Roderick McColl

Magnetic resonance imaging of cerebellar–prefrontal and cerebellar–parietal functional connectivity

Recent studies of the cerebellum indicated its involvement in a diverse array of functions, and analyses of non-human primate neuroanatomy have revealed connections between cerebellum and cerebral cortex that might support cerebellar contributions to a wider range of functions than traditionally thought. These include cortico-ponto-cerebellar projections originating throughout cerebral cortex, in addition to projections from the dentate nucleus of the cerebellum to prefrontal and posterior parietal cortices via the thalamus. Such projections likely serve as important substrates for cerebellar involvement in human cognition, assuming their analogues are prominent in the human brain. These connections can be examined from a functional perspective through the use of functional connectivity MRI (FCMRI), a technique that allows the in vivo examination of coherence in MR signal among functionally related brain regions. Using this approach, low-frequency fluctuations in MR signal in the dentate nucleus correlated with signal fluctuations in cerebellar, thalamic, limbic, striatal, and cerebrocortical regions including parietal and frontal sites, with prominent coherence in dorsolateral prefrontal cortex. These findings indicate that FCMRI is a useful tool for examining functional relationships between the cerebellum and other brain regions, and they support the findings from non-human primate studies showing anatomic projections from cerebellum to regions of cerebral cortex with known involvement in higher cognitive functions. To our knowledge, this represents the first demonstration of functional coherence between the dentate nucleus and parietal and prefrontal cortices in the human brain, suggesting the presence of cerebellar-parietal and cerebellar-prefrontal functional connectivity.

The neuro-ophthalmology of multiple sclerosis

Multiple sclerosis (MS) is the most common disabling neurological disease in young people. Most CNS lesions involve neuroanatomically non-eloquent zones that often do not result in symptomatic complaints. By contrast, tissue-injury mechanisms involving inflammatory demyelination can involve more eloquent sites, such as the optic nerve and brainstem, which can correspondingly produce the development of well recognised syndromes such as optic neuritis and internuclear ophthalmoplegia, respectively. In this review we discuss the broad landscape of abnormalities that affect the afferent visual system and the ocular motor apparatus, and emphasise relevant features, the recognition and treatment of which are of importance to general neurological practice. The commonness of visual sensory and eye movement abnormalities in MS highlights the importance of understanding the principles addressed in this review.

Activation of the insular cortex during dynamic exercise in humans

1 The insular cortex has been implicated as a region of cortical cardiovascular control, yet its role during exercise remains undefined. The purpose of the present investigation was to determine whether the insular cortex was activated during volitional dynamic exercise and to evaluate further its role as a site for regulation of autonomic activity. 2 Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3 Increases in regional cerebral blood flow (rCBF) distribution were determined for each individual using single‐photon emission‐computed tomography (SPECT) co‐registered with magnetic resonance (MR) images to define exact anatomical sites of cerebral activation during each condition. 4 The rCBF significantly increased in the left insula during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling alone. 5 These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical stimulation support the role of leg muscle afferent input towards the full activation of leg motor areas.

Assessment of Coronary Arterial Flow and Flow Reserve in Humans With Magnetic Resonance Imaging

BACKGROUND The noninvasive measurement of absolute epicardial coronary arterial flow and flow reserve would be useful in the evaluation of patients with coronary circulatory disorders. Phase-contrast magnetic resonance imaging (PC-MRI) has been used to measure coronary arterial flow in animals, but its accuracy in humans is unknown. METHODS AND RESULTS Twelve subjects (7 men, 5 women: age 44 to 67 years) underwent PC-MRI measurements of flow in the left anterior descending coronary artery or one of its diagonal branches at rest and after administration of adenosine (140 microgram . kg(-1) . min (-1) IV). Immediately thereafter, intracoronary Doppler velocity (IDV) and flow measurements were made during cardiac catheterization at rest and after intravenous administration of adenosine. For the 12 patients, the correlation between MRI and invasive measurements of coronary arterial flow and coronary arterial flow reserve was excellent: coronary flow (MRI) (mL/min)= 0.85 x coronary flow (IDV) (mL/min)+17 (mL/min), r=.89, and coronary flow reserve (MRI) =0.79 x coronary velocity reserve (IDV) + 0.34, r=.89. For the range of coronary arterial flows (18 to 161 mL/min) measured by MRI, the limit of agreement between MRI and catheterization measurements of flow was -13+/-30 mL/min; for the range of coronary reserves (0.7 to 3.7) measured by MRI, the limit of agreement between the two techniques was 0.1+/-0.4. CONCLUSIONS Cine velocity-encoded PC-MRI can noninvasively measure absolute coronary arterial flow in the left anterior descending artery in humans. PC-MRI can detect pharmacologically induced changes in coronary arterial flow and can reliably distinguish between those subjects with normal and abnormal coronary artery flow reserve.

Changes in supraspinal activation patterns following robotic locomotor therapy in motor-incomplete spinal cord injury.

Objectives. Body weight-supported treadmill training (BWSTT) is a task-specific rehabilitation strategy that enhances functional locomotion in patients following spinal cord injury (SCI). Supraspinal centers may play an important role in the recovery of over-ground locomotor function in patients with motor-incomplete SCI. The purpose of this study was to evaluate the potential for supraspinal reorganization associated with 12 weeks of robotic BWSTT using functional magnetic resonance imaging (fMRI). Methods. Four men with motor-incomplete SCI participated in this study. Time since onset ranged from 14 weeks to 48 months post-SCI injury. All subjects were trained with BWSTT 3 times weekly for 12 weeks. This training was preceded and followed by fMRI study of supraspinal activity during a movement task. Testing of locomotor disability included the Walking Index for Spinal Cord Injury (WISCI II) and over-ground gait speed. Results. All subjects demonstrated some degree of change in the blood-oxygen-level-dependent (BOLD) signal following BWSTT. fMRI results demonstrated greater activation in sensorimotor cortical regions (S1, S2) and cerebellar regions following BWSTT. Conclusions. Intensive task-specific rehabilitative training, such as robotic BWSTT, can promote supraspinal plasticity in the motor centers known to be involved in locomotion. Furthermore, improvement in over-ground locomotion is accompanied by an increased activation of the cerebellum.

Brain connectivity in non-reading impaired children and children diagnosed with developmental dyslexia

Diffusion Tensor Imaging (DTI) was used to investigate the relationship between white matter and reading abilities in reading impaired and non-reading impaired children. Seventeen children (7 non-reading impaired, 10 reading impaired) participated in this study. DTI was performed with 2mm isotropic resolution to cover the entire brain along 30 noncollinear directions. Voxelwise analyses were conducted on data processed through Tract Based Spatial Statistics (TBSS). The data replicated previous results seen across multiple studies and extended findings to include measures of both real word and pseudoword decoding. Negative correlations were observed in the left posterior corpus callosum between fractional anisotropy (FA) values and both measures of decoding. Positive correlations between FA values and real word and pseudoword decoding were observed in the left superior corona radiata. This extension of findings regarding correlations between the corona radiata and reading skills suggests an important direction for future research into the neurological substrates of reading.

Cerebral Atrophy after Traumatic White Matter Injury: Correlation with Acute Neuroimaging and Outcome

Traumatic brain injury (TBI) is a pathologically heterogeneous disease, including injury to both neuronal cell bodies and axonal processes. Global atrophy of both gray and white matter is common after TBI. This study was designed to determine the relationship between neuroimaging markers of acute diffuse axonal injury (DAI) and cerebral atrophy months later. We performed high-resolution magnetic resonance imaging (MRI) at 3 Tesla (T) in 20 patients who suffered non-penetrating TBI, during the acute (within 1 month after the injury) and chronic stage (at least 6 months after the injury). Volume of abnormal fluid-attenuated inversion-recovery (FLAIR) signal seen in white matter in both acute and follow-up scans was quantified. White and gray matter volumes were also quantified. Functional outcome was measured using the Functional Status Examination (FSE) at the time of the chronic scan. Change in brain volumes, including whole brain volume (WBV), white matter volume (WMV), and gray matter volume (GMV), correlates significantly with acute DAI volume (r = -0.69, -0.59, -0.58, respectively; p <0.01 for all). Volume of acute FLAIR hyperintensities correlates with volume of decreased FLAIR signal in the follow-up scans (r = -0.86, p < 0.001). FSE performance correlates with acute hyperintensity volume and chronic cerebral atrophy (r = 0.53, p = 0.02; r = -0.45, p = 0.03, respectively). Acute axonal lesions measured by FLAIR imaging are strongly predictive of post-traumatic cerebral atrophy. Our findings suggest that axonal pathology measured as white matter lesions following TBI can be identified using MRI, and may be a useful measure for DAI-directed therapies.

Regionally Selective Atrophy after Traumatic Axonal Injury

OBJECTIVES To determine the spatial distribution of cortical and subcortical volume loss in patients with diffuse traumatic axonal injury and to assess the relationship between regional atrophy and functional outcome. DESIGN Prospective imaging study. Longitudinal changes in global and regional brain volumes were assessed using high-resolution magnetic resonance imaging-based morphometric analysis. SETTING Inpatient traumatic brain injury unit. PATIENTS OR OTHER PARTICIPANTS Twenty-five patients with diffuse traumatic axonal injury and 22 age- and sex-matched controls. MAIN OUTCOME MEASURE Changes in global and regional brain volumes between initial and follow-up magnetic resonance imaging were used to assess the spatial distribution of posttraumatic volume loss. The Glasgow Outcome Scale-Extended score was the primary measure of functional outcome. RESULTS Patients underwent substantial global atrophy with mean whole-brain parenchymal volume loss of 4.5% (95% confidence interval, 2.7%-6.3%). Decreases in volume (at a false discovery rate of 0.05) were seen in several brain regions including the amygdala, hippocampus, thalamus, corpus callosum, putamen, precuneus, postcentral gyrus, paracentral lobule, and parietal and frontal cortices, while other regions such as the caudate and inferior temporal cortex were relatively resistant to atrophy. Loss of whole-brain parenchymal volume was predictive of long-term disability, as was atrophy of particular brain regions including the inferior parietal cortex, pars orbitalis, pericalcarine cortex, and supramarginal gyrus. CONCLUSION Traumatic axonal injury leads to substantial posttraumatic atrophy that is regionally selective rather than diffuse, and volume loss in certain regions may have prognostic value for functional recovery.

Blood oxygenation level-dependent (BOLD) contrast magnetic resonance imaging (MRI) for prediction of breast cancer chemotherapy response: A pilot study

To determine whether a simple noninvasive method of assessing tumor oxygenation is feasible in the clinical setting and can provide useful, potentially predictive information. Tumor microcirculation and oxygenation play critical roles in tumor growth and responsiveness to cytotoxic treatment and may provide prognostic indicators for cancer therapy. Deoxyhemoglobin is paramagnetic and can serve as an endogenous contrast agent causing signal loss in echo planar magnetic resonance imaging (MRI) (blood oxygenation level‐dependent [BOLD]‐MRI). We used BOLD‐MRI to provide early evaluation of response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Diffusion Tensor Imaging Biomarkers for Traumatic Axonal Injury: Analysis of Three Analytic Methods

Traumatic axonal injury (TAI) is a common mechanism of traumatic brain injury not readily identified using conventional neuroimaging modalities. Novel imaging modalities such as diffusion tensor imaging (DTI) can detect microstructural compromise in white matter (WM) in various clinical populations including TAI. DTI-derived data can be analyzed using global methods (i.e., WM histogram or voxel-based approaches) or a regional approach (i.e., tractography). While each of these methods produce qualitatively comparable results, it is not clear which is most useful in clinical research and ultimately in clinical practice. This study compared three methods of analyzing DTI-derived data with regard to detection of WM injury and their association with clinical outcomes. Thirty patients with TAI and 19 demographically similar normal controls were scanned using a 3 Tesla magnet. Patients were scanned approximately eight months postinjury, and underwent an outcomes assessment at that time. Histogram analysis of fractional anisotropy (FA) and mean diffusivity showed global WM integrity differences between patients and controls. Voxel-based and tractography analyses showed significant decreases in FA within centroaxial structures involved in TAI. All three techniques were associated with functional and cognitive outcomes. DTI measures of microstructural integrity appear robust, as the three analysis techniques studied showed adequate utility for detecting WM injury.