The role of protecting groups in the formation of organogels through a nano-fibrillar network formed by self-assembling terminally protected tripeptides

A series of eight synthetic self-assembling terminally blocked tripeptides have been studied for gelation. Some of them form gels in various aromatic solvents including benzene, toluene, xylene, and chlorobenzene. It has been found that the protecting groups play an important role in the formation of organogels. It has been observed that, if the C-terminal has been changed from methyl ester to ethyl ester the gelation property does not change significantly (keeping the N-terminal protecting group same), while the change of the protecting group from ethyl ester to isopropyl ester completely abolishes the gelation property. Similarly, keeping the identical C-terminal protecting group (methyl ester) the results of the gelation study indicate that the substitution of N-terminal protection Boc-(tert-butyloxycarbonyl) to Cbz-(benzyloxycarbonyl) does change the gelation property insignificantly, while the change from Boc- to pivaloyl (Piv-) or acetyl (Ac-) group completely eliminates the gelation property. Morphological studies of the dried gels of two of the peptides indicate the presence of an entangled nano-fibrillar network that might be responsible for gelation. FTIR studies of the gels demonstrate that an intermolecular hydrogen bonding network is formed during gelation. Results of X-ray powder diffraction studies for these gelator peptides in different states (dried gels, gel, and bulk solids) reflected that the structure in the wet gel is distinctly different from the dried gel and solid state structures. Single crystal X-ray diffraction studies of a non-gelator peptide, which is structurally similar to the gelator molecules reveal that the peptide forms an antiparallel beta-sheet structure in crystals. (c) 2007 Elsevier Ltd. All rights reserved.

Conceptual and perceptual processing in prospective remembering

McDaniel, Robinson-Riegler, and Einstein (1998) recently reported findings in support of the proposal that prospective remembering is largely conceptually driven. In each of the three experiments they reported, however, the task in which the prospective memory target was encountered at test had a predominantly conceptual focus, thereby potentially facilitating retrieval of conceptually encoded features of the studied target event. We report two experiments in which we manipulated the dimension (perceptual or conceptual) along which a target event varied between study and test while using a processing task, at both study and test, compatible with the relevant dimension of target change. When the target was encountered in a sentence validity task at study and test, and the semantic context in which a target was encountered was changed between these two occasions, prospective remembering declined (Experiment 1). A similar decline occurred, using a readability rating task, when the perceptual context (font in which the word was printed) was altered (Experiment 2). These results indicate that both perceptual and conceptual processes can support prospective remembering.

Effect of phonetic complexity on word reading and repetition in deep dyslexia

This investigation moves beyond the traditional studies of word reading to identify how the production complexity of words affects reading accuracy in an individual with deep dyslexia (JO). We examined JO’s ability to read words aloud while manipulating both the production complexity of the words and the semantic context. The classification of words as either phonetically simple or complex was based on the Index of Phonetic Complexity. The semantic context was varied using a semantic blocking paradigm (i.e., semantically blocked and unblocked conditions). In the semantically blocked condition words were grouped by semantic categories (e.g., table, sit, seat, couch,), whereas in the unblocked condition the same words were presented in a random order. JO’s performance on reading aloud was also compared to her performance on a repetition task using the same items. Results revealed a strong interaction between word complexity and semantic blocking for reading aloud but not for repetition. JO produced the greatest number of errors for phonetically complex words in semantically blocked condition. This interaction suggests that semantic processes are constrained by output production processes which are exaggerated when derived from visual rather than auditory targets. This complex relationship between orthographic, semantic, and phonetic processes highlights the need for word recognition models to explicitly account for production processes.

Age-related changes in the functional neuroanatomy of overt speech production

Alterations of existing neural networks during healthy aging, resulting in behavioral deficits and changes in brain activity, have been described for cognitive, motor, and sensory functions. To investigate age-related changes in the neural circuitry underlying overt non-lexical speech production, functional MRI was performed in 14 healthy younger (21–32 years) and 14 healthy older individuals (62–84 years). The experimental task involved the acoustically cued overt production of the vowel /a/ and the polysyllabic utterance /pataka/. In younger and older individuals, overt speech production was associated with the activation of a widespread articulo-phonological network, including the primary motor cortex, the supplementary motor area, the cingulate motor areas, and the posterior superior temporal cortex, similar in the /a/ and /pataka/ condition. An analysis of variance with the factors age and condition revealed a significant main effect of age. Irrespective of the experimental condition, significantly greater activation was found in the bilateral posterior superior temporal cortex, the posterior temporal plane, and the transverse temporal gyri in younger compared to older individuals. Significantly greater activation was found in the bilateral middle temporal gyri, medial frontal gyri, middle frontal gyri, and inferior frontal gyri in older vs. younger individuals. The analysis of variance did not reveal a significant main effect of condition and no significant interaction of age and condition. These results suggest a complex reorganization of neural networks dedicated to the production of speech during healthy aging.

Measuring quality of life in aphasia: results from two scales

Background: Although aphasia affects quality of life (QoL), the impact within specific domains (e.g., psychosocial, communication) is poorly understood. Moreover, the complex and multidimensional nature of QoL renders it difficult to measure accurately using a single global scale. Aims: Using two recently developed QoL scales, the Stroke and Aphasia Quality of Life Scale-39, (SAQOL; Hilari, Byng, Lamping, & Smith, 2003a) and the American Speech Language Hearing Association’s Quality of Communication Life Scale (QCL; Paul et al., 2004), this study aimed to document the domains of QoL that were most affected for participants with aphasia compared to control participants, as well as to determine the relationship between the two scales, their sub-domains, and linguistic variables in aphasia. Methods & Procedures: The two scales were administered to a group of 19 participants with aphasia (14 male, 5 female), ages ranging from 27 to 79 years, and 19 age- and gender-matched control participants. Various types and severity of aphasia were represented in the aphasia group. The performances of aphasia and control groups were compared, and correlation analyses examined the relationship between the two scales and their sub-domains in the aphasia group only. Outcomes & Results: Compared to control participants, QoL was lower in participants with aphasia, with the communication sub-domain of SAQOL and socialisation/ activities sub-domain of QCL being the most affected areas of functioning. Between the two scales, the communication sub-domain of SAQOL correlated with the socialisation/ activities sub-domain and the QCL mean. Moreover, linguistic variables correlated strongly with psychosocial, communication and socialisation/activities sub-domains of QoL. Conclusions: Measuring QoL using the SAQOL and the QCL captures different but equally important aspects of experiences of living with aphasia. When interpreted together, they provide a holistic picture of functioning in aphasia that includes broad overviews of QoL from the SAQOL and a finer-grained analysis of communication impairments on QoL from the QCL.

Effects of utterance length on lip kinematics in aphasia

Most existing models of language production and speech motor control do not explicitly address how language requirements affect speech motor functions, as these domains are usually treated as separate and independent from one another. This investigation compared lip movements during bilabial closure between five individuals with mild aphasia and five age and gender-matched control speakers when the linguistic characteristics of the stimuli were varied by increasing the number of syllables. Upper and lower lip movement data were collected for mono-, bi- and tri-syllabic nonword sequences using an AG 100 EMMA system. Each task was performed under both normal and fast rate conditions. Single articulator kinematic parameters (peak velocity, amplitude, duration,and cyclic spatio-temporal index) were measured to characterize lip movements. Results revealed that compared to control speakers, individuals with aphasia showed significantly longer movement duration and lower movement stability for longer items (bi- and tri-syllables). Moreover, utterance length affected the lip kinematics, in that the monosyllables had smaller peak velocities, smaller amplitudes and shorter durations compared to bi- and trisyllables, and movement stability was lowest for the trisyllables. In addition, the rate-induced changes (smaller amplitude and shorter duration with increased rate) were most prominent for the short items (i.e., monosyllables). These findings provide further support for the notion that linguistic changes have an impact on the characteristics of speech movements, and that individuals with aphasia are more affected by such changes than control speakers.

Word frequency and bigram frequency effects on linguistic processing and speech motor performance in individuals with aphasia and normal speakers

Models of normal word production are well specified about the effects of frequency of linguistic stimuli on lexical access, but are less clear regarding the same effects on later stages of word production, particularly word articulation. In aphasia, this lack of specificity of down-stream frequency effects is even more noticeable because there is relatively limited amount of data on the time course of frequency effects for this population. This study begins to fill this gap by comparing the effects of variation of word frequency (lexical, whole word) and bigram frequency (sub-lexical, within word) on word production abilities in ten normal speakers and eight mild–moderate individuals with aphasia. In an immediate repetition paradigm, participants repeated single monosyllabic words in which word frequency (high or low) was crossed with bigram frequency (high or low). Indices for mapping the time course for these effects included reaction time (RT) for linguistic processing and motor preparation, and word duration (WD) for speech motor performance (word articulation time). The results indicated that individuals with aphasia had significantly longer RT and WD compared to normal speakers. RT showed a significant main effect only for word frequency (i.e., high-frequency words had shorter RT). WD showed significant main effects of word and bigram frequency; however, contrary to our expectations, high-frequency items had longer WD. Further investigation of WD revealed that independent of the influence of word and bigram frequency, vowel type (tense or lax) had the expected effect on WD. Moreover, individuals with aphasia differed from control speakers in their ability to implement tense vowel duration, even though they could produce an appropriate distinction between tense and lax vowels. The results highlight the importance of using temporal measures to identify subtle deficits in linguistic and speech motor processing in aphasia, the crucial role of phonetic characteristics of stimuli set in studying speech production and the need for the language production models to account more explicitly for word articulation.

Speech motor control in fluent and dysfluent speech production of an individual with apraxia of speech and Broca’s aphasia

Apraxia of speech (AOS) is typically described as a motor-speech disorder with clinically well-defined symptoms, but without a clear understanding of the underlying problems in motor control. A number of studies have compared the speech of subjects with AOS to the fluent speech of controls, but only a few have included speech movement data and if so, this was primarily restricted to the study of single articulators. If AOS reflects a basic neuromotor dysfunction, this should somehow be evident in the production of both dysfluent and perceptually fluent speech. The current study compared motor control strategies for the production of perceptually fluent speech between a young woman with apraxia of speech (AOS) and Broca’s aphasia and a group of age-matched control speakers using concepts and tools from articulation-based theories. In addition, to examine the potential role of specific movement variables on gestural coordination, a second part of this study involved a comparison of fluent and dysfluent speech samples from the speaker with AOS. Movement data from the lips, jaw and tongue were acquired using the AG-100 EMMA system during the reiterated production of multisyllabic nonwords. The findings indicated that although in general kinematic parameters of fluent speech were similar in the subject with AOS and Broca’s aphasia to those of the age-matched controls, speech task-related differences were observed in upper lip movements and lip coordination. The comparison between fluent and dysfluent speech characteristics suggested that fluent speech was achieved through the use of specific motor control strategies, highlighting the potential association between the stability of coordinative patterns and movement range, as described in Coordination Dynamics theory.

Clustered functional MRI of overt speech production

To investigate the neural network of overt speech production, eventrelated fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speechrelated movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the corticaland subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum,reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.

Mapping therapy for sentence production impairments in nonfluent aphasia

This study investigated a new treatment in which sentence production abilities were trained in a small group of individuals and nonfluent aphasia. It was based upon a mapping therapy approach which holds that sentence production and comprehension impairments are due to difficulties in mapping between the meaning form (thematic roles) and the syntactic form of sentences. We trained production of both canonical and noncanonical reversible sentences.Three patients received treatment and two served as control participants. Patients who received treatment demonstrated acquisition of all trained sentence structures. They also demonstrated across-task generalisation of treated and some untreated sentence structures on two tasks of constrained sentence production, and showed some improvements on a narrative task. One control participant improved on some of these measures and the other did not. There was no noted improvement in sentence comprehension abilities following treatment. Results are discussed with reference to the heterogeneity of underlying impairments in sentence production impairments in nonfluent patients, and the possible mechanisms by which improvement in sentence production might have been achieved in treatment.

A cognitive and psycholinguistic investigation of neologisms

Background: Jargon aphasia with neologisms (i.e., novel nonword utterances) is a challenging language disorder that lacks a definitive theoretical description as well as clear treatment recommendations (Marshall, 2006). Aim: The aims of this two part investigation were to determine the source of neologisms in an individual with jargon aphasia (FF), to identify potential facilitatory semantic and/or phonological cuing effects in picture naming, and to determine whether the timing of the cues relative to the target picture mediated the cuing advantage. Methods and Procedures: FF’s underlying linguistic deficits were determined using several cognitive and linguistic tests. A series of computerized naming experiments using a modified version of the 175 item-Philadelphia Naming Test (Roach, Schwartz, Martin, Grewal, & Brecher, 1996) manipulated the cue type (semantic versus phonological) and relatedness (related versus unrelated). In a follow-up experiment, the relative timing of phonological cues was manipulated to test the effect of timing on the cuing advantage. The accuracy of naming responses and error patterns were analyzed. Outcome and Results: FF’s performance on the linguistic and cognitive test battery revealed a severe naming impairment with relatively spared word and nonword repetition, auditory comprehension of words and monitoring, and fairly well preserved semantic abilities. This performance profile was used to evaluate various explanations for neologisms including a loss of phonological codes, monitoring failure, and impairments in semantic system. The primary locus of his deficit appears to involve the connection between semantics to phonology, specifically, when word production involves accessing the phonological forms following semantic access. FF showed a significant cuing advantage only for phonological cues in picture naming, particularly when the cue preceded or coincided with the onset of the target picture. Conclusions: When integrated with previous findings, the results from this study suggest that the core deficit of this and at least some other jargon aphasics is in the connection from semantics to phonology. The facilitative advantage of phonological cues could potentially be exploited in future clinical and research studies to test the effectiveness of these cues for enhancing naming performance in individuals like FF.

Speech-like and non-speech lip kinematics and coordination in aphasia

Background and aims: In addition to the well-known linguistic processing impairments in aphasia, oro-motor skills and articulatory implementation of speech segments are reported to be compromised to some degree in most types of aphasia. This study aimed to identify differences in the characteristics and coordination of lip movements in the production of a bilabial closure gesture between speech-like and nonspeech tasks in individuals with aphasia and healthy control subjects. Method and procedure: Upper and lower lip movement data were collected for a speech-like and a nonspeech task using an AG 100 EMMA system from five individuals with aphasia and five age and gender matched control subjects. Each task was produced at two rate conditions (normal and fast), and in a familiar and a less-familiar manner. Single articulator kinematic parameters (peak velocity, amplitude, duration, and cyclic spatio-temporal index) and multi-articulator coordination indices (average relative phase and variability of relative phase) were measured to characterize lip movements. Outcome and results: The results showed that when the two lips had similar task goals (bilabial closure) in speech-like versus nonspeech task, kinematic and coordination characteristics were not found to be different. However, when changes in rate were imposed on the bilabial gesture, only speech-like task showed functional adaptations, indicated by a greater decrease in amplitude and duration at fast rates. In terms of group differences, individuals with aphasia showed smaller amplitudes and longer movement durations for upper lip, higher spatio-temporal variability for both lips, and higher variability in lip coordination than the control speakers. Rate was an important factor in distinguishing the two groups, and individuals with aphasia were limited in implementing the rate changes. Conclusion and implications: The findings support the notion of subtle but robust differences in motor control characteristics between individuals with aphasia and the control participants, even in the context of producing bilabial closing gestures for a relatively simple speech-like task. The findings also highlight the functional differences between speech-like and nonspeech tasks, despite a common movement coordination goal for bilabial closure.

Phonological therapy in jargon aphasia: effects on naming and neologisms

Background: Jargon aphasia is one of the most intractable forms of aphasia with limited recommendation on amelioration of associated naming difficulties and neologisms. The few naming therapy studies that exist in jargon aphasia have utilized either semantic or phonological approaches but the results have been equivocal. Moreover, the effect of therapy on characteristics of neologisms is less explored. Aims: This study investigates the effectiveness of a phonological naming therapy (i.e., phonological component analysis, PCA) on picture naming abilities and on quantitative and qualitative changes in neologisms for an individual with jargon aphasia (FF). Methods: FF showed evidence of jargon aphasia with severe naming difficulties and produced a very high proportion of neologisms. A single-subject multiple probe design across behaviors was employed to evaluate the effects of PCA therapy on the accuracy for three sets of words. In therapy, a phonological components analysis chart was used to identify five phonological components (i.e., rhymes, first sound, first sound associate, final sound, number of syllables) for each target word. Generalization effects—change in percent accuracy and error pattern—were examined comparing pre-and post-therapy responses on the Philadelphia Naming Test and these responses were analyzed to explore the characteristics of the neologisms. The quantitative change in neologisms was measured by change in the proportion of neologisms from pre- to post-therapy and the qualitative change was indexed by the phonological overlap between target and neologism. Results: As a consequence of PCA therapy, FF showed a significant improvement in his ability to name the treated items. His performance in maintenance and follow-up phases remained comparable to his performance during the therapy phases. Generalization to other naming tasks did not show a change in accuracy but distinct differences in error pattern (an increase in proportion of real word responses and a decrease in proportion of neologisms) were observed. Notably, the decrease in neologisms occurred with a corresponding trend for increase in the phonological similarity between the neologisms and the targets. Conclusions: This study demonstrated the effectiveness of a phonological therapy for improving naming abilities and reducing the amount of neologisms in an individual with severe jargon aphasia. The positive outcome of this research is encouraging, as it provides evidence for effective therapies for jargon aphasia and also emphasizes that use of the quality and quantity of errors may provide a sensitive outcome measure to determine therapy effectiveness, in particular for client groups who are difficult to treat.