Left Temporal Cortex Research Articles

Cognitive Reserve Modulates Brain Structure and Cortical Architecture in the Alzheimer's Disease.

Cognitive reserve (CR) explains the individual resilience to neurodegeneration. The present study investigated the effect of CR in modulating brain cortical architecture. 278 individuals [110 Alzheimer's disease (AD), 104 amnestic mild cognitive impairment (aMCI) due to AD, 64 healthy subjects (HS)] underwent a neuropsychological evaluation and 3T-MRI. Cortical thickness (CTh) and fractal dimension (FD) were assessed. Years of formal education were used as an index of CR by which participants were divided into high and low CR (HCR and LCR). Within-group differences in cortical architecture were assessed as a function of CR. Associations between cognitive scores and cortical measures were also evaluated. aMCI-HCR compared to aMCI-LCR patients showed significant decrease of CTh in the right temporal and in the left prefrontal lobe. Moreover, they showed increased FD in the right temporal and in the left temporo-parietal lobes. Patients with AD-HCR showed reduced CTh in several brain areas and reduced FD in the left temporal cortices when compared with AD-LCR subjects. HS-HCR showed a significant increase of CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortices. Finally, aMCI-HCR showed significant positive associations between brain measures and memory and executive performance. CR modulates the cortical architecture at pre-dementia stage only. Indeed, only patients with aMCI showed both atrophy (likely due to neurodegeneration) alongside richer brain folding (likely due to reserve mechanisms) in temporo-parietal areas. This opposite trend was not observed in AD and HS. Our data confirm the existence of a limited time-window for CR modulation at the aMCI stage.

Predictive coding across the left fronto-temporal hierarchy during language comprehension.

We used magnetoencephalography (MEG) and event-related potentials (ERPs) to track the time-course and localization of evoked activity produced by expected, unexpected plausible, and implausible words during incremental language comprehension. We suggest that the full pattern of results can be explained within a hierarchical predictive coding framework in which increased evoked activity reflects the activation of residual information that was not already represented at a given level of the fronto-temporal hierarchy ("error" activity). Between 300 and 500ms, the three conditions produced progressively larger responses within left temporal cortex (lexico-semantic prediction error), whereas implausible inputs produced a selectively enhanced response within inferior frontal cortex (prediction error at the level of the event model). Between 600 and 1,000ms, unexpected plausible words activated left inferior frontal and middle temporal cortices (feedback activity that produced top-down error), whereas highly implausible inputs activated left inferior frontal cortex, posterior fusiform (unsuppressed orthographic prediction error/reprocessing), and medial temporal cortex (possibly supporting new learning). Therefore, predictive coding may provide a unifying theory that links language comprehension to other domains of cognition.

영어 통사적 이동의 신경상관물:기능적 자기공명영상 연구

This paper investigated the neural processes of sentence comprehension, focusing on a particular syntactic operation of syntactic movement and utilizing a functional magnetic resonance imaging(fMRI). English constructions (i.e., wh-questions known to undergo syntactic movement) were presented to English native speakers in a visual comprehension task and compared with carefully matched control sentences. We found that wh-questions as compared to yes/no questions induced activation in the left inferior frontal gyrus(or Broca’s area), precentral gyrus, and posterior superior temporal cortex, consistent with a previous study utilizing a Hebrew auditory comprehension task. This finding suggests that the processing of syntactic movement includes a consistent set of brain regions, irrespective of task or language.

Neural circuits underpinning face tuning in male depression.

Reading bodies and faces is essential for efficient social interactions, though it may be thought-provoking for individuals with depression. Yet aberrations in the face sensitivity and underwriting neural circuits are not well understood, in particular, in male depression. Here, we use cutting-edge analyses of time course and dynamic topography of gamma oscillatory neuromagnetic cortical activity during administration of a task with Arcimboldo-like images. No difference in face tuning was found between individuals with depression and their neurotypical peers. Furthermore, this behavioral outcome nicely dovetails with magnetoencephalographic data: at early processing stages, the gamma oscillatory response to images resembling a face was rather similar in patients and controls. These bursts originated primarily from the right medioventral occipital cortex and lateral occipital cortex. At later processing stages, however, its topography altered remarkably in depression with profound engagement of the frontal circuits. Yet the primary difference in depressive individuals as compared with their neurotypical peers occurred over the left middle temporal cortices, a part of the social brain, engaged in feature integration and meaning retrieval. The outcome suggests compensatory recruitment of neural resources in male depression.

TDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and objectiveTranscranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. MethodsData from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. ResultsIn M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = −3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. ConclusionsOur data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects.

Neuromodulation of verb-transitivity judgments

This study aimed to further clarify the roles of the temporal and frontal lobes of the brain in the processing of verb argument structure. Left inferior frontal brain areas have long been considered important for sentence processing, but recent research links left posterior temporal cortex to knowledge of verb argument structure. We applied cathodal High-Definition transcranial Direct Current Stimulation to 45 participants in a between-subjects design, with 15 participants each for inferior-frontal-cortex stimulation, posterior-temporal-cortex stimulation, and sham stimulation. Set up as a training task during stimulation, participants made overt judgments on the number of participant roles associated with individual verbs. Stimulation of posterior temporal cortex did not yield results that were different from sham stimulation, speeding up task responses overall. By contrast, stimulation of inferior frontal cortex yielded differential results for intransitive versus transitive verbs, speeding up responses to intransitive verbs and increasing accuracy to transitive verbs, relative to other conditions. The transitivity effect, specific to inferior frontal stimulation, suggests a role for inferior frontal cortex in access to verb-argument-structure information, possibly specific to situations of high cognitive load and in which participant roles have to be established for production, as opposed to comprehension.

Neuroanatomical Correlates of Semantic Features of Narrative Speech in Semantic and Logopenic Variants of Primary Progressive Aphasia.

The semantic variant of a primary progressive aphasia (svPPA) is characterized by progressive disruption of semantic knowledge. This study aimed to compare the semantic features of words produced during a narrative speech in svPPA and the logopenic variant of PPA (lvPPA) and to explore their neuroanatomical correlates. Six patients with svPPA and sixteen with lvPPA underwent narrative speech tasks. For all the content words, a semantic depth index (SDI) was determined based on the taxonomic structure of a large lexical database. Study participants underwent an MRI examination. Cortical thickness measures were extracted according to the Desikan atlas. Correlations were computed between SDI and the thickness of cortical regions. Mean SDI was lower for svPPA than for lvPPA. Correlation analyses showed a positive association between the SDI and the cortical thickness of the bilateral temporal pole, parahippocampal and entorhinal cortices, and left middle and superior temporal cortices. Disruption of semantic knowledge observed in svPPA leads to the production of generic terms in narrative speech, and the SDI may be useful for quantifying the level of semantic impairment. The measure was associated with the cortical thickness of brain regions associated with semantic memory.

Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here, we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left-hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. In contrast, poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. Little insight was gained from functional disconnection symptom mapping. These results demonstrate that while left-lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

Morphometric features of drug-resistant essential tremor and recovery after stereotactic radiosurgical thalamotomy.

Essential tremor (ET) is the most common movement disorder. Its neural underpinnings remain unclear. Here, we quantified structural covariance between cortical thickness (CT), surface area (SA), and mean curvature (MC) estimates in patients with ET before and 1 year after ventro-intermediate nucleus stereotactic radiosurgical thalamotomy, and contrasted the observed patterns with those from matched healthy controls. For SA, complex rearrangements within a network of motion-related brain areas characterized patients with ET. This was complemented by MC alterations revolving around the left middle temporal cortex and the disappearance of positive-valued covariance across both modalities in the right fusiform gyrus. Recovery following thalamotomy involved MC readjustments in frontal brain centers, the amygdala, and the insula, capturing nonmotor characteristics of the disease. The appearance of negative-valued CT covariance between the left parahippocampal gyrus and hippocampus was another recovery mechanism involving high-level visual areas. This was complemented by the appearance of negative-valued CT/MC covariance, and positive-valued SA/MC covariance, in the right inferior temporal cortex and bilateral fusiform gyrus. Our results demonstrate that different morphometric properties provide complementary information to understand ET, and that their statistical cross-dependences are also valuable. They pinpoint several anatomical features of the disease and highlight routes of recovery following thalamotomy.

The role of the anterior temporal cortex in action: evidence from fMRI multivariate searchlight analysis during real object grasping

Intelligent manipulation of handheld tools marks a major discontinuity between humans and our closest ancestors. Here we identified neural representations about how tools are typically manipulated within left anterior temporal cortex, by shifting a searchlight classifier through whole-brain real action fMRI data when participants grasped 3D-printed tools in ways considered typical for use (i.e., by their handle). These neural representations were automatically evocated as task performance did not require semantic processing. In fact, findings from a behavioural motion-capture experiment confirmed that actions with tools (relative to non-tool) incurred additional processing costs, as would be suspected if semantic areas are being automatically engaged. These results substantiate theories of semantic cognition that claim the anterior temporal cortex combines sensorimotor and semantic content for advanced behaviours like tool manipulation.

Learning From Mistakes: Cognitive and Metabolic Correlates of Errors on Picture Naming in the Alzheimer's Disease Spectrum.

Analysis of subtypes of picture naming errors produced by patients with Alzheimer's disease (AD) have seldom been investigated yet may clarify the cognitive and neural underpinnings of naming in the AD spectrum. To elucidate the neurocognitive bases of picture naming in AD through a qualitative analysis of errors. Over 1000 naming errors produced by 70 patients with amnestic, visuospatial, linguistic, or frontal AD were correlated with general cognitive tests and with distribution of hypometabolism on FDG-PET. Principal component analysis identified 1) a Visual processing factor clustering visuospatial tests and unrecognized stimuli, pure visual errors and visual-semantic errors, associated with right parieto-occipital hypometabolism; 2) a Concept-Lemma factor grouping language tests and anomias, circumlocutions, superordinates, and coordinates, correlated with left basal temporal hypometabolism; 3) a Lemma-Phonology factor including the digit span and phonological errors, linked with left temporo-parietal hypometabolism. Regression of brain metabolism on individual errors showed that errors due to impairment of basic and higher-order processing of object visual attributes, or of their interaction with semantics, were related with bilateral occipital and left occipito-temporal dysfunction. Omissions and superordinates were linked to degradation of broad and basic concepts in the left basal temporal cortex. Semantic-lexical errors derived from faulty semantically- and phonologically-driven lexical retrieval in the left superior and middle temporal gyri. Generation of nonwords was underpinned by impairment of phonology within the left inferior parietal cortex. Analysis of individual naming errors allowed to outline a comprehensive anatomo-functional model of picture naming in classical and atypical AD.

Altered Variability and Concordance of Dynamic Resting-State Functional Magnetic Resonance Imaging Indices in Patients With Major Depressive Disorder and Childhood Trauma.

Childhood trauma is a non-specific risk factor for major depressive disorder (MDD). resting-state functional magnetic resonance imaging (R-fMRI) studies have demonstrated changes in regional brain activity in patients with MDD who experienced childhood trauma. However, previous studies have mainly focused on static characteristics of regional brain activity. This study aimed to determine the specific brain regions associated with MDD with childhood trauma by performing temporal dynamic analysis of R-fMRI data in three groups of patients: patients with childhood trauma-associated MDD (n = 48), patients without childhood trauma-associated MDD (n = 30), and healthy controls (n = 103). Dynamics and concordance of R-fMRI indices were calculated and analyzed. In patients with childhood trauma-associated MDD, a lower dynamic amplitude of low-frequency fluctuations was found in the left lingual gyrus, whereas a lower dynamic degree of centrality was observed in the right lingual gyrus and right calcarine cortex. Patients with childhood trauma-associated MDD showed a lower voxel-wise concordance in the left middle temporal and bilateral calcarine cortices. Moreover, group differences (depressed or not) significantly moderated the relationship between voxel-wise concordance in the right calcarine cortex and childhood trauma history. Overall, patients with childhood trauma-associated MDD demonstrated aberrant variability and concordance in intrinsic brain activity. These aberrances may be an underlying neurobiological mechanism that explains MDD from the perspective of temporal dynamics.

Anosognosia in Dementia: Evaluation of Perfusion Correlates Using 99mTc-HMPAO SPECT and Automated Brodmann Areas Analysis.

(1) Background: Considerable inconsistency exists regarding the neural substrates of anosognosia in dementia in previous neuroimaging studies. The purpose of this study was the evaluation of anosognosia perfusion correlates across various types of dementia using automated Brodmann areas (BAs) analysis and comparison with a database of normal subjects. (2) Methods: We studied 72 patients: 32 with Alzheimer’s disease, 26 with frontotemporal dementia—FTD (12 behavioral FTD, 9 semantic FTD, 5 Progressive Non-Fluent Aphasia), 11 with corticobasal syndrome, and 3 with progressive supranuclear palsy. Addenbrook’s Cognitive Examination—Revised (ACE-R) mean(±SD) was 55.6(±22.8). For anosognosia measurement, the Anosognosia Questionnaire—Dementia was used. Total anosognosia score mean(±SD) was 22.1(±17.9), cognitive anosognosia score mean(±SD) was 18.1(±15.1) and behavioral–mood anosognosia score mean(±SD) was 3.3(±4.7). (3) Results: Higher anosognosia total score was associated with hypoperfusion in the inferior temporal, anterior cingulate, and inferior frontal cortices of the right hemisphere (BAs 20R, 24R, 32R, 45R). Higher anosognosia cognitive score was correlated with hypoperfusion in the left middle and anterior temporal cortices, and right dorsal anterior cingulate cortex (BAs 21L, 22L, 32R). No association was found with behavioral–mood anosognosia. (4) Conclusions: Automated analysis of brain perfusion Single Photon Emission Computed Tomography could be useful for the investigation of anosognosia neural correlates in dementia.

Cortical Thickness Abnormalities at Different Stages of the Illness Course in Schizophrenia

Questions of whether and how cortical thickness (CTh) alterations differ over the course of schizophrenia (SCZ) have yet to be resolved. To characterize CTh alterations across illness stages in SCZ. PubMed, Embase, Web of Science, and Science Direct were screened for CTh studies published before June 15, 2021. Original studies comparing whole-brain CTh alterations from healthy controls in individuals at clinical high-risk (CHR), first episode of psychosis (FEP), and long-term illness stages of SCZ were included. This preregistered systematic review and meta-analysis followed PRISMA reporting guidelines. Separate and pooled meta-analyses were performed using seed-based d mapping. Meta-regression analyses were conducted. Cortical thickness differences from healthy control individuals across illness stages. Ten studies comprising 859 individuals with CHR (mean [SD] age, 21.02 [2.66] years; male, 573 [66.7%]), 12 studies including 671 individuals with FEP (mean [SD] age, 22.87 [3.99] years; male, 439 [65.4%]), and 10 studies comprising 579 individuals with long-term SCZ (mean [SD] age, 41.58 [6.95] years; male, 396 [68.4%]) were included. Compared with healthy control individuals, individuals with CHR showed cortical thinning in bilateral medial prefrontal cortex (z = -1.01; P < .001). Individuals with FEP showed cortical thinning in right lateral superior temporal cortex (z = -1.34; P < .001), right anterior cingulate cortex (z = -1.44; P < .001), and right insula (z = -1.14; P = .002). Individuals with long-term SCZ demonstrated CTh reductions in right insula (z = -3.25; P < .001), right inferior frontal cortex (z = -2.19; P < .001), and left (z = -2.37; P < .001) and right (z = -1.94; P = .002) temporal pole. There were no significant CTh differences between CHR and FEP. Individuals with long-term SCZ showed greater cortical thinning in right insula (z = -2.58; P < .001), right inferior frontal cortex (z = -2.32; P < .001), left lateral temporal cortex (z = -1.91; P = .002), and right temporal pole (z = -1.82; P = .002) than individuals with FEP. Combining all studies on SCZ, accelerated age-related CTh reductions were found in bilateral lateral middle temporal cortex and right pars orbitalis in inferior frontal cortex. The absence of significant differences between FEP and CHR noted in this systematic review and meta-analysis suggests that the onset of psychosis was not associated with robust CTh reduction. The greater cortical thinning in long-term SCZ compared with FEP with accelerated age-related reduction in CTh suggests progressive neuroanatomic alterations following illness onset. Caution in interpretation is needed because heterogeneity in samples and antipsychotic treatment may confound these results.

Stereo-electroencephalography evidence of an eccentrically located seizure-onset zone around a polymorphous low-grade neuroepithelial tumor of the young: illustrative case.

BACKGROUNDPolymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a newly identified low-grade brain tumor with frequent epileptic presentation. Despite the facilitated use of invasive electroencephalography owing to the growing availability of stereo-electroencephalography (SEEG), intracranial features of tumor-related seizures are still scarcely described. This report provides the first description of SEEG-recorded seizures in PLNTY to provide an insight into its surgical strategy.OBSERVATIONSSpontaneous clinical seizures were recorded with SEEG in a young adult patient with drug-resistant epilepsy associated with a PLNTY in the left lateral temporal cortex. The seizure onset was characterized by low-voltage fast activity (LVFA) and showed eccentric localization with respect to the tumor: LVFA was localized in the anterior portion of the tumor and spread toward the adjacent polar cortex. The language risks associated with the resection of the posterior temporal cortex could thus be minimized.LESSONSPLNTY can show a focal and eccentric seizure-onset zone around the tumor. The present findings serve to improve the functional and seizure outcomes using the staged invasive approach in PLNTY.

Effective connectivity within the neural system for object-directed action representation during aware and unaware tool processing

Previous brain functional specialization evidence has shown that both aware and unaware visual processing of manipulable objects activate left premotor, parietal, and posterior temporal cortices, which are thought to constitute object-directed action and object-function processing streams. An open question is whether, both under supraliminal and subliminal processing conditions, there is directional spread of activation along these functional streams, leading to causal inter-regional connectivity effects. In this study, we used Dynamic Causal Modelling to estimate the effective connectivity influences within the premotor-parieto-temporal network, as a function of factorial contrasts for Manipulability (manipulable vs non-manipulable objects) and Perceptual Awareness (above vs below perceptual threshold). We modeled forward and backward connections originating from visual area V4, as a region underlying object texture segregation, and spreading through the left premotor-parieto-temporal network. Both above and below perceptual threshold, the visual processing of manipulable objects was associated with a specific increase of reciprocal effective connectivity coupling among left premotor-parieto-temporal regions. Aware and unaware manipulable object processing differed from each other for their distinct patterns of top-down activation enhancement exerted, in the former case, by left premotor-parieto-temporal regions on area V4 and, in the latter case, by left premotor on temporal regions. Although it is only under aware processing conditions that effective connectivity in the action representation system may promote object visual contour segregation in area V4, our results suggest that the encoding of object-action and object-function information can occur through left-hemispheric premotor, parietal, and temporal causal interdependencies, even when the object is not consciously perceived.

Altered voxel-level whole-brain functional connectivity in multiple system atrophy patients with depression symptoms

BackgroundIt is yet unknown if the whole-brain resting-state network is altered in multiple system atrophy with symptoms of depression. This study aimed to investigate if and how depression symptoms in multiple system atrophy are associated with resting-state network dysfunction.MethodsWe assessed the resting-state functional network matric using Degree centrality (DC) coupling with a second ROI-wise functional connectivity (FC) algorithm in a multimodal imaging case-control study that enrolled 32 multiple system atrophy patients with depression symptoms (MSA-D), 30 multiple system atrophy patients without depression symptoms (MSA-ND), and 34 healthy controls (HC).ResultsCompared to HC, MSA-D showed more extensive DC hub dysfunction in the left precentral and right middle frontal cortex than MSA-ND. A direct comparison between MSA-D and MSA-ND detected increased DC in the right anterior cingulum cortex, but decreased DC in the left cerebellum lobule IV and lobule V, left middle pole temporal cortex, and right superior frontal cortex. Only right anterior cingulum cortex mean DC values showed a positive correlation with depression severity, and used ACC as seed, a second ROI-wise functional connectivity further revealed MSA-D patients showed decreased connectivity between the ACC and right thalamus and right middle temporal gyrus (MTG).ConclusionsThese findings revealed that dysfunction of rACC, right middle temporal lobe and right thalamus involved in depressed MSA. Our study might help to the understanding of the neuropathological mechanism of depression in MSA.

Brain Networks Involved in Depression in Patients with Frontotemporal Dementia and Parkinson's Disease: An Exploratory Resting-State Functional Connectivity MRI Study.

Depression is characterized by feelings of sadness, loss, or anger that may interfere with everyday activities. Such a neuropsychiatric condition is commonly reported in multiple neurodegenerative disorders, which are quite different from each other. This study aimed at investigating the brain networks involved in depression in patients with frontotemporal dementia (FTD) and Parkinson’s disease (PD) as compared to healthy controls (HC). Fifty participants were included in the study: 17 depressed FTD/PD patients; 17 non-depressed FTD/PD patients; and 16 non-depressed HCs matched for age and gender. We used the Beck depression inventory (BDI-II) to measure depression in all groups. On the same day, 3T brain magnetic resonance with structural and resting-state functional sequences were acquired. Differences in resting-state functional connectivity (FC) between depressed and non-depressed patients in all the experimental groups were assessed by using seed-to-seed and network-to-network approaches. We found a significant seed-to-seed hyperconnectivity patterns between the left thalamus and the left posterior temporal fusiform cortex, which differentiated FTD/PD depressed patients from the HCs. Network-to-network analysis revealed a significant hyperconnectivity among the default-mode network (left lateral-parietal region), the medial prefrontal cortex and the left lateral prefrontal cortex (i.e., part of the central executive network). We investigated whether such FC patterns could be related to the underlying neurodegenerative disorder by replicating the analyses with two independent samples (i.e., non-depressed PD and non-depressed FTD patients) and adding clinical parameters as covariates. We found no FC differences in these groups, thus suggesting how the FC pattern we found may signal a common depression-related neural pathway implicated in both the neurocognitive disorders.

Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods.

Rationale and ObjectivesPro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults.Materials and MethodsSeventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC).ResultsElevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults.ConclusionOur results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.

Dysgraphia Phenotypes in Native Chinese Speakers With Primary Progressive Aphasia.

Most primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants. This study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors. All PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively. The findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.