Shifts in learning assistants' self-determination due to COVID-19 disruptions in Calculus II course delivery.

BACKGROUND: The Learning Assistant (LA) model with its subsequent support and training has evidenced significant gains for undergraduate STEM learning and persistence, especially in high-stakes courses like Calculus. Yet, when a swift and unexpected transition occurs from face-to-face to online, remote learning of the LA environment, it is unknown how LAs are able to maintain their motivation (competence, autonomy, and relatedness), adapt to these new challenges, and sustain their student-centered efforts. This study used Self-Determination Theory (SDT) to model theoretical aspects of LAs' motivations (persistence and performance) both before and after changes were made in delivery of a Calculus II course at Texas Tech University due to COVID-19 interruptions. RESULTS: Analysis of weekly written reflections, a focus group session, and a post-course questionnaire of 13 Calculus II LAs throughout Spring semester of 2020 showed that LAs' reports of competence proportionally decreased when they transitioned online, which was followed by a moderate proportional increase in reports of autonomy (actions they took to adapt to distance instruction) and a dramatic proportional increase in reports of relatedness (to build structures for maintaining communication and building community with undergraduate students). CONCLUSIONS: Relatedness emerged as the most salient factor from SDT to maintain LA self-determination due to the COVID-19 facilitated interruption to course delivery in a high-stakes undergraduate STEM course. Given that online learning continues during the pandemic and is likely to continue after, this research provides an understanding to how LAs responded to this event and the mounting importance of relatedness when LAs are working with undergraduate STEM learners. Programmatic recommendations are given for enhancing LA preparation including selecting LAs for autonomy and relatedness factors (in addition to competence), modeling mentoring for remote learners, and coaching in best practices for online instruction.

Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms.

OBJECTIVE: Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. METHODS: We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. RESULTS: We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. CONCLUSION: Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the 'aberrant salience hypothesis' of psychosis in schizophrenia.

Disrupted iron regulation in the brain and periphery in cocaine addiction.

Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery. We determined iron concentration in the brain, using quantitative susceptibility mapping, and in the periphery, using iron markers in circulating blood, in 44 patients with cocaine addiction and 44 healthy controls. Cocaine-addicted individuals showed excess iron accumulation in the globus pallidus, which strongly correlated with duration of cocaine use, and mild iron deficiency in the periphery, which was associated with low iron levels in the red nucleus. Our findings show that iron dysregulation occurs in cocaine addiction and suggest that it arises consequent to chronic cocaine use. Putamen enlargement in these individuals was unrelated to iron concentrations, suggesting that these are co-occurring morphological changes that may respectively reflect predisposition to, and consequences of cocaine addiction. Understanding the mechanisms by which cocaine affects iron metabolism may reveal novel therapeutic targets, and determine the value of iron levels in the brain and periphery as biomarkers of vulnerability to, as well as progression and response to treatment of cocaine addiction.

Neuroinflammatory and morphological changes in late-life depression: the NIMROD study.

We studied neuroinflammation in individuals with late-life depression, as a risk factor for dementia, using [11C]PK11195 positron emission tomography (PET). Five older participants with major depression and 13 controls underwent PET and multimodal 3T magnetic resonance imaging (MRI), with blood taken to measure C-reactive protein (CRP). We found significantly higher CRP levels in those with late-life depression and raised [11C]PK11195 binding compared with controls in brain regions associated with depression, including subgenual anterior cingulate cortex, and significant hippocampal subfield atrophy in cornu ammonis 1 and subiculum. Our findings suggest neuroinflammation requires further investigation in late-life depression, both as a possible aetiological factor and a potential therapeutic target.

In the face of threat: neural and endocrine correlates of impaired facial emotion recognition in cocaine dependence.

The ability to recognize facial expressions of emotion in others is a cornerstone of human interaction. Selective impairments in the recognition of facial expressions of fear have frequently been reported in chronic cocaine users, but the nature of these impairments remains poorly understood. We used the multivariate method of partial least squares and structural magnetic resonance imaging to identify gray matter brain networks that underlie facial affect processing in both cocaine-dependent (n = 29) and healthy male volunteers (n = 29). We hypothesized that disruptions in neuroendocrine function in cocaine-dependent individuals would explain their impairments in fear recognition by modulating the relationship with the underlying gray matter networks. We found that cocaine-dependent individuals not only exhibited significant impairments in the recognition of fear, but also for facial expressions of anger. Although recognition accuracy of threatening expressions co-varied in all participants with distinctive gray matter networks implicated in fear and anger processing, in cocaine users it was less well predicted by these networks than in controls. The weaker brain-behavior relationships for threat processing were also mediated by distinctly different factors. Fear recognition impairments were influenced by variations in intelligence levels, whereas anger recognition impairments were associated with comorbid opiate dependence and related reduction in testosterone levels. We also observed an inverse relationship between testosterone levels and the duration of crack and opiate use. Our data provide novel insight into the neurobiological basis of abnormal threat processing in cocaine dependence, which may shed light on new opportunities facilitating the psychosocial integration of these patients.

Probabilistic tractography of the optic radiations--an automated method and anatomical validation.

Accurately tracing the optic radiations in living humans has important implications for studying the relationship between tract structure or integrity and visual function, in health and disease. Probabilistic tractography is an established method for tracing white matter tracts in humans. Prior studies have used this method to trace the optic radiations, but operator-dependent factors, particularly variability in seed voxel placement and choice of connectivity threshold to select between tract and non-tract voxels, remain potential causes of significant variability. Methods using prior information to modify tract images risk introducing error by underestimating individual variability, particularly in subjects with abnormal anatomy. Finally, existing methods lack thorough validation against a histological standard, causing difficulty in evaluating individual methods, and quantitatively comparing methods. Here we describe a method for producing binary optic radiation images using an existing, well-validated tractography method. All stages are automated, including mask image generation, and thresholds are objectively selected by comparing tract images with existing probabilistic histological data in stereotaxic space. Data from two subject groups are presented; the first used to derive analysis parameters, and the second to test these parameters in an independent sample. Validation utilised a novel variant of receiver operating characteristic analysis, providing both justification for this method and a metric by which tractography methods might be compared generally. The resulting tracts match the histological data well; images generated in individuals matched the histological group data about as well as did images derived in individuals from that histological data set, with a low false positive rate.

Registration accuracy for VBM studies varies according to region and degenerative disease grouping.

Voxel-based morphometry studies are frequently cited as having the advantage of being objective compared to region-of-interest methods. This statement assumes, however, that all regions are treated equally both in controls and diseased cohorts. This study aimed to test whether this statement is correct by analyzing fiducial landmarks in controls, Alzheimer's disease (as a model of mild generalized atrophy model); Frontotemporal Dementia (focal atrophy model) and Semantic Dementia (extreme focal atrophy model). Standard SPM5 and DARTEL were evaluated using either raw or skull-stripped/bias corrected scans. The results indicated that with all methods there was variability in the degree of misregistration across regions and that there was a disease grouping interaction-most severely in the extreme focal atrophy model (Semantic Dementia). Preprocessing improved VBM outputs both with standard SPM and DARTEL. In the latter case, this occurred to an extreme degree-DARTEL using raw data was grossly insensitive to a ground truth (manually verified hippocampal atrophy in AD) whereas DARTEL after preprocessing yielded excellent results with respect to this yardstick.

Atrophy patterns in histologic vs clinical groupings of frontotemporal lobar degeneration.

OBJECTIVE: Predictable patterns of atrophy are associated with the clinical subtypes of frontotemporal dementia (FTD): behavioral variant (bvFTD), semantic dementia (SEMD), and progressive nonfluent aphasia (PNFA). Some studies of pathologic subtypes have also suggested specific atrophy patterns; however, results are inconsistent. Our aim was to test the hypothesis that clinical, but not pathologic, classification (FTD with ubiquitin inclusions [FTD-U] and FTD with tau inclusions [FTD-T]) is associated with predictable patterns of regional atrophy. METHODS: Magnetic resonance scans of nine FTD-U and six FTD-T patients (histologically confirmed) were compared with 25 controls using voxel-based morphometry (VBM). Analyses were conducted with the patient group classified according to histologic or clinical variant. Additionally, three Alzheimer pathology patients who had the syndrome of SEMD in life (FTD-A) were analyzed. RESULTS: The VBM studies in clinical variants confirmed established patterns of atrophy (SEMD, rostral temporal; bvFTD, mesial frontal; PNFA, left insula). FTD-U and FTD-T VBM results were very similar, showing severe atrophy in the temporal poles, mesial frontal lobe, and insulae. A conjunction analysis confirmed this similarity. Subgroup analysis found that SEMD associated with either FTD-T or FTD-U was associated with similar rostral temporal atrophy; however, FTD-A had a qualitatively different pattern of left hippocampal atrophy. CONCLUSIONS: While there is predictable atrophy for clinical variants of frontotemporal dementia (FTD), histologic FTD variants show no noticeable differences. Reports of specific atrophy profiles are likely the result of idiosyncrasies in small groups. Semantic dementia associated with Alzheimer pathology, however, presented a distinct atrophy pattern.

Use of magnetic resonance imaging for anatomical phenotyping of the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a fatal, inherited neurodegenerative CAG disorder characterized by marked brain atrophy. We used magnetic resonance imaging (MRI) with manual volumetry for three dimensional (3D) morphological phenotyping of ex vivo brains of R6/2 mice, the most commonly used model of HD. High resolution 3D images were acquired for 18 week old wild-type (WT) and R6/2 mice. Although overall brain volumes were the same between genotypes, decreases in volumes were found in the cortex and striatum of R6/2 mice, with significant volume increases in the lateral ventricles and globus pallidus. There was no change in the volume of the amygdala, internal capsule or hippocampal formation. There was a significant increase in signal intensity in the globus pallidus, amygdala, cortex and striatum in R6/2 mice that may reflect neuronal atrophy. This study clearly shows the potential of MRI for morphological phenotyping of rodent models of HD and other neurological diseases. Having obtained proof-of-principle for the technique using ex vivo tissue, it is now our intention to carry out in vivo measurement of developing pathology in HD transgenic mice, and correlate this with behavioral deficits.

Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry.

The R6/2 mouse is the most common mouse model used for Huntington's disease (HD), a fatal, inherited neurodegenerative CAG disorder characterized by marked brain atrophy. We scanned 47 R6/2 transgenic and 42 wildtype (WT) ex vivo mouse brains at 18 weeks of age using high resolution, three-dimensional magnetic resonance imaging (MRI) for automated voxel-based morphometry (VBM) analysis. We found differences between genotypes in specific brain structures. Many of these changes were bilateral and were found in regions known to be involved in the behavioral deficits present in both R6/2 mice and HD patients. In particular, changes were evident in the basal ganglia, hippocampus, cortex and hypothalamus. In the striatum, changes were heterogenous and reminiscent of striosomal distribution. Changes were also seen in the cerebellum, as might be expected in a mouse carrying a repeat length typical of juvenile onset HD. Many of these changes were not detected by manual 2D morphometry from the same MR images. These data indicate that VBM will be a valuable technique for in vivo measurement of developing pathology in HD transgenic mice, and may be particularly useful for correlating histologically undetectable changes with behavioral deficits.

Analysis of acute traumatic axonal injury using diffusion tensor imaging.

Traumatic axonal injury (TAI) contributes significantly to mortality and morbidity following traumatic brain injury (TBI), but is poorly characterized by conventional imaging techniques. Diffusion tensor imaging (DTI) may provide better detection as well as insights into the mechanisms of white matter injury. DTI data from 33 patients with moderate-to-severe TBI, acquired at a median of 32 h postinjury, were compared with data from 28 age-matched controls. The global burden of whole brain white matter injury (GB(WMI)) was quantified by measuring the proportion of voxels that lay below a critical fractional anisotropy (FA) threshold, identified from control data. Mechanisms of change in FA maps were explored using an Eigenvalue analysis of the diffusion tensor. When compared with controls, patients showed significantly reduced mean FA (p < 0.001) and increased apparent diffusion coefficient (ADC; p = 0.017). GB(WMI) was significantly greater in patients than in controls (p < 0.01), but did not distinguish patients with obvious white matter lesions seen on structural imaging. It predicted classification of DTI images as head injury with a high degree of accuracy. Eigenvalue analysis showed that reductions in FA were predominantly the result of increases in radial diffusivity (p < 0.001). DTI may help quantify the overall burden of white matter injury in TBI and provide insights into underlying pathophysiology. Eigenvalue analysis suggests that the early imaging changes seen in white matter are consistent with axonal swelling rather than axonal truncation. This technique holds promise for examining disease progression, and may help define therapeutic windows for the treatment of diffuse brain injury.

Development of a combined microPET-MR system.

As evidenced by the success of PET-CT, there are many benefits from combining imaging modalities into a single scanner. The combination of PET and MR offers potential advantages over PET-CT, including improved soft tissue contrast, access to the multiplicity of contrast mechanisms available to MR, simultaneous imaging and fast MR sequences for motion correction. In addition, PET-MR is more suitable than PET-CT for cancer screening due to the elimination of the radiation dose from CT. A key issue associated with combining PET and MR is the fact that the performance of the photomultiplier tubes (PMTs) used in conventional PET detectors is degraded in the magnetic field required for MR. Two approaches have been adopted to circumvent that issue: retention of conventional, magnetic field-sensitive PMT-based PET detectors by modification of other features of the MR or PET system, or the use of new, magnetic field-insensitive devices in the PET detectors including avalanche photo-diodes (APDs) and silicon photomultipliers (SiPMs). Taking the former approach, we are assembling a modified microPET Focus 120 within a gap in a novel, 1T superconducting magnet. The PMTs are located in a low magnetic field (approximately 30mT) through a combination of magnet design and the use of fiber optic 'bundles'. Two main features of the modified PET system have been tested, namely the effect of using long fiber optic bundles in the PET detector, and the impact of magnetic field upon the performance of the position sensitive PMTs. The design of a modified microPET-MR system for small animal imaging is completed, and assembly and testing is underway.

Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices.

Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain. While conventional magnetic resonance imaging underestimates the extent of pathology following closed head injury, diffusion-weighted imaging has been shown to more accurately delineate the extent of cerebral damage. There have only been a few case studies of DTI in chronic head injury survivors. This study used DTI to investigate changes in anisotropy and diffusivity in survivors of head injury at least 6 months after their injury. The relationship between cognition and diffusion abnormality was also investigated. The voxel-based analysis revealed significant bilateral decreases in anisotropy, in major white matter tracts and association fibers in the temporal, frontal, parietal and occipital lobes. Statistically significant increases in diffusivity were also found in widespread areas of the cortex. A significant positive correlation was found between diffusivity and impairment of learning and memory in the left posterior cingulate, left hippocampal formation and left temporal, frontal and occipital cortex. The common pattern of abnormality despite heterogeneous injury mechanism and lesion location in the group suggests that these cellular changes reflect secondary insults. The importance of diffusion abnormalities in head injury outcome is emphasized by the significant correlation between a learning and memory index and diffusivity in areas known to subserve this cognitive function.

Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury.

Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO(2)) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with (15)O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO(2) and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO(2) and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO(2) and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 mumol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann-Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO(2) threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.

Imaging of cerebral blood flow and metabolism in brain injury in the ICU.

The heterogeneity of the initial insult and subsequent pathophysiology has made both the study of human head injury and design of randomised controlled trials exceptionally difficult. The combination of multimodality bedside monitoring and functional brain imaging positron emission tomography (PET) and magnetic resonance (MR), incorporated within a Neurosciences Critical Care Unit, provides the resource required to study critically ill patients after brain injury from initial ictus through recovery from coma and rehabilitation to final outcome. Methods to define cerebral ischemia in the context of altered cerebral oxidative metabolism have been developed, traditional therapies for intracranial hypertension re-evaluated and bedside monitors cross-validated. New modelling and analytical approaches have been developed.

Short-term grief after an elective abortion.

OBJECTIVE: To identify the short-term grief response after elective abortion. DESIGN: Descriptive, comparative study. SETTING: Instruments were administered in a women's health clinic. PARTICIPANTS: Ninety-three women, 45 who had a history of elective abortion within the past 1 to 14 months and 48 who had never had an abortion. Inclusion criteria included no perinatal losses within the past 5 years; no documented psychiatric history; and ability to read, write, and comprehend English. MAIN OUTCOME MEASURES: Nature and intensity of short-term grief. RESULTS: Women with a history of elective abortion experienced grief in terms of loss of control, death anxiety, and dependency. Although there were no statistically significant differences in the intensity of grief in women who had a history of elective abortion and the comparison group, there was an overall trend toward higher grief intensities in the abortion group. Presence of living children, perceived pressure to have the abortion, and the number of abortions appear to affect the intensity of the short-term grief response. CONCLUSION: Elective abortion has the potential for eliciting a short-term grief response. Research is needed to identify which women are at greatest risk. This grief response should be acknowledged and appropriate interventions undertaken.

Design of biplanar gradient coils for magnetic resonance imaging of the human torso and limbs.

A method is described for design of gradient coils of unconventional geometry for MRI that is based on the superpositions of magnetic fields arising from individual current elements calculated by the Biot-Savart Law. Use of an optimization method based on a genetic algorithm enables a wide diversity in the shapes of coil that can be modeled. To exemplify this a two axis, biplanar gradient set is presented; this geometry offers good access for rectangular objects whilst holding the coils closer to the region of interest than is possible for cylindrical configurations. The inner dimensions of the gradient set were 40.0 x 24.4 x 40.0 cm and the gradient efficiencies were 0.3 and 0.4 mT m(-1) A(-1) in the z- and y- directions respectively over a 15 cm diameter region. Correction of signals arising from regions for which gradient linearity was not optimized was successful for the monotonic region within the set; the largest cuboid from which the MR signal could be processed to produce an undistorted image is of dimensions 36.3 x 17.2 x 24.4 cm.

Laparoscopic cholecystectomy in an academic hospital: evaluation of changes in perioperative outcomes.

OBJECTIVE: Evaluate changes in perioperative outcomes over an 82-month period in patients undergoing laparoscopic cholecystectomy by a single attending surgeon in an academic hospital. METHODS: A retrospective review of 1025 consecutive patients undergoing laparoscopic cholecystectomy from September 1992 to February 1997 was compared to the initial 600 patients from May 1990 to August 1992. Statistical analysis included Chi square with Yates correction and Fischer's exact test. RESULTS: Over the 82-month period there were no significant differences in the overall conversion rate to open cholecystectomy (p=0.26), intraoperative complications (p = 0.81), postoperative complications (p = 0.054) or mortality rates (p=0.66). There were 3 (0.5%) bile duct injuries in the initial 600 patients and only 1 (0.1%) in the group of 1025 patients (p=0.065). There was an increase (p<0.001) in laparoscopic cholecystectomies performed for acute cholecystitis and biliary dyskinesia and an increase (p<0.001) in the percentage of cases performed overall and for acute cholecystitis by the surgery residents over the last 54 months. Despite this, the conversion rates to open cholecystectomy in patients with acute cholecystitis decreased (p < 0.001) over the last 54 months. Additionally, more patients (p < 0.001) were discharged on the day of surgery in the most recent group. CONCLUSION: Laparoscopic cholecystectomy can be performed safely by surgery residents under the direct supervision of an experienced laparoscopist without significant changes in perioperative outcomes. Despite an increased percentage of cases being performed for acute cholecystitis over the last 54 months, conversion rates to open cholecystectomy and biliary tract injury rates have decreased, and the perioperative morbidity has remained the same.