Phylogenetic reorganization of the basal ganglia: A necessary, but not the only, bridge over a primate Rubicon of acoustic communication

In this response to commentaries, we revisit the two main arguments of our target article. Based on data drawn from a variety of research areas – vocal behavior in nonhuman primates, speech physiology and pathology, neurobiology of basal ganglia functions, motor skill learning, paleoanthropological concepts – the target article, first, suggests a two-stage model of the evolution of the crucial motor prerequisites of spoken language within the hominin lineage: (1) monosynaptic refinement of the projections of motor cortex to brainstem nuclei steering laryngeal muscles, and (2) subsequent “vocal-laryngeal elaboration” of cortico-basal ganglia circuits, driven by human-specific FOXP2 mutations. Second, as concerns the ontogenetic development of verbal communication, age-dependent interactions between the basal ganglia and their cortical targets are assumed to contribute to the time course of the acquisition of articulate speech. Whereas such a phylogenetic reorganization of cortico-striatal circuits must be considered a necessary prerequisite for ontogenetic speech acquisition, the 30 commentaries – addressing the whole range of data sources referred to – point at several further aspects of acoustic communication which have to be added to or integrated with the presented model. For example, the relationships between vocal tract movement sequencing – the focus of the target article – and rhythmical structures of movement organization, the connections between speech motor control and the central-auditory and central-visual systems, the impact of social factors upon the development of vocal behavior (in nonhuman primates and in our species), and the interactions of ontogenetic speech acquisition – based upon FOXP2-driven structural changes at the level of the basal ganglia – with preceding subvocal stages of acoustic communication as well as higher-order (cognitive) dimensions of phonological development. Most importantly, thus, several promising future research directions unfold from these contributions – accessible to clinical studies and functional imaging in our species as well as experimental investigations in nonhuman primates

Influence of sublexical frequencies on the speech production in aphasia and apraxia of speech

The aim of this study was to evaluate the influence of sublexical frequencies on the speech production of patients with apraxia of speech and patients with a phonological disorder. Recent studies have discussed syllable frequency as an important parameter which influences phonetically and / or phonologically disturbed speech. In the current investigation frequencies for the units syllable, phoneme, biphoneme, onset and rhyme were evaluated. The focus of our analysis was how the frequencies of the target units relate to those of the units realised by the patients. The results are discussed with regard to the pathomechanisms underlying of apraxia of speech and phonological impairment

Explicit and implicit facilitation of word production in spoken picture naming: The effectiveness of segmental cues and mouth-shape information

This study examined the immediate effectiveness of different word form specific cues on picture naming in patients with anomia or apraxia of speech. The aim was to determine which cue (segmental: initial phoneme, subsegmental: mouth-shape of the initial phoneme) facilitates word production depending on the mode of presentation (explicit/implicit) and the underlying impairment of the patient (anomia/apraxia of speech). The results differed between the two patient groups. The anomic patients showed a positive effect of explicit segmental cues only whereas the patients with apraxia of speech were facilitated by explicit and implicit segmental cues as well as by explicit mouth-shape cues

Nonverbal Semantics Test (NVST)—A Novel Diagnostic Tool to Assess Semantic Processing Deficits: Application to Persons with Aphasia after Cerebrovascular Accident

Assessment of semantic processing capacities often relies on verbal tasks which are, however, sensitive to impairments at several language processing levels. Especially for persons with aphasia there is a strong need for a tool that measures semantic processing skills independent of verbal abilities. Furthermore, in order to assess a patient’s potential for using alternative means of communication in cases of severe aphasia, semantic processing should be assessed in different nonverbal conditions. The Nonverbal Semantics Test (NVST) is a tool that captures semantic processing capacities through three tasks—Semantic Sorting, Drawing, and Pantomime. The main aim of the current study was to investigate the relationship between the NVST and measures of standard neurolinguistic assessment. Fifty-one persons with aphasia caused by left hemisphere brain damage were administered the NVST as well as the Aachen Aphasia Test (AAT). A principal component analysis (PCA) was conducted across all AAT and NVST subtests. The analysis resulted in a two-factor model that captured 69% of the variance of the original data, with all linguistic tasks loading high on one factor and the NVST subtests loading high on the other. These findings suggest that nonverbal tasks assessing semantic processing capacities should be administered alongside standard neurolinguistic aphasia tests. View Full-Tex

Dual, HLA-B27 Subtype-dependent Conformation of a Self-peptide

The products of the human leukocyte antigen subtypes HLA-B*2705 and HLA-B*2709 differ only in residue 116 (Asp vs. His) within the peptide binding groove but are differentially associated with the autoimmune disease ankylosing spondylitis (AS); HLA-B*2705 occurs in AS-patients, whereas HLA-B*2709 does not. The subtypes also generate differential T cell repertoires as exemplified by distinct T cell responses against the self-peptide pVIPR (RRKWRRWHL). The crystal structures described here show that pVIPR binds in an unprecedented dual conformation only to HLA-B*2705 molecules. In one binding mode, peptide pArg5 forms a salt bridge to Asp116, connected with drastically different interactions between peptide and heavy chain, contrasting with the second, conventional conformation, which is exclusively found in the case of B*2709. These subtype-dependent differences in pVIPR binding link the emergence of dissimilar T cell repertoires in individuals with HLA-B*2705 or HLA-B*2709 to the buried Asp116/His116 polymorphism and provide novel insights into peptide presentation by major histocompatibility antigens

Allele-Dependent Similarity between Viral and Self-Peptide Presentation by Hla-B27 Subtypes

Molecular mimicry is discussed as a possible mechanism that may contribute to the development of autoimmune diseases. It could also be involved in the differential association of the human major histocompatibility subtypes HLA-B(*)2705 and HLA-B(*)2709 with ankylosing spondylitis. These two subtypes differ only in residue 116 of the heavy chain (Asp in B(*)2705 and His in B(*)2709), but the reason for the differential disease association is not understood. Using x-ray crystallography, we show here that the viral peptide pLMP2 (RRRWRRLTV, derived from latent membrane protein 2 (residues 236-244) of Epstein-Barr virus) is presented by the B(*)2705 and B(*)2709 molecules in two drastically deviating conformations. Extensive structural similarity between pLMP2 and the self-peptide pVIPR (RRKWRRWHL, derived from vasoactive intestinal peptide type 1 receptor (residues 400-408)) is observed only when the peptides are presented by B(*)2705 because of a salt bridge between Arg(5) of both peptides and the subtype-specific heavy chain residue Asp(116). Combined with functional studies using pLMP2/pVIPR-cross-reactive cytotoxic T cell lines and clones, together with target cells presenting these peptides or a modified peptide analogue, our results reveal that a pathogen-derived peptide can exhibit major histocompatibility complex class I subtype-dependent, drastically distinct binding modes. Furthermore, the results demonstrate that molecular mimicry between pLMP2 and pVIPR in the HLA-B27 context is an allele-dependent property

Rehabilitation of impaired speech function (dysarthria, dysglossia)

Speech disorders can result (1) from sensorimotor impairments of articulatory movements = dysarthria, or (2) from structural changes of the speech organs, in adults particularly after surgical and radiochemical treatment of tumors = dysglossia. The decrease of intelligibility, a reduced vocal stamina, the stigmatization of a conspicuous voice and manner of speech, the reduction of emotional expressivity all mean greatly diminished quality of life, restricted career opportunities and diminished social contacts. Intensive therapy based on the pathophysiological facts is absolutely essential: Functional exercise therapy plays a central role; according to symptoms and their progression it can be complemented with prosthetic and surgical approaches. In severe cases communicational aids have to be used. All rehabilitation measures have to take account of frequently associated disorders of body motor control and/or impairment of cognition and behaviour

In Time with the Beat: Entrainment in Patients with Phonological Impairment, Apraxia of Speech, and Parkinson’s Disease

In the present study, we investigated if individuals with neurogenic speech sound impairments of three types, Parkinson’s dysarthria, apraxia of speech, and aphasic phonological impairment, accommodate their speech to the natural speech rhythm of an auditory model, and if so, whether the effect is more significant after hearing metrically regular sentences as compared to those with an irregular pattern. This question builds on theories of rhythmic entrainment, assuming that sensorimotor predictions of upcoming events allow humans to synchronize their actions with an external rhythm. To investigate entrainment effects, we conducted a sentence completion task relating participants’ response latencies to the spoken rhythm of the prime heard immediately before. A further research question was if the perceived rhythm interacts with the rhythm of the participants’ own productions, i.e., the trochaic or iambic stress pattern of disyllabic target words. For a control group of healthy speakers, our study revealed evidence for entrainment when trochaic target words were preceded by regularly stressed prime sentences. Persons with Parkinson’s dysarthria showed a pattern similar to that of the healthy individuals. For the patient groups with apraxia of speech and with phonological impairment, considerably longer response latencies with differing patterns were observed. Trochaic target words were initiated with significantly shorter latencies, whereas the metrical regularity of prime sentences had no consistent impact on response latencies and did not interact with the stress pattern of the target words to be produced. The absence of an entrainment in these patients may be explained by the more severe difficulties in initiating speech at all. We discuss the results in terms of clinical implications for diagnostics and therapy in neurogenic speech disorders. View Full-Tex

Effectively incorporating selected multimedia content into medical publications

Until fairly recently, medical publications have been handicapped by being restricted to non-electronic formats, effectively preventing the dissemination of complex audiovisual and three-dimensional data. However, authors and readers could significantly profit from advances in electronic publishing that permit the inclusion of multimedia content directly into an article. For the first time, the de facto gold standard for scientific publishing, the portable document format (PDF), is used here as a platform to embed a video and an audio sequence of patient data into a publication. Fully interactive three-dimensional models of a face and a schematic representation of a human brain are also part of this publication. We discuss the potential of this approach and its impact on the communication of scientific medical data, particularly with regard to electronic and open access publications. Finally, we emphasise how medical teaching can benefit from this new tool and comment on the future of medical publishing

FCET2EC (From controlled experimental trial to = 2 everyday communication): How effective is intensive integrative therapy for stroke-induced chronic aphasia under routine clinical conditions? A study protocol for a randomized controlled trial

Background: Therapy guidelines recommend speech and language therapy (SLT) as the “gold standard” for aphasia treatment. Treatment intensity (i.e., ≥5 hours of SLT per week) is a key predictor of SLT outcome. The scientific evidence to support the efficacy of SLT is unsatisfactory to date given the lack of randomized controlled trials (RCT), particularly with respect to chronic aphasia (lasting for >6 months after initial stroke). This randomized waiting list-controlled multi-centre trial examines whether intensive integrative language therapy provided in routine in- and outpatient clinical settings is effective in improving everyday communication in chronic post-stroke aphasia. Methods/Design: Participants are men and women aged 18 to 70 years, at least 6 months post an ischemic or haemorrhagic stroke resulting in persisting language impairment (i.e., chronic aphasia); 220 patients will be screened for participation, with the goal of including at least 126 patients during the 26-month recruitment period. Basic language production and comprehension abilities need to be preserved (as assessed by the Aachen Aphasia Test).Therapy consists of language-systematic and communicative-pragmatic exercises for at least 2 hours/day and at least 10 hours/week, plus at least 1 hour self-administered training per day, for at least three weeks. Contents of therapy are adapted to patients’ individual impairment profiles.Prior to and immediately following the therapy/waiting period, patients’ individual language abilities are assessed via primary and secondary outcome measures. The primary (blinded) outcome measure is the A-scale (informational content, or 'understandability’, of the message) of the Amsterdam-Nijmegen Everyday Language Test (ANELT), a standardized measure of functional communication ability. Secondary (unblinded) outcome measures are language-systematic and communicative-pragmatic language screenings and questionnaires assessing life quality as viewed by the patient as well as a relative.The primary analysis tests for differences between the therapy group and an untreated (waiting list) control group with respect to pre- versus post 3-week-therapy (or waiting period, respectively) scores on the ANELT A-scale. Statistical between-group comparisons of primary and secondary outcome measures will be conducted in intention-to-treat analyses. Long-term stability of treatment effects will be assessed six months post intensive SLT (primary and secondary endpoints)