Elizabeth K. Geary

Thalamic integrity underlies executive dysfunction in traumatic brain injury

Objective: To quantify the effects of traumatic brain injury on integrity of thalamocortical projection fibers and to evaluate whether damage to these fibers accounts for impairments in executive function in chronic traumatic brain injury. Methods: High-resolution (voxel size: 0.78 mm × 0.78 mm × 3 mm3) diffusion tensor MRI of the thalamus was conducted on 24 patients with a history of single, closed-head traumatic brain injury (TBI) (12 each of mild TBI and moderate to severe TBI) and 12 age- and education-matched controls. Detailed neuropsychological testing with an emphasis on executive function was also conducted. Fractional anisotropy was extracted from 12 regions of interest in cortical and corpus callosum structures and 7 subcortical regions of interest (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei). Results: Relative to controls, patients with a history of brain injury showed reductions in fractional anisotropy in both the anterior and posterior corona radiata, forceps major, the body of the corpus callosum, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. Fractional anisotropy from cortico-cortico and corpus callosum regions of interest did not account for significant variance in neuropsychological function. However, fractional anisotropy from the thalamic seed voxels did account for variance in executive function, attention, and memory. Conclusions: The data provide preliminary evidence that traumatic brain injury and resulting diffuse axonal injury results in damage to the thalamic projection fibers and is of clinical relevance to cognition.

Verbal learning differences in chronic mild traumatic brain injury

Following mild traumatic brain injury (TBI), a percentage of individuals report chronic memory and attention difficulties. Traditional neuropsychological assessments often fail to find evidence for such complaints. We hypothesized that mild TBI patients may, in fact, experience subtle cognitive deficits that reflect diminished initial acquisition that can be explained by changes in cerebral white matter microstructure. In the data presented here, a sample of nonlitigating and gainfully employed mild TBI patients demonstrated statistically significant differences from age and education matched control participants in performance on the first trial of a verbal learning task. Performance on this trial was associated with reduced fractional anisotropy in the uncinate fasciculus and the superior longitudinal fasciculus providing an anatomical correlate for the cognitive findings. Mild TBI patients were not impaired relative to control participants on total learning or memory composite variables. Performance on the first learning trial was not related to any psychological variables including mood. We concluded that patients with mild TBI demonstrate diminished verbal learning that is not often interpreted in standard neuropsychological assessment.

Anatomical Correlates of Age-Related Working Memory Declines

Aging studies consistently show a relationship between decreased gray matter volume and decreased performance on working memory tasks. Few aging studies have investigated white matter changes in relation to functional brain changes during working memory tasks. Twenty-five younger and 25 older adults underwent anatomical magnetic resonance imaging (MRI) scans to measure gray matter volume, diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) as a measure of white matter integrity, and functional magnetic resonance imaging (fMRI) while performing a working memory task. Significant increases in activation (fMRI) were seen in the left dorsal and ventral lateral prefrontal cortex with increased working memory load and with increased age (older showing greater bilateral activation). Partial correlational analyses revealed that even after controlling for age, frontal FA correlated significantly with fMRI activation during performance on the working memory task. These findings highlight the importance of white matter integrity in working memory performance associated with normal aging.

Thalamic Projection Fiber Integrity in de novo Parkinson Disease

BACKGROUND AND PURPOSE: Postmortem studies of advanced PD have revealed disease-related pathology in the thalamus with an apparent predilection for specific thalamic nuclei. In the present study, we used DTI to investigate in vivo the microstructural integrity of 6 thalamic regions in de novo patients with PD relative to healthy controls. MATERIALS AND METHODS: Forty subjects (20 with early stage untreated PD and 20 age- and sex-matched controls) were studied with a high-resolution DTI protocol at 3T to investigate the integrity of thalamic nuclei projection fibers. Two blinded, independent raters drew ROIs in the following 6 thalamic regions: AN, VA, VL, DM, VPL/VPM, and PU. FA values were then calculated from the projection fibers in each region. RESULTS: FA values were reduced significantly in the fibers projecting from the AN, VA, and DM, but not the VPL/VPM and PU, in the PD group compared with the control group. In addition, there was a reduction in FA values that approached significance in the VL of patients with PD. These findings were consistent across both raters. CONCLUSIONS: The present study provides preliminary in vivo evidence of thalamic projection fiber degeneration in de novo PD and sheds light on the extent of disrupted thalamic circuitry as a result of the disease itself.

Atrophy of Basal Ganglia Nuclei and Negative Symptoms in Temporal Lobe Epilepsy

Recent work has identified the presence of negative symptoms in a subset of temporal lobe epilepsy (TLE) patients. The authors hypothesized that negative symptoms in TLE are associated with disruption in the mesolimbic system. Basal ganglia and anterior cingulate region of interest volumes were compared between 22 TLE patients with negative symptoms, 22 TLE patients without negative symptoms, and 22 comparison subjects. The negative symptom group showed significantly reduced volumes in the putamen and globus pallidus. It appears that these structures within the broader mesolimbic system contribute to the phenomenon of negative symptoms in TLE.

Imaging chronic traumatic brain injury as a risk factor for neurodegeneration

Population‐based studies have supported the hypothesis that a positive history of traumatic brain injury (TBI) is associated with an increased incidence of neurological disease and psychiatric comorbidities, including chronic traumatic encephalopathy, Alzheimers disease, Parkinsons disease, and amyotrophic lateral sclerosis. These epidemiologic studies, however, do not offer a clear definition of that risk, and leave unanswered the bounding criteria for greater lifetime risk of neurodegeneration. Key factors that likely mediate the degree of risk of neurodegeneration include genetic factors, significant premorbid and comorbid medical history (e.g. depression, multiple head injuries and repetitive subconcussive impact to the brain, occupational risk, age at injury, and severity of brain injury). However, given the often‐described concerns in self‐report accuracy as it relates to history of multiple TBIs, low frequency of patient presentation to a physician in the case of mild brain injuries, and challenges with creating clear distinctions between injury severities, disentangling the true risk for neurodegeneration based solely on population‐based studies will likely remain elusive. Given this reality, multiple modalities and approaches must be combined to characterize who are at risk so that appropriate interventions to alter progression of neurodegeneration can be evaluated. This article presents data from a study that highlights uses of neuroimaging and areas of needed research in the link between TBI and neurodegenerative disease.

Verbal Learning Strategy Following Mild Traumatic Brain Injury

That learning and memory deficits persist many years following mild traumatic brain injury (mTBI) is controversial due to inconsistent objective evidence supporting subjective complaints. Our prior work demonstrated significant reductions in performance on the initial trial of a verbal learning task and overall slower rate of learning in well-motivated mTBI participants relative to demographically matched controls. In our previous work, we speculated that differences in strategy use could explain the differences in rate of learning. The current study serves to test this hypothesis by examining strategy use on the California Verbal Learning Test-Second Edition. Our present findings support the primary hypothesis that mTBI participants under-utilize semantic clustering strategies during list-learning relative to control participants. Despite achieving comparable total learning scores, we posit that the persisting learning and memory difficulties reported by some mTBI patients may be related to reduced usage of efficient internally driven strategies that facilitate learning. Given that strategy training has demonstrated improvements in learning and memory in educational and occupational settings, we offer that these findings have translational value in offering an additional approach in remediation of learning and memory complaints reported by some following mTBI.

Neuroimaging of hypoxic-ischemic brain injury

Hypoxic-ischemic brain injury (HI-BI) is a common cause of neurological morbidity in children and adults. Recent developments in neuroimaging techniques may permit in vivo identification of the structural and functional anatomy of HI-BI, and offer opportunities for the development of neuroimaging-guided prognosis. This article provides an update on the types and possible roles of currently-available neuroimaging techniques. The applications and limitations of these techniques to the study and clinical evaluation of persons with HI-BI are discussed, and the need of further research is highlighted.

Cerebral Small Vessel Disease, Hypertension, and Cognitive Function

Vascular cognitive impairment (VCI) is a heterogeneous condition arising from a variety of neurovascular pathology, including large vessel ischemic infarction, hemorrhage, and the combination of cerebrovascular and Alzheimer’s pathology (1). However, VCI is primarily associated with subcortical gray and white matter pathology arising from small vessel disease. Hypertension is a major factor in the development of small vessel disease. In this chapter, we will focus on linkages between hypertension, small vessel disease, cognitive decline, and dementia.

Discriminant validity for the proposed NINDS-CSN harmonization vascular cognitive impairment neuropsychological assessment protocols

a marked demyelination of the white matter and/or cortical involvement with brain atrophy, demonstrated by magnetic resonanz imaging is present. DMS type 3 is associated with older age with or without major motor disability. In these cases we found no clear correlation between the course and severity of MS and the dementia syndrome itself. Conclusions: In ptients with MS the development of dementia is very heterogenous. DMS type 1 and 2 are directly associated with the progression of the chronic autoimmune disease and the involvement of cortical and/or white matter structures. In DMS type 3 cases a comorbid condition with Alzheimer Dementia is discussed. It seems as DMS is not as rare as described in literature. Further epidemiologic studies are necessary to evaluate the incidence of DMS in a greater population homozygosity at the 129 codon and proved a new four OPRI on one allele with the following repeat order: R1R2R2R3R3R2R2R3R4. At autopsy, diffuse spongiosity, neuronal loss and gliosis were seen but pathological prion protein deposition was seen in the molecular layer of the cerebellum only as atypical, plaque-like patches. Conclusions: Our patient is the seventh published one with 4 OPRI of the PRNP: the order of the repeats is unique to this case and the clinical picture was atypical because of the prominent amyotrophy. The neuropathological findings with plaque-like prion protein deposits in the cerebellar molecular layer are also atypical. Our case emphasizes the heterogeneity of genetic prion diseases.