss induces wider spread reorganization of representations of the body that are nonadjacent to the affected cortical territory. Data from upper extremity amputees reveal intrusion of the representation of the ipsilateral intact limb into the former hand territory. Here we test for the first time whether this reorganization of the intact limb into the deprived cortex is specific to the neurological organization of the upper limbs or reflects large scale adaptation that is triggered by any unilateral amputation. BOLD activity was measured as human subjects with upper limb and lower limb traumatic amputation and their controls moved the toes on each foot, open and closed each hand and pursed their lips. Subjects with amputation were asked to imagine moving the missing limb while remaining still. Bayesian pattern component modeling of fMRI data showed that intact ipsilateral movements and contralateral movements of the hand and foot were distinctly represented in the deprived sensorimotor cortex years after upper limb amputation. In contrast, there was evidence reminiscent of contralateral specificity for hand and foot movements following lower limb amputation, like that seen in controls. We propose the cortical reorganization of the intact limb to be a function of use-dependent plasticity that is more specific to the consequence of upper limb loss of forcing an asymmetric reliance on the intact hand and arm. The contribution of this reorganization to phantom pain or a heightened risk of overuse and resultant maladaptive plasticity needs investigating before targeting such reorganization in intervention.

Can this data be saved? Techniques for high motion in resting state scans of first grade children.

Motion remains a significant technical hurdle in fMRI studies of young children. Our aim was to develop a straightforward and effective method for obtaining and preprocessing resting state data from a high-motion pediatric cohort. This approach combines real-time monitoring of head motion with a preprocessing pipeline that uses volume censoring and concatenation alongside independent component analysis based denoising. We evaluated this method using a sample of 108 first grade children (age 6-8) enrolled in a longitudinal study of math development. Data quality was assessed by analyzing the correlation between participant head motion and two key metrics for resting state data, temporal signal-to-noise and functional connectivity. These correlations should be minimal in the absence of noise-related artifacts. We compared these data quality indicators using several censoring thresholds to determine the necessary degree of censoring. Volume censoring was highly effective at removing motion-corrupted volumes and ICA denoising removed much of the remaining motion artifact. With the censoring threshold set to exclude volumes that exceeded a framewise displacement of 0.3 mm, preprocessed data met rigorous standards for data quality while retaining a large majority of subjects (83 % of participants). Overall, results show it is possible to obtain usable resting-state data despite extreme motion in a group of young, untrained subjects.

Chronically deafferented sensory cortex recovers a grossly typical organization after allogenic hand transplantation.

Amputation induces substantial reorganization of the body part somatotopy in primary sensory cortex (S1 complex, hereafter S1) [1, 2], and these effects of deafferentiation increase with time [3]. Determining whether these changes are reversible is critical for understanding the potential to recover from deafferenting injuries. Earlier BOLD fMRI data demonstrate increased S1 activity in response to stimulation of an allogenically transplanted hand [4]. Here, we report the first evidence that the representation of a transplanted hand can actually recapture the pre-amputation S1 hand territory. A 54-year-old male received a unilateral hand transplant 35 years after traumatic amputation of his right hand. Despite limited sensation, palmar tactile stimulation delivered 4 months post-transplant evoked contralateral S1 responses that were indistinguishable in location and amplitude from those detected in healthy matched controls. We find no evidence for persistent intrusion of representations of the face within the representation of the transplanted hand, although such intrusions are commonly reported in amputees [5, 6]. Our results suggest that even decades after complete deafferentiation, restoring afferent input to S1 leads to re-establishment of the gross hand representation within its original territory. Unexpectedly, large ipsilateral S1 responses accompanied sensory stimulation of the patient's intact hand. These may reflect a change in interhemispheric inhibition that could contribute to maintaining latent hand representations during the period of amputation.

Reliability of glutamate and GABA quantification using proton magnetic resonance spectroscopy.

The consistency and reliability of proton magnetic resonance spectroscopy (1H-MRS) assessments of neurotransmitter concentration has not been widely examined over multiple days. The purpose of this study was to determine the reliability of glutamate and GABA measures using a single-voxel 1H-MRS protocol in healthy men and women. Glutamate and GABA quantitations were obtained from the primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) in 13 healthy individuals across 3 data collection sessions, including a baseline (Visit 1), 2-week (Visit 2), and 2-month time point (Visit 3). Glutamate concentrations were similar across visits in M1 (p=0.72) and the DLPFC (p=0.52). Reliability across days was excellent in M1 (R=0.93), and in the DLPFC (R=0.99). GABA concentrations were similar across visits in M1 (p=0.44) and in the DLPFC (p=0.59). Reliability of GABA concentration across days was excellent in M1 (R=0.93), and in the DLPFC (R=0.97). 1H-MRS is a reliable method for quantifying glutamate and GABA concentration in M1 and the DLPFC in humans.

The first step for neuroimaging data analysis: DICOM to NIfTI conversion.

BACKGROUND: Clinical imaging data are typically stored and transferred in the DICOM format, whereas the NIfTI format has been widely adopted by scientists in the neuroimaging community. Therefore, a vital initial step in processing the data is to convert images from the complicated DICOM format to the much simpler NIfTI format. While there are a number of tools that usually handle DICOM to NIfTI conversion seamlessly, some variations can disrupt this process. NEW METHOD: We provide some insight into the challenges faced with image conversion. First, different manufacturers implement the DICOM format differently which complicates the conversion. Second, different modalities and sub-modalities may need special treatment during conversion. Lastly, the image transferring and archiving can also impact the DICOM conversion. RESULTS: We present results in several error-prone domains, including the slice order for functional imaging, phase encoding direction for distortion correction, effect of diffusion gradient direction, and effect of gantry correction for some imaging modality. COMPARISON WITH EXISTING METHODS: Conversion tools are often designed for a specific manufacturer or modality. The tools and insight we present here are aimed at different manufacturers or modalities. CONCLUSIONS: The imaging conversion is complicated by the variation of images. An understanding of the conversion basics can be helpful for identifying the source of the error. Here we provide users with simple methods for detecting and correcting problems. This also serves as an overview for developers who wish to either develop their own tools or adapt the open source tools created by the authors.

Former hand territory activity increases after amputation during intact hand movements, but is unaffected by illusory visual feedback.

BACKGROUND: In healthy adults, hand movements are controlled largely by the contralateral primary motor cortex. Following amputation, however, movements of the intact hand are accompanied by increased activity in the sensorimotor cortices of both cerebral hemispheres. OBJECTIVE: The authors tested whether use of the intact hand reactivates the cortical territory formerly devoted to the now missing hand and whether these effects can be augmented by motor imagery (MI) and/or exposure to illusory visual "feedback" (VF) of the absent hand created with a mirror. METHODS: Functional magnetic resonance imaging (fMRI) was used to delineate the boundaries of normative sensorimotor hand representations in healthy controls. Brain activity from 11 unilateral hand amputees was recorded while they performed aurally paced thumb-finger sequencing movements with their intact hands under 4 conditions: (1) motor execution of the intact hand alone (ME), (2) ME with corresponding MI of the amputated hand, (3) ME with VF of the amputated hand, and (4) ME with MI and VF. RESULTS: Intact hand movements increased activity specifically within the former sensorimotor hand territory during all conditions, an effect that may be attributable to decreased levels of interhemispheric inhibition and/or use-dependent functional reorganization following amputation. This effect was not significantly increased by the addition of VF and/or MI of the amputated hand. However, in amputees, MI was associated with an expansion of this ipsilateral response into parietal, premotor, and presupplementary motor areas. CONCLUSION: Active engagement of the intact hand may be critical for therapies seeking to stimulate the former hand territory.

Towards a microcoil for intracranial and intraductal MR microscopy.

Implantable RF-coils have enabled sub-mm resolution magnetic resonance images (MRI) of deep structures. Scaling down the size of RF coils has similarly provided a gain in signal-to-noise ratio in nuclear-magnetic-resonance spectroscopy. By combining both approaches we designed, fabricated, and imaged with an implantable microcoil catheter. While typical implantable catheters use a transverse magnetization, the axial magnetization of the microcoil provides improved sensitivity and allows visualization of the tissue beyond the distal end of the catheter. The microcoil catheter was designed with a diameter of 1 mm for future integration with intracranial devices, and for intraductal use in breast oncology. We modified the NMR-microcoil design to allow implantation of the RF coil, by winding the microcoil on medical-grade silicone tubing and incorporating leads on the catheter to connect circuit components. In order to achieve proper turn spacing, we coated copper wire with 25 microm of biocompatible polymer (Parylene C). Tuning and matching circuitry insured that the impedance of the RF coil was approximately 50 ohm at the operating frequency for 3-T proton MR applications. A duplexer was used to enable use of the microcoil catheter as a transceiver. Experimental verification of the coil design was achieved through ex vivo imaging of neural tissue. As expected, the microcoil catheter provided microscale images with 20-microm in-plane-resolution and 170-microm-thick slices. While 3-T MRI typically provides 1 to 30 voxels per-cubic-millimeter, in this paper we report that the MRI microcoil can provide hundreds, and even thousands of voxels in the same volume.