The Association between Individual Food Groups, Limbic System White Matter Tracts, and Episodic Memory: Initial Data from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study.

(1) Background: Many studies link food intake with clinical cognitive outcomes, but evidence for brain biomarkers, such as memory-related limbic white matter (WM) tracts, is limited. We examined the association between food groups, limbic WM tracts integrity, and memory performance in community-dwelling individuals. (2) Methods: We included 117 non-demented individuals (ALBION study). Verbal and visual episodic memory tests were administered, and a composite z-score was calculated. Diffusion tensor imaging tractography was applied for limbic WM tracts (fornix-FX, cingulum bundle-CB, uncinate fasciculus-UF, hippocampal perforant pathway zone-hPPZ). Food intake was evaluated through four 24-h recalls. We applied linear regression models adjusted for demographics and energy intake. (3) Results: We found significant associations between (a) higher low-to-moderate alcohol intake and higher FX fractional anisotropy (FA), (b) higher full-fat dairy intake and lower hPPZ FA, and (c) higher red meat and cold cuts intake and lower hPPZ FA. None of the food groups was associated with memory performance. (4) Conclusions: Despite non-significant associations between food groups and memory, possibly due to participants' cognitive profile and/or compensatory mechanisms, the study documented a possible beneficial role of low-to-moderate alcohol and a harmful role of full-fat dairy and red meat and cold cuts on limbic WM tracts.

Objective Sleep Function is Associated with Hippocampal Subfield Volumes in Community-Dwelling Adults.

BACKGROUND: Sleep patterns often shift as people age, a phenomenon frequently associated with the onset of neurodegenerative conditions. Additionally, distinct alterations occur in brain structure as individuals grow older, particularly within the hippocampus, a region known for its role in cognition and sleep regulation. Yet, how exactly do changes in sleep relate to specific subfields within the hippocampus is still unclear. METHODS: We conducted a study involving non-demented healthy adults from the Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) cohort. Participants underwent objective sleep measurements using wrist Actiwatch and WatchPAT devices. Further, all participants underwent the same Magnetic Resonance Imaging (MRI) protocol, including a 3D high resolution T1-weighted sequence, on the same 3.0 Tesla MRI scanner using an eight-channel head coil. The study aimed to examine the relationship between objectively measured sleep metrics and the morphology of twenty-two distinct hippocampal subregions. RESULTS: In total, 75 non-demented participants with 63 mean years of age were included in the study. Results indicated that a higher frequency of awakenings during sleep was associated with increased volume in the right presubiculum body (beta = 0.630, p False Discovery Rate (FDR) <0.036). Longer sleep duration showed a tendency to be associated with smaller volumes of the right presubiculum body, hinting at a possible negative impact of prolonged sleep on this brain region. Similar trends were observed regarding sleep apnea and the presubiculum body volume. Further analysis based on age stratification revealed that in younger participants, longer sleep duration was linked to decreased volume of the presubiculum body, while a greater number of awakenings was correlated with increased volume of the same region. Among older participants, higher frequencies of awakenings were associated with larger volumes in various hippocampal subfields. CONCLUSIONS: These findings shed light on the complex relationship between sleep characteristics and brain structure, highlighting potential age-related differences. The study provides valuable insights into how sleep disruptions may impact hippocampal morphology and cognitive function of cognitively healthy adults. Further research is warranted to elucidate the underlying mechanisms and implications for neurodegenerative diseases.

A Methodological Approach to Quantifying Silent Pauses, Speech Rate, and Articulation Rate across Distinct Narrative Tasks: Introducing the Connected Speech Analysis Protocol (CSAP).

The examination of connected speech may serve as a valuable tool for exploring speech output in both healthy speakers and individuals with language disorders. Numerous studies incorporate various fluency and silence measures into their analyses to investigate speech output patterns in different populations, along with the underlying cognitive processes that occur while speaking. However, methodological inconsistencies across existing studies pose challenges in comparing their results. In the current study, we introduce CSAP (Connected Speech Analysis Protocol), which is a specific methodological approach to investigate fluency metrics, such as articulation rate and speech rate, as well as silence measures, including silent pauses' frequency and duration. We emphasize the importance of employing a comprehensive set of measures within a specific methodological framework to better understand speech output patterns. Additionally, we advocate for the use of distinct narrative tasks for a thorough investigation of speech output in different conditions. We provide an example of data on which we implement CSAP to showcase the proposed pipeline. In conclusion, CSAP offers a comprehensive framework for investigating speech output patterns, incorporating fluency metrics and silence measures in distinct narrative tasks, thus allowing a detailed quantification of connected speech in both healthy and clinical populations. We emphasize the significance of adopting a unified methodological approach in connected speech studies, enabling the integration of results for more robust and generalizable conclusions.

Exploring Pragmatic Deficits in Relation to Theory of Mind and Executive Functions: Evidence from Individuals with Right Hemisphere Stroke.

Research investigating pragmatic deficits in individuals with right hemisphere damage focuses on identifying the potential mechanisms responsible for the nature of these impairments. Nonetheless, the presumed shared cognitive mechanisms that could account for these deficits have not yet been established through data-based evidence from lesion studies. This study aimed to examine the co-occurrence of pragmatic language deficits, Theory of Mind impairments, and executive functions while also exploring their associations with brain lesion sites. Twenty-five patients suffering from unilateral right hemisphere stroke and thirty-seven healthy participants were recruited for this study. The two groups were tested in pragmatics, Theory of Mind, and executive function tasks. Structural imaging data were also obtained for the identification of the lesion sites. The findings of this study suggest a potential convergence among the three aforementioned cognitive mechanisms. Moreover, we postulate a hypothesis for a neural circuitry for communication impairments observed in individuals with right hemisphere damage.

Is There a Role of Inferior Frontal Cortex in Motor Timing? A Study of Paced Finger Tapping in Patients with Non-Fluent Aphasia.

The aim of the present study was to investigate the deficits in timing reproduction in individuals with non-fluent aphasia after a left hemisphere lesion including the inferior frontal gyrus, in which Broca's region is traditionally localised. Eighteen stroke patients with non-fluent aphasia and twenty-two healthy controls were recruited. We used a finger-tapping Test, which consisted of the synchronisation and the continuation phase with three fixed intervals (450 ms, 650 ms and 850 ms). Participants firstly had to tap simultaneously with the device's auditory stimuli (clips) (synchronisation phase) and then continue their tapping in the same pace when the stimuli were absent (continuation phase). Patients with aphasia demonstrated less accuracy and greater variability during reproduction in both phases, compared to healthy participants. More specifically, in the continuation phase, individuals with aphasia reproduced longer intervals than the targets, whereas healthy participants displayed accelerated responses. Moreover, patients' timing variability was greater in the absence of the auditory stimuli. This could possibly be attributed to deficient mental representation of intervals and not experiencing motor difficulties (due to left hemisphere stroke), as the two groups did not differ in tapping reproduction with either hand. Given that previous findings suggest a potential link between the IFG, timing and working memory, we argue that patients' extra-linguistic cognitive impairments should be accounted for, as possible contributing factors to timing disturbances.

Investigating Aphasia Recovery: Demographic and Clinical Factors.

Post-stroke language recovery remains one of the main unresolved topics in the field of aphasia. In recent years, there have been efforts to identify specific factors that could potentially lead to improved language recovery. However, the exact relationship between the recovery of particular language functions and possible predictors, such as demographic or lesion variables, is yet to be fully understood. In the present study, we attempted to investigate such relationships in 42 patients with aphasia after left hemisphere stroke, focusing on three language domains: auditory comprehension, naming and speech fluency. Structural imaging data were also obtained for the identification of the lesion sites. According to our findings, patients demonstrated an overall improvement in all three language domains, while no demographic factor significantly contributed to aphasia recovery. Interestingly, specific lesion loci seemed to have a differential effect on language performance, depending on the time of testing (i.e., acute/subacute vs. chronic phase). We argue that this variability concerning lesion-deficit associations reflects the dynamic nature of aphasia and further discuss possible explanations in the framework of neuroplastic changes during aphasia recovery.

Common Neuroanatomical Substrate of Cholinergic Pathways and Language-Related Brain Regions as an Explanatory Framework for Evaluating the Efficacy of Cholinergic Pharmacotherapy in Post-Stroke Aphasia: A Review.

Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided meaningful results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and other cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in the common neuroanatomical substrate of cholinergic pathways and language related brain areas as a framework for interpreting the efficacy of cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.

Specific disruption of the ventral anterior temporo-frontal network reveals key implications for language comprehension and cognition.

Recent investigations have raised the question of the role of the anterior lateral temporal cortex in language processing (ventral language network). Here we present the language and overall cognitive performance of a rare male patient with chronic middle cerebral artery cerebrovascular accident with a well-documented lesion restricted to the anterior temporal cortex and its connections via the extreme capsule with the pars triangularis of the inferior frontal gyrus (i.e. Broca's region). The performance of this unique patient is compared with that of two chronic middle cerebral artery cerebrovascular accident male patients with damage to the classic dorsal posterior temporo-parietal language system. Diffusion tensor imaging is used to reconstruct the relevant white matter tracts of the three patients, which are also compared with those of 10 healthy individuals. The patient with the anterior temporo-frontal lesion presents with flawless and fluent speech, but selective impairment in accessing lexico-semantic information, in sharp contrast to the impairments in speech, sentence comprehension and repetition observed after lesions to the classic dorsal language system. The present results underline the contribution of the ventral language stream in lexico-semantic processing and higher cognitive functions, such as active selective controlled retrieval.

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia.

Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients' personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease.

Structural and functional brain changes in X-linked Charcot-Marie-Tooth disease: insights from a multimodal neuroimaging study.

PURPOSE: Brain involvement in X-linked Charcot-Marie-Tooth disease (CMTX) has been previously reported. We studied the brain structural and functional integrity using a multimodal neuroimaging approach in patients with no current central nervous system (CNS) symptoms, in order to further delineate the disease's phenotype. METHODS: Seventeen CMTX patients with no current CNS symptoms and 24 matched healthy controls underwent brain magnetic resonance imaging (MRI). Structural integrity was evaluated performing Gray matter analysis with voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI). Functional integrity was evaluated with resting-state functional MRI (rs-fMRI). RESULTS: Decreased gray matter density was detected in CMTX patients compared to healthy controls in bilateral hippocampus, left thalamus, left postcentral gyrus, left superior parietal lobule, left cerebellum crus I and II, and vermis VI. DTI analysis showed increased fractional anisotropy and radial diffusivity in the right anterior insula and increased axial diffusivity in right cerebellum crus I in CMTX patients. rs-fMRI revealed decreased spontaneous neural activity on left precentral gyrus in patients compared to healthy controls. CONCLUSION: Advanced magnetic resonance (MR) neuroimaging techniques in CMTX patients revealed structural and functional involvement of multiple motor and extra-motor brain areas. MR neuroimaging techniques have the potential to delineate the CNS phenotype of a peripheral neuropathy like CMTX.

Neurocognitive Profiles of Caucasian Moyamoya Disease Patients in Greece: A Case Series.

The impact of Moyamoya Disease (MMD) on cognition inadult Caucasian patients has not yet been thoroughly investigated. The current study is the first to present detailed neuropsychological data on a series of Greek patients with MMD. A group of eight patients was assessed with an extensive neuropsychological battery, including measures of episodic memory, working memory, executive functions, language, and social cognition. The results indicated that MMD may be characterized by a trichotomous neurocognitive profile, characterized by prominent impairment in working memory, executive functions, and social cognition. Overall, we stress the need for a thorough cognitive evaluation of MMD patients and further highlight the potential importance of social cognition in this particular disease. Possible associations between the three impaired cognitive domains in our group are also discussed.

The Role of the Right Hemisphere White Matter Tracts in Chronic Aphasic Patients After Damage of the Language Tracts in the Left Hemisphere.

The involvement of the right hemisphere (RH) in language, and especially after aphasia resulting from left hemisphere (LH) lesions, has been recently highlighted. The present study investigates white matter structure in the right hemisphere of 25 chronic post-stroke aphasic patients after LH lesions in comparison with 24 healthy controls, focusing on the four cortico-cortical tracts that link posterior parietal and temporal language-related areas with Broca's region in the inferior frontal gyrus of the LH: the Superior Longitudinal Fasciculi II and III (SLF II and SLF III), the Arcuate Fasciculus (AF), and the Temporo-Frontal extreme capsule Fasciculus (TFexcF). Additionally, the relationship of these RH white matter tracts to language performance was examined. The patients with post-stroke aphasia in the chronic phase and the healthy control participants underwent diffusion tensor imaging (DTI) examination. The aphasic patients were assessed with standard aphasia tests. The results demonstrated increased axial diffusivity in the RH tracts of the aphasic patients. Patients were then divided according to the extent of the left hemisphere white matter loss. Correlations of language performance with radial diffusivity (RD) in the right hemisphere homologs of the tracts examined were demonstrated for the TFexcF, SLF III, and AF in the subgroup with limited damage to the LH language networks and only with the TFexcF in the subgroup with extensive damage. The results argue in favor of compensatory roles of the right hemisphere tracts in language functions when the LH networks are disrupted.

Evidence for Cognitive Deficits in X-Linked Charcot-Marie-Tooth Disease.

OBJECTIVE: X-linked Charcot-Marie-Tooth disease (CMTX) is an hereditary neuropathy caused by mutations in GJB1 coding for connexin-32, found in Schwann cells, but also expressed in oligodendrocytes. Reports have identified CNS involvement in CMTX, but no systematic study of cognitive function has been published. METHODS: We assessed 24 CMTX patients (13 males; 9GJB1 mutations) with a comprehensive neuropsychological battery, including tests of memory, language, and executive functions. RESULTS: No differences in cognitive performance were observed between males and females. A case-by-case investigation revealed selective deficits in individual patients. One subgroup (29%) demonstrated executive abnormalities; and a non-overlapping subgroup (29%), prominent reading (decoding) abnormalities. CONCLUSIONS: The present data provide evidence for cognitive deficits in CMTX. Emerging neuropsychological patterns are also discussed.

MOG antibody-associated demyelinating disease mimicking typical multiple sclerosis: A case for expanding anti-MOG testing?

MOG-antibody associated demyelinating disease is a new emerging diagnostic entity. Recently, international recommendations for testing of anti-MOG antibodies were published. Herein, we describe a case of anti-MOG antibody-associated demyelinating disease initially diagnosed as typical MS, and, at presentation, not fulfilling the proposed recommendations. This case highlights the expanding spectrum of anti-MOG antibody-associated demyelinating disease, illustrating the distinct and overlapping features of MS and MOG-antibody associated demyelinating disease, providing evidence that on rare occasions these recommendations may prove too restrictive.

Investigating Gray and White Matter Structural Substrates of Sex Differences in the Narrative Abilities of Healthy Adults.

Linguistic aspects of narration have been investigated in healthy populations, in a wide variety of languages and speech genres with very different results. There is some evidence indicating that linguistic elements, such as speech rate (i.e., the measure indicating the amount of speech produced in a certain time period), mean length of utterance (MLU) (i.e., the index reflecting sentence grammatical structure), frequency of nouns and verbs, might be affected by non-linguistic factors such as sex. On the other hand, despite the existence of neuroimaging evidence of structural differences between males and females, it is yet unknown how such differences could explain between-sex disparities in linguistic abilities in natural speech contexts. To date, no study has evaluated discourse production elements in relation to sex differences and their neural correlates in terms of brain structure, a topic that could provide unique insights on the relationship between language and the brain. The aim of the present study was to determine sex differences in narrative skills in healthy adults and to investigate white and gray matter structural correlates of linguistic skills in each group. Twenty-seven male and 30 female (N = 57) right-handed, neurologically intact, monolingual Greek speakers, matched for age and years of education, participated. Narrations of a personal medical event were elicited. Linguistic elements of speech rate (words per minute), MLUs, frequency of nouns and verbs were calculated for each speech sample, by two independent raters. Structural 3D T1 images were segmented and parcellated using FreeSurfer and whole-brain between-sex differences in cortical thickness, cortical volume and surface area, were obtained. Between-group differences in white matter diffusion tensor scalars were examined via Tract-Based Spatial-Statistics and whole-brain tractography and automated tract delineation using Automated Fiber Quantification. Speech rate and noun frequency were significantly lower for men, while verb frequency was significantly higher for women, but no differences were identified for MLU. Regarding cortical measures, males demonstrated increased volume, surface area and cortical thickness in several bilateral regions, while no voxel-wise or tractography-based between-group differences in white matter metrics were observed. Regarding the relationship between sex and speech variables, hierarchical regression analyses showed that the superior/middle frontal cluster in surface area may serve as a significant predictor of speech rate variance, but only in females. We discuss several possible interpretations of how sex-related speech abilities could be represented differently in men and women in gray matter structures within the broad language network.

Silent pauses in aphasia.

Pauses may be studied as an aspect of the temporal organization of speech, as well as an index of internal cognitive processes, such as word access, selection and retrieval, monitoring, articulatory planning, and memory. Several studies have demonstrated specific distributional patterns of pauses in typical speech. However, evidence from patients with language impairment is sparse and restricted to small-scale studies. The aim of the present study is to investigate empty pause distribution and associations between pause variables and linguistic elements in aphasia. Eighteen patients with chronic aphasia following a left hemisphere stroke were recruited. The control group consisted of 19 healthy adults matched for age, gender, and years of formal schooling. Speech samples from both groups were transcribed, and silent pauses were annotated using ELAN. Our results indicate that in both groups, pause duration distribution follows a log-normal bimodal model with significantly different thresholds between the two populations, yet specific enough for each distribution to justify classification into two distinct groups of pauses for each population: short and long. Moreover, we found differences between the patient and control group, prominently with regard to long pause duration and rate. Long pause indices were also associated with fundamental linguistics elements, such as mean length of utterance. Overall, we argue that post-stroke aphasia may induce quantitative but not qualitative alterations of pause patterns during speech, and further suggest that long pauses may serve as an index of internal cognitive processes supporting sentence planning. Our findings are discussed within the context of pause pattern quantification strategies as potential markers of cognitive changes in aphasia, further stressing the importance of such measures as an integral part of language assessment in clinical populations.