Jennifer Faber

Widespread affections of large fiber tracts in postoperative temporal lobe epilepsy.

Temporal lobe epilepsy with hippocampus sclerosis (HS) is the most frequent focal epilepsy and often refractory to anticonvulsant therapy. Secondary structural damage has been reported in several studies of temporal lobe epilepsy and unilateral hippocampal sclerosis. Applying diffusion tensor imaging (DTI) we investigated alterations in white matter following temporal lobe surgery in patients with medial temporal lobe epilepsy. We examined 40 patients who underwent surgery at our hospital for HS between 1996 and 2006 with diffusion tensor imaging (DTI). Images were obtained at a 3 T MRI scanner employing 60 gradient directions. Tract-based spatial statistics (TBSS), a novel voxel-based approach, was applied to analyze the data. Both patients with left- as well as right-sided surgery exhibited widespread degradation of fractional anisotropy (FA) in main fiber tracts not limited to the respective temporal lobe such as the uncinate fasciculus, the fronto-occipital fasciculus, the superior longitudinal fasciculus, the corpus callosum and the corticospinal tract on the respective hemisphere. Patients with left-hemispheric surgery showed more widespread affections ipsilaterally and also FA decrease in the contralateral inferior longitudinal fasciculus. DTI demonstrates widespread clusters of abnormal diffusivity and anisotropy in prominent white matter tracts linking mesial temporal lobe structures with other brain areas. Alterations in the ipsilateral mesial temporal lobe can be attributed to be a result of surgery, whereas extratemporal FA decrease is more likely the result of the underlying seizure disorder.

Relationships between personality characteristics of people who stutter and the impact of stuttering on everyday life

OBJECTIVE This study investigates the association between the five-factor model of personality measured by the NEO Five-Factor Inventory (NEO-FFI) and the Overall Assessment of the Speakers Experience of Stuttering (OASES). The OASES measures the adverse impact of stuttering on a persons life. DESIGN Participants in the present study were 112 persons who stutter from Germany. METHODS All participants filled in both the NEO-FFI and the OASES questionnaires. RESULTS Results revealed a strong positive correlation between the personality trait Neuroticism and scores on the OASES. Moreover, Extraversion was negatively correlated with the OASES scores. CONCLUSIONS The findings suggest that people with higher Neuroticism and lower Extraversion scores experience a greater impact of stuttering on their daily life. The results underscore the importance of considering personality as a potential moderator or mediator factor in future stuttering research and, potentially, also in treatment. EDUCATIONAL OBJECTIVES The reader will learn (a) about the different personality dimensions reflected by the NEO-FFI, (b) why it is important to consider the impact of stuttering on everyday life from the perspective of the people who stutter and (c) how personality is linked to the Overall Assessment of the Speakers Experience of Stuttering (OASES).

Elevated in vivo [18F]-AV-1451 uptake in a patient with progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder first described in 1964 and pathologically characterized by filamentous accumulation of phosphorylated tau protein in the basal ganglia and the midbrain. In Alzheimer’s disease, which is characterized by the deposition of mainly intraneuronal paired helical filaments of tau of the 3and 4-repeat isoforms, the PET ligand [18F]-AV-1451 has been proven to bind to tau filaments in ex vivo and in vivo studies. In PSP, aggregation of mainly the 4-repeat isoform has been described, frequently in the form of straight filaments in neurons and glial cells. Previous ex vivo studies indicated suboptimal binding of [18F]-AV-1451 to straight filaments and, consequently, to tau pathology in brain slices of PSP patients. However, in vivo studies on [18F]-AV1451 binding in PSP are not published. We performed [18F]-AV-1451 PET (Fig. 1A) in a 70-yearold patient who presented with a 3-year history of dizziness, visual problems, and repeated falls. Clinically, he had typical Richardson syndrome and a PSP Rating Scale score of 38 and fulfilled all clinical research criteria for the probable diagnosis of PSP including supranuclear vertical gaze palsy. MRI did not show significant midbrain atrophy (Fig. 1B), whereas striatal dopamine transporter density as measured in [123-I]-FP-CIT SPECT was reduced. The PET scan was coregistered to his transaxial T1-weighted MRI and then normalized to Montr eal Neurological Institute (MNI) space using SPM 8 (fil.ion.ucl.ac. uk/spm). We computed voxelwise z-transformed deviations from a set of 19 scans of healthy controls (norm cohort, provided by Avid Radiopharmaceuticals, Inc., Philadelphia, PA). Areas of deviations greater than 1.96 standard deviations (95% confidence interval) of the norm cohort were highlighted and superimposed onto an MRI template (Fig. 1 C/D). The areas of greatest deviation from the norm cohort in the imaging findings are located where suspected from neuropathological studies, that is, bilateral pallidum (Fig. 1C) and the upper midbrain in the area of the rostral interstitial nucleus of the medial longitudinal fasciculus containing the interneurons of the oculomotor system controlling vertical gaze (see Fig. 1D). This finding implies that in principle [18F]-AV-1451 is suitable for detecting areas of tau pathology in patients with PSP. However, the results do not allow distinguishing if the tracer does bind to straight filaments in vivo or to paired helical filaments potentially additionally present in PSP. Moreover, it is possible that similar to other tracers, [18F]-AV-1451 binding may not be entirely restricted to a specific protein feature. Although highly unlikely, a second pathology may also be present (eg, Alzheimer’s disease). A greater number of patients — including atypical PSP syndromes — with in vivo examinations in different stages of the disease, longitudinal follow-up, and subsequent postmortem validation are necessary to substantiate this finding and to allow assessing stage-dependent measures of sensitivity and specificity.

Association between scalp hair-whorl direction and hemispheric language dominance

Asymmetry is a common phenomenon in higher organisms. In humans, the cortical representation of language exhibits a high degree of asymmetry with a prevalence of about 90% of left hemispheric dominance, the underlying mechanisms of which are largely unknown. Another sign that exhibits a form of lateralization is the scalp hair-whorl direction, which is either clockwise or anti-clockwise. The scalp hair-whorl develops from the same germ layer as the nervous system, the ectoderm, between the 10th and 16th week in utero and has been shown to be associated with various neurodevelopmental disorders. Here, we use an established fMRI paradigm to examine the association of a solely biological marker of asymmetry, hair-whorl direction and language lateralization. We show that the mechanism that influences hair-whorl direction and handedness [Klar, A.J.S., 2003. Human handedness and scalp hair-whorl direction develop from a common genetic mechanism. Genetics 1651, 269-276.] also affects cerebral language dominance.

Genetic variation on the BDNF gene is not associated with differences in white matter tracts in healthy humans measured by tract‐based spatial statistics

The brain‐derived neurotrophic factor (BDNF) is a member of the neurotrophin family and involved in nerve growth and survival. It has also become a major research focus in the investigation of both cognitive and affective processes in the human brain in the last years. Especially, a single nucleotide polymorphism on the BDNF gene called BDNF Val66Met gained a lot of attention, because of its effect on activity‐dependent BDNF secretion and its link to negative emotionality and impaired memory processes. A well‐replicated finding from genetic structural imaging showed that carriers of the less frequent 66Met allele show diminished gray matter volume in several areas of the temporal lobe. New imaging techniques like diffusion tensor imaging now allow investigating the influence of BDNF Val66Met on white matter integrity. We applied tract‐based spatial statistics in a brain image dataset including n = 99 healthy participants. No significant differences between the 66Met and homozygous 66Val carriers were observed when correcting for multiple comparisons. In summary, the BDNF Val66Met polymorphism seems not to play a substantial role with respect to the modulation of the white matter integrity in healthy subjects. Although not in the focus of this study, we also investigated the influence of Eysencks Personality Questionnaire on the white matter tracts. No significant results could be observed.

In vivo Patterns of Tau Pathology, Amyloid-β Burden, and Neuronal Dysfunction in Clinical Variants of Alzheimer’s Disease

The clinical heterogeneity of Alzheimers disease is not reflected in the rather diffuse cortical deposition of amyloid-β. We assessed the relationship between clinical symptoms, in vivo tau pathology, amyloid distribution, and hypometabolism in variants of Alzheimers disease using novel multimodal PET imaging techniques. Tau pathology was primarily observed in brain regions related to clinical symptoms and overlapped with areas of hypometabolism. In contrast, amyloid-β deposition was diffusely distributed over the entire cortex. Tau PET imaging may thus serve as a valuable biomarker for the localization of neuronal injury in vivo and may help to validate atypical subtypes of Alzheimers disease.

Investigating personality in stuttering: Results of a case control study using the NEO-FFI

UNLABELLED A recent study by Iverach et al. (Journal of Communication Disorders, 2010) compared persons who stutter with two normative samples in the context of the five-factor model of personality measured by the NEO Five-Factor Inventory (NEO-FFI). Persons who stutter were characterized by higher Neuroticism, lower Conscientiousness and lower Agreeableness scores in contrast to the normative data from an Australian and a United States sample. Moreover, the authors report that the scores on all five personality dimensions in the stuttering group were within those of the normative samples. A shortcoming of the Iverach et al. study is the lack of a matched control group. In the present study we compared persons who stutter with a control group matched to age and gender. Furthermore, none of the controls had a history of personal and family stuttering. The findings with respect to Neuroticism could be replicated in our sample. But in contrast to Iverach et al. we found higher Conscientiousness and Agreeableness scores in persons who stutter compared to the control group. LEARNING OUTCOMES The reader of the present study will learn that elevated Neuroticism scores can be observed in persons who stutter across cultures such as Germany or Australia. With respect to other personality dimensions such as Conscientiousness or Agreeableness the picture is much more difficult.

Progressive fiber tract affections after temporal lobe surgery

Several studies reported changes in white matter architecture following temporal lobe surgery in patients with temporal lobe epilepsy (TLE) at short intervals after surgery. We investigated 20 patients with left‐sided TLE using diffusion‐imaging at two time points, that is, at 3–6 months and 12 months after surgery, to investigate postsurgical plasticity. We observed a loss of fiber tract integrity mainly in fiber tracts of the ipsilateral temporal lobe. Our data show that the remodeling of brain connectivity after surgical interventions continues for longer time periods. The functional implications of these plastic changes will have to be explored.

The role of the DRD2 C957T polymorphism in neuroticism in persons who stutter and healthy controls.

The present study investigates for the first time the influence of the DRD2 C957T polymorphism on personality in persons who stutter. In a recent study, the CC genotype of this single nucleotide polymorphism has been associated with stuttering, which could not be replicated in a follow-up study. Here, we demonstrate, in N=105 persons who stutter, that carriers of the CC and the CT genotype significantly have the highest neuroticism scores. This shows that the inclusion of personality measures in the investigation of the biological underpinnings of stuttering represents an important new avenue. In healthy control persons, a sex by C+/− allele interaction effect could be demonstrated. Female but not male carriers of the C+ variant report the highest neuroticism scores. Because neuroticism has been reported to be associated with stuttering before, the present data support the idea that this personality trait acts as an endophenotype for stuttering, contributing towards bridging the gap from gene variation to the complex pathology. This idea is supported by an additional path model showing that the polymorphism DRD2 C957T influences the self-reported severity of stuttering mainly by its influence on neuroticism (independent of the variable sex).

Tau pathology burden associated with level of cognitive reserve in Alzheimer’s disease.

longitudinal study helps in identifying aging windows in APOE-ε4 carriers, which are predictive of metabolic and neurological changes. Female APOE-ε4 rats demonstrate a state of bioenergetic deficit after the perimenopausal transition. Coincident increase in ketone body levels may reflect a metabolic state, which is shifting to a ketogenic system from a glucogenic system, andmay be related to an increase in white matter catabolism. Grant support: National Institute on Aging (NIA) grants R01AG032236 and P01AG026572 to RDB, Paul Slavic Trust and Alzheimer’s Association.