Bilateral occipital lobe infarct neglect deficit (BLIND) syndrome.

Cortical blindness is characterized by loss of vision due to dysfunction of the visual cortices, most commonly secondary to bilateral ischemic infarcts of the occipital lobe. Other causes include surgery such as aortic valve replacement, laryngeal surgery, craniotomy, cerebral angiography, head trauma, and partial seizures. Visual anosognosia is a distinct feature of cortical blindness, wherein patients claim they can see and confabulate visual perceptions, despite loss of sight. We herewith present a rare phenomenon known as Anton Syndrome, an eponym named after the Austrian neurologist and psychiatrist, Gabriel Anton (1858-1933). There are a limited number of cases of Anton's Syndrome in the literature, with only 28 case reports published from 1965-2016. Although he was bestowed a neurologic eponym, Anton was an advocate of eugenics and racial hygiene. He publicly advocated for 'superior breeding' and 'selection' in order to 'build a brave and noble race.' We therefore propose replacing the eponym with Bilateral Occipital Lobe Infarct Neglect Deficit (BLIND) Syndrome, with intention of raising awareness of this unique presentation as well as of the widespread interest in eugenics in the early 1900s amongst physicians, notably Gabriel Anton.

Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.

Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.

Paroxysmal atrial fibrillation with high vs. low arrhythmia burden: atrial remodelling and ablation outcome.

AIMS: The relation between atrial tachyarrhythmia (ATA) burden in paroxysmal atrial fibrillation (AF), atrial remodelling, and efficacy of catheter ablation (CA) is unknown. We investigated whether high vs. low-burden paroxysmal AF patients have distinct clinical characteristics or electro-mechanical properties of the left atrium (LA) and whether burden impacts outcome of CA. METHODS AND RESULTS: Atrial tachyarrhythmia burden, defined as the percentage of time spent in ATA, was assessed by insertable cardiac monitors in 105 patients before and after CA. Clinical characteristics and electro-mechanical properties of LA were compared between patients with high vs. low ATA burden. Catheter ablation efficacy was assessed by reduction in ATA burden and 1-year freedom from any ATA. Median ATA burden was 2.7% (highest tertile 9.3%). Clinical characteristics and electrical properties of LA (refractoriness, conduction velocity, low voltage) did not differ between high (≥9.3%) vs. low ATA burden (<9.3%) patients. High ATA burden patients had larger LA diameter (46.5 ± 6 vs. 42.5 ± 6mm, P < 0.01), volume (93.8 ± 22 vs. 80.4 ± 21mL, P = 0.01), and lower LA reservoir and contractile strain (19.7 ± 6 vs. 24.7 ± 6%, P < 0.01; 10.3 ± 3 vs. 12.8 ± 4%, P = 0.01). Catheter ablation reduced ATA burden by 100% (100-100) in both groups (P = 1.0). Freedom from ATA after CA was equally high (83% vs. 89%, P = 0.38). CONCLUSION: Paroxysmal AF patients with high ATA burden have altered LA mechanical properties, reflected by larger size and impaired function. Despite mechanical remodelling of the atria, they are excellent responders to CA. Most likely the lack of fibrosis and/or advanced electrical remodelling explain why pulmonary veins remain the dominant trigger for AF in this patient cohort.

[Second look: practical diagnostic and therapeutic checks in neurorehabilitation]. / Der zweite Blick: praktische diagnostische und therapeutische Checks in der rehabilitativen Neurologie.

Post-acute inpatient neurorehabilitation facilities are increasingly treating patients who are not only severely ill and multimorbid but who are also referred from non-neurological departments. These patients are still often medically unstable so that the previous diagnostics and treatment must be reevaluated and when necessary adapted or supplemented. Certain interdisciplinary diagnostic and therapeutic problems, such as antithrombotic therapy, regularly reoccur. This article presents these problems in a checklist fashion, which should provide indications in individual cases when previously carried out measures need to be questioned and adapted.

Efficacy of advanced pace-mapping technology for idiopathic premature ventricular complexes ablation.

PURPOSE: Catheter ablation is an effective treatment for premature ventricular complexes (PVCs). Activation mapping is accurate but requires PVCs at the time of the ablation. Pace-mapping correlation (PMC) is a supplemental tool recently developed as an integrated module for an electro-anatomical mapping platform. Our study sought to investigate whether pace-mapping technology provides similar ablation results in patients with low versus high idiopathic PVC burden at the time of ablation and the relationship between sites with the highest PMC and the earliest local activation time (LAT). METHODS: A total of 59 consecutive patients undergoing catheter ablation for idiopathic PVCs were enrolled. Twelve out of 59 patients (20%) were classified in the low PVC burden group (defined as < 2 PVCs/min) and 47/59 (80%) in the high PVC burden group. RESULTS: The most common origin of PVCs was the right ventricular outflow tract (RVOT) followed by aortic cusps, coronary sinus, parahisian region, and aorto-mitral continuity. Procedural and 1-month success rate were 95 and 87% respectively. PVC burden at the time of ablation did not influence the success rate. The median distance between the earliest LAT points and the highest PMC points was 6.4 (4.9-10.6) mm. CONCLUSIONS: Pace-mapping correlation is useful and accurate in localizing the origin of idiopathic PVCs irrespective of the initial PVC burden. It provides optimal ablation results when combined with LAT. Success rate at mid-term follow-up is higher when the origin of PVCs is located in the RVOT as compared to other locations.

Liquid-state carbon-13 hyperpolarization generated in an MRI system for fast imaging.

Hyperpolarized (HP) tracers dramatically increase the sensitivity of magnetic resonance imaging (MRI) to monitor metabolism non-invasively and in vivo. Their production, however, requires an extra polarizing device (polarizer) whose complexity, operation and cost can exceed that of an MRI system itself. Furthermore, the lifetime of HP tracers is short and some of the enhancement is lost during transfer to the application site. Here, we present the production of HP tracers in water without an external polarizer: by Synthesis Amid the Magnet Bore, A Dramatically Enhanced Nuclear Alignment (SAMBADENA) is achieved within seconds, corresponding to a hyperpolarization of ∼20%. As transfer of the tracer is no longer required, SAMBADENA may permit a higher polarization at the time of detection at a fraction of the cost and complexity of external polarizers. This development is particularly promising in light of the recently extended portfolio of biomedically relevant para-hydrogen-tracers and may lead to new diagnostic applications.

A benefit-cost framework of motivation for a specific activity.

How can an individual be motivated to perform a target exercise or activity? This question arises in training, therapeutic, and education settings alike, yet despite-or even because of-the large range of extant motivation theories, finding a clear answer to this question can be challenging. Here we propose an application-friendly framework of motivation for a specific activity or exercise that incorporates core concepts from several well-regarded psychological and economic theories of motivation. The key assumption of this framework is that motivation for performing a given activity is determined by the expected benefits and the expected costs of (performance of) the activity. Benefits comprise positive feelings, gains, and rewards experienced during performance of the activity (intrinsic benefits) or achieved through the activity (extrinsic benefits). Costs entail effort requirements, time demands, and other expenditure (intrinsic costs) as well as unwanted associated outcomes and missing out on alternative activities (extrinsic costs). The expected benefits and costs of a given exercise are subjective and state dependent. We discuss convergence of the proposed framework with a selection of extant motivation theories and briefly outline neurobiological correlates of its main components and assumptions. One particular strength of our framework is that it allows to specify five pathways to increasing motivation for a target exercise, which we illustrate and discuss with reference to previous empirical data.

Increasing self-directed training in neurorehabilitation patients through competition.

This proof-of-concept study aimed to test whether competition could be a useful tool to increase intensity and amount of self-directed training in neurorehabilitation. Stroke patients undergoing inpatient neurorehabilitation (n=93) conducted self-directed endurance training on a (wheelchair-compatible) bicycle trainer under three experimental conditions: a "Competition" condition and two noncompetition control conditions (repeated randomized within-subject design). Training performance and perceived exertion were recorded and statistically analyzed. Three motivational effects of competition were found. First, competition led to an increase in self-directed training. Patients exercised significantly more intensively under competition than in the two noncompetition control conditions. Second, (winning a) competition had a positive influence on performance in the subsequent training session. Third, training performance was particularly high during rematch competitions; that is to say, during second encounter competitions against an opponent that the patient had just beaten. No systematic effect of competition upon perceived exertion (controlled for training performance) was found. Together, our results demonstrate that competition is a potent motivational tool to increase self-directed training in neurorehabilitation.

Changing health behavior motivation from I-must to I-want.

In the past, medicine was dominated by acute diseases. Since treatments were unknown to patients they followed their medical doctors´ directives-at least for the duration of the disease. Behavior was thus largely motivated by avoiding expected costs associated with alternative behaviors (I-must). The health challenges prevailing today are chronic conditions resulting from the way we chose to live. Traditional directive communication has not been successful in eliciting and maintaining appropriate lifestyle changes. An approach successful in other fields is to motivate behavior by increasing expected rewards (I-want). Drawing on neuroeconomic and marketing research, we outline strategies including simplification, repeated exposure, default framing, social comparisons, and consumer friendliness to foster sustained changes in preference. We further show how these measures could be integrated into the health care system.

Motivation: What have we learned and what is still missing?

This final chapter deliberates three overarching topics and conclusions of the research presented in this volume: the endurance of the concept of extrinsic vs intrinsic motivation, the importance of considering subjective costs of activities when aiming to understand and enhance motivation, and current knowledge of the neurobiological underpinnings of motivation. Furthermore, three topics for future motivation research are outlined, namely the assessment and determinants of intrinsic benefits, the reconciliation of activity-specific motivation models with generalized motivation impairments in clinical populations, and the motivational dynamics of groups.

A statistical cerebroarterial atlas derived from 700 MRA datasets.

OBJECTIVES: The cerebroarterial system is a complex network of arteries that supply the brain cells with vitally important nutrients and oxygen. The inter-individual differences of the cerebral arteries, especially at a finer level, are still not understood sufficiently. The aim of this work is to present a statistical cerebroarterial atlas that can be used to overcome this problem. METHODS: Overall, 700 Time-of-Flight (TOF) magnetic resonance angiography (MRA) datasets of healthy subjects were used for atlas generation. Therefore, the cerebral arteries were automatically segmented in each dataset and used for a quantification of the vessel diameters. After this, each TOF MRA dataset as well as the corresponding vessel segmentation and vessel diameter dataset were registered to the MNI brain atlas. Finally, the registered datasets were used to calculate a statistical cerebroarterial atlas that incorporates information about the average TOF intensity, probability for a vessel occurrence and mean vessel diameter for each voxel. RESULTS: Visual analysis revealed that arteries with a diameter as small as 0.5 mm are well represented in the atlas with quantitative values that are within range of anatomical reference values. Moreover, a highly significant strong positive correlation between the vessel diameter and occurrence probability was found. Furthermore, it was shown that an intensity-based automatic segmentation of cerebral vessels can be considerable improved by incorporating the atlas information leading to results within the range of the inter-observer agreement. CONCLUSION: The presented cerebroarterial atlas seems useful for improving the understanding about normal variations of cerebral arteries, initialization of cerebrovascular segmentation methods and may even lay the foundation for a reliable quantification of subtle morphological vascular changes.

Common exonic missense variants in the C2 domain of the human KIBRA protein modify lipid binding and cognitive performance.

The human KIBRA gene has been linked to human cognition through a lead intronic single-nucleotide polymorphism (SNP; rs17070145) that is associated with episodic memory performance and the risk to develop Alzheimer's disease. However, it remains unknown how this relates to the function of the KIBRA protein. Here, we identified two common missense SNPs (rs3822660G/T [M734I], rs3822659T/G [S735A]) in exon 15 of the human KIBRA gene to affect cognitive performance, and to be in almost complete linkage disequilibrium with rs17070145. The identified SNPs encode variants of the KIBRA C2 domain with distinct Ca(2+) dependent binding preferences for monophosphorylated phosphatidylinositols likely due to differences in the dynamics and folding of the lipid-binding pocket. Our results further implicate the KIBRA protein in higher brain function and provide direction to the cellular pathways involved.

Decomposing the Hounsfield unit: probabilistic segmentation of brain tissue in computed tomography.

PURPOSE: The aim of this study was to present and evaluate a standardized technique for brain segmentation of cranial computed tomography (CT) using probabilistic partial volume tissue maps based on a database of high resolution T1 magnetic resonance images (MRI). METHODS: Probabilistic tissue maps of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) were derived from 600 normal brain MRIs (3.0 Tesla, T1-3D-turbo-field-echo) of 2 large community-based population studies (BiDirect and SEARCH Health studies). After partial tissue segmentation (FAST 4.0), MR images were linearly registered to MNI-152 standard space (FLIRT 5.5) with non-linear refinement (FNIRT 1.0) to obtain non-binary probabilistic volume images for each tissue class which were subsequently used for CT segmentation. From 150 normal cerebral CT scans a customized reference image in standard space was constructed with iterative non-linear registration to MNI-152 space. The inverse warp of tissue-specific probability maps to CT space (MNI-152 to individual CT) was used to decompose a CT image into tissue specific components (GM, WM, CSF). RESULTS: Potential benefits and utility of this novel approach with regard to unsupervised quantification of CT images and possible visual enhancement are addressed. Illustrative examples of tissue segmentation in different pathological cases including perfusion CT are presented. CONCLUSION: Automated tissue segmentation of cranial CT images using highly refined tissue probability maps derived from high resolution MR images is feasible. Potential applications include automated quantification of WM in leukoaraiosis, CSF in hydrocephalic patients, GM in neurodegeneration and ischemia and perfusion maps with separate assessment of GM and WM.

Zero field splitting of the chalcogen diatomics using relativistic correlated wave-function methods.

The spectrum arising from the (π*)(2) configuration of the chalcogen dimers, namely, the X(2)1, a2, and b0(+) states, is calculated using wave-function theory based methods. Two-component (2c) and four-component (4c) multireference configuration interaction (MRCI) and Fock-space coupled cluster (FSCC) methods are used as well as two-step methods spin-orbit complete active space perturbation theory at 2nd order (SO-CASPT2) and spin-orbit difference dedicated configuration interaction (SO-DDCI). The energy of the X(2)1 state corresponds to the zero-field splitting of the ground state spin triplet. It is described with high accuracy by the 2- and 4-component methods in comparison with experiment, whereas the two-step methods give about 80% of the experimental values. The b0(+) state is well described by 4c-MRCI, SO-CASPT2, and SO-DDCI, but FSCC fails to describe this state and an intermediate Hamiltonian FSCC ansatz is required. The results are readily rationalized by a two-parameter model; Δε, the π* spinor splitting by spin-orbit coupling and K, the exchange integral between the π(1)* and the π(-1)* spinors with, respectively, angular momenta 1 and -1. This model holds for all systems under study with the exception of Po(2).

Impact of common KIBRA allele on human cognitive functions.

The rs17070145 polymorphism (C → T substitution, intron 9) of the KIBRA gene has recently been associated with episodic memory and cognitive flexibility. These findings were inconsistent across reports though, and largely lacked gene-gene or gene-environment interactions. The aim of the present study was to determine the impact of the rs17070145 polymorphism on clinically relevant cognitive domains and its interaction with the modifiers 'lifestyle' and 'cardiovascular risk factors'. Five-hundred forty-five elderly volunteers (mean age 64 years, ±7 years, 56% women) accomplished a comprehensive cognitive testing. Principal component analysis was used to reveal the internal structure of the data, rendering four composite scores: verbal memory, word fluency, executive function/psychomotor speed, and working memory. Lifestyle was assessed with a detailed questionnaire, age-associated risk factors by clinical interview and examination. There was no main effect of the rs17070145 genotype on any cognitive composite scores. However, we found worse performance in executive functions for T-allele carriers in the presence of arterial hypertension (ß=-0.365, p=0.0077 and 0.031 after Bonferroni correction). This association was further modified by gender, showing the strongest association in hypertensive females (ß=-0.500, p=0.0072 and 0.029 after Bonferroni correction). The effect of KIBRA on cognitive function seems to be complex and modified by gender and arterial hypertension.

Physical activity and memory functions: an interventional study.

Previous studies have suggested beneficial effects of physical activity on cognition. Here, we asked in an interventional approach if physical activity performed at different intensity levels would differentially affect episodic memory function. Additionally, we tried to identify mechanisms mediating these changes. Sixty-two healthy elderly individuals were assessed for level of physical activity, aerobic fitness, episodic memory score, neurotrophin and catecholamine levels, and received a magnetic resonance image of the brain at baseline and after a six months intervention of medium or low-intensity physical activity or control. Increase in total physical activity was positively associated with increase in memory score over the entire cohort, without significant differences between intensity groups. It was also positively associated with increases in local gray matter volume in prefrontal and cingulate cortex, and BDNF levels (trend). In conclusion, we showed that physical activity conveys the beneficial effects on memory function independently of its intensity, possibly mediated by local gray matter volume and neurotrophic factors. Our findings may carry significant implications for prevention of cognitive decline in the elderly.

Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function.

OBJECTIVE: C-reactive protein is a marker of inflammation and vascular disease. It also seems to be associated with an increased risk of dementia. To better understand potential underlying mechanisms, we assessed microstructural brain integrity and cognitive performance relative to serum levels of high-sensitivity C-reactive protein (hs-CRP). METHODS: We cross-sectionally examined 447 community-dwelling and stroke-free individuals from the Systematic Evaluation and Alteration of Risk Factors for Cognitive Health (SEARCH) Health Study (mean age 63 years, 248 female). High-field MRI was performed in 321 of these subjects. Imaging measures included fluid-attenuated inversion recovery sequences for assessment of white matter hyperintensities, automated quantification of brain parenchyma volumes, and diffusion tensor imaging for calculation of global and regional white matter integrity, quantified by fractional anisotropy (FA). Psychometric analyses covered verbal memory, word fluency, and executive functions. RESULTS: Higher levels of hs-CRP were associated with worse performance in executive function after adjustment for age, gender, education, and cardiovascular risk factors in multiple regression analysis (beta = -0.095, p = 0.02). Moreover, higher hs-CRP was related to reduced global fractional anisotropy (beta = -0.237, p < 0.001), as well as regional FA scores of the frontal lobes (beta = -0.246, p < 0.001), the corona radiata (beta = -0.222, p < 0.001), and the corpus callosum (beta = -0.141, p = 0.016), in particular the genu (beta = -0.174, p = 0.004). We did not observe a significant association of hs-CRP with measures of white matter hyperintensities or brain atrophy. CONCLUSION: These data suggest that low-grade inflammation as assessed by high-sensitivity C-reactive protein is associated with cerebral microstructural disintegration that predominantly affects frontal pathways and corresponding executive function.

Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.