Compensatory neural mechanisms in cognitively unimpaired Parkinson disease.
Annals of neurology
2016; 79 (3): 448-463
The Use of Magnetic Resonance Spectroscopy in the Subacute Evaluation of Athletes Recovering from Single and Multiple Mild Traumatic Brain Injury
JOURNAL OF NEUROTRAUMA
2012; 29 (13): 2297-2304
Cognitive impairments in Parkinson's disease (PD) are thought to be caused in part by dopamine dysregulation. However, even when nigrostriatal dopamine neuron loss is severe enough to cause motor symptoms, many patients remain cognitively unimpaired. It is unclear what brain mechanisms allow these patients to remain cognitively unimpaired despite substantial dopamine dysregulation.31 cognitively unimpaired PD participants OFF dopaminergic-medications were scanned using fMRI while they performed a working memory task, along with 23 controls. We first compared the PD_OFF medication group with controls to determine whether PD participants engage compensatory frontostriatal mechanisms during working memory. We then studied the same PD participants ON dopaminergic-medications to determine whether these compensatory brain changes are altered with dopamine.Controls and PD showed working memory load-dependent activation in the bilateral putamen, anterior-dorsal insula, supplementary motor area, and anterior cingulate cortex. Compared to controls, PD_OFF showed compensatory hyper-activation of bilateral putamen and posterior insula, and machine learning algorithms identified robust differences in putamen activation patterns. Compared to PD_OFF, PD_ON showed reduced compensatory activation in the putamen. Loss of compensatory hyper-activation ON dopaminergic-medication correlated with slower performance on the working memory task and slower cognitive speed on the Symbol Digit Modality Test.Our results provide novel evidence that PD patients maintain normal cognitive performance through compensatory hyper-activation of the putamen. Dopaminergic-medication down-regulates this hyper-activation and the degree of down-regulation predicts behavior. Identifying cognitive compensatory mechanisms in PD is important for understanding how some patients maintain intact cognitive performance, despite nigrostriatal dopamine loss. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ana.24585
View details for PubMedID 26696272
Concussion in athletics: ongoing clinical and brain imaging research controversies
BRAIN IMAGING AND BEHAVIOR
2012; 6 (2): 224-243
Advanced neuroimaging techniques have shown promise in highlighting the subtle changes and nuances in mild traumatic brain injury (MTBI) even though clinical assessment has shown a return to pre-injury levels. Here we use ¹H-magnetic resonance spectroscopy (¹H-MRS) to evaluate the brain metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) in the corpus callosum in MTBI. Specifically, we looked at the NAA/Cho, NAA/Cr, and Cho/Cr ratios in the genu and splenium. We recruited 20 normal volunteers (NV) and 28 student athletes recovering from the subacute phase of MTBI. The MTBI group was categorized based upon the number of MTBIs and time from injury to ¹H-MRS evaluation. Significant reductions in NAA/Cho and NAA/Cr ratios were seen in the genu of the corpus callosum, but not in the splenium, for MTBI subjects, regardless of the number of MTBIs. MTBI subjects recovering from their first MTBI showed the greatest alteration in NAA/Cho and NAA/Cr ratios. Time since injury to ¹H-MRS acquisition was based upon symptom resolution and did not turn out to be a significant factor. We observed that as the number of MTBIs increased, so did the length of time for symptom resolution. Unexpected findings from this study are that MTBI subjects showed a trend of increasing NAA/Cho and NAA/Cr ratios that coincided with increasing number of MTBIs.
View details for DOI 10.1089/neu.2011.2294
View details for Web of Science ID 000308399900005
View details for PubMedID 22780855
Default Mode Network in Concussed Individuals in Response to the YMCA Physical Stress Test
JOURNAL OF NEUROTRAUMA
2012; 29 (5): 756-765
Concussion, the most common form of traumatic brain injury, proves to be increasingly complex and not mild in nature as its synonymous term mild traumatic brain injury (mTBI) would imply. Despite the increasing occurrence and prevalence of mTBI there is no universally accepted definition and conventional brain imaging techniques lack the sensitivity to detect subtle changes it causes. Moreover, clinical management of sports induced mild traumatic brain injury has not changed much over the past decade. Advances in neuroimaging that include electroencephalography (EEG), functional magnetic resonance imaging (fMRI), resting-state functional connectivity, diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) offer promise in aiding research into understanding the complexities and nuances of mTBI which may ultimately influence clinical management of the condition. In this paper the authors review the major findings from these advanced neuroimaging methods along with current controversy within this field of research. As mTBI is frequently associated with youth and sports injury this review focuses on sports-related mTBI in the younger population.
View details for DOI 10.1007/s11682-012-9167-2
View details for Web of Science ID 000305908900006
View details for PubMedID 22669496
Metabolic alterations in corpus callosum may compromise brain functional connectivity in MTBI patients: An H-1-MRS study
2012; 509 (1): 5-8
We hypothesize that the evolution of mild traumatic brain injury (mTBI) may be related to differential effects of a concussive blow on the functional integrity of the brain default mode network (DMN) at rest and/or in response to physical stress. Accordingly, in this resting-state functional magnetic resonance imaging (fMRI) study, we examined 14 subjects 10±2 days post-sports-related mTBI and 15 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the DMN is disrupted at the resting state and/or following the physical stress test. First, all mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. Second, the functional integrity within the DMN, a main resting-state network, remained resilient to a single concussive blow. Specifically, the major regions of interest (ROIs) constituting the DMN (e.g., the posterior cingulate cortex [PCC]/precuneus area, the medial prefrontal cortex [MPFC], and left and right lateral parietal cortices [LLP and RLP]) and the connectivity within these four ROIs was similar between NVs and mTBI subjects prior to the YMCA physical stress test. However, the YMCA physical stress test disrupted the DMN, significantly reducing the magnitude of the connection between the PCC and left lateral parietal ROI, and PCC and right lateral parietal ROI, as well as between the PCC and MPFC in mTBI subjects. Thus while the DMN remained resilient to a single mTBI without exertion at 10 days post-injury, it was altered in response to limited physical stress. This may explain some clinical features of mTBI and provide some insight into its mechanism. This important finding should be considered by clinical practitioners when making decisions regarding return-to-play and clearing mTBI athletes for sports participation.
View details for DOI 10.1089/neu.2011.2125
View details for Web of Science ID 000301442900006
View details for PubMedID 22040294
Alteration of brain default network in subacute phase of injury in concussed individuals: Resting-state fMRI study
2012; 59 (1): 511-518
After clinical resolution of signs and symptoms of mild traumatic brain injury (MTBI) it is still not clear if there are residual abnormalities of structural or functional brain networks. We have previously documented disrupted interhemispheric functional connectivity in 'asymptomatic' concussed individuals during the sub-acute phase of injury. Testing of 15 normal volunteers (NV) and 15 subacute MTBI subjects was performed within 24h of clinical symptoms resolution and medical clearance for the first stage of aerobic activity. In this MRS study we report: (a) both in the genu and splenium of the corpus callosum NAA/Cho and NAA/Cr ratios were significantly (p<0.05) lower in MTBI subjects shortly after the injury compared to NVs, and (b) the metabolic ratio NAA/Cho in the splenium significantly correlated with the magnitude of inter-hippocampal functional connectivity in normal volunteers, but not in MTBI. This novel finding supports our hypothesis that the functional disruption of interhemispheric brain networks in MTBI subjects results from compromised metabolic integrity of the corpus callosum and that this persists despite apparent clinical return to baseline.
View details for DOI 10.1016/j.neulet.2011.11.013
View details for Web of Science ID 000301097100002
View details for PubMedID 22108503
Alteration of brain functional network at rest and in response to YMCA physical stress test in concussed athletes: RsFMRI study
2011; 55 (4): 1716-1727
There are a number of symptoms, both neurological and behavioral, associated with a single episode of r mild traumatic brain injury (mTBI). Neuropsychological testing and conventional neuroimaging techniques are not sufficiently sensitive to detect these changes, which adds to the complexity and difficulty in relating symptoms from mTBI to their underlying structural or functional deficits. With the inability of traditional brain imaging techniques to properly assess the severity of brain damage induced by mTBI, there is hope that more advanced neuroimaging applications will be more sensitive, as well as specific, in accurately assessing mTBI. In this study, we used resting state functional magnetic resonance imaging to evaluate the default mode network (DMN) in the subacute phase of mTBI. Fourteen concussed student-athletes who were asymptomatic based upon clinical symptoms resolution and clearance for aerobic exercise by medical professionals were scanned using resting state functional magnetic resonance imaging. Nine additional asymptomatic yet not medically cleared athletes were recruited to investigate the effect of a single episode of mTBI versus multiple mTBIs on the resting state DMN. In concussed individuals the resting state DMN showed a reduced number of connections and strength of connections in the posterior cingulate and lateral parietal cortices. An increased number of connections and strength of connections was seen in the medial prefrontal cortex. Connections between the left dorso-lateral prefrontal cortex and left lateral parietal cortex showed a significant reduction in magnitude as the number of concussions increased. Regression analysis also indicated an overall loss of connectivity as the number of mTBI episodes increased. Our findings indicate that alterations in the brain resting state default mode network in the subacute phase of injury may be of use clinically in assessing the severity of mTBI and offering some insight into the pathophysiology of the disorder.
View details for DOI 10.1016/j.neuroimage.2011.07.081
View details for Web of Science ID 000296265500050
View details for PubMedID 21846504
Are functional deficits in concussed individuals consistent with white matter structural alterations: combined FMRI & DTI study
EXPERIMENTAL BRAIN RESEARCH
2010; 204 (1): 57-70
There is still controversy in the literature whether a single episode of mild traumatic brain injury (mTBI) results in short- and/or long-term functional and structural deficits in the concussed brain. With the inability of traditional brain imaging techniques to properly assess the severity of brain damage induced by a concussive blow, there is hope that more advanced applications such as resting state functional magnetic resonance imaging (rsFMRI) will be more specific in accurately diagnosing mTBI. In this rsFMRI study, we examined 17 subjects 10±2 days post-sports-related mTBI and 17 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the resting state brain network is disrupted following a single concussive blow. We hypothesized that advanced brain imaging techniques may reveal subtle alterations of functional brain connections in asymptomatic mTBI subjects. There are several findings of interest. All mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. The mTBI subjects revealed a disrupted functional network both at rest and in response to the YMCA physical stress test. Specifically, interhemispheric connectivity was significantly reduced in the primary visual cortex, hippocampal and dorsolateral prefrontal cortex networks (p<0.05). The YMCA physical stress induced nonspecific and similar changes in brain network connectivity patterns in both the mTBI and NV groups. These major findings are discussed in relation to underlying mechanisms, clinical assessment of mTBI, and current debate regarding functional brain connectivity in a clinical population. Overall, our major findings clearly indicate that functional brain alterations in the acute phase of injury are overlooked when conventional clinical and neuropsychological examinations are used.
View details for DOI 10.1016/j.neuroimage.2011.01.024
View details for Web of Science ID 000288843500033
View details for PubMedID 21255654
Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study
EXPERIMENTAL BRAIN RESEARCH
2010; 202 (2): 341-354
There is still controversy in the literature whether a single episode of mild traumatic brain injury (MTBI) results in short-term functional and/or structural deficits as well as any induced long-term residual effects. With the inability of traditional structural brain imaging techniques to accurately diagnosis MTBI, there is hope that more advanced applications like functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) will be more specific in diagnosing MTBI. In this study, 15 subjects who have recently suffered from sport-related MTBI and 15 age-matched normal controls underwent both fMRI and DTI to investigate the possibility of traumatic axonal injury associated with functional deficits in recently concussed but asymptomatic individuals. There are several findings of interest. First, MTBI subjects had a more disperse brain activation pattern with additional increases in activity outside of the shared regions of interest (ROIs) as revealed by FMRI blood oxygen level-dependent (BOLD) signals. The MTBI group had additional activation in the left dorsal-lateral prefrontal cortex during encoding phase of spatial navigation working memory task that was not observed in normal controls. Second, neither whole-brain analysis nor ROI analysis showed significant alteration of white matter (WM) integrity in MTBI subjects as evidenced by fractional anisotropy FA (DTI) data. It should be noted, however, there was a larger variability of fractional anisotropy (FA) in the genu, and body of the corpus callosum in MTB subjects. Moreover, we observed decreased diffusivity as evidenced by apparent diffusion coefficient (ADC) at both left and right dorsolateral prefrontal cortex (DL-PFC) in MTBI subjects (P < 0.001). There was also a positive correlation (P < 0.05) between ADC and % change of fMRI BOLD signals at DL-PFC in MTBI subjects, but not in normal controls. Despite these differences we conclude that overall, no consistent findings across advanced brain imaging techniques (fMRI and DTI) were observed. Whether the lack of consistency across research techniques (fMRI & DTI) is due to time frame of scanning, unique nature of MTBI and/or technological issues involved in FA and Apparent Diffusion Coefficient (ADC) quantification is yet to be determined.
View details for DOI 10.1007/s00221-010-2294-3
View details for Web of Science ID 000278737200006
View details for PubMedID 20496060
Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting.
View details for DOI 10.1007/s00221-009-2141-6
View details for Web of Science ID 000276220300008
View details for PubMedID 20039023