Project description:BackgroundParkinson's disease is a chronic degenerative movement disorder. The mainstay of treatment is medical. In certain patients Deep Brain Stimulation (DBS) may be offered. However, DBS has been associated with post-operative neuropsychology changes, especially in verbal memory.ObjectivesFirstly, to determine if pre-surgical thalamic and hippocampal volumes were related to verbal memory changes following DBS. Secondly, to determine if clinical factors such as age, duration of symptoms or motor severity (UPDRS Part III score) were related to verbal memory changes.MethodsA consecutive group of 40 patients undergoing bilateral Subthalamic Nucleus (STN)-DBS for PD were selected. Brain MRI data was acquired, pre-processed and structural volumetric data was extracted using FSL. Verbal memory test scores for pre- and post-STN-DBS surgery were recorded. Linear regression was used to investigate the relationship between score change and structural volumetric data.ResultsA significant relationship was demonstrated between change in List Learning test score and thalamic (left, p = 0.02) and hippocampal (left, p = 0.02 and right p = 0.03) volumes. Duration of symptoms was also associated with List Learning score change (p = 0.02 to 0.03).ConclusionVerbal memory score changes appear to have a relationship to pre-surgical MRI structural volumetric data. The findings of this study provide a basis for further research into the use of pre-surgical MRI to counsel PD patients regarding post-surgical verbal memory changes.
Project description:Dopaminergic stimulation has been proposed as a treatment strategy for post-traumatic brain injured patients in minimally conscious state based on a clinical trial using amantadine, a weak dopamine transporter blocker. However, a specific contribution of dopaminergic neuromodulation in minimally conscious state is undemonstrated. In a phase 0 clinical trial, we evaluated 13 normal volunteers and seven post-traumatic minimally conscious state patients using 11C-raclopride PET to estimate dopamine 2-like receptors occupancy in the striatum and central thalamus before and after dopamine transporter blockade with dextroamphetamine. If a presynaptic deficit was observed, a third and a fourth 11C-raclopride PET were acquired to evaluate changes in dopamine release induced by l-DOPA and l-DOPA+dextroamphetamine. Permutation analysis showed a significant reduction of dopamine release in patients, demonstrating a presynaptic deficit in the striatum and central thalamus that could not be reversed by blocking the dopamine transporter. However, administration of the dopamine precursor l-DOPA reversed the presynaptic deficit by restoring the biosynthesis of dopamine from both ventral tegmentum and substantia nigra. The advantages of alternative pharmacodynamic approaches in post-traumatic minimally conscious state patients should be tested in clinical trials, as patients currently refractory to amantadine might benefit from them.
Project description:IntroductionPrevious research indicates disruption of learning and memory in children who have experienced traumatic brain injury (TBI).ObjectiveThis research evaluates the impact of pediatric TBI on volumetric differences along the long axis of the hippocampus, a region of the brain that is critical for explicit memory.MethodsStructural brain data and behavioral measures were collected 6 weeks following TBI or extracranial injury (EI), in children aged 8-15 years and from a group of age matched typically developing controls (TDC). Total hippocampal volume and hippocampal subregion volumes corresponding to hippocampal head, body, and tail were compared across groups and were examined in relation to verbal and visual memory.ResultsGroup differences were evident such that hippocampal body volume was found to be smaller for TBI and EI groups compared to the TDC group. Analysis restricted to the TBI group indicated that hippocampal head volume was associated with severity of injury. The relation between severity of injury and hippocampal head volume is particularly important considering results from our investigation of hippocampal volume-to-memory performance relations indicating positive correlations between hippocampal head volume and performance on memory measures for both the TBI group and the TDC group. Significant negative correlations between hippocampal body volume and memory were evident for the TBI group but not EI or TDC groups. Correlations between memory performance and hippocampal tail volume were not significant for the TBI or TDC groups, although for the EI group, a positive correlation was found between hippocampal tail volume and memory.ConclusionTogether these results underscore an important relation between hippocampal structure and memory function during the subacute stage of recovery from pediatric TBI.
Project description:Traumatic brain injury (TBI) often leads to heterogeneous clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism (SNP) in the dopamine D2 receptor (DRD2) may influence cognitive deficits following TBI. However, part of the association with DRD2 has been attributed to genetic variability within the adjacent ankyrin repeat and kinase domain containing 1 protein (ANKK1). Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether a novel DRD2 C957T polymorphism (rs6277) influences outcome on a cognitive battery at 6 months following TBI-California Verbal Learning Test (CVLT-II), Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), and Trail Making Test (TMT). Results in 128 Caucasian subjects show that the rs6277 T-allele associates with better verbal learning and recall on CVLT-II Trials 1-5 (T-allele carrier 52.8 ± 1.3 points, C/C 47.9 ± 1.7 points; mean increase 4.9 points, 95% confidence interval [0.9 to 8.8]; p = 0.018), Short-Delay Free Recall (T-carrier 10.9 ± 0.4 points, C/C 9.7 ± 0.5 points; mean increase 1.2 points [0.1 to 2.5]; p = 0.046), and Long-Delay Free Recall (T-carrier 11.5 ± 0.4 points, C/C 10.2 ± 0.5 points; mean increase 1.3 points [0.1 to 2.5]; p = 0.041) after adjusting for age, education years, Glasgow Coma Scale, presence of acute intracranial pathology on head computed tomography scan, and genotype of the ANKK1 SNP rs1800497 using multivariable regression. No association was found between DRD2 C947T and non-verbal processing speed (WAIS-PSI) or mental flexibility (TMT) at 6 months. Hence, DRD2 C947T (rs6277) may be associated with better performance on select cognitive domains independent of ANKK1 following TBI.
Project description:The temporal lobes are critical for encoding and retrieving episodic memories. The temporal lobes are preferentially disrupted following a traumatic brain injury (TBI), likely contributing to the difficulties observed in episodic memory. However, the underlying neural changes that precipitate or maintain these difficulties in individuals with TBI remains poorly understood. Here, we use functional magnetic resonance imaging (fMRI) to interrogate the relationship between temporal lobe activation and encoding of episodic stimuli. Participants encoded face, scene, and animal stimuli during an fMRI run. In an out-of-scanner task, participants were required to correctly identify previously displayed stimuli over two presentation runs (each in-scanner stimuli presented twice). Forty-three patients with moderate-severe TBI were recruited and compared with 38 demographically similar healthy controls. The pattern of behavioural performance between groups depended on the stimuli presentation run. The TBI group demonstrated poorer episodic memory for faces and scenes during the first presentation, but not the second presentation. When episodic memory was analysed across all presentation runs, behavioural deficits were only apparent for faces. Interestingly, processing of faces emerged as the only between group-difference on fMRI, whereby TBI participants had an increased signal in the middle temporal gyrus extending to the superior temporal sulcus. These findings provide evidence to suggest that following TBI: (a) episodic memory is preferentially impaired for complex stimuli such as faces, and (b) robust behavioural inefficiencies are reflected in increased activation in specific temporal lobe structures during encoding.
Project description:Impaired working memory is a common and disabling consequence of traumatic brain injury (TBI) that is caused by aberrant brain processing. However, little is known about the extent to which deficits are perpetuated by specific working memory subprocesses. Using a combined functional magnetic resonance imaging (fMRI) and working memory paradigm, we tested the hypothesis that the pattern of brain activation subserving working memory following TBI would interact with both task demands and specific working memory subcomponents: encoding, maintenance, and retrieval. Forty-three patients with moderate-severe TBI, of whom 25 were in the acute phase of recovery (M = 2.16 months, SD = 1.48 months, range = 0.69 - 6.64 months) and 18 in the chronic phase of recovery (M = 23.44 months, SD = 6.76 months, range = 13.35 - 34.82 months), were compared with 38 demographically similar healthy controls. Behaviourally, we found that working memory deficits were confined to the high cognitive load trials in both acute (P = 0.006) and chronic (P = 0.024) cohorts. Furthermore, results for a subset of the sample (18 chronic TBI and 17 healthy controls) who underwent fMRI revealed that the TBI group showed reduced brain activation when simply averaged across all task trials (regardless of cognitive load or subcomponent). However, interrogation of the subcomponents of working memory revealed a more nuanced pattern of activation. When examined more closely, patterns of brain activity following TBI were found to interact with both task demands and the working memory subcomponent: increased activation was observed during encoding in the left inferior occipital gyrus whereas decreased activation was apparent during maintenance in the bilateral cerebellum and left calcarine sulcus. Taken together, findings indicate an inability to appropriately modulate brain activity according to task demand that is specific to working memory encoding and maintenance.
Project description:Axonal injury is a major contributor to adverse outcomes following brain trauma. However, the extent of axonal injury cannot currently be assessed reliably in living humans. Here, we used two experimental methods with distinct noise sources and limitations in the same cohort of 15 patients with severe traumatic brain injury to assess axonal injury. One hundred kilodalton cut-off microdialysis catheters were implanted at a median time of 17 h (13-29 h) after injury in normal appearing (on computed tomography scan) frontal white matter in all patients, and samples were collected for at least 72 h. Multiple analytes, such as the metabolic markers glucose, lactate, pyruvate, glutamate and tau and amyloid-β proteins, were measured every 1-2 h in the microdialysis samples. Diffusion tensor magnetic resonance imaging scans at 3 T were performed 2-9 weeks after injury in 11 patients. Stability of diffusion tensor imaging findings was verified by repeat scans 1-3 years later in seven patients. An additional four patients were scanned only at 1-3 years after injury. Imaging abnormalities were assessed based on comparisons with five healthy control subjects for each patient, matched by age and sex (32 controls in total). No safety concerns arose during either microdialysis or scanning. We found that acute microdialysis measurements of the axonal cytoskeletal protein tau in the brain extracellular space correlated well with diffusion tensor magnetic resonance imaging-based measurements of reduced brain white matter integrity in the 1-cm radius white matter-masked region near the microdialysis catheter insertion sites. Specifically, we found a significant inverse correlation between microdialysis measured levels of tau 13-36 h after injury and anisotropy reductions in comparison with healthy controls (Spearman's r = -0.64, P = 0.006). Anisotropy reductions near microdialysis catheter insertion sites were highly correlated with reductions in multiple additional white matter regions. We interpret this result to mean that both microdialysis and diffusion tensor magnetic resonance imaging accurately reflect the same pathophysiological process: traumatic axonal injury. This cross-validation increases confidence in both methods for the clinical assessment of axonal injury. However, neither microdialysis nor diffusion tensor magnetic resonance imaging have been validated versus post-mortem histology in humans. Furthermore, future work will be required to determine the prognostic significance of these assessments of traumatic axonal injury when combined with other clinical and radiological measures.
Project description:We used the California Verbal Learning Test, Second Edition (CVLT-II), one component of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), to determine feasibility of a remote assessment protocol. We compared telephone-administered CVLT-II data from MS patients to data acquired in person from an independent sample of patients and healthy controls. Mixed factor analyses of variance (ANOVAs) showed no significant differences between patient groups, but between-group effects comparing patients and healthy controls were significant. In this study, CVLT-II assessment by conventional in-person and remote telephone assessment yielded indistinguishable results. The findings indicate that telephone-administered CVLT-II is feasible. Further validation studies are underway.
Project description:ObjectiveThe primary objective of this study was to track the incidence and progression of traumatic microbleeds (TMBs) for up to five years following traumatic brain injury (TBI).MethodsThirty patients with mild, moderate, or severe TBI received initial MRI within 48 h of injury and continued in a longitudinal study for up to five years. The incidence and progression of MRI findings was assessed across the five year period. In addition to TMBs, we noted the presence of other imaging findings including diffusion weighted imaging (DWI) lesions, extra-axial and intraventricular hemorrhage, hematoma, traumatic meningeal enhancement (TME), fluid-attenuated inversion recovery (FLAIR) hyperintensities, and encephalomalacia.ResultsTMBs were observed in 60% of patients at initial presentation. At one-year follow-up, TMBs were more persistent than other neuroimaging findings, with 83% remaining visible on MRI. In patients receiving serial MRI 2-5 years post-injury, acute TMBs were visible on all follow-up scans. In contrast, most other imaging markers of TBI had either resolved or evolved into ambiguous abnormalities on imaging by one year post-injury.ConclusionsThese findings suggest that TMBs may serve as a uniquely persistent indicator of TBI and reinforce the importance of acute post-injury imaging for accurate characterization of persistent imaging findings.
Project description:Traumatic brain injury (TBI) is a leading cause of death and disability in people under 45. Advanced imaging techniques to identify injury and classify severity in the first few hours and days following trauma could improve patient stratification and aid clinical decision making. Traumatic cerebral microbleeds (TCMBs), detectable on magnetic resonance susceptibility weighted imaging (SWI), can be used as markers of long-term clinical outcome. However, the relationship between TCMBs and injury severity in the first few hours after injury, and their natural evolution, is unknown.We obtained SWI scans in 10 healthy controls, and 13 patients scanned 3-24h following TBI and again at 7-15days. TCMBs were identified and total volume quantified for every lesion in each scan.TCMBs were present in 6 patients, all with more severe injury classified by GCS. No lesions were identified in patients with an initial GCS of 15. Improvement in GCS in the first 15days following injury was significantly associated with a reduction in microbleed volume over the same time-period.MRI is feasible in severely injured patients in the first 24h after trauma. Detection of TCMBs using SWI provides an objective early marker of injury severity following trauma. TCMBs revealed in this time frame, offer the potential to help determine the degree of injury, improving stratification, in order to identify patients who require admission to hospital, transfer to a specialist center, or an extended period of intubation on intensive care.