Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Digital Atlasing and Standardization in the Mouse Brain

Computer Systems, Imagery and Medi

Apraxia of speech and cerebellar mutism syndrome: a case study

Background Cerebellar mutism syndrome (CMS) or posterior fossa syndrome (PFS) consists of a constellation of neuropsychiatric, neuropsychological and neurogenic speech and language deficits. It is most commonly observed in children after posterior fossa tumor surgery. The most prominent feature of CMS is mutism, which generally starts after a few days after the operation, has a limited duration and is typically followed by motor speech deficits. However, the core speech disorder subserving CMS is still unclear. Case presentation This study investigates the speech and language symptoms following posterior fossa medulloblastoma surgery in a 12-year-old right-handed boy. An extensive battery of formal speech (DIAS = Diagnostic Instrument Apraxia of Speech) and language tests were administered during a follow-up of 6 weeks after surgery. Although the neurological and neuropsychological (affective, cognitive) symptoms of this patient are consistent with Schmahmann’s syndrome, the speech and language symptoms were markedly different from what is typically described in the literature. In-depth analyses of speech production revealed features consistent with a diagnosis of apraxia of speech (AoS) while ataxic dysarthria was completely absent. In addition, language assessments showed genuine aphasic deficits as reflected by distorted language production and perception, wordfinding difficulties, grammatical disturbances and verbal fluency deficits. Conclusion To the best of our knowledge this case might be the first example that clearly demonstrates that a higher level motor planning disorder (apraxia) may be the origin of disrupted speech in CMS. In addition, identification of non-motor linguistic disturbances during follow-up add to the view that the cerebellum not only plays a crucial role in the planning and execution of speech but also in linguistic processing. Whether the cerebellum has a direct or indirect role in motor speech planning needs to be further investigated

Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints

The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease

The Brain Atlas Concordance Problem: Quantitative Comparison of Anatomical Parcellations

Many neuroscientific reports reference discrete macro-anatomical regions of the brain which were delineated according to a brain atlas or parcellation protocol. Currently, however, no widely accepted standards exist for partitioning the cortex and subcortical structures, or for assigning labels to the resulting regions, and many procedures are being actively used. Previous attempts to reconcile neuroanatomical nomenclatures have been largely qualitative, focusing on the development of thesauri or simple semantic mappings between terms. Here we take a fundamentally different approach, discounting the names of regions and instead comparing their definitions as spatial entities in an effort to provide more precise quantitative mappings between anatomical entities as defined by different atlases. We develop an analytical framework for studying this brain atlas concordance problem, and apply these methods in a comparison of eight diverse labeling methods used by the neuroimaging community. These analyses result in conditional probabilities that enable mapping between regions across atlases, which also form the input to graph-based methods for extracting higher-order relationships between sets of regions and to procedures for assessing the global similarity between different parcellations of the same brain. At a global scale, the overall results demonstrate a considerable lack of concordance between available parcellation schemes, falling within chance levels for some atlas pairs. At a finer level, this study reveals spatial relationships between sets of defined regions that are not obviously apparent; these are of high potential interest to researchers faced with the challenge of comparing results that were based on these different anatomical models, particularly when coordinate-based data are not available. The complexity of the spatial overlap patterns revealed points to problems for attempts to reconcile anatomical parcellations and nomenclatures using strictly qualitative and/or categorical methods. Detailed results from this study are made available via an interactive web site at http://obart.info

An Analysis of the Abstracts Presented at the Annual Meetings of the Society for Neuroscience from 2001 to 2006

Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001–2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain

Sensory and cognitive mechanisms of change detection in the context of speech

The aim of this study was to dissociate the contributions of memory-based (cognitive) and adaptation-based (sensory) mechanisms underlying deviance detection in the context of natural speech. Twenty healthy right-handed native speakers of English participated in an event-related design scan in which natural speech stimuli, /de:/ (“deh”) and /deI/ (“day”); (/te:/ (“teh”) and /teI/ (“tay”) served as standards and deviants within functional magnetic resonance imaging event-related “oddball” paradigm designed to elicit the mismatch negativity component. Thus, “oddball” blocks could involve either a word deviant (“day”) resulting in a “word advantage” effect, or a non-word deviant (“deh” or “tay”). We utilized an experimental protocol controlling for refractoriness similar to that used previously when deviance detection was studied in the context of tones. Results showed that the cognitive and sensory mechanisms of deviance detection were located in the anterior and posterior auditory cortices, respectively, as was previously found in the context of tones. The cognitive effect, that was most robust for the word deviant, diminished in the “oddball” condition. In addition, the results indicated that the lexical status of the speech stimulus interacts with acoustic factors exerting a top-down modulation of the extent to which novel sounds gain access to the subject’s awareness through memory-based processes. Thus, the more salient the deviant stimulus is the more likely it is to be released from the effects of adaptation exerted by the posterior auditory cortex

Workflow and Atlas System for Brain-Wide Mapping of Axonal Connectivity in Rat

Detailed knowledge about the anatomical organization of axonal connections is important for understanding normal functions of brain systems and disease-related dysfunctions. Such connectivity data are typically generated in neuroanatomical tract-tracing experiments in which specific axonal connections are visualized in histological sections. Since journal publications typically only accommodate restricted data descriptions and example images, literature search is a cumbersome way to retrieve overviews of brain connectivity. To explore more efficient ways of mapping, analyzing, and sharing detailed axonal connectivity data from the rodent brain, we have implemented a workflow for data production and developed an atlas system tailored for online presentation of axonal tracing data. The system is available online through the Rodent Brain WorkBench (www.rbwb.org; Whole Brain Connectivity Atlas) and holds experimental metadata and high-resolution images of histological sections from experiments in which axonal tracers were injected in the primary somatosensory cortex. We here present the workflow and the data system, and exemplify how the online image repository can be used to map different aspects of the brain-wide connectivity of the rat primary somatosensory cortex, including not only presence of connections but also morphology, densities, and spatial organization. The accuracy of the approach is validated by comparing results generated with our system with findings reported in previous publications. The present study is a contribution to a systematic mapping of rodent brain connections and represents a starting point for further large-scale mapping efforts

Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping

To facilitate fine-scale phenotyping of whole specimens, we describe here a set of tissue fixation-embedding, detergent-clearing and staining protocols that can be used to transform excised organs and whole organisms into optically transparent samples within 1–2 weeks without compromising their cellular architecture or endogenous fluorescence. PACT (passive CLARITY technique) and PARS (perfusion-assisted agent release in situ) use tissue-hydrogel hybrids to stabilize tissue biomolecules during selective lipid extraction, resulting in enhanced clearing efficiency and sample integrity. Furthermore, the macromolecule permeability of PACT- and PARS-processed tissue hybrids supports the diffusion of immunolabels throughout intact tissue, whereas RIMS (refractive index matching solution) grants high-resolution imaging at depth by further reducing light scattering in cleared and uncleared samples alike. These methods are adaptable to difficult-to-image tissues, such as bone (PACT-deCAL), and to magnified single-cell visualization (ePACT). Together, these protocols and solutions enable phenotyping of subcellular components and tracing cellular connectivity in intact biological networks