Ruth Adam

Bio: Ruth Adam is an academic researcher from Ludwig Maximilian University of Munich. The author has contributed to research in topics: Diffusion MRI & Multisensory integration. The author has an hindex of 6, co-authored 10 publications receiving 279 citations. Previous affiliations of Ruth Adam include Heidelberg University.

A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms

Abstract: Objective To establish a fully automated, robust imaging marker for cerebral small vessel disease (SVD) and related cognitive impairment that is easy to implement, reflects disease burden, and is strongly associated with processing speed, the predominantly affected cognitive domain in SVD. Methods We developed a novel magnetic resonance imaging marker based on diffusion tensor imaging, skeletonization of white matter tracts, and histogram analysis. The marker (peak width of skeletonized mean diffusivity [PSMD]) was assessed along with conventional SVD imaging markers. We first evaluated associations with processing speed in patients with genetically defined SVD (n = 113). Next, we validated our findings in independent samples of inherited SVD (n = 57), sporadic SVD (n = 444), and memory clinic patients with SVD (n = 105). The new marker was further applied to healthy controls (n = 241) and to patients with Alzheimer's disease (n = 153). We further conducted a longitudinal analysis and interscanner reproducibility study. Results PSMD was associated with processing speed in all study samples with SVD (p-values between 2.8 × 10−3 and 1.8 × 10−10). PSMD explained most of the variance in processing speed (R2 ranging from 8.8% to 46%) and consistently outperformed conventional imaging markers (white matter hyperintensity volume, lacune volume, and brain volume) in multiple regression analyses. Increases in PSMD were linked to vascular but not to neurodegenerative disease. In longitudinal analysis, PSMD captured SVD progression better than other imaging markers. Interpretation PSMD is a new, fully automated, and robust imaging marker for SVD. PSMD can easily be applied to large samples and may be of great utility for both research studies and clinical use. Ann Neurol 2016;80:581–592.

Serum neurofilament light chain levels are related to small vessel disease burden

Abstract: Background and Purpose Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment Methods Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortica I Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]). Results Serum NfL levels were elevated in both SVD samples (P<1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R-2=0.52, P= 1.2e-09;sporadic SVD, R-2=0.21, &1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R-2=0.27, P=7.6e-05;sporadic SVD, R-2=0.06, P=4.8e-08), focal neurological symptoms (CADASIL, NIHSS, P=4.2e-05) and disability (CADASIL, mRS, P=3.0e-06). Conclusions We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.

The Curious Incident of Attention in Multisensory Integration: Bottom-up vs. Top-down

Abstract: The role attention plays in our experience of a coherent, multisensory world is still controversial. On the one hand, a subset of inputs may be selected for detailed processing and multisensory integration in a top-down manner, i.e., guidance of multisensory integration by attention. On the other hand, stimuli may be integrated in a bottom-up fashion according to low-level properties such as spatial coincidence, thereby capturing attention. Moreover, attention itself is multifaceted and can be described via both top-down and bottom-up mechanisms. Thus, the interaction between attention and multisensory integration is complex and situation-dependent. The authors of this opinion paper are researchers who have contributed to this discussion from behavioural, computational and neurophysiological perspectives. We posed a series of questions, the goal of which was to illustrate the interplay between bottom-up and top-down processes in various multisensory scenarios in order to clarify the standpoint taken by each author and with the hope of reaching a consensus. Although divergence of viewpoint emerges in the current responses, there is also considerable overlap: In general, it can be concluded that the amount of influence that attention exerts on MSI depends on the current task as well as prior knowledge and expectations of the observer. Moreover stimulus properties such as the reliability and salience also determine how open the processing is to influences of attention.

Editorial: A Matter of Bottom-Up or Top-Down Processes: The Role of Attention in Multisensory Integration.

Abstract: Our everyday environments are multisensory and our brains handle this rich information in an extremely efficient way. Yet, attention's role in the process of multisensory integration (MSI) is still the object of intense debate. Whilst some evidence supports that attention guides MSI via top-down selection of inputs, others suggest that bottom-up integration can occur pre-attentively capitalizing on temporal and spatial correlations. Understanding the role of attention in MSI is further complicated by the fact that attention itself refers to a variety of different selection mechanisms. Thus, the interplay between attention and MSI can take many forms and lead, as evident in the literature, to mixed findings and apparent contradictions (e. Research Topic aims at helping clarify the nature of this interplay by posing a specific and narrow question. The reader will find a collection of 10 empirical papers plus an opinion and a review article which can broadly be classified into those addressing the contribution of bottom-up processing in MSI, and those exploring top-down modulations. One framework for exploring the interplay between attention and MSI is to assume that attention leads to reweighting of sensory information (Bresciani and Ernst, 2007). Focusing on bottom-up contributions, Vercillo and Gori address such potential reweighting using the Maximum Likelihood Estimate model. The effect of attention on the weighting of sensory information could be disentangled by measuring observer's audio-tactile spatial estimates, showing that bottom-up attention increases precision and alters sensory weighting in MSI. These findings corroborate selective attention's role in adjusting the brain's computations for achieving an integrated multisensory percept. Keeping the bottom-up perspective, Hazan et al. address visual search in the barn owl. Similar to ventriloquism (e.g., Pick et al., 1969) and visual search in humans (Onat et al., 2007), the owls' visual search behavior was modulated by sound, demonstrating that audiovisual interactions guided visual attention. Visual search mechanisms might be similar among mammalian and non-mammalian species, owing to correlations between visual and auditory events in nature. An ultimate demonstration of the effect of bottom-up processes would consist in showing MSI for sub-threshold stimuli, in the absence of top-down biases. Aller et al. take a step in this direction showing that the visibility of a visual event under continuous flash suppression (CFS) increases when a sound is congruent (instead of incongruent). Albeit, as the authors argue, possible top-down processes may still exert an influence, the CFS framework provides a

Regulating the blink: Cognitive reappraisal modulates attention

Abstract: Our brain is unable to fully process all the sensory signals we encounter. Attention is the process that helps selecting input from all available information for detailed processing and it is largely influenced by the affective value of the stimuli. This study examined if attentional bias toward emotional stimuli can be modulated by cognitively changing their emotional value. Participants were presented with negative and neutral images from four different scene-categories depicting humans ("Reading", "Working", "Crying" and "Violence"). Using cognitive reappraisal subjects decreased and increased the negativity of one negative (e.g., "Crying") and one neutral (e.g., "Reading") category respectively, whereas they only had to watch the other two categories (e.g., "Working" and "Violence") without changing their feelings. Subsequently, subjects performed the attentional blink paradigm. Two targets were embedded in a stream of distractors, with the previously seen human pictures serving as the first target (T1) and rotated landmark/landscape images as the second (T2). Subjects then reported T1 visibility and the orientation of T2. We investigated if the detection accuracy of T2 is influenced by the change of the emotional value of T1 due to the reappraisal manipulation. Indeed, T2 detection rate was higher when T2 was preceded by a negative image that was only viewed compared to negative images that were reappraised to be neutral. Thus, more resources were captured by images that have been reappraised before, i.e., their negativity has been reduced. This modulatory effect of reappraisal on attention was not found for neutral images. Possibly upon re-exposure to negative stimuli subjects had to recall the previously performed affective change. In this case resources may be allocated to maintain the reappraised value and therefore hinder the detection of a temporally close target. Complimentary self-reported ratings support the reappraisal manipulation of negative images.

Small vessel disease: mechanisms and clinical implications

Abstract: Small vessel disease is a disorder of cerebral microvessels that causes white matter hyperintensities and several other common abnormalities (eg, recent small subcortical infarcts and lacunes) seen on brain imaging. Despite being a common cause of stroke and vascular dementia, the underlying pathogenesis is poorly understood. Research in humans has identified several manifestations of cerebral microvessel endothelial dysfunction including blood-brain barrier dysfunction, impaired vasodilation, vessel stiffening, dysfunctional blood flow and interstitial fluid drainage, white matter rarefaction, ischaemia, inflammation, myelin damage, and secondary neurodegeneration. These brain abnormalities are more dynamic and widespread than previously thought. Relationships between lesions and symptoms are highly variable but poorly understood. Major challenges are the determination of which vascular dysfunctions are most important in pathogenesis, which abnormalities are reversible, and why lesion progression and symptomatology are so variable. This knowledge will help to identify potential targets for intervention and improve risk prediction for individuals with small vessel disease.

Vascular dysfunction-The disregarded partner of Alzheimer's disease

Abstract: Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

Integration of touch and sound in auditory cortex

Abstract: Summary To form a coherent percept of the environment, our brain combines information from different senses. Such multisensory integration occurs in higher association cortices; but supposedly, it also occurs in early sensory areas. Confirming the latter hypothesis, we unequivocally demonstrate supra-additive integration of touch and sound stimulation at the second stage of the auditory cortex. Using high-resolution fMRI of the macaque monkey, we quantified the integration of auditory broad-band noise and tactile stimulation of hand and foot in anaesthetized animals. Integration was found posterior to and along the lateral side of the primary auditory cortex in the caudal auditory belt. Integration was stronger for temporally coincident stimuli and obeyed the principle of inverse effectiveness: greater enhancement for less effective stimuli. These findings demonstrates that multisensory integration occurs early and close to primary sensory areas and—because it occurs in anaesthetized animals—suggests that this integration is mediated by preattentive bottom-up mechanisms.