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M R McNeil

Publications and source records attributed to M R McNeil.

At least 37 records · Page 2Linked to original sources
PubMed1994

Recognition of the lipid intermediate for arabinogalactan/arabinomannan biosynthesis and its relation to the mode of action of ethambutol on mycobacteria.

Despite major advances in our understanding of the structure of mycobacterial cell walls, little is known of their biogenesis, and yet they are the site of action of many anti-tuberculosis drugs and implicated in much of the pathology of tuberculosis and leprosy. A family of monoglycosyl polyprenylphosphates was isolated from Mycobacterium smegmatis, containing arabinose, ribose, and mannose. The isoprenoid nature of the lipid components was established by 1H NMR, and fast atom bombardment mass spectroscopy (FAB-MS) demonstrated the presence of C50 decaprenyl-P derivatives and smaller amounts of the C35 octahydroheptaprenyl-P products. The configuration of the mycobacterial decaprenol was established as mono-trans, octa-cis, pointing to carriers of unusual structure. Combined gas chromatography (GC)/MS, FAB-MS/MS, and 1H NMR allowed characterization of one of the primary components as beta-D-arabinofuranosyl-1-monophosphodecaprenol. Pulse-chase metabolic labeling of cells with D-[14C]glucose indicated that the decaprenyl-P-arabinose is an active intermediate in the biosynthesis of the arabinan of cell wall arabinogalactan and arabinomannan. The identification of polyprenyl-P-ribose suggests the existence of ribose-containing polysaccharides in the cell walls of M. smegmatis or/and of a novel epimerase in the D-arabinose biosynthetic pathway. Ethambutol, a powerful anti-tuberculosis drug known to inhibit arabinogalactan and arabinomannan biosynthesis, results in the rapid accumulation of decaprenyl-P-arabinose, indicating that the drug interferes with either the transfer of arabinose from the donor or, alternatively, the synthesis of the arabinose acceptor itself.

Arabinose↗
PubMed1994

New pyruvylated, glycosylated acyltrehaloses from Mycobacterium smegmatis strains, and their implications for phage resistance in mycobacteria.

Phage resistance and apparent lysogenization of Mycobacterium smegmatis due to infection with mycobacteriophage D29 results in the emergence of new variations of the pyruvylated, acylated trehaloses described by Saadat and Ballou, J. Biol. Chem. 258 (1983) 1813-1818. Thin-layer chromatography of the glycolipids from two strains of phage-resistant M. smegmatis (mc(2)22 and mc(2)11) and comparison with those from phage-sensitive strains revealed a new, more mobile glycolipid in each case. The structures of these acyltrehalose-containing lipooligosaccharides were elucidated by a combination of gas-liquid chromatography-mass spectrometry, methylation analysis, 1H and 13C NMR spectroscopy, and fast-atom bombardment mass spectrometry. The glycolipid from M. smegmatis mc(2)22 is beta-D-Glcp-(1-->3)-4,6-O-(1-methoxycarbonylethylidene)-beta-D-Glc p-(1-->4)- beta-D-Glcp-(1-->6)-2-O-acyl-alpha-D-Glcp-(<==>1)-3,4-O-acyl-alpha-D-Glc p and that from M. smegmatis mc(2)11 is 4,6-O-(1-methoxycarbonylethylidene)-3-O-Me-beta-D-Glcp-(1-->3)-4,6 -O- (1-methoxycarbonylethylidene)-beta-D-Glcp-(1-->4)-beta-D-Glcp-(1-- >6)-2-O-acyl- alpha-D-Glcp-(1<==>1)-3,4-di-O-acyl-alpha-D-Glcp. These differ from the original pyruvylated glycolipids of Saadat and Ballou in the extent of their O-acylation and O-methylation. The findings are the first example of the definition of a chemical basis for phage resistance and presumed lysogeny in mycobacteria, and show parallels to related changes in gram-negative enteric bacteria.

Acylation↗
PubMed1994

Enzymatic evidence for the presence of a critical terminal hexa-arabinoside in the cell walls of Mycobacterium tuberculosis.

A species of Cellulomonas was isolated from soil by enrichment culture and shown to secrete enzymes capable of degrading mycobacterial cell wall arabinogalactan, both the insoluble peptidoglycan-bound and base-solubilized forms. The major degradation product was purified and characterized as a hexa-arabinofuranoside, [beta-D-Araf-(1-->2)-alpha-Araf-(1-->]2-->3,5-alpha-D-Ara f-(1-->5)-D-Araf. The non-reducing ends of this unit are the sites of mycolic acid attachment and, as they also appear in lipoarabinomannan (LAM), the point of mannose capping in some mycobacteria. Thus, elaboration of the structure of this focal hexasaccharide is critical to our understanding of much of the physiology and pathogenesis of mycobacteria. The extracellular enzymes of Cellulomonas sp. also released the disaccharide, alpha-D-Araf-(1-->5)-D-Araf, from internal linear regions of arabinan and, surprisingly, convert the linear galactan backbone into cyclic oligosaccharides of the structure [-->5-D-Galf-(1-->6)-beta-D-Galf-(1-->]n where n is 2, 3 or 4. Thus, the preparation contains Schardinger-like enzyme activity. This group of enzymes are powerful tools for the dissection of the mycolylarabino-galactan-peptidoglycan (mAGP) complex of mycobacteria towards understanding its role in drug resistance, disease processes and mycobacterial physiology.

Actinomycetales↗
PubMed1994

Loci of Mycobacterium avium ser2 gene cluster and their functions.

The highly antigenic glycopeptidolipids present on the surface of members of the Mycobacterium avium complex serve to distinguish these bacteria from all others and to define the various serovars that compose this complex. Previously, the genes responsible for the biosynthesis of the disaccharide hapten [2,3-di-O-methyl-alpha-L-fucopyranosyl-(1-->3)-alpha-L-rhamnopyranose] of serovar 2 of the M. avium complex were isolated, localized to a contiguous 22- to 27-kb fragment of the M. avium genome, and designated the ser2 gene cluster (J. T. Belisle, L. Pascopella, J. M. Inamine, P. J. Brennan, and W. R. Jacobs, Jr., J. Bacteriol. 173:6991-6997, 1991). In the present study, transposon saturation mutagenesis was used to map the specific genetic loci within the ser2 gene cluster required for expression of this disaccharide. Four essential loci, termed ser2A, -B, -C, and -D, constituting a total of 5.7 kb within the ser2 gene cluster, were defined. The ser2B and ser2D loci encode the methyltransferases required to methylate the fucose at the 3 and 2 positions, respectively. The rhamnosyltransferase was encoded by ser2A, whereas either ser2C or ser2D encoded the fucosyltransferase. The ser2C and ser2D loci are also apparently involved in the de novo synthesis of fucose. Isolation of the truncated versions of the hapten induced by the transposon insertions provides genetic evidence that the glycopeptidolipids of M. avium serovar 2 are synthesized by an initial transfer of the rhamnose unit to the peptide core followed by fucose and finally O methylation of the fucosyl unit.

Amino Acid Sequence↗
PubMed1993

Trehalose-containing lipooligosaccharides of Mycobacterium gordonae: presence of a mono-O-methyltetra-O-acyltrehalose "core" and branching in the oligosaccharide backbone.

Past evidence has indicated that Mycobacterium gordonae, as isolated from soil and as an occasional opportunistic pathogen, exists as a serocomplex. We now demonstrate that the basis of seroreactivity and diversity is a novel series of alkali-labile, trehalose-containing lipooligosaccharides (LOS). The structures from two strains were established by per-O-methylation, partial acid hydrolysis, infrared and high-field NMR spectroscopy, electron-impact MS, and fast atom bombardment/mass spectrometry of the native lipooligosaccharides and hydrolysis products. The structure of the major lipooligosaccharide, LOS-I, of M. gordonae strain 989 was defined as 2-O-CH3-4-O-CH3CO-alpha-L-Fucp-(1-->3)- beta-D-Glcp-(1-->3)-2-O-CH3-alpha-L-Rhap-(1-->3)-[beta-D-Xylp++ +-(1-->2)-]- alpha-L-Rhap-(1-->3)-beta-D-Glcp-(1-->3)-alpha-L-Rhap-(1-->3 )-6-O- CH3-alpha-D-Glcp-(1<-->1)-2,3,4,6-tetra-O-acyl-alpha-D-Glcp, which was further glycosylated at C-3 of the terminal 2-O-CH3-4-O-CH3CO-alpha-L-Fucp by an incompletely defined N-acyl derivative of 4-amino-4,6-dideoxy-2,3-di-O-CH3-Galp. The structure of the major lipooligosaccharide, LOS-I, of a second strain of M. gordonae (strain 990) was defined as alpha-L-Rhap-(1-->2)-3-O-CH3-alpha-L-Rhap- (1-->3)-[beta-D-Xylp-(1-->2)-]-alpha-L-Rhap-(1-->3)-beta-D-G lcp- (1-->3)[beta-D-Xylp-(1-->2)-]-alpha-L-Rhap- (1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-alpha-L-Rhap-(1--> 3)-6-O-CH3- alpha-D-Glcp-(1<-->1)-2,3,4,6-tetra-O-acyl-alpha-D-Glcp. The other minor LOSs from both strains were also defined. Both families of LOSs from the two strains contain a novel mono-6'-O-CH3-2,3,4,6-tetra-O-acyltrehalose unit, representing the first example of such a unit among the LOSs isolated to date from mycobacteria. Also, the more polar antigenic products, LOS-I, -II', -II", and -III from M. gordonae 989 and LOS-I, -II, and -II' from M. gordonae 990, are characterized by branching of the oligosaccharide backbone, the first instance of sugar branching in these products. In the case of LOS-I and -III from M. gordonae 989, the branch consists of a terminal (t)-beta-D-Xylp unit, whereas in LOS-II' and -II", they are (t)-3-O-CH3-beta-D-Xylp and (t)-alpha-D-Araf, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Acylation↗
PubMed1993

Isolation and characterization of a novel glucuronosyl diacylglycerol from Mycobacterium smegmatis.

A glucuronic acid-containing diacylglycerol was isolated from exponentially growing Mycobacterium smegmatis. Structural analysis of the purified glycolipid, performed by gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and high resolution proton NMR, indicated the structure 3-(O-alpha-D-glucuronopyranosyl)-1,2-diacyl-sn-glycerol. Two forms of the glycolipid were observed differing in fatty acid composition. Both molecular species contained a hexadecanoic acid residue, whereas the second acyl group was either tuberculostearic acid (10-methylstearic acid) or octadecenoic acid. The inherent antigenicity of the glycolipid was shown by its ability to bind to anti-Mycobacterium avium (serovar 26) and anti-Mycobacterium tuberculosis sera by Western blot-type thin-layer chromatography. This is the second instance of the isolation of a glycosyl diacylglycerol from members of the Mycobacterium genus, further confirming its close relationship to Gram-positive bacteria.

Antigens, Bacterial↗
PubMed1993

Expression of the core lipopeptide of the glycopeptidolipid surface antigens in rough mutants of Mycobacterium avium.

Toward studying the genetics, biosynthesis, and roles in the pathogenesis of the dominant surface glycopeptidolipid antigens of Mycobacterium avium, rough colony variants of M. avium serovar 2 were picked, cultured in quantity, and their lipid composition examined. Two of the rough (Rg) variants, Rg-3 and Rg-4, were devoid of glycopeptidolipids or any more elemental structures and thus were similar to those described previously. Two others, Rg-0 and Rg-1, each contained two novel lipopeptides, devoid of any of the carbohydrate substituents that confer serotypic activity on the glycopeptidolipids. The application of gas chromatography, fast atom bombardment-mass spectrometry and 1H NMR to lipopeptide I established the structure C32:2-beta-OH-fatty acyl-D-Phe-D-allo-Thr-D-Ala-L-alaninol. Lipopeptide II represented a minor variation of this structure: C32:1-beta-OH-fatty acyl-D-Phe-D-allo-Thr-D-Ala-L-alaninol. These newly discovered lipopeptides are identical to the fatty acyl-tripeptide-amino alcohol "core" component of the glycopeptidolipids of the M. avium complex, and thus the Rg-0 and Rg-1 variants represent a form of "deep rough" mutation in M. avium. Separately, we report that these rough variants of M. avium differ genetically from the smooth, virulent form by major deletions of portions of the genes responsible for glycopeptidolipid synthesis (Belisle, J. T., Klaczkiewicz, K., Brennan, P. J., Jacobs, W. R., Jr., and Inamine, J. M. (1993) J. Biol. Chem. 268, 10517-10523). The isolation of different sets of spontaneous mutants of M. avium differentially defective in the capacity to synthesize glycopeptidolipids provides the means to explore their biosynthesis and roles in opportunistic pathogenesis.

Amino Acid Sequence↗
PubMed1993

Further structural definition of a new family of glycopeptidolipids from Mycobacterium xenopi.

The highly antigenic surface glycolipids of serovars of the Mycobacterium avium complex are glycopeptidolipids of the general structure [formula: see text] However, it has recently been shown [Rivière, M., & Puzo, G. (1991) J. Biol. Chem. 266, 9057-9063; Rivière, M., & Puzo, G. (1992) Biochemistry 31, 3575-3580] that the characteristic glycopeptidolipid of a strain of Mycobacterium xenopi is of the structure [formula: see text] [monosaccharide, 3-O-CH3-6-deoxy-alpha-L-talopyranose; tetrasaccharide, 2,3,4-tri-O-CH3-alpha-L-rhamnopyranose(1-->3)2-O-lauryl-alpha-L- rhamnopyranose(1-->3)2,4-di-O-acetyl/lauryl-6-deoxy-alpha-L-glucopyranos e]. The type of analyses previously applied to the glycopeptidolipids of M. avium combined with fast atom bombardment mass spectrometry allowed the recognition of other variants of this structure in other strains of M. xenopi: [formula: see text] in which the monosaccharide is 2-O-acetyl-3-O-CH3-6-deoxy-alpha-L-talopyranose or 3-O-CH3-6-deoxy-alpha-L-talopyranose, and the disaccharide is 4-O-octanoyl(or decanoyl)-alpha-L- rhamnopyranose(1-->3)2-O-lauryl-alpha-L-rhamnopyranose or alpha-L-rhamnopyranose(1-->3)2-O-lauryl-alpha-L-rhamnopyranose. Recognition of serine-containing glycopeptidolipids substituted in one case with a tetrasaccharide and in another case with a disaccharide unit implies that M. xenopi, an important opportunistic pathogen, exists as a serocomplex in nature.

Amino Acid Sequence↗
PubMed1993

An investigation of attention allocation deficits in aphasia.

Nine aphasic and 18 normal adults participated in a dual task with components of phoneme monitoring and semantic judgment. Subjects listened to lists of recorded spoken words and were required to detect semantic and phonetic targets. Two within-subject variables were manipulated: the probability of target occurrence for each dual-task component (.2, .5, and .8) and the explicitness of instruction (explicit vs. implicit). Only in the explicit condition were subjects told about the probability structure and given the attention allocation strategy congruent with that structure. Reaction times were recorded on-line for analysis by an IBM-AT. The results showed that normal subjects' overall latencies in detecting phonetic targets decreased as the target occurrence probability increased in both implicit and explicit instruction conditions. The detection latencies for semantic targets showed a similar probability effect but only in the explicit condition. By contrast, the aphasic subjects did not show the probability effect in any condition, although they performed above the chance level on both semantic and phonetic tasks. The presence of the probability effects for the normal subjects indicated that an efficient attention allocation mechanism was operating so as to optimize the performance level. On the other hand, the absence of probability effects for the aphasic subjects suggests that their attention control system might be inefficient so that task-demand cues (probability and attention allocation instruction) were not utilized properly.

Adult↗
PubMed1993

Structural definition of the non-reducing termini of mannose-capped LAM from Mycobacterium tuberculosis through selective enzymatic degradation and fast atom bombardment-mass spectrometry.

The application of extracellular arabinases from a Cellulomonas sp. and fast atom bombardment-mass spectrometry (FAB-MS) provided new insight into the structure of lipoarabinomannan (LAM) of Mycobacterium tuberculosis, a key molecule in the pathogenesis and physiology of the tubercle bacillus. Previously, the non-reducing arabinan ends of LAM from the virulent (Erdman) strain of M. tuberculosis were shown to be 'capped' by short (alpha 1-->2)-linked mannopyranose (Manp)-containing oligosaccharides, a product called ManLAM. The structural relationship between these Manp units and the underlying arabinofuranose (Araf)-containing arabinan was examined by digesting ManLAM from M.tuberculosis Erdman with the Cellulomonas enzyme, resolving fragments by various means and subjecting the derivatized oligoglycosylalditols to FAB-MS. The sequences Manp2Araf4, Manp3Araf4 and Manp1-6Araf6 were recognized as the major terminal motifs. Upon complete structural definition, all of the Ara6-containing products were shown to be based on a 3,5-linked branched Araf unit, whereas those containing Ara4 were linear. Minor non-mannosylated terminal arrangements containing Ara4-6, branched, linear and cyclical, were also recognized. In addition, the mannan 'core' of ManLAM was isolated from enzyme digests and shown to contain segments of the phosphatidylinositol anchor and a 'stub' of the arabinan side-chain in the form of a 'linker' alpha-Araf-(1-->5)-Araf unit attached to C-2, apparently of the penultimate 2,6-linked Manp residue. The structural unravelling of this complex molecule further substantiates the case for structural and biological similarities to the enterobacterial lipopolysaccharides/lipoglycans and other important 'capped' lipooligomers such as the lipooligosaccharides of Neisseria species and the lipophosphoglycan of Leishmania promastigotes.

Carbohydrate Sequence↗
PubMed1992

Structural elucidation of a novel family of acyltrehaloses from Mycobacterium tuberculosis.

Analysis of the lipids of Mycobacterium tuberculosis H37Rv, by both normal- and reverse-phase thin-layer chromatography, revealed a series of novel glycolipids based on 2,3-di-O-acyltrehalose. The structures of these acylated trehaloses were elucidated by a combination of gas chromatography-mass spectrometry, 1H, 13C, two-dimensional 1H-1H, and 1H-13C nuclear magnetic resonance spectrometry. The fatty acyl substituents were mainly of three types: saturated straight-chain C16-C19 acids; C21-C25 "mycosanoic acids"; and C24-C28 "mycolipanolic acids." Analysis of one of the major 2,3-di-O-acyltrehaloses by two-dimensional 1H-chemical shift correlated and 1H-detected heteronuclear multiple-bond correlation spectroscopy established that the C18 saturated straight-chain acyl group was located at the 2 position and that the C24 mycosanoyl substituent was at the 3 position of the same "right-hand" glucosyl residue. At least six molecular species differing only in their fatty acid content comprised this family of di-O-acylated trehaloses. We regard these acyltrehaloses as elemental forms of the multiglycosylated acyltrehaloses (the lipooligosaccharides) perhaps due to an inability of the majority of isolates of virulent tubercle bacilli to glycosylate core acyltrehaloses. The acyltrehaloses are minor but consistent components of virulent M. tuberculosis and apparently the basis of the specific serological activity long associated with its lipid fractions.

Acylation↗
PubMed1992

Characterization of the specific antigenicity of Mycobacterium fortuitum.

Mycobacterium fortuitum, biovar, fortuitum, the cause of serious skin and soft-tissue infections, can be differentiated from M. fortuitum, biovar. peregrinum, and other rapidly growing opportunistic mycobacteria by the presence of a unique antigenic glycolipid. The glycolipid is among the simplest of the acyl-trehalose-containing lipooligosaccharide class. The application of 1H and 13C NMR, methylation analysis, FAB/MS, and other procedures demonstrated the structure, beta-D-Glcp-(1----6)-2-O-acyl-alpha-D-Glcp-(1 in equilibrium with 1)-3,4,6-tri-O-acyl-alpha-D-Glcp. Thus, practically all environmental mycobacteria, many of them opportunistic pathogens, can be differentiated serologically and chemically on the basis of unique sugar arrangements within a few classes of glycolipids. The simplicity of the structure in M. fortuitum fortuitum combined with the distinct roughness of the parent strain raises the intriguing possibility that it is a spontaneous rough variant of the other mycobacteria with more elaborate glycolipids.

Antigens, Bacterial↗
PubMed1992

Lipoarabinomannan of Mycobacterium tuberculosis. Capping with mannosyl residues in some strains.

Previously we had demonstrated that the termini of the arabinan component of mycobacterial cell wall arabinogalactan, the site of mycolic acid location, consists mostly of clusters of a pentaarabinofuranoside, [beta-D-Araf-(1----2)-alpha-D-Araf-(1----]2----(3 and 5)-alpha-D-Araf. Subsequently, the same arrangement was shown to dominate the non-reducing ends of lipoarabinomannan (LAM), a key component in the interaction of mycobacteria with host cell. Accordingly, we had proposed that mycobacteria universally elaborate the same Araf-containing motifs in two settings for different pathophysiological purposes. However, we now report that the termini of LAM from the virulent, Erdman, strain of Mycobacterium tuberculosis, unlike those from the attenuated H37Ra strain, are extensively capped with mannosyl (Manp) residues, either a single alpha-D-Manp, a dimannoside (alpha-D-Manp-(1----2)-alpha-D-Manp), or a trimannoside (alpha-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp ). The use of monoclonal antibodies demonstrates a clear difference in the antigenicity of the basic and mannose-capped LAM. The possibility that these structures are a factor in the virulence of some strains of M. tuberculosis and represent an example of carbohydrate mimicry in mycobacterial infections is discussed.

Carbohydrate Conformation↗
PubMed1991

Perceptual characteristics of vowel and prosody production in apraxic, aphasic, and dysarthric speakers.

Narrow phonetic transcriptions and prosodic judgments were made of single-word imitations by apraxic (AOS), conduction aphasic (CA), and ataxic dysarthric (AD) speakers. AOS and AD subjects showed similar vowel error patterns, particularly predominant errors in low, tense, and back vowels, more distortions than other types of vowel errors, and predominant errors in initial position of words and in monosyllabic words. The CA subjects displayed a different vowel error pattern, notably more substitutions than distortions, more errors in polysyllabic than monosyllabic words, and more errors in noninitial than initial positions of words. Analysis of prosodic features identifiable at the single-word level (e.g., syllabic stress, juncture, and struggles to initiate or complete productions) indicated that syllabic stress errors and more difficulty initiating than completing word production were characteristic of AOS and AD but not CA subjects.

Adult↗
PubMed1990

Effects of speech rate on the absolute and relative timing of apraxic and conduction aphasic sentence production.

The purpose of this investigation was to provide a constructive replication of the Kent and McNeil (1987, In Phonetic approaches to speech production in aphasia and related disorders. San Diego: College-Hill Press) study of the speech timing characteristics of apraxic and conduction aphasic speakers. Acoustic analysis was used to obtain absolute utterance durations, segment durations, and vowel formant trajectories from utterances produced under control, fast, and slow rate conditions. Segment-to-whole ratios and slope values were calculated. Results support the hypothesis presented by Kent and McNeil (1987) that there is a phonetic-motoric component contributing to the speech patterns of both the apraxic and conduction aphasic speakers sampled. Theories of rate control in normal and disordered speakers are discussed.

Aged↗
PubMed1990

Perceptual characteristics of consonant production by apraxic speakers.

Single-word repetitions by 4 brain-damaged adults with apraxia of speech (AOS) but without concomitant aphasia were transcribed using a standard narrow phonetic transcription system. Analysis of consonant productions yielded a profile of AOS slightly different from the traditionally accepted one. Among the results was the atypical finding that consonant distortions exceeded all other error types including sound substitutions. In addition, errors predominated in the medial position of words, and monosyllabic words had approximately the same error rate per number of consonants as did multisyllabic words. Results are discussed with reference to previous perceptual descriptions of AOS and in relationship to Broca's aphasia. Results are also interpreted relative to linguistic and motoric components of speech production models.

Aged↗
PubMed1990

Oral structure nonspeech motor control in normal, dysarthric, aphasic and apraxic speakers: isometric force and static position control.

This study investigated the isometric force and static position control of the upper lip, lower lip, tongue, jaw, and finger in four subject groups (normal control, apraxia of speech, conduction aphasia, and ataxic dysarthria) at two force and displacement levels. Results from both the force and position tasks suggested that the apraxic and dysarthric groups tended to produce significantly greater instability than the normal group, although the pattern of instability across articulators was not systematic within or across the force and position experiments for subjects within or between groups. The conduction aphasic group produced force and position stability that typically was not significantly different from any of the remaining three groups, suggesting that their force and position stability as indexed in the present study fell somewhere between that of the normal group and the apraxic and dysarthric groups. It is suggested that other analyses of force and position control, such as descriptive accounts of the trial-by-trial time histories, might shed additional light on the speech and orofacial sensorimotor control deficits in persons with apraxia, dysarthria, and conduction aphasia.

Adult↗