Relationship of Morphometrics and Symptom Severity in Female Type I Chiari Malformation Patients with Biological Resilience.

Abstract.

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In the present study we report the relationship among MRI-based skull and cervical spine morphometric measures as well as symptom severity (disability—as measured by Oswestry Head and Neck Pain Scale and social isolation—as measured by the UCLA Loneliness scale) on biomarkers of allostatic load using estrogen, interleukin-6, C-reactive protein, and cortisol in a sample of 46 CMI patients. Correlational analyses showed that McRae line length was negatively associated with interleukin-6 and C-reactive protein levels, and Analysis of Variance (ANOVA) showed joint effects of morphometric measures (McRae line length, anterior CSF space) and symptom severity (disability and loneliness) on estrogen and intereukin-6 levels. These results are consistent with allostatic load. That is, when the combination of CSF crowding and self-report symptom (disability and loneliness) severity exceed the capacity of biological resilience factors, then biomarkers such as neuroprotective estrogen levels drop, rather than rise, with increasing symptom severity.

Contributors.

Mohamad Motaz Al Samma, Monica A. Garcia, Maitane García, James R. Houston, Dorothy Loth, Richard Labuda, Sarel Vorster, Petra M. Klinge, Francis Loth, Douglas L. Delahanty, & Philip A. Allen

Publication.

The Cerebellum

The role of elastin on the mechanical properties of the anterior leaflet in porcine triscuspid valves.

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Abstract. Elastin is present in the extracellular matrix (ECM) of connective tissues, and its mechanical properties are well documented. In Marfan syndrome, however, the inability to properly code for the protein fibrillin-1 prematurely leads to the degradation and loss of elastin fiber integrity in the ECM. In this study, the role of elastin in the ECM of the anterior leaflet of the tricuspid valve was investigated by examining the biomechanical behavior of porcine leaflets before and after the application of the enzyme elastase. Five loading protocols were applied to the leaflet specimens in two groups (elastase-treated and control samples). The mechanical response following elastase application yielded a significantly stiffer material in both the radial and circumferential directions. At a physiological level of stress (85 kPa), the elastase group had an average strain of 26.21% and 6.32% in the radial and circumferential directions, respectively, at baseline prior to elastase application. Following elastase treatment, the average strain was 5.28% and 0.97% in the radial and circumferential directions, respectively. No statistically significant change was found in the control group following sham treatment with phosphate-buffered saline (PBS). Two-photon microscopy images confirmed that after the removal of elastin, the collagen fibers displayed a loss of undulation. With a significant reduction in radial compliance, the ability to withstand physiological loads may be compromised. As such, an extracellular matrix that is structurally deficient in elastin may hinder normal tricuspid valve function.

Contributors.

Samuel D. Salinas, Yasmeen M. Farra, Keyvan Amini Khoiy, James R. Houston, Chung-Hao Lê, Chiara Bellini, & Rouzbeh Amini.

Publication.

PLoS One

Influence of pain on cognitive dysfunction and emotion dysregulation in Chiari malformation Type I

Abstract.

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Conceptual biopsychosocial model of pain and consequence on the quality of life. Chronic pain has reciprocal relationships with biological, psychological, and social function, which have evocative interactions on each other and on health-related quality of life. Figure inspired by Dueñas and colleagues.

It has been well demonstrated that the cerebellum is associated with cognitive and affective processing as well as the traditionally conceptualized motor function. In the present chapter, we explore the behavioral and neurobiological implications of a common congenital cerebellar condition, Chiari malformation Type I, on cognitive and affective processing. We also emphasize the associations between Chiari-related chronic pain, cognitive dysfunction, and emotion dysregulation. Based on our review of the literature, we argue that chronic pain can account for a substantial amount of the cognitive dysfunction and emotion dysregulation in Chiari malformation Type I. Yet, there also exists aspects of Chiari-related cognitive dysfunction and emotion dysregulation that appear to be at least partially independent of chronic pain and more directly associated with abnormalities in CSF flow dynamics and cerebro-cerebellar communication pathways.

Contributors.

James R. Houston, Jahangir Maleki, Francis Loth, Petra M. Klinge, & Philip A. Allen

Publication.

Cerebellum and Emotion, a volume of Advances in Experimental Medicine and Biology

Functional connectivity abnormalities in Type I Chiari: Associations with cognition and pain.

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Abstract.

There is initial evidence of microstructural abnormalities in the fibre-tract pathways of the cerebellum and cerebrum of individuals diagnosed with Type I Chiari malformation. However, it is unclear whether abnormal white matter architecture and macro-level morphological deviations that have been observed in Chiari translate to differences in functional connectivity. Furthermore, common symptoms of Chiari include pain and cognitive deficits, but the relationship between these symptoms and functional connectivity has not been explored in this population. Eighteen Type I Chiari patients and 18 age-, sex- and education-matched controls underwent resting-state functional MRI to measure functional connectivity. Participants also completed a neuropsychological battery and completed self-report measures of chronic pain. Group differences in functional connectivity were identified. Subsequently, pathways of significant difference were re-analyzed after controlling for the effects of attention performance and self-reported chronic pain. Chiari patients exhibited functional hypoconnectivity between areas of the cerebellum and cerebrum. Controlling for attention eliminated all deficits with the exception of that from the posterior cerebellar pathway. Similarly, controlling for pain also eliminated deficits except for those from the posterior cerebellar pathway and vermis VII. Patterns of Chiari hyperconnectivity were also found between regions of the cerebellum and cerebrum in Chiari patients. Hyperconnectivity in all regions was eliminated after controlling for attention except between left lobule VIII and the left postcentral gyrus and between vermis IX and the precuneus. Similarly, hyperconnectivity was eliminated after controlling for pain except between the default mode network and globus pallidus, left lobule VIII and the left postcentral gyrus, and Vermis IX and the precuneus. Evidence of both hyper- and hypoconnectivity were identified in Chiari, which is posited to support the hypothesis that the effect of increased pain in Chiari draws on neural resources, requiring an upregulation in inhibitory control mechanisms and resulting in cognitive dysfunction. Areas of hypoconnectivity in Chiari patients also suggest disruption in functional pathways, and potential mechanisms are discussed.

Contributors.

Michelle L. Houston, James R. Houston, Ken Sakaie, Petra M. Klinge, Sarel Vorster, Mark Luciano, Francis Loth, & Philip A. Allen

Publication.

Brain Communications

Adult Age Differences in Self-Reported Pain and Anterior CSF Space in Chiari Malformation.

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Abstract.

Chiari malformation type I (CMI) is a neural disorder with sensory, cognitive, and motor defects, as well as headaches. Radiologically, the cerebellar tonsils extend below the foramen magnum. To date, the relationships among adult age, brain morphometry, surgical status, and symptom severity in CMI are unknown. The objective of this study was to better understand the relationships among these variables using causal modeling techniques. Adult CMI patients (80% female) who either had (n = 150) or had not (n = 151) undergone posterior fossa decompression surgery were assessed using morphometric measures derived from magnetic resonance images (MRI). MRI-based morphometry showed that the area of the CSF pocket anterior to the cervico-medullary junction (anterior CSF space) correlated with age at the time of MRI (r = − .21). Also, self-reported pain increased with age (r = .11) and decreased with anterior CSF space (r = − .18). Age differences in self-reported pain were mediated by anterior CSF space in the cervical spine area—and this effect was particularly salient for non-decompressed CMI patients. As CMI patients age, the anterior CSF space decreases, and this is associated with increased pain—especially for non-decompressed CMI patients. It is recommended that further consideration of age-related decreases in anterior CSF space in CMI patients be given in future research.

Contributors.

Maitane García, Maggie S. Eppelheimer, James R. Houston, Michelle L. Houston, Blaise Simplice Talla Nwotchouang, Kevin P. Kaut, Richard Labuda, J Rajiv Bapuraj, Jahangir Maleki, Petra M. Klinge, Sarel Vorster, Mark G. Luciano, Francis Loth, & Philip A. Allen

Publication.

The Cerebellum

Impact of Surgical Status, Loneliness, and Disability on Interleukin 6, C-Reactive Protein, Cortisol, and Estrogen in Females with Symptomatic Type I Chiari Malformation.

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Abstract.

Chiari malformation type I (CMI) provides an opportunity for examining possible moderators of allostatic load. CMI patients who had (n = 43) and had not (n = 19) undergone decompression surgery completed questionnaires regarding pain, disability, and loneliness, and provided serum samples for IL-6, CRP, estrogen, and free estradiol assays, and saliva samples to assess diurnal cortisol curves. ANOVAs examining surgical status (decompressed versus non-decompressed), loneliness (high vs. low), and disability (high vs. low) as independent variables and biomarker variables as dependent factors found that loneliness was associated with higher levels of cortisol, F(1, 37) = 4.91, p = .04, η2P = .11, and lower levels of estrogen, F(1, 36) = 7.29, p = .01, η2P = .17, but only in decompressed patients. Results highlight the possible impact of loneliness on biological stress responses and the need to intervene to reduce loneliness in patients with symptomatic CMI.

Contributors.

Monica A. Garcia, Xuan Li, Philip A. Allen, Douglas L. Delahanty, Maggie S. Eppelheimer, James R. Houston, Dawn M. Johnson, Francis Loth, Jahangir Maleki, Sarıl Vorster, & Mark G. Luciano

Publication.

The Cerebellum

An Electrophysiological Study of Aging and Perceptual Letter-Matching

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Abstract.

Background: Previous studies on perceptual letter-matching have found that younger and older adults showed “fast-same” effects for response time and “false-different” effects for errors but the effects were more pronounced for older adults. According to the Noisy Operator Theory, internal noise in visual processing distorts “same” trials into appearing different whereas distortion for “different” trials does not affect performance. Older adults have a “noisier” representation of items within perceptual processing which can impact perceptual matching. However, EEG measures may provide a more direct measure of letter-matching decisions.

Methods: We measured the P300 event-related potential (ERP) amplitude, an index of familiarity in stimulus categorization, and behavioral measures (response time and accuracy) to assess letter-matching performance.

Results: Individuals responded faster to “same” trials than to “different” trials but were less accurate. Older adults showed similar P300 amplitudes across trial type whereas younger adults produced a larger amplitude for “same” than “different” trials, suggesting that older adults showed less familiarity for “same” trials than did younger adults – a prediction of the Noisy Operator Theory.

Conclusions: These ERP results are consistent with the Noisy Operator Theory –suggesting that an age-related increase in internal noise affected letter-matching performance.

Contributors.

Peter R. Mallik, Philip A. Alen, Mei-Ching Lien, Elliott Jardin, Michelle L. Hughes, James R. Houston, & Brianna K. Jurosic

Publication.

Experimental Aging Research

Clivus length distinguishes between asymptomatic healthy controls and symptomatic adult women with Chiari malformation type I

Abstract.

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Purpose: While the presence of cerebellar tonsillar descent in radiological images has been used as evidence of Chiari malformation type I (CMI), tonsillar ectopia alone is insufficient to identify individuals with symptomatic CMI. This study sought to identify differences in brain morphology between symptomatic CMI and healthy controls in adult females.

Methods: Two hundred and ten adult females with symptomatic CMI and 90 age-and body mass index-matched asymptomatic female controls were compared using seven brain morphometric measures visible on magnetic resonance images. The CMI and control groups were divided into four subgroups based on the tonsillar position (TP) relative to the foramen magnum: group 1 was made up of healthy controls with normal TP (TP < 0 mm); group 2 was comprised of control individuals with low-lying TP (1-5 mm); group 3 was comprised of symptomatic CMI patients with low-lying TP (1-5 mm); group 4 contained symptomatic CMI patients with severe tonsillar descent (6-13 mm).

Results: All morphometrics for symptomatic CMI with severe tonsillar descent were significantly different than those for both control groups. The CMI group with low-lying TP was significantly different for four measures when compared to controls with normal TP. However, only clivus length was statistically different between the CMI and healthy control groups with low-lying TP.

Conclusion: This study demonstrates that clivus length distinguishes adult female healthy individuals with low-lying tonsils from those with symptomatic CMI. Further investigation is required to understand the importance of a shorter clivus length on CMI symptomatology and pathophysiology.

Contributors.

Blaise Simplice Talla Nwotchouang, Maggie Eppelheimer, Alaaddin Ibrahimy, James R. Houston, Dipankar Biswas, Richard Labuda, Jayapalli Rajiv Bapuraj, Philip A. Allen, David Frim, Francis Loth

Publication.

Neuroradiology

Evidence of neural microstructure abnormalities in Type I Chiari Malformation: Associations among fiber tract integrity, pain, and cognitive dysfunction

Abstract.

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Background: Previous case-control investigations of Type I Chiari malformation (CMI) have reported cognitive deficits and microstructural white matter abnormalities as measured by diffusion tensor imaging (DTI). CMI is also typically associated with pain, including occipital headache, but the relationship between pain symptoms and microstructure is not known.

Methods: Eighteen female CMI patients and 18 adult age and education-matched control participants underwent diffusion tensor imaging (DTI), were tested using digit symbol coding and digit span tasks, and completed a self-report measure of chronic pain. Tissue microstructure indices were used to examine microstructural abnormalities in CMI as compared with healthy controls. Group differences in DTI parameters were then reassessed after controlling for self-reported pain. Finally, DTI parameters were correlated with performance on the digit symbol coding and digit span tasks within each group.

Results: CMI patients exhibited greater fractional anisotropy (FA), lower radial diffusivity (RD), and lower mean diffusivity (MD) in multiple brain regions compared to controls in diffuse white matter regions. Group differences no longer existed after controlling for self-reported pain. A significant correlation between FA and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding performance was observed for controls, but not for the CMI group.

Conclusion. Diffuse microstructural abnormalities appear to be a feature of CMI, manifesting predominantly as greater FA and less diffusivity on DTI sequences. These white matter changes are associated with the subjective pain experience of CMI patients and may reflect reactivity to neuroinflammatory responses. However, this hypothesis will require further deliberate testing in future studies.

Contributors.

James R. Houston, Michelle Hughes, Ilana J. Bennett, Philip A. Allen, Jeffrey M. Rogers, Mei-Ching Lien, Haylie Stoltz, Ken Sakaie, Francis Loth, Jahangir Maleki, Sarel J. Vorster, Mark G. Luciano

Publication.

Pain Medicine

Event-related brain potentials reveal differences in emotional processing in alexithymia

Abstract.

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The inability to recognize and describe emotions in the self is known as Alexithymia. Such inability, occurring more frequently in men, has been attributed to late suppression of emotion. In the present study we used event-related potentials (ERPs) to examine the locus of processing emotional differences in alexithymia. We tested men, both those scoring high (score > 61) and controls who scored low (score < 51) on the Toronto Alexithymia Scale-20 on an emotional face discrimination task (angry, happy, vs. neutral faces). We assessed three ERP components: P1 (100-200 ms after stimulus onset; an index of early perceptual processing), N170 (140-190 ms after stimulus onset; an index of early facial processing) and P3 (300-600 ms after stimulus onset; an index of late attentional suppression). While controls showed a stronger P3 effect for angry faces relative to happy and neutral faces, Alexithymic men showed no significant differences in P3 across emotions. Alexithymic men showed similar P1 and N170 amplitudes as controls but these components were delayed related to controls. These results suggest that the locus of processing differences between alexithymic men and controls occur both early in perceptual processing and later in conscious processing.

Contributors.

Elliott Jardin, Philip Allen, Ronald F. Levant, Mei-Ching Lien, Eric R McCurdy, Anthony Villalba, Peter Mallik, James R. Houston, Zachary T. Gerdes

Publication.

Journal of Cognitive Psychology

Evidence for sex differences in morphological abnormalities in Type I Chiari malformation

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Abstract.

Background and Purpose. Relatively little is known about the influence of individual difference variables on the presentation of macro-level brain morphology in Type I Chiari malformation (CMI). The goal of the present study is to examine how case-control differences in Chiari are affected by patient sex.

Materials and Methods. Patient-provided MR images were acquired through the Chiari1000 database. Twenty-four morphometric measurements were taken using mid-sagittal images of 104 participants (26 male CMI, 26 female CMI, 26 male control, 26 female control) using internally-developed and validated custom software, Morphpro. Casecontrol comparisons were conducted separately by sex using age and BMI-match healthy control participants. Probability-based t-tests, effect sizes (Cohen’s d), and confidence intervals were used to compare casecontrol differences separately by sex.

Results. Male and female case-control comparisons yielded largely the same trends of CMI-related morphometrics abnormalities. Both groups yielded reductions in PCF structure heights. However, there was evidence for greater PCF structure height reductions in male CMI patients as measured by Cohen’s d.

Conclusion. Case-control differences indicated strong consistency in the morphometric abnormalities of CMI malformation in males and females. However, despite the higher prevalence rates of CMI in females, the results from the present study suggest that male morphometric abnormalities may be greater in magnitude. These findings also provide insight into the inconsistent findings from previous morphometric studies of CMI and emphasize the importance of controlling for individual differences when conducting case-control comparisons in CMI.

Contributors.

James R. Houston, Natalie J. Allen, Maggie S. Eppelheimer, Jayapalli Rajiv Bapuraj, Philip A. Allen, Sarel Vorster, Mark G. Luciano, Francis Loth

Publication.

The Neuroradiology Journal

Changes in brain morphology quantified following posterior fossa decompression surgery in Chiari Malformation Type I

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Abstract.

Introduction. While 84% of patients surgically treated for Chiari Malformation type 1 (CM1) demonstrate improved quality of life after posterior fossa decompression surgery, there are many risks associated with this surgery. Surgical planning to identify candidates likely to improve postoperatively may benefit from an improved understanding of morphological changes after decompression surgery. To evaluate these changes, we quantified 59 morphological parameters on 42 CM1 adult female patients before and after CM1 decompression surgery.

Methods. Fifty-nine morphological parameters in the posterior cranial fossa, cranio- cervical, and intracranial regions in the midsagittal plane were evaluated using 42 T1- weighted magnetic resonance images of female CM1 patients before and after surgery, and 42 healthy female controls. Morphological differences before and after surgery were compared through the development of a technique to establish the opisthion location, a key reference point not present after surgery.

Results. In addition to the expected reduction of the cranio-caudal dimension of the cerebellum, objective analyses showed a significant increase in the area of the cerebrospinal fluid spaces, posterior (6x) and inferior (2.6x) to the cerebellum (+113 ± 102 and +140 ± 127 mm2, respectively). This increased area was primarily impacted by an average reduction in the occipital bone length of 24.5 ± 7.3 mm following surgery. Based on multiple angles, results demonstrated a 2°– 4° anterior rotation of the cerebellum after surgery.

Conclusion. Our results show that decompression surgery results in significant changes in the cerebellum and cerebrospinal fluid spaces. Further investigation should determine how these morphological changes impact clinical outcomes.

Contributors.

Maggie S. Eppelheimer, Dipankar Biswas, Audrey M. Braun, James R. Houston, Philip A. Allen, Francis Loth, Jayapalli Rajiv Bapuraj, Richard Labuda, Dorothy M. Loth, David Frim

Publication.

Neuroradiology

Type I Chiari Malformation, RBANS Performance, and Brain Morphology: Connecting the Dots on Cognition and Macro-Level Brain Structure

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Abstract.

Background: Idiopathic descent of cerebellar tonsils into the cervical spine in Chiari malformation Type I (CMI) is typically associated with occipital headache. Accumulating evidence from experimental studies suggests cognitive effects of CMI. The aim of the current study was to examine the relationship between cognition and CMI using a battery of standardized neuropsychological and symptom inventory instruments.

Methods: Eighteen untreated adults with CMI, and 18 gender, age, and education matched healthy controls completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and standardized measures of pain, mood, and disability. Morphometric measurements of key neural and osseous elements were also obtained from structural brain magnetic resonance images, for correlation with symptom outcomes.

Results: CMI patients exhibited deficits in RBANS attention, immediate memory, delayed memory, and Total Score. After controlling for pain and associated affective disturbance, the significant group effect for RBANS attention remained. CMI patients also presented seven morphometric differences comprising the cerebellum and posterior cranial fossa compartment that differed from healthy controls, some of which were associated with self-reported pain and disability. Notably, group differences in tonsillar position were associated with self-reported pain, disability, and delayed memory.

Conclusion: Adult CMI is associated with domain-specific cognitive change, detectable using a standard clinical instrument. The extent of cognitive impairment is independent of pain or affective symptomatology and may be related to the key pathognomonic feature of the condition.

Contributors.

James R. Houston, Jeffrey M. Rogers, Mei-Ching Lien, Natalie J. Allen, Michelle L. Hughes, Jayapalli Rajiv Bapuraj, Maggie S. Eppelheimer, Francis Loth, Marcus A. Stoodley, Sarel J. Vorster, Mark G. Luciano

Publication.

Neuropsychology

Are their age differences in consolidated episodic memory?

Abstract.

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Background/Study Context: While most aging research on memory uses a retention interval of one hour or less, episodic consolidation takes longer (e.g., 6-24 hours for synaptic consolidation, Dudai, 2004; McGaugh, 2000).  In three experiments, we examined age differences in recall followed by recognition in which the retention interval was varied in younger and older adults. 

Methods: In Experiment 1 (n = 24 for both age groups), zero-, 1- and 24-hour retention intervals were used for recall for all participants, and a 24-hour retention interval was used for recognition.  In Experiment 2 (n = 24 for both age groups), just a 24-hour retention interval was used.  In Experiment 3 (n = 20 for both age groups), a within-subjects design was used in which participants recalled one word list after one hour and again after 24 hours, and recalled another word list just after 24 hours (with recognition for both conditions after the 24-hour recall). 

Results: In Experiment 1, older adults recalled fewer words at both the 1- and 24-hour retention intervals, but the magnitude of the age difference did not differ.  In Experiment 2 (just 24-hour retention interval), there were no age differences in recall.  In Experiment 3, in the two-recall condition, older adults showed lower recall at both 1-hour and 24-hour retention intervals (but the magnitude of the age difference remained constant across retention interval).  In the single-recall just 24-hour retention condition, there were no age differences.  There were no age differences in recognition in any of the three experiments. 

Conclusion: These results suggest that recall declines for a 24-hour retention interval relative to a zero or one-hour retention interval (Experiments 1 and 3) for both age groups. However, when the first recall attempt occurs after a 24-hour retention interval, there are no age differences.These replicated results suggest that older adults do not benefit as much as younger adults from pre-consolidated rehearsal, but that rehearsal-based age differences do not increase in magnitude from the last rehearsal to memory consolidation.Furthermore, (along with Mather & Knight, 2005), the present results indicate that there are no age differences in recall when the first recall attempt occurs after a long retention interval—when memory consolidation is likely to have occurred before the first retrieval attempt.

Contributors.

Philip A. Allen, Michelle L. Hughes, James R. Houston, Elliott Jardin, Peter Mallik, Conor McLennan, Douglas L. Delahanty

Publication.

Experimental Aging Research

Quantification of Cerebellar Crowding in Type I Chiari Malformation

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Abstract.

This study was focused on a semi-automated morphometric analysis of the cerebellum in the mid-sagittal plane as an alternative to tonsillar descent alone in the evaluation of Chiari malformation type 1 (CMI) patients. Morphometric analyses of posterior fossa structures were performed on mid-sagittal MRI images of 375 individuals (females, > 18 years, 235 CMI and 140 healthy controls). Twenty-six parameters including linear, angular and area measurements together with non-dimensional ratios were calculated. Eighteen parameters were found to be significantly different between CMI and control subjects. Smaller posterior cranial fossa (PCF) area in CMI subjects was attributed to a smaller PCF area anterior to the brainstem. The cerebellar area was found to be larger in CMI subjects as compared to controls (15.1%), even without inclusion of the tonsillar area below the foramen magnum (FM) (8.4%). The larger cerebellar area in CMI subjects was due to cranial–caudal elongation of the cerebellum, predominately below the fastigium. The cerebrospinal fluid spaces below the FM were smaller in CMI subjects as compared to controls. Overall, greater cerebellar crowding was identified in CMI subjects relative to healthy controls. These observations may improve our understanding of the pathophysiology of CMI in adult female patients.

Contributors.

Dipankar Biswas, Maggie S. Eppelheimer, James R. Houston, Alaaddin Ibrahimy, J. Rajiv Bapuraj, Richard Labuda, Philip A. Allen, David Frim, Francis Loth

Publication.

Annals of Biomedical Engineering

An electrophysiological study of cognitive and emotion processing in Type I Chiari Malformation

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Abstract

Type I Chiari malformation (CMI) is a neurological condition in which the cerebellar tonsils descend into the cervical spinal subarachnoid space resulting in cervico-medullary compression. Early case-control investigations have indicated cognitive deficits in the areas of attention, memory, processing speed, and visuospatial function. The present study further examined cognitive and emotional processing deficits associated with CMI using a dual-task paradigm. Nineteen CMI patients recruited during pre-surgical consultation and 19 matched control participants identified emotional expressions in separate single and asynchronous dual-task designs. To extend earlier behavioral studies of cognitive effects in CMI, we recorded event-related potentials (ERPs) in the dual-task design. Though response times were slower for CMI patients across the two tasks, behavioral and ERP analyses indicated that patients did not differ from matched controls in the ability to allocate attentional resources between the two tasks. P1 ERP component analyses provided no indication of an emotional arousal deficit in our CMI sample while P3 ERP component analyses suggested a CMI-related deficit in emotional regulation. P3 analysis also yielded evidence for a frontalization of neurophysiological activity in CMI patients. Pain and related depression and anxiety factors accounted for CMI deficits in single task, but not dual-task, response times. Results are consistent with a dysfunctional fronto-parietal attentional network resulting from either the indirect effects of chronic pain or the direct effects of CMI pathophysiology stemming from cervico-medullary compression.

Contributors

James R. Houston, Michelle L. Hughes, Mei-Ching Lien, Bryn A. Martin, Francis Loth, Mark G. Luciano, Sarel Vorster, Philip A. Allen

Publication

The Cerebellum

A retrospective 2D morphometric analysis of adult female Chiari type I patients with commonly reported and related conditions

Abstract

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Purpose. Researchers have sought to better understand Chiari type I malformation (CMI) through morphometric measurements beyond tonsillar position (TP). Soft tissue and bone structures within the brain and craniocervical junction have been shown to be different for CMI patients compared to healthy controls. Yet, several morphological characteristics have not been consistently associated with CMI. CMI is also associated with different prevalent conditions (PCs) such as syringomyelia, pseudotumor, Ehlers-Danlos syndrome (EDS), scoliosis, and craniocervical instability. The goal of this study was two-fold: (1) to identify unique morphological characteristics of PCs, and (2) to better explain inconsistent results from case-control comparisons of CMI.

Methods. Image, demographic, and PC information was obtained through the Chiari1000, a self-report web-accessed database. 28 morphometric measurements (MMs) were performed on the cranial MR images of 236 pre-surgery adult female CMI participants and 140 female healthy control participants. Custom software was used to measure 28 soft tissue and bone structures within the posterior cranial fossa (PCF) compartment, craniocervical junction, oral cavity, and intracranial area based on mid-sagittal MR imaging for each participant.

Results. Morphometric analysis of adult females indicated a smaller McRae line length in CMI participants with syringomyelia compare to those without syringomyelia. TP was reduced in CMI participants with EDS compared to those without EDS. Basion to posterior axial line was significantly longer in CMI participants with scoliosis compared to those without scoliosis. No additional MMs were found to differ between CMI participants with and without a specific PC. Four morphometric differences were found to be consistently different between CMI participants and healthy controls regardless of PC: larger TP and a smaller clivus length, fastigium, and corpus callosum height in CMI participants.

Conclusion. Syringomyelia, EDS, and scoliosis were the only PCs that showed significant morphometric differences between CMI participants. Additionally, four mid-sagittal MR-based MMs were found to be significantly different between healthy controls and CMI participants regardless of the presence of one or more PCs. This study suggests that the prevalence of comorbid conditions are not strongly related to CMI morphology, and that inconsistent findings in the radiographic literature cannot be explained by varying prevalence of comorbid conditions in CMI study samples.

Contributors

Maggie S. Eppelheimer, James R. Houston, Jayapalli Rajiv Bapuraj, Richard Labuda, Dorothy M. Loth, Audrey M. Braun, Natalie J. Allen, Soroush Heidari Pahlavian, Dipankar Biswas, Aintzane Urbizu, Bryn A. Martin, Cormac O. Maher, Philip A. Allen, Francis Loth

Publication

Frontiers in Neuroanatomy

Chiari Registry Project: Assessment of Surgical Outcome on Self-Focused Attention, Pain and Delayed Recall - (in press)

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Abstract

Background. Prior research has typically found a negative relationship between chronic pain and memory, and we examined whether cognitive control processes (e.g., reflection and rumination) moderated this relationship in individuals with Chiari malformation Type I (CM). CM is a neurological condition in which the cerebellar tonsils descend into the medullary and upper cervical spine regions potentially resulting in severe headaches and neck pain.

Methods. CM patients who had (n=341) and had not (n=297) undergone decompression surgery completed the McGill Pain Questionnaire-Short Form-Revised (SF-MPQ-2), the Rey Auditory Verbal Learning Test (RAVLT), and the Rumination-Reflection Questionnaire (RRQ). Immediate recall scores were compared to those of 102 healthy controls, and delayed recall performance was compared across other variables within the CM group.

Results. CM patients performed more poorly on immediate recall than did controls. Within CM patients, we observed main effects for reflection and age, and a Pain x Reflection x Surgical Status (surgery vs. no surgery) interaction in which non-decompressed individuals with low levels of pain and high levels of reflection showed superior delayed recall relative to non- decompressed individuals with higher pain and all decompressed individuals.

Conclusions. CM patients show an immediate recall deficit relative to controls, regardless of surgical status. Also, high levels of reflection were associated with better delayed recall performance in non-decompressed CM patients with lower pain levels. High levels of chronic pain may overwhelm increased focused attention abilities, but higher levels of reflection partially overcome the distracting effects of pain and this may represent a type of resilience. 

Contributors

Philip A. Allen, Douglas Delahanty, Kevin P. Kaut, Xuan Li, Monica Garcia, James R. Houston, David M. Tokar, Francis Loth, Jahangir Maleki, Sarel Vorster, Mark G. Luciano

Publication

Psychological Medicine

A Morphometric Assessment of type I Chiari Malformation above the McRae line: A Retrospective Case-Control Study in 302 Adult Female Subjects

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Quick Note

Thank you to Audrey Braun for her hard work on this project.

Abstract

Purpose. Type I Chiari malformation (CMI) is a radiologically-defined structural dysmorphism of the hindbrain and posterior cranial fossa (PCF). Traditional radiographic identification of CMI relies on the measurement of the cerebellar tonsils in relation to the foramen magnum with or without associated abnormalities of the neuraxis. The primary goal of this retrospective study was to comprehensively assess morphometric parameters above the McCrea line in a group of female CMI patients and normal controls.

Material and Methods. 29 morphological measurements were taken on 302 mid-sagittal MR images of adult female CMI patients (N=162) and healthy controls (N=140).  All MR images were voluntarily provided by CMI subjects through an online database and control participant images were obtained through the Human Connectome Project and a local hospital system. 

Results. Analyses were performed on the full dataset of adult female MR images and a restricted dataset of 229 participants that were equated for age, race, and body mass index. 18 group differences were identified in the PCF area that grouped into three clusters; PCF structures heights, clivus angulation, and odontoid process irregularity. 14 group differences persisted after equating CMI and control groups on demographic characteristics. 

Conclusion. PCF structures reliably differ in adult female CMI patients relative to healthy controls. These differences reflect structural abnormalities in the osseous and soft tissue structures of the clivus, odontoid process, and cerebellum. Clinical and pathophysiological implications are discussed.

Contributors

James R. Houston, Maggie S. Eppelheimer, Soroush Heidari Pahlavian, Dipankar Biswas, Aintzane Urbizu, Bryn A. Martin, Jayapalli Rajiv Bapuraj, Mark Luciano, Philip A. Allen, Francis Loth

Publication

Journal of Neuroradiology

Emotional Arousal Deficit or Emotional Regulation Bias? An Electrophysiological Study of Age-Related Differences in Emotion perception

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Thank you to Ann Rossmiller and Elizabeth Walker for your contributions to this project!

Abstract

Background/Study Context: Adult age differences in emotion processing have been attributed to age-related decline in earlier emotional perception and age-related bias in later emotional regulation. Yet, the relationship between the processes of early emotion perception and bias in emotional regulation and their influence on behavioral outcomes remains unclear. Event-related potentials (ERPs) have the temporal precision to allow for the online measure of neurophysiological activity and provide potential insight into the complex dynamics of emotion processing and aging.

Methods: ERPS were used as the primary measure to examine the hypotheses that younger adults will differ in emotional arousal and emotional bias as represented by the early P1 waveform and later P3 waveform, respectively. Thirty-two younger and older adults (16 each) performed a facial emotion discrimination task in which they identified standardized angry, happy, or neutral expressions of faces from the NimStim database (Tottenham et al., 2009).

Results: Younger adults showed a greater P1 ERP for angry faces relative to happy faces at parietal channels, while older adults did not exhibit any emotional modulation of the P1. In contrast, both younger and older adults showed a greater late P3 ERP for angry faces compared to happy faces.

Conclusion: Our results provide evidence for an age-related deficit in early emotion perception and autonomic arousal. Younger adults, but not older adults, exhibited a pattern of neurophysiological activity believed to reflect preconscious and reflexive identification of threat (Vuilleumier, 2005). Despite these age group differences in early emotion processing, younger and older adults did not exhibit differences in neurophysiological processes believed to reflect emotion regulation.

Contributors

James R. Houston, Joshua W. Pollock, Mei-Ching Lien, Philip A. Allen

Publication

Experimental Aging Research