Central Nervous System Function in Youth With Type 1 Diabetes 12 Years After Disease Onset

OBJECTIVE—In this study, we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospectively from diagnosis

Bilateral deep transcranial magnetic stimulation of motor and prefrontal cortices in Parkinson’s disease: a comprehensive review

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by both motor and non-motor symptoms, many of which are resistant to currently available treatments. Since the discovery that non-invasive transcranial magnetic stimulation (TMS) can cause dopamine release in PD patients, there has been growing interest in the use of TMS to fill existing gaps in the treatment continuum for PD. This review evaluates the safety and efficacy of a unique multifocal, bilateral Deep TMS protocol, which has been evaluated as a tool to address motor and non-motor symptoms of PD. Six published clinical trials have delivered a two-stage TMS protocol with an H-Coil targeting both the prefrontal cortex (PFC) and motor cortex (M1) bilaterally (220 PD patients in total; 108 from two randomized, sham-controlled studies; 112 from open label or registry studies). In all studies TMS was delivered to M1 bilaterally (Stage 1) and then to the PFC bilaterally (Stage 2) with approximately 900 pulses per stage. For Stage 1 (M1), two studies delivered 10 Hz at 90% motor threshold (MT) while four studies delivered 1 Hz at 110% MT. For Stage 2 (PFC), all studies delivered 10 Hz at 100% MT. The results suggest that this two-stage Deep TMS protocol is a safe, moderately effective treatment for motor symptoms of PD, and that severely impaired patients have the highest benefits. Deep TMS also improves mood symptoms and cognitive function in these patients. Further research is needed to establish optimal dosing and the long-term durability of treatment effects

Perfusion and diffusion magnetic resonance imaging studies of cerebral ischaemia

Magnetic resonance imaging (MRI) has opened up new avenues of anatomical and physiological research. Its non-invasive nature and the ability to obtain images with a high degree of spatial resolution, have been exploited in this research as well as in routine clinical investigations. However, the use of standard MRI techniques in the investigation of the acute phases of cerebrovascular diseases such as stroke, has been hampered by impaired sensitivity to detect areas of ischaemic damage. The relatively recent development of the MRI techniques of diffusion and perfusion imaging, described in this thesis, have the capability to fill this gap. The diffusive mobility of water is a sensitive indicator of tissue energy status, and perfusion imaging provides quantitative measurements of cerebral blood flow (CBF). This thesis describes the implementation of these two techniques in experimental studies of cerebral ischaemia. Special emphasis is placed upon the improvement of the temporal resolution of these methods in order that time course studies of the rapidly evolving pathophysiology can be carried out. In particular, an innovative modification of the spin-labelling perfusion technique of flow-sensitive alternating inversion recovery (FAIR), has been developed that allows rapid, mapping of CBF. This method was implemented in an important study of reperfusion injury. High time-resolution sequences for rapid, quantitative diffusion imaging were implemented on both high-field and low-field MRI systems. The high-field environment sensitises the images to various artefacts and a novel enhancement of a standard rapid imaging technique was required in order to obtain accurate measurements. On the low-field system, fast imaging of the trace of the diffusion tensor (trace(D)) was optimised and employed during a study of repeated ischaemic episodes that is a model of transient ischaemic attacks. The combination of these two MRI techniques has provided unique insights into experimental cerebral ischaemia

Efficacy of Deep TMS with the H1 Coil for Anxious Depression

(1) Background: While the therapeutic efficacy of Transcranial Magnetic Stimulation (TMS) for major depressive disorder (MDD) is well established, less is known about the technique’s efficacy for treating comorbid anxiety. (2) Methods: Data were retrospectively analyzed from randomized controlled trials (RCTs) that used Deep TMS with the H1 Coil for MDD treatment. The primary endpoint was the difference relative to sham treatment following 4 weeks of stimulation. The effect size was compared to literature values for superficial TMS and medication treatments. (3) Results: In the pivotal RCT, active Deep TMS compared with sham treatment showed significantly larger improvements in anxiety score (effect size = 0.34, p = 0.03 (FDR)) which were sustained until 16 weeks (effect size = 0.35, p = 0.04). The pooled effect size between all the RCTs was 0.55, which compares favorably to alternative treatments. A direct comparison to Figure-8 Coil treatment indicated that treatment with the H1 Coil was significantly more effective (p = 0.042). In contrast to previously reported studies using superficial TMS and medication for which anxiety has been shown to be a negative predictor of effectiveness, higher baseline anxiety was found to be predictive of successful outcome for the H1-Coil treatment. (4) Conclusions: Deep TMS is effective in treating comorbid anxiety in MDD and, unlike alternative treatments, the outcome does not appear to be adversely affected by high baseline anxiety levels

Quantitative imaging assessment of blood-brain barrier permeability in humans

Abstract The blood–brain barrier (BBB) is a functional and structural barrier separating the intravascular and neuropil compartments of the brain. It characterizes the vascular bed and is essential for normal brain functions. Dysfunction in the BBB properties have been described in most common neurological disorders, such as stroke, traumatic injuries, intracerebral hemorrhage, tumors, epilepsy and neurodegenerative disorders. It is now obvious that the BBB plays an important role in normal brain activity, stressing the need for applicable imaging and assessment methods. Recent advancements in imaging techniques now make it possible to establish sensitive and quantitative methods for the assessment of BBB permeability. However, most of the existing techniques require complicated and demanding dynamic scanning protocols that are impractical and cannot be fulfilled in some cases. We review existing methods for the evaluation of BBB permeability, focusing on quantitative magnetic resonance-based approaches and discuss their drawbacks and limitations. In light of those limitations we propose two new approaches for BBB assessment with less demanding imaging sequences: the “post-pre” and the “linear dynamic” methods, both allow semi-quantitative permeability assessment and localization of dysfunctional BBB with simple/partial dynamic imaging protocols and easy-to-apply analysis algorithms. We present preliminary results and show an example which compares these new methods with the existing standard assessment method. We strongly believe that the establishment of such “easy to use” and reliable imaging methods is essential before BBB assessment can become a routine clinical tool. Large clinical trials are awaited to fully understand the significance of BBB permeability as a biomarker and target for treatment in neurological disorders.</p

Reduced variance in monozygous twins for multiple MR parameters: Implications for disease studies and the genetic basis of brain structure

Twin studies offer the opportunity to determine the relative contribution of genes versus environment in traits of interest. Here, we investigate the extent to which variance in brain structure is reduced in monozygous twins with identical genetic make-up. We investigate whether using twins as compared to a control population reduces variability in a number of common magnetic resonance (MR) structural measures, and we investigate the location of areas under major genetic influences. This is fundamental to understanding the benefit of using twins in studies where structure is the phenotype of interest. Twenty-three pairs of healthy MZ twins were compared to matched control pairs. Volume, T2 and diffusion MR imaging were performed as well as spectroscopy (MRS). Images were compared using (i) global measures of standard deviation and effect size, (ii) voxel-based analysis of similarity and (iii) intra-pair correlation. Global measures indicated a consistent increase in structural similarity in twins. The voxel-based and correlation analyses indicated a widespread pattern of increased similarity in twin pairs, particularly in frontal and temporal regions. The areas of increased similarity were most widespread for the diffusion trace and least widespread for T2. MRS showed consistent reduction in metabolite variation that was significant in the temporal lobe N-acetylaspartate (NAA). This study has shown the distribution and magnitude of reduced variability in brain volume, diffusion, T2 and metabolites in twins. The data suggest that evaluation of twins discordant for disease is indeed a valid way to attribute genetic or environmental influences to observed abnormalities in patients since evidence is provided for the underlying assumption of decreased variability in twins

The Right Supramarginal Gyrus Is Important for Proprioception in Healthy and Stroke-Affected Participants: A Functional MRI Study

Human proprioception is essential for motor control, yet its central processing is still debated. Previous studies of passive movements and illusory vibration have reported inconsistent activation patterns related to proprioception, particularly in high-order sensorimotor cortices. We investigated brain activation specific to proprioception, its laterality, and changes following stroke. Twelve healthy and three stroke-affected individuals with proprioceptive deficits participated. Proprioception was assessed clinically with the Wrist Position Sense Test, and participants underwent functional magnetic resonance imaging scanning. An event-related study design was used, where each proprioceptive stimulus of passive wrist movement was followed by a motor response of mirror -copying with the other wrist. Left (LWP) and right (RWP) wrist proprioception were tested separately. Laterality indices (LIs) were calculated for the main cortical regions activated during proprioception. We found proprioception-related brain activation in high-order sensorimotor cortices in healthy participants especially in the supramarginal gyrus (SMG LWP z = 4.51, RWP z = 4.24) and the dorsal premotor cortex (PMd LWP z = 4.10, RWP z = 3.93). Right hemispheric dominance was observed in the SMG (LI LWP mean 0.41, SD 0.22; RWP 0.29, SD 0.20), and to a lesser degree in the PMd (LI LWP 0.34, SD 0.17; RWP 0.13, SD 0.25). In stroke-affected participants, the main difference in proprioception-related brain activation was reduced laterality in the right SMG. Our findings indicate that the SMG and PMd play a key role in proprioception probably due to their role in spatial processing and motor control, respectively. The findings from stroke--affected individuals suggest that decreased right SMG function may be associated with decreased proprioception. We recommend that clinicians pay particular attention to the assessment and rehabilitation of proprioception following right hemispheric lesions

White matter microstructure in opiate addiction

Heroin addiction has been associated with impaired neuronal connectivity and cognitive deficits. One mechanism that potentially explains these findings is alterations in white matter connectivity secondary to chronic opiate use. However, few studies have quantitavely examined white matter deficits in opiate addiction (OA). Here, we investigated white matter microstructure in OA using diffusion tensor imaging (DTI). We performed voxel-wise analysis of fractional anisotropy (FA) in 24 participants with OA and 29 healthy controls. The OA group showed reduced FA in multiple pathways including the corpus callosum, thalamic radiation and inferior longitudinal fasciculus. This FA reduction was mainly the result of increased radial diffusivity (λ ⊥), indicative of myelin pathology. Longer duration of OA was also associated with axonal diffusivity (λ 1), most robustly in superior longitudinal fasciculi and right frontal white matter suggesting axonal injury in long-term users. Together, the findings indicate that chronic OA use has widespread and diverse effects on neuronal connectivity and function. © 2010 The Authors, Addiction Biolog