Altered fornix integrity is associated with sleep apnea-related hypoxemia in mild cognitive impairment.

INTRODUCTION: The limbic system is critical for memory function and degenerates early in the Alzheimer's disease continuum. Whether obstructive sleep apnea (OSA) is associated with alterations in the limbic white matter tracts remains understudied. METHODS: Polysomnography, neurocognitive assessment, and brain magnetic resonance imaging (MRI) were performed in 126 individuals aged 55-86 years, including 70 cognitively unimpaired participants and 56 participants with mild cognitive impairment (MCI). OSA measures of interest were the apnea-hypopnea index and composite variables of sleep fragmentation and hypoxemia. Microstructural properties of the cingulum, fornix, and uncinate fasciculus were estimated using free water-corrected diffusion tensor imaging. RESULTS: Higher levels of OSA-related hypoxemia were associated with higher left fornix diffusivities only in participants with MCI. Microstructure of the other white matter tracts was not associated with OSA measures. Higher left fornix diffusivities correlated with poorer episodic verbal memory. DISCUSSION: OSA may contribute to fornix damage and memory dysfunction in MCI. HIGHLIGHTS: Sleep apnea-related hypoxemia was associated with altered fornix integrity in MCI. Altered fornix integrity correlated with poorer memory function. Sleep apnea may contribute to fornix damage and memory dysfunction in MCI.

Assessment of verb and sentence processing deficits in stroke-induced aphasia: the Italian version of the Northwestern Assessment of Verbs and Sentences (NAVS-I).

Background: The Northwestern Assessment of Verbs and Sentences (NAVS) assesses verb and sentence production and comprehension in aphasia. Results from the original English version and from its adaptation to German have shown that the NAVS is able to capture effects of verb-argument structure (VAS) complexity (i.e., lower accuracy for two- and three-argument vs. one-argument verbs) and syntactic complexity (i.e., lower accuracy for non-canonical vs. canonical sentences) in both agrammatic participants and individuals with mild (residual) forms of aphasia. The NAVS has been recently adapted to Italian (NAVS-I) and tested on a group of healthy participants, with results showing longer reaction times to complex vs. simple verbs and sentences. Aims: The present study aimed to test the ability of NAVS-I to i) capture verb/sentence production and comprehension deficits in Italian-speaking individuals with agrammatism or with fluent aphasia, and ii) differentiate individuals with aphasia from healthy age-matched participants, with the overall goal to validate its use in clinical practice. Methods & Procedures: Forty-four healthy participants and 28 individuals with aphasia (10 with agrammatic speech production) were administered the NAVS-I, which includes tasks assessing production and comprehension of verbs requiring one, two or three arguments, as well as production and comprehension of canonical and non-canonical sentences. Outcomes & Results: On the Verb Naming Task (VNT), better production of one- (vs. two- and three-) argument verbs was found in the agrammatic group, whereas, verb production in the fluent group was solely predicted by word length and imageability. No effects of argument optionality (i.e., greater difficulty for optionally transitive verbs than for 1-argument verbs) were found. Sentence-level tasks found no differences between the agrammatic and the fluent group in production or comprehension of both canonical and non-canonical sentences; rather, sentence comprehension accuracy was predicted by demographic variables and by aphasia severity. At the individual level, performance on the NAVS-I was significantly different from that of healthy speakers in 26/28 patients. Conclusions: Data show that the NAVS-I is able to capture effects of argument structure complexity in verb production, and effects of syntactic complexity in sentence production and comprehension. In addition, our results point to verb production as the task with greater capability to differentiate agrammatism from other (fluent) forms of aphasia. The study provides support for the use of the NAVS-I in the diagnosis of aphasia, as it is able to detect language deficits at the individual level, even in participants with mild (residual) forms of aphasia.

REM sleep is reduced in late middle-aged and older APOE4 allele carriers.

STUDY OBJECTIVES: Apolipoprotein E ɛ4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD). In addition, APOE4 carriers may exhibit sleep disturbances, but conflicting results have been reported, such that there is no clear consensus regarding which aspects of sleep are impacted. Our objective was to compare objective sleep architecture between APOE4 carriers and non-carriers, and to investigate the modulating impact of age, sex, cognitive status and obstructive sleep apnea. METHODS: 198 dementia-free participants aged >55 years old (mean age: 68.7 ± 8.08 years old, 40.91% women, 41 APOE4 carriers) were recruited in this cross-sectional study. They underwent polysomnography, APOE4 genotyping and a neuropsychological evaluation. ANCOVAs assessed the effect of APOE4 status on sleep architecture, controlling for age, sex, cognitive status and the apnea-hypopnea index. Interaction terms were added between APOE4 status and covariates. RESULTS: REM sleep percentage (F=9.95, p=0.002, ηp2=0.049) and duration (F=9.23, p=0.003, ηp2=0.047) were lower in APOE4 carriers. The results were replicated in a subsample of 112 participants without moderate-to-severe obstructive sleep apnea. There were no significant interactions between APOE4 status and age, sex, cognitive status and obstructive sleep apnea in the whole sample. CONCLUSIONS: Our results show that APOE4 carriers exhibit lower REM sleep duration, including in cognitively unimpaired individuals, possibly resulting from early neurodegenerative processes in regions involved in REM sleep generation and maintenance.

Behavioral thermoregulation in primates: A review of literature and future avenues.

Primates face severe challenges from climate change, with warming expected to increase animals' thermoregulatory demands. Primates have limited long-term options to cope with climate change, but possess a remarkable capacity for behavioral plasticity. This creates an urgency to better understand the behavioral mechanisms primates use to thermoregulate. While considerable information exists on primate behavioral thermoregulation, it is often scattered in the literature in a manner that is difficult to integrate. This review evaluates the status of the available literature on primate behavioral thermoregulation to facilitate future research. We surveyed peer-reviewed publications on primate thermoregulation for N = 17 behaviors across four thermoregulatory categories: activity budgeting, microhabitat use, body positioning, and evaporative cooling. We recorded data on the primate taxa evaluated, support for a thermoregulatory function, thermal variable assessed, and naturalistic/manipulative study conditions. Behavioral thermoregulation was pervasive across primates, with N = 721 cases of thermoregulatory behaviors identified across N = 284 published studies. Most genera were known to utilize multiple behaviors ( x ¯ = 4.5 ± 3.1 behaviors/genera). Activity budgeting behaviors were the most commonly encountered category in the literature (54.5% of cases), while evaporative cooling behaviors were the least represented (6.9% of cases). Behavioral thermoregulation studies were underrepresented for certain taxonomic groups, including lemurs, lorises, galagos, and Central/South American primates, and there were large within-taxa disparities in representation of genera. Support for a thermoregulatory function was consistently high across all behaviors, spanning both hot- and cold-avoidance strategies. This review reveals asymmetries in the current literature and avenues for future research. Increased knowledge of the impact thermoregulatory behaviors have on biologically relevant outcomes is needed to better assess primate responses to warming environments and develop early indicators of thermal stress.

Measurement matters for assessing the role of chronically altered perfusion in post-stroke aphasia.

This scientific commentary refers to 'Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities', by Ivanova et al. (https://doi.org/10.1093/braincomms/fcad252).

Obstructive sleep apnea and cognitive functioning in the older general population: The moderating effect of age, sex, ApoE4, and obesity.

Research on the relationship between obstructive sleep apnea and cognitive functioning has yielded conflicting results, particularly in the older population, and moderators of this association have rarely been studied. Here we investigated the cross-sectional association between obstructive sleep apnea and cognitive functioning as well as the moderating effect of age, sex, apolipoprotein E4, and obesity on this association among community-dwelling older people. We analysed data from 496 participants (71.4 ± 4.4 years; 45.6% men) of the HypnoLaus study who underwent polysomnography and a battery of neuropsychological tests. The sample was categorised as no-to-mild obstructive sleep apnea (apnea-hypopnea index 0-14.9/h; reference), moderate obstructive sleep apnea (apnea-hypopnea index 15.0-29.9/h), or severe obstructive sleep apnea (apnea-hypopnea index ≥30/h). Regression and moderation analyses were performed with adjustment for confounders. Apolipoprotein E4 and obesity moderated the association between severe obstructive sleep apnea and processing speed, whereas no moderating effects were found for age and sex. In apolipoprotein E4 carriers only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.13, p = 0.024). In obese participants only, severe obstructive sleep apnea was associated with lower performance in Stroop condition 1 (B = 3.02, p = 0.025) and Stroop condition 2 (B = 3.30, p = 0.034). Severe obstructive sleep apnea was also associated with lower executive function in the whole sample according to Stroop condition 3 (B = 3.44, p = 0.020) and Stroop interference score (B = 0.24, p = 0.006). Our findings support associations of severe obstructive sleep apnea (but not moderate obstructive sleep apnea) with lower performance in processing speed and executive function in the older general population. Apolipoprotein E4 and obesity appear to be vulnerability factors that strengthen the association between severe obstructive sleep apnea and lower performance in processing speed.

The production of adjectives in narratives by individuals with primary progressive aphasia.

Adjectives (e.g., hungry) are an important part of language, but have been little studied in individuals with impaired language. Adjectives are used in two different ways in English: attributively, to modify a noun (the hungry dog); or predicatively, after a verb (the dog is hungry). Attributive adjectives have a more complex grammatical structure than predicative adjectives, and may therefore be particularly prone to disruption in individuals with grammatical impairments. We investigated adjective production in three subtypes of primary progressive aphasia (PPA: agrammatic, semantic, logopenic), as well as in agrammatic stroke aphasia and a group of healthy control participants. Participants produced narratives based on picture books, and we coded every adjective they produced for its syntactic structure. Compared to healthy controls, the two agrammatic groups, but not the other two patient groups, produced significantly fewer attributive adjectives per sentence. All four patient groups were similar to controls for their rate of predicative adjective production. In addition, we found a significant correlation in the agrammatic PPA participants between their rate of producing attributive adjective and impaired production of sentences with complex syntactic structure (subject cleft sentences like It was the boy that chased the girl); no such correlation was found for predicative adjectives. Irrespective of structure, we examined the lexical characteristics of the adjectives that were produced, including length, frequency, semantic diversity and neighborhood density. Overall, the lexical characteristics of the produced adjectives were largely consistent with the language profile of each group. In sum, the results suggest that attributive adjectives present a particular challenge for individuals with agrammatic language production, and add a new dimension to the description of agrammatism. Our results further suggest that attributive adjectives may be a fruitful target for improved treatment and recovery of agrammatic language.

Neural mechanisms of sentence production: a volumetric study of primary progressive aphasia.

Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task. Verb retrieval deficits partly mediated the relationship between L IFG/MFG and performance on the NAVS-SPPT. These findings underscore the importance of L IFG/MFG for sentence production and suggest that this relationship is partly accounted for by verb retrieval deficits, but not phonological loop integrity. In contrast, it is possible that the posterior temporal cortex is associated with auditory short-term memory ability, to the extent that DSF performance is a valid measure of this in aphasia.

A pilot randomized controlled trial comparing nutritious meal kits and no-prep meals to improve food security and diet quality among food pantry clients.

BACKGROUND: Food pantry clients have high rates of food insecurity and greater risk for and prevalence of diet-related diseases. Many clients face time, resource, and physical constraints that limit their ability to prepare healthy meals using foods typically provided by pantries. We compared two novel approaches to alleviate those barriers and encourage healthier eating: meal kits, which bundle ingredients with a recipe on how to prepare a healthy meal, and nutritious no-prep meals, which can be eaten after thawing or microwaving. METHODS: Participants were adult pantry clients from a large food pantry in the Southern sector of Dallas, Texas. We conducted a repeated measures between-subjects study with 70 clients randomized to receive 14-days of meal kits (n = 35) or no-prep meals (n = 35). Participants completed questionnaires at baseline and two-week follow-up on demographics, hedonic liking of study meals, perceived dietary quality, and food security. Two-way repeated measures analysis of variance was used to examine group and time effects, and group by time interactions. We also describe feasibility and satisfaction outcomes to inform future implementation. RESULTS: Sixty-six participants completed the study (94%). Participants were predominantly Hispanic or Latino(a) (63%) and African American or Black (31%) women (90%). There was a significant interaction on hedonic liking of study meals (ηp²=0.16, F(1,64) = 11.78, p < .001), such that participants that received meal kits had greater improvements in hedonic liking over time than participants in the no-prep group. We observed significant improvements in perceived dietary quality (ηp²=0.36, F(1,64) = 36.38, p < .001) and food security (ηp²=0.36, F(1,64) = 36.38, p < .001) across both groups over time, but no between group differences or significant interactions indicating one intervention was more effective than the other. Program satisfaction was high across both groups, but higher among the meal kit group (ηp²=0.09, F(1,64) = 6.28, p = .015). CONCLUSIONS: Results suggest nutritious meal kits and no-prep meals may be desirable nutrition intervention strategies for pantry clients and have potential to increase food security and perceived dietary quality in the short-term. Our findings are limited by a small sample and short follow-up. Future studies should continue to test both interventions, and include longer follow-up, objective measures of dietary quality, and relevant clinical outcomes. TRIAL REGISTRATION: This trial was registered on 25/10/2022 on ClinicalTrials.gov, identifier: NCT05593510.

A pilot randomized controlled trial comparing nutritious meal kits and no-prep meals to improve food security and diet quality among food pantry clients.

Background: Food pantry clients have high rates of food insecurity and greater risk for and prevalence of diet-related diseases. Many clients face time, resource, and physical constraints that limit their ability to prepare healthy meals using foods typically provided by pantries. We compared two novel approaches to alleviate those barriers and encourage healthier eating: meal kits, which bundle ingredients with a recipe on how to prepare a healthy meal, and nutritious no-prep meals, which can be eaten after thawing or microwaving. Methods: Participants were adult pantry clients from a large food pantry in the Southern sector of Dallas, Texas. We conducted a repeated measures between-subjects study with 70 clients randomized to receive 14-days of meal kits (n=35) or no-prep meals (n=35). Participants completed questionnaires at baseline and twoweek follow-up on demographics, hedonic liking of study meals, perceived dietary quality, and food security. Two-way repeated measures analysis of variance was used to examine group and time effects, and group by time interactions. We also describe feasibility and satisfaction outcomes to inform future implementation. Results: Sixty-six participants completed the study (94%). Participants were predominantly Hispanic or Latino(a) (63%) and African American or Black (31%) women (90%). There was a significant interaction on hedonic liking of study meals (ηp2=0.16, F(1,64)=11.78, p<.001), such that participants that received meal kits had greater improvements in hedonic liking over time than participants in the no-prep group. We observed significant improvements in perceived dietary quality (ηp2=0.36, F(1,64)=36.38, p<.001) and food security (ηp2=0.36, F(1,64)=36.38, p<.001) across both groups over time, but no between group differences or significant interactions indicating one intervention was more effective than the other. Program satisfaction was high across both groups, but higher among the meal kit group (ηp2=0.09, F(1,64)=6.28, p=.015). Conclusions: Results suggest nutritious meal kits and no-prep meals may be desirable nutrition intervention strategies for pantry clients and have potential to increase food security and perceived dietary quality in the short-term. Our findings are limited by a small sample and short follow-up. Future studies should continue to test both interventions, and include longer follow-up, objective measures of dietary quality, and relevant clinical outcomes. Trial Registration: This trial was registered on 25/10/2022 on Clinicaltrials.gov, identifier: NCT05593510.

Age- and sex-specific associations between obstructive sleep apnea risk and cognitive decline in middle-aged and older adults: A 3-year longitudinal analysis of the Canadian longitudinal study on aging.

BACKGROUND: Whether obstructive sleep apnea (OSA) increases the risk of cognitive decline and how sex and age influence this association is not clear. Here, we characterized the sex- and age-specific associations between OSA risk and 3-year cognitive change in middle-aged and older adults. METHODS: We included 24,819 participants aged 45-85 (52% women) from the Canadian Longitudinal Study on Aging. OSA risk was measured at baseline using the STOP combined to body mass index (STOP-B). Neuropsychological tests assessed memory, executive functioning, and psychomotor speed at baseline and at 3-year follow-up. We conducted age- and sex-specific linear mixed models to estimate the predictive role of baseline STOP-B score on 3-year cognitive change. RESULTS: Men at high-risk for OSA aged 45-59 years showed a steeper decline in psychomotor speed (+13.2 [95% CI: -1.6, 27.9]) compared to men at low-risk. Men at high-risk for OSA aged 60-69 showed a steeper decline in mental flexibility (-1.2 [-1.9, -0.5]) and processing speed (+0.6 [0.3, 0.9]) than those at low-risk. Women at high-risk for OSA aged 45-59 showed a steeper decline in processing speed (+0.1 [-0.2, 0.4]) than women at low-risk, while women at high-risk ≥70 years had a steeper decline in memory (-0.2 [-0.6, 0.1]) and processing speed (+1.0 [0.4, 1.5]). CONCLUSIONS: Associations between OSA risk and cognitive decline over 3 years depend on age and sex. Being at high-risk for OSA is associated with a generalized cognitive decline in attention and processing speed, while a memory decline is specific to older women (≥70 years).

REM sleep is associated with the volume of the cholinergic basal forebrain in aMCI individuals.

BACKGROUND: Rapid-eye movement (REM) sleep highly depends on the activity of cholinergic basal forebrain (BF) neurons and is reduced in Alzheimer's disease. Here, we investigated the associations between the volume of BF nuclei and REM sleep characteristics, and the impact of cognitive status on these links, in late middle-aged and older participants. METHODS: Thirty-one cognitively healthy controls (66.8 ± 7.2 years old, 13 women) and 31 participants with amnestic Mild Cognitive Impairment (aMCI) (68.3 ± 8.8 years old, 7 women) were included in this cross-sectional study. All participants underwent polysomnography, a comprehensive neuropsychological assessment and Magnetic Resonance Imaging examination. REM sleep characteristics (i.e., percentage, latency and efficiency) were derived from polysomnographic recordings. T1-weighted images were preprocessed using CAT12 and the DARTEL algorithm, and we extracted the gray matter volume of BF regions of interest using a probabilistic atlas implemented in the JuBrain Anatomy Toolbox. Multiple linear regressions were performed between the volume of BF nuclei and REM sleep characteristics controlling for age, sex and total intracranial volume, in the whole cohort and in subgroups stratified by cognitive status. RESULTS: In the whole sample, lower REM sleep percentage was significantly associated to lower nucleus basalis of Meynert (Ch4) volume (ß = 0.32, p = 0.009). When stratifying the cohort according to cognitive status, lower REM sleep percentage was significantly associated to both lower Ch4 (ß = 0.48, p = 0.012) and total BF volumes (ß = 0.44, p = 0.014) in aMCI individuals, but not in cognitively unimpaired participants. No significant associations were observed between the volume of the BF and wake after sleep onset or non-REM sleep variables. DISCUSSION: These results suggest that REM sleep disturbances may be an early manifestation of the degeneration of the BF cholinergic system before the onset of dementia, especially in participants with mild memory deficits.

Are unrefreshing naps associated with nocturnal sleep architecture specificities in idiopathic hypersomnia?

STUDY OBJECTIVES: Unrefreshing naps are supportive clinical features of idiopathic hypersomnia (IH) and are reported by more than 50% of IH patients. They are, however, not mandatory for the diagnosis, and their pathophysiological nature is not understood. This study aimed at verifying whether IH patients with and without unrefreshing naps constitute two subtypes of IH based on their demographic/clinical characteristics, and sleep architecture. METHODS: One hundred twelve IH patients underwent a polysomnography (PSG) followed by a multiple sleep latency test (MSLT). They completed questionnaires on excessive daytime sleepiness, mood, and sleep quality. They were met by sleep medicine physicians who conducted a semi-structured clinical interview and questioned them on refreshing aspects of their naps. Patients who reported unrefreshing naps were compared to patients reporting refreshing naps on questionnaires, MSLT and PSG variables, with age as a covariable. As sensitivity analyses, we performed the same comparisons in participants presenting objective markers of IH and those diagnosed with IH based only on clinical judgment (subjective IH), separately. RESULTS: In the whole sample, 61% of patients reported unrefreshing naps. These participants had less awakenings, a lower percentage of N1 sleep, less sleep stage transitions, and a higher percentage of REM sleep on the nighttime PSG compared to the refreshing naps subgroup. When subjective and objective IH patients were tested separately, more group differences were observed on PSG for subjective IH patients. CONCLUSIONS: Patients with unrefreshing naps have less fragmented sleep compared to those with refreshing naps. Future studies should investigate whether this group difference indicates a weaker arousal drive.

Altered resting-state functional connectivity patterns in late middle-aged and older adults with obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cognitive decline, and has been associated with structural brain alterations in regions relevant to memory processes and Alzheimer's disease. However, it is unclear whether OSA is associated with disrupted functional connectivity (FC) patterns between these regions in late middle-aged and older populations. Thus, we characterized the associations between OSA severity and resting-state FC between the default mode network (DMN) and medial temporal lobe (MTL) regions. Second, we explored whether significant FC changes differed depending on cognitive status and were associated with cognitive performance. Methods: Ninety-four participants [24 women, 65.7 ± 6.9 years old, 41% with Mild Cognitive Impairment (MCI)] underwent a polysomnography, a comprehensive neuropsychological assessment and a resting-state functional magnetic resonance imaging (MRI). General linear models were conducted between OSA severity markers (i.e., the apnea-hypopnea, oxygen desaturation and microarousal indices) and FC values between DMN and MTL regions using CONN toolbox. Partial correlations were then performed between OSA-related FC patterns and (i) OSA severity markers in subgroups stratified by cognitive status (i.e., cognitively unimpaired versus MCI) and (ii) cognitive scores in the whole sample. All analyzes were controlled for age, sex and education, and considered significant at a p < 0.05 threshold corrected for false discovery rate. Results: In the whole sample, a higher apnea-hypopnea index was significantly associated with lower FC between (i) the medial prefrontal cortex and bilateral hippocampi, and (ii) the left hippocampus and both the posterior cingulate cortex and precuneus. FC patterns were not associated with the oxygen desaturation index, or micro-arousal index. When stratifying the sample according to cognitive status, all associations remained significant in cognitively unimpaired individuals but not in the MCI group. No significant associations were observed between cognition and OSA severity or OSA-related FC patterns. Discussion: OSA severity was associated with patterns of lower FC in regions relevant to memory processes and Alzheimer's disease. Since no associations were found with cognitive performance, these FC changes could precede detectable cognitive deficits. Whether these FC patterns predict future cognitive decline over the long-term needs to be investigated.

The role of category ambiguity in normal and impaired lexical processing: can you paint without the paint?

Introduction: Many words are categorially ambiguous and can be used as a verb (to paint) or as a noun (the paint) due to the presence of unpronounced morphology or "zero morphology". On this account, the verb "paint" is derived from the noun "paint" through the addition of a silent category-changing morpheme. Past studies have uncovered the syntactic and semantic properties of these categorially ambiguous words, but no research has been conducted on how people process them during normal or impaired lexical processing. Are these two different uses of "paint" processed in the same way? Does this morphosyntactic structure have an effect on online sentence processing? Methods: This study presents two experiments that investigate the effect of morphosyntactic complexity in categorially ambiguous words presented in isolation (experiment 1) and in a sentential context (experiment 2). The first experiment tested the ability to process categorially unambiguous and ambiguous nouns and verbs in 30 healthy older adults and 12 individuals with aphasia, using a forced choice phrasal-completion task, in which individuals choose whether the or to is most compatible with target words. Results: Healthy controls and individuals with fluent aphasia all showed: (1) a bias toward the base category in selection rates for the and to, where the was selected more frequently for words identified to be base nouns, and to was selected more frequently for base verbs, and (2) longer reaction times for ambiguous (over unambiguous) words. However, individuals with non-fluent agrammatic aphasia showed a base-category effect only for nouns, with chance performance for verbs. The second experiment, using an eye-tracking while reading paradigm with 56 young healthy adults, showed a reading time slowdown for derived forms (to paint) compared to their base-category counterparts (the paint) in sentence contexts. Discussion: These findings suggest that categorially ambiguous words likely share a common root, and are related by zero-derivation, and that impaired access to the base-category (i.e., verbs like to visit) precludes associated morphological processes and therefore the retrieval of the derived-category (i.e., nouns like the visit) in non-fluent agrammatic aphasia. This study provides insights into the theory of zero morphology, and the principles that need to be accounted for in models of the lexicon.

Treatment-induced neural reorganization in aphasia is language-domain specific: Evidence from a large-scale fMRI study.

Studies investigating the effects of language intervention on the re-organization of language networks in chronic aphasia have resulted in mixed findings, likely related to-among other factors-the language function targeted during treatment. The present study investigated the effects of the type of treatment provided on neural reorganization. Seventy individuals with chronic stroke-induced aphasia, recruited from three research laboratories and meeting criteria for agrammatism, anomia or dysgraphia were assigned to either treatment (N = 51) or control (N = 19) groups. Participants in the treatment group received 12-weeks of language intervention targeting sentence comprehension/production, naming, or spelling. At baseline and post-testing, all participants performed an fMRI story comprehension task, with blocks of auditorily-presented stories alternated with blocks of reversed speech. Participants in the treatment, but not control, group significantly improved in the treated language domain. FMRI region-of-interest (ROI) analyses, conducted within regions that were either active (or homologous to active) regions in a group of 22 healthy participants on the story comprehension task, revealed a significant increase in activation from pre-to post-treatment in right-hemisphere homologues of these regions for participants in the sentence and spelling, but not naming, treatment groups, not predicted by left-hemisphere lesion size. For the sentence (but not the spelling) treatment group, activation changes within right-hemisphere homologues of language regions were positively associated with changes in measures of verb and sentence comprehension. These findings support previous research pointing to recruitment of right hemisphere tissue as a viable route for language recovery and suggest that sentence-level treatment may promote greater neuroplasticity on naturalistic, language comprehension tasks, compared to word-level treatment.

Medial temporal lobe and obstructive sleep apnea: Effect of sex, age, cognitive status and free-water.

Medial temporal structures, namely the hippocampus, the entorhinal cortex and the parahippocampal gyrus, are particularly vulnerable to Alzheimer's disease and hypoxemia. Here, we tested the associations between obstructive sleep apnea (OSA) severity and medial temporal lobe volumes in 114 participants aged 55-86 years (35 % women). We also investigated the impact of sex, age, cognitive status, and free-water fraction correction on these associations. Increased OSA severity was associated with larger hippocampal and entorhinal cortex volumes in women, but not in men. Greater OSA severity also correlated with increased hippocampal volumes in participants with amnestic mild cognitive impairment, but not in cognitively unimpaired participants, regardless of sex. Using free-water corrected volumes eliminated all significant associations with OSA severity. Therefore, the increase in medial temporal subregion volumes may possibly be due to edema. Whether these structural manifestations further progress to neuronal death in non-treated OSA patients should be investigated.

Structural disconnections associated with language impairments in chronic post-stroke aphasia using disconnectome maps.

Inconsistent findings have been reported about the impact of structural disconnections on language function in post-stroke aphasia. This study investigated patterns of structural disconnections associated with chronic language impairments using disconnectome maps. Seventy-six individuals with post-stroke aphasia underwent a battery of language assessments and a structural MRI scan. Support-vector regression disconnectome-symptom mapping analyses were performed to examine the correlations between disconnectome maps, representing the probability of disconnection at each white matter voxel and different language scores. To further understand whether significant disconnections were primarily representing focal damage or a more extended network of seemingly preserved but disconnected areas beyond the lesion site, results were qualitatively compared to support-vector regression lesion-symptom mapping analyses. Part of the left white matter perisylvian network was similarly disconnected in 90% of the individuals with aphasia. Surrounding this common left perisylvian disconnectome, specific structural disconnections in the left fronto-temporo-parietal network were significantly associated with aphasia severity and with lower performance in auditory comprehension, syntactic comprehension, syntactic production, repetition and naming tasks. Auditory comprehension, repetition and syntactic processing deficits were related to disconnections in areas that overlapped with and extended beyond lesion sites significant in SVR-LSM analyses. In contrast, overall language abilities as measured by aphasia severity and naming seemed to be mostly explained by focal damage at the level of the insular and central opercular cortices, given the high overlap between SVR-DSM and SVR-LSM results for these scores. While focal damage seems to be sufficient to explain broad measures of language performance, the structural disconnections between language areas provide additional information on the neural basis of specific and persistent language impairments at the chronic stage beyond lesion volume. Leveraging routinely available clinical data, disconnectome mapping furthers our understanding of anatomical connectivity constraints that may limit the recovery of some language abilities in chronic post-stroke aphasia.

Harnessing anti-cytomegalovirus immunity for local immunotherapy against solid tumors.

Tumor infiltration by T cells profoundly affects cancer progression and responses to immunotherapy. However, the tumor immunosuppressive microenvironment can impair the induction, trafficking, and local activity of antitumor T cells. Here, we investigated whether intratumoral injection of virus-derived peptide epitopes could activate preexisting antiviral T cell responses locally and promote antitumor responses or antigen spreading. We focused on a mouse model of cytomegalovirus (CMV), a highly prevalent human infection that induces vigorous and durable T cell responses. Mice persistently infected with murine CMV (MCMV) were challenged with lung (TC-1), colon (MC-38), or melanoma (B16-F10) tumor cells. Intratumoral injection of MCMV-derived T cell epitopes triggered in situ and systemic expansion of their cognate, MCMV-specific CD4+ or CD8+ T cells. The MCMV CD8+ T cell epitopes injected alone provoked arrest of tumor growth and some durable remissions. Intratumoral injection of MCMV CD4+ T cell epitopes with polyinosinic acid:polycytidylic acid (pI:C) preferentially elicited tumor antigen-specific CD8+ T cells, promoted tumor clearance, and conferred long-term protection against tumor rechallenge. Notably, secondary proliferation of MCMV-specific CD8+ T cells correlated with better tumor control. Importantly, intratumoral injection of MCMV-derived CD8+ T cell-peptide epitopes alone or CD4+ T cell-peptide epitopes with pI:C induced potent adaptive and innate immune activation of the tumor microenvironment. Thus, CMV-derived peptide epitopes, delivered intratumorally, act as cytotoxic and immunotherapeutic agents to promote immediate tumor control and long-term antitumor immunity that could be used as a stand-alone therapy. The tumor antigen-agnostic nature of this approach makes it applicable across a broad range of solid tumors regardless of their origin.