Group ICA for identifying biomarkers in schizophrenia: ‘Adaptive’ networks via spatially constrained ICA show more sensitivity to group differences than spatio-temporal regression

AbstractBrain functional networks identified from fMRI data can provide potential biomarkers for brain disorders. Group independent component analysis (GICA) is popular for extracting brain functional networks from multiple subjects. In GICA, different strategies exist for reconstructing subject-specific networks from the group-level networks. However, it is unknown whether these strategies have different sensitivities to group differences and abilities in distinguishing patients. Among GICA, spatio-temporal regression (STR) and spatially constrained ICA approaches such as group information guided ICA (GIG-ICA) can be used to propagate components (indicating networks) to a new subject that is not included in the original subjects. In this study, based on the same a priori network maps, we reconstructed subject-specific networks using these two methods separately from resting-state fMRI data of 151 schizophrenia patients (SZs) and 163 healthy controls (HCs). We investigated group differences in the estimated functional networks and the functional network connectivity (FNC) obtained by each method. The networks were also used as features in a cross-validated support vector machine (SVM) for classifying SZs and HCs. We selected features using different strategies to provide a comprehensive comparison between the two methods. GIG-ICA generally showed greater sensitivity in statistical analysis and better classification performance (accuracy 76.45±8.9%, sensitivity 0.74±0.11, specificity 0.79±0.11) than STR (accuracy 67.45±8.13%, sensitivity 0.65±0.11, specificity 0.71±0.11). Importantly, results were also consistent when applied to an independent dataset including 82 HCs and 82 SZs. Our work suggests that the functional networks estimated by GIG-ICA are more sensitive to group differences, and GIG-ICA is promising for identifying image-derived biomarkers of brain disease.

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Variation in the gene Tas1r3 reveals complex temporal properties of mouse brainstem taste responses to sweeteners

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00001.2021 ◽

2021 ◽

Author(s):

Stuart A. McCaughey

Keyword(s):

Sweet Taste ◽

Current Data ◽

Burst Firing ◽

Group Differences ◽

Solitary Tract ◽

Neural Responses ◽

Phasic Response ◽

Temporal Properties ◽

Spatio Temporal ◽

Activity Dependent

The gene Tas1r3 codes for the protein T1R3, which dimerizes with T1R2 to form a sweetener-binding receptor in taste cells. Tas1r3 influences sweetener preferences in mice, as shown by work with a 129.B6-Tas1r3 segregating congenic strain on a 129P3/J (129) genetic background; members of this strain vary in whether they do or do not have one copy of a donor fragment with the C57BL/6ByJ (B6) allele for Tas1r3 (B6/129 and 129/129 mice, respectively). Taste-evoked neural responses were measured in the nucleus of the solitary tract (NST), the first central gustatory relay, in B6/129 and 129/129 littermates, in order to examine how the activity dependent on the T1R2/T1R3 receptor is distributed across neurons and over time. Responses to sucrose were larger in B6/129 than in 129/129 mice, but only during a later, tonic response portion (> 600 ms) sent to different cells than the earlier, phasic response. Similar results were found for artificial sweeteners, whose responses were best considered as complex spatio-temporal patterns. There were also group differences in burst firing of NST cells, with a significant positive correlation between bursting prevalence and sucrose response size in only the 129/129 group. The results indicate that sweetener transduction initially occurs through T1R3-independent mechanisms, after which the T1R2/T1R3 receptor initiates a separate, spatially-distinct response, with the later period dominating sweet taste perceptions and driving sugar preferences. Furthermore, the current data suggest that burst firing is distributed across NST neurons non-randomly and in a manner that may amplify weak incoming gustatory signals.

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E3 ubiquitin ligases

Essays in Biochemistry ◽

10.1042/bse0410015 ◽

2005 ◽

Vol 41 ◽

pp. 15-30 ◽

Cited By ~ 123

Author(s):

Helen C. Ardley ◽

Philip A. Robinson

Keyword(s):

Protein Complexes ◽

Loss Of Function ◽

Direct Role ◽

Cellular Processes ◽

Substrate Protein ◽

Protein Ubiquitination ◽

C Terminus ◽

Full Complement ◽

Spatio Temporal ◽

Eukaryotic Organisms

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.

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Elucidating cyclic AMP signaling in subcellular domains with optogenetic tools and fluorescent biosensors

Biochemical Society Transactions ◽

10.1042/bst20190246 ◽

2019 ◽

Vol 47 (6) ◽

pp. 1733-1747 ◽

Cited By ~ 3

Author(s):

Christina Klausen ◽

Fabian Kaiser ◽

Birthe Stüven ◽

Jan N. Hansen ◽

Dagmar Wachten

Keyword(s):

Cyclic Amp ◽

Adenosine Monophosphate ◽

Adenylyl Cyclases ◽

Temporal Precision ◽

Fluorescent Biosensors ◽

Subcellular Domains ◽

Spatio Temporal ◽

Hydrolysis Of ◽

Shed Light ◽

Cyclic Amp Signaling

The second messenger 3′,5′-cyclic nucleoside adenosine monophosphate (cAMP) plays a key role in signal transduction across prokaryotes and eukaryotes. Cyclic AMP signaling is compartmentalized into microdomains to fulfil specific functions. To define the function of cAMP within these microdomains, signaling needs to be analyzed with spatio-temporal precision. To this end, optogenetic approaches and genetically encoded fluorescent biosensors are particularly well suited. Synthesis and hydrolysis of cAMP can be directly manipulated by photoactivated adenylyl cyclases (PACs) and light-regulated phosphodiesterases (PDEs), respectively. In addition, many biosensors have been designed to spatially and temporarily resolve cAMP dynamics in the cell. This review provides an overview about optogenetic tools and biosensors to shed light on the subcellular organization of cAMP signaling.

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Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

American Journal of Audiology ◽

10.1044/2020_aja-20-00018 ◽

2020 ◽

Vol 29 (4) ◽

pp. 710-727

Author(s):

Beula M. Magimairaj ◽

Naveen K. Nagaraj ◽

Alexander V. Sergeev ◽

Natalie J. Benafield

Keyword(s):

Auditory Processing ◽

Short Term Memory ◽

Group Differences ◽

Long Term Memory ◽

Short Term ◽

Significant Group ◽

Term Memory ◽

Memory And Attention ◽

Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

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Exploring the Potential Impact of Sentence-Level Comprehension and Sentence-Level Fluency on Deaf Students' Passage Comprehension

Journal of Speech Language and Hearing Research ◽

10.1044/2020_jslhr-19-00205 ◽

2020 ◽

Vol 63 (7) ◽

pp. 2281-2292

Author(s):

Ying Zhao ◽

Xinchun Wu ◽

Hongjun Chen ◽

Peng Sun ◽

Ruibo Xie ◽

...

Keyword(s):

Independent Predictor ◽

Vocabulary Knowledge ◽

Group Differences ◽

Regression Analyses ◽

Deaf Students ◽

Mediating Role ◽

Sentence Level ◽

Mediating Mechanisms ◽

Potential Impact ◽

The Relationship

Purpose This exploratory study aimed to investigate the potential impact of sentence-level comprehension and sentence-level fluency on passage comprehension of deaf students in elementary school. Method A total of 159 deaf students, 65 students ( M age = 13.46 years) in Grades 3 and 4 and 94 students ( M age = 14.95 years) in Grades 5 and 6, were assessed for nonverbal intelligence, vocabulary knowledge, sentence-level comprehension, sentence-level fluency, and passage comprehension. Group differences were examined using t tests, whereas the predictive and mediating mechanisms were examined using regression modeling. Results The regression analyses showed that the effect of sentence-level comprehension on passage comprehension was not significant, whereas sentence-level fluency was an independent predictor in Grades 3–4. Sentence-level comprehension and fluency contributed significant variance to passage comprehension in Grades 5–6. Sentence-level fluency fully mediated the influence of sentence-level comprehension on passage comprehension in Grades 3–4, playing a partial mediating role in Grades 5–6. Conclusions The relative contributions of sentence-level comprehension and fluency to deaf students' passage comprehension varied, and sentence-level fluency mediated the relationship between sentence-level comprehension and passage comprehension.

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Phonomotor Versus Semantic Feature Analysis Treatment for Anomia in 58 Persons With Aphasia: A Randomized Controlled Trial

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-l-18-0257 ◽

2019 ◽

Vol 62 (12) ◽

pp. 4464-4482 ◽

Cited By ~ 9

Author(s):

Diane L. Kendall ◽

Megan Oelke Moldestad ◽

Wesley Allen ◽

Janaki Torrence ◽

Stephen E. Nadeau

Keyword(s):

Randomized Controlled Trial ◽

Response Latency ◽

Controlled Trial ◽

Semantic Knowledge ◽

Semantic Feature ◽

Feature Analysis ◽

Group Differences ◽

Randomized Controlled ◽

Confrontation Naming ◽

Semantic Feature Analysis

Purpose The ultimate goal of anomia treatment should be to achieve gains in exemplars trained in the therapy session, as well as generalization to untrained exemplars and contexts. The purpose of this study was to test the efficacy of phonomotor treatment, a treatment focusing on enhancement of phonological sequence knowledge, against semantic feature analysis (SFA), a lexical-semantic therapy that focuses on enhancement of semantic knowledge and is well known and commonly used to treat anomia in aphasia. Method In a between-groups randomized controlled trial, 58 persons with aphasia characterized by anomia and phonological dysfunction were randomized to receive 56–60 hr of intensively delivered treatment over 6 weeks with testing pretreatment, posttreatment, and 3 months posttreatment termination. Results There was no significant between-groups difference on the primary outcome measure (untrained nouns phonologically and semantically unrelated to each treatment) at 3 months posttreatment. Significant within-group immediately posttreatment acquisition effects for confrontation naming and response latency were observed for both groups. Treatment-specific generalization effects for confrontation naming were observed for both groups immediately and 3 months posttreatment; a significant decrease in response latency was observed at both time points for the SFA group only. Finally, significant within-group differences on the Comprehensive Aphasia Test–Disability Questionnaire ( Swinburn, Porter, & Howard, 2004 ) were observed both immediately and 3 months posttreatment for the SFA group, and significant within-group differences on the Functional Outcome Questionnaire ( Glueckauf et al., 2003 ) were found for both treatment groups 3 months posttreatment. Discussion Our results are consistent with those of prior studies that have shown that SFA treatment and phonomotor treatment generalize to untrained words that share features (semantic or phonological sequence, respectively) with the training set. However, they show that there is no significant generalization to untrained words that do not share semantic features or phonological sequence features.

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Perceptual Characteristics of Consonant Production in Apraxia of Speech and Aphasia

American Journal of Speech-Language Pathology ◽

10.1044/2019_ajslp-18-0169 ◽

2019 ◽

Vol 28 (4) ◽

pp. 1411-1431 ◽

Cited By ~ 3

Author(s):

Lauren Bislick ◽

William D. Hula

Keyword(s):

Error Rate ◽

Error Rates ◽

Group Differences ◽

Diagnostic Process ◽

Apraxia Of Speech ◽

Contextual Variables ◽

Error Type ◽

Type Distribution ◽

Phonetic Features ◽

Syllable Position

Purpose This retrospective analysis examined group differences in error rate across 4 contextual variables (clusters vs. singletons, syllable position, number of syllables, and articulatory phonetic features) in adults with apraxia of speech (AOS) and adults with aphasia only. Group differences in the distribution of error type across contextual variables were also examined. Method Ten individuals with acquired AOS and aphasia and 11 individuals with aphasia participated in this study. In the context of a 2-group experimental design, the influence of 4 contextual variables on error rate and error type distribution was examined via repetition of 29 multisyllabic words. Error rates were analyzed using Bayesian methods, whereas distribution of error type was examined via descriptive statistics. Results There were 4 findings of robust differences between the 2 groups. These differences were found for syllable position, number of syllables, manner of articulation, and voicing. Group differences were less robust for clusters versus singletons and place of articulation. Results of error type distribution show a high proportion of distortion and substitution errors in speakers with AOS and a high proportion of substitution and omission errors in speakers with aphasia. Conclusion Findings add to the continued effort to improve the understanding and assessment of AOS and aphasia. Several contextual variables more consistently influenced breakdown in participants with AOS compared to participants with aphasia and should be considered during the diagnostic process. Supplemental Material https://doi.org/10.23641/asha.9701690

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Examining the Role of Language in Play Among Children With and Without Developmental Disabilities

Language Speech and Hearing Services in Schools ◽

10.1044/2020_lshss-19-00084 ◽

2020 ◽

Vol 51 (3) ◽

pp. 795-806 ◽

Cited By ~ 1

Author(s):

Elizabeth J. Short ◽

Rachael Cooper Schindler ◽

Rita Obeid ◽

Maia M. Noeder ◽

Laura E. Hlavaty ◽

...

Keyword(s):

Developmental Disabilities ◽

Autism Spectrum ◽

Free Play ◽

Group Differences ◽

Typically Developing ◽

Play Skills ◽

Critical Aspect ◽

Hyperactivity Disorder ◽

Better Than

Purpose Play is a critical aspect of children's development, and researchers have long argued that symbolic deficits in play may be diagnostic of developmental disabilities. This study examined whether deficits in play emerge as a function of developmental disabilities and whether our perceptions of play are colored by differences in language and behavioral presentations. Method Ninety-three children participated in this study (typically developing [TD]; n = 23, developmental language disorders [DLD]; n = 24, attention-deficit/hyperactivity disorder [ADHD]; n = 26, and autism spectrum disorder [ASD]; n = 20). Children were videotaped engaging in free-play. Children's symbolic play (imagination, organization, elaboration, and comfort) was scored under conditions of both audible language and no audible language to assess diagnostic group differences in play and whether audible language impacted raters' perception of play. Results Significant differences in play were evident across diagnostic groups. The presence of language did not alter play ratings for the TD group, but differences were found among the other diagnostic groups. When language was audible, children with DLD and ASD (but not ADHD) were scored poorly on play compared to their TD peers. When language was not audible, children with DLD were perceived to play better than when language was audible. Conversely, children with ADHD showed organizational deficits when language was not available to support their play. Finally, children with ASD demonstrated poor play performance regardless of whether language was audible or not. Conclusions Language affects our understanding of play skills in some young children. Parents, researchers, and clinicians must be careful not to underestimate or overestimate play based on language presentation. Differential skills in language have the potential to unduly influence our perceptions of play for children with developmental disabilities.

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Studying Multilingualism and Group Differences in Adult Communication

Perspectives on Communication Disorders and Sciences in Culturally and Linguistically Diverse Populations ◽

10.1044/cds17.3.59 ◽

2010 ◽

Vol 17 (3) ◽

pp. 59-64

Author(s):

Loraine K. Obler

Keyword(s):

Older Adults ◽

Research Center ◽

Group Differences ◽

Aging Brain

The focus of this article is on the study of bilingual and multilingual adults at the Howard Goodglass Aphasia Research Center and the Language in the Aging Brain Laboratory by Drs. Obler and Albert along with former students and colleagues. Summaries of studies examining research in healthy bilingual adults, healthy monolingual older adults, and monolingual and bilingual individuals with aphasia are presented.

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