Anterior Parahippocampal Gyrus Research Articles

Endogenous phenotype of diagnostic transition from major depressive disorder to bipolar disorder: a prospective cohort study

IntroductionThis study investigated sensor-level electroencephalography (EEG) power and related source-level cortical activity using resting-state EEG in patients with MDD and BD.ObjectivesThis study aims to comparing bipolar disorder (BD) and major depressive disorder (MDD) to understand neuropathology of these disorders.MethodsA total of 68 patients with MDD were enrolled and recorded EEG. Among patients with MDD, 17 patients with MDD converted to BD during the study periods. Clinical symptoms and EEG measures were compared between two groups. This study applied machine learning to differentiate the two groups using sensor and source-level featuresResultsAt the sensor level, patients with BD showed higher power of AF3 channel in the theta beta band(p=0.011) and FC5 channel in the low alpha band(p=0.014), compared to MDD. At the source-level, compared to MDD, patients with BD showed higher activity in the right anterior cingulate(p=0.011) and left parahippocampal gyrus(p=0.035). The best classification performance for MDD and BD showed an accuracy of 80.88%, a sensitivity of 76.47%, and a specificity of 82.35% based on theta and low alpha band power and activity features.ConclusionsOur findings might suggest different theta and low alpha band activity between patients with BD and MDD might serve clinically as a candidate neuromarker for differentiating two distinct mood disorders.Disclosure of InterestNone Declared

Estradiol associations with brain functional connectivity in postmenopausal women.

Previous studies have found that estrogens play a role in functional connectivity in the brain; however, little research has been done regarding how estradiol is associated with functional connectivity in postmenopausal women. The purpose of this study was to examine the relationship between estradiol and functional connectivity in postmenopausal women. Structural and blood oxygenation level-dependent resting-state magnetic resonance imaging scans of 88 cognitively healthy postmenopausal individuals were obtained along with blood samples collected the same day as the magnetic resonance imaging to assess hormone levels. We generated connectivity values in CONN toolbox version 20.b, an SPM-based software. A regression analysis was run using estradiol level and regions of interest (ROI), including the hippocampus, parahippocampus, dorsolateral prefrontal cortex, and precuneus. Estradiol level was found to enhance parahippocampal gyrus anterior division left functional connectivity during ROI-to-ROI regression analysis. Estradiol enhanced functional connectivity between the parahippocampal gyrus anterior division left and the precuneus as well as the parahippocampal gyrus anterior division left and parahippocampal gyrus posterior division right. An exploratory analysis showed that years since the final menstrual period was related to enhanced connectivity between regions within the frontoparietal network. These results illustrated the relationship between estradiol level and functional connectivity in postmenopausal women. They have implications for understanding how the functioning of the brain changes for individuals after menopause that may eventually lead to changes in cognition and behavior in older ages.

Sticky criticism? Affective and neural responses to parental criticism and praise in adolescents with depression.

Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied. Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views. In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more. Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.

Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have a high prevalence of chronic WTC-related post-traumatic stress disorder (WTC-PTSD). We investigated neural mechanisms underlying WTC-PTSD by applying eigenvector centrality (EC) metrics and data-driven methods on resting state functional magnetic resonance (fMRI). We identified how EC differences relate to WTC-exposure and behavioral symptoms. We found that connectivity differentiated significantly between WTC-PTSD and non-PTSD responders in nine brain regions, as these differences allowed an effective discrimination of PTSD and non-PTSD responders based solely on analysis of resting state data. Further, we found that WTC exposure duration (months on site) moderates the association between PTSD and EC values in two of the nine brain regions; the right anterior parahippocampal gyrus and the left amygdala (p = 0.010; p = 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, a dimensional measure of symptom severity was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Functional neuroimaging can provide effective tools to identify neural correlates of diagnostic and dimensional indicators of PTSD.

Shared genetic etiology between ADHD, task-related behavioral measures and brain activation during response inhibition in a youth ADHD case–control study

Impaired response inhibition is commonly present in individuals with attention-deficit/hyperactivity disorder (ADHD) and their unaffected relatives, suggesting impaired response inhibition as a candidate endophenotype in ADHD. Therefore, we explored whether behavioral and neural correlates of response inhibition are related to polygenic risk scores for ADHD (PRS-ADHD). We obtained functional magnetic resonance imaging of neural activity and behavioral measures during a stop-signal task in the NeuroIMAGE cohort, where inattention and hyperactivity-impulsivity symptoms were assessed with the Conners Parent Rating Scales. Our sample consisted of 178 ADHD cases, 103 unaffected siblings, and 173 controls (total N = 454; 8–29 years), for whom genome-wide genotyping was available. PRS-ADHD was constructed using the PRSice-2 software. We found PRS-ADHD to be associated with ADHD symptom severity, a slower and more variable response to Go-stimuli, and altered brain activation during response inhibition in several regions of the bilateral fronto-striatal network. Mean reaction time and intra-individual reaction time variability mediated the association of PRS-ADHD with ADHD symptoms (total, inattention, hyperactivity-impulsivity), and activity in the left temporal pole and anterior parahippocampal gyrus during failed inhibition mediated the relationship of PRS-ADHD with hyperactivity-impulsivity. Our findings indicate that PRS-ADHD are related to ADHD severity on a spectrum of clinical, sub-threshold, and normal levels; more importantly, we show a shared genetic etiology of ADHD and behavioral and neural correlates of response inhibition. Given the modest sample size of our study, future studies with higher power are warranted to explore mediation effects, suggesting that genetic liability to ADHD may adversely affect attention regulation on the behavioral level and point to a possible response inhibition-related mechanistic pathway from PRS-ADHD to hyperactivity-impulsivity.

Item-Level Scores on the Boston Naming Test as an Independent Predictor of Perirhinal Volume in Individuals with Mild Cognitive Impairment.

We explored the methodological value of an item-level scoring procedure applied to the Boston Naming Test (BNT), and the extent to which this scoring approach predicts grey matter (GM) variability in regions that sustain semantic memory. Twenty-seven BNT items administered as part of the Alzheimer's Disease Neuroimaging Initiative were scored according to their "sensorimotor interaction" (SMI) value. Quantitative scores (i.e., the count of correctly named items) and qualitative scores (i.e., the average of SMI scores for correctly named items) were used as independent predictors of neuroanatomical GM maps in two sub-cohorts of 197 healthy adults and 350 mild cognitive impairment (MCI) participants. Quantitative scores predicted clusters of temporal and mediotemporal GM in both sub-cohorts. After accounting for quantitative scores, the qualitative scores predicted mediotemporal GM clusters in the MCI sub-cohort; clusters extended to the anterior parahippocampal gyrus and encompassed the perirhinal cortex. This was confirmed by a significant yet modest association between qualitative scores and region-of-interest-informed perirhinal volumes extracted post hoc. Item-level scoring of BNT performance provides complementary information to standard quantitative scores. The concurrent use of quantitative and qualitative scores may help profile lexical-semantic access more precisely, and might help detect changes in semantic memory that are typical of early-stage Alzheimer's disease.

Late dominance of the right hemisphere during narrative comprehension

PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults. The protocol consisted of two runs, each interleaving 7 blocks of the story comprehension task with 15 blocks of an auditorily presented math task as a control for phonological processing, working memory, and attention processes. Sources at the cortical surface were estimated with a frequency-resolved beamformer. Beta-band power was estimated in the frequency range of 16–24 Hz over 1-sec epochs starting from 400 msec after stimulus onset until the end of a story or math problem presentation. These power estimates were compared to 1-second epochs of data before the stimulus block onset. The task-related cortical engagement was inferred from beta-band power decrements. Group-level source activations were statistically compared using non-parametric permutation testing. A story-math contrast of beta-band power changes showed greater bilateral cortical engagement within the fusiform gyrus, inferior and middle temporal gyri, parahippocampal gyrus, and left inferior frontal gyrus (IFG) during story comprehension. A math-story contrast of beta power decrements showed greater bilateral but left-lateralized engagement of the middle frontal gyrus and superior parietal lobule. The evolution of cortical engagement during five temporal windows across the presentation of stories showed significant involvement during the first interval of the narrative of bilateral opercular and insular regions as well as the ventral and lateral temporal cortex, extending more posteriorly on the left and medially on the right. Over time, there continued to be sustained right anterior ventral temporal engagement, with increasing involvement of the right anterior parahippocampal gyrus, STG, MTG, posterior superior temporal sulcus, inferior parietal lobule, frontal operculum, and insula, while left hemisphere engagement decreased. Our findings are consistent with prior imaging studies of narrative comprehension, but in addition, they demonstrate increasing right-lateralized engagement over the course of narratives, suggesting an important role for these right-hemispheric regions in semantic integration as well as social and pragmatic inference processing.

Functional connectivity with medial temporal regions differs across cultures during post-encoding rest.

Connectivity of the brain at rest can reflect individual differences and impact behavioral outcomes, including memory. The present study investigated how culture influences functional connectivity with regions of the medial temporal lobe. In this study, 46 Americans and 59 East Asians completed a resting state scan after encoding pictures of objects. To investigate cross-cultural differences in resting state functional connectivity, left parahippocampal gyrus (anterior and posterior regions) and left hippocampus were selected as seed regions. These regions were selected, because they were previously implicated in a study of cultural differences during the successful encoding of detailed memories. Results revealed that left posterior parahippocampal gyrus had stronger connectivity with temporo-occipital regions for East Asians compared with Americans and stronger connectivity with parieto-occipital regions for Americans compared with East Asians. Left anterior parahippocampal gyrus had stronger connectivity with temporal regions for East Asians than Americans and stronger connectivity with frontal regions for Americans than East Asians. Although connectivity did not relate to memory performance, patterns did relate to cultural values. The degree of independent self-construal and subjective value of tradition were associated with functional connectivity involving left anterior parahippocampal gyrus. Findings are discussed in terms of potential cultural differences in memory consolidation or more general trait or state-based processes, such as holistic versus analytic processing.

P177 Investigating the neural differences in individuals with chronic widespread pain or fibromyalgia and the effect of sleep: a cross-sectional study using data from UK Biobank

Abstract Background/Aims Sleep problems are common in fibromyalgia (FM) and chronic widespread pain (CWP), and may result in similar structural brain changes as those seen in chronic pain. However, the exact neural mechanisms are not fully understood. Studies to date are relatively small and yield conflicting results. The aim of this study is to investigate structural differences in brain regions of interest (ROI) in participants with FM or CWP from UK Biobank, a large-scale biomedical database, compared with healthy controls. We also explore the potential interaction of sleep on the volume of these ROIs, with the hypothesis that low sleep duration with chronic pain amplifies the atrophy seen. Methods Using T1 structural brain imaging data from UK Biobank, we defined cases as those experiencing CWP for 3+ months at the imaging visit or with a diagnosis of FM. Age- and sex-matched controls did not report any pain or chronic pain diagnoses at the imaging visit. Low sleep duration was defined as less than 7 hours of sleep in a 24-hour period in line with the recommended sleep duration of 7-9 hours. 22 brain ROIs were selected based on the existing literature. Pre-processed image-derived phenotype data for grey matter volumes were compared in brain ROIs using 2-way independent ANOVAs in SPSS. Results 429 cases and 429 controls were included: (n = 664/858 [77.4%] female; mean [SD] age 62.0 ± 7.4). The volume of the grey matter in the bilateral insular cortices and anterior parahippocampal gyri, and the volume of the right pallidum, were all significantly smaller in cases compared to controls, p < 0.05. In addition to the significant difference between the controls and cases in the right anterior parahippocampal gyrus, the interaction effect of sleep duration on pain was also significant, p < 0.05. Even though there were no significant differences between the controls and cases in the grey matter volumes of the left posterior division of the cingulate gyrus, bilateral superior frontal gyri, right middle frontal gyrus, left posterior division of the parahippocampal gyrus, right precuneus cortex and left inferior frontal gyrus, pars opercularis, and the volume of the right thalamus, there was a significant interaction effect of sleep duration and pain status on their volumes, p < 0.05. Conclusion This large-scale study confirms differences in grey matter volumes in key brain ROIs in those with chronic pain, highlighting neural changes in individuals suffering from CWP or FM, and a novel interaction of sleep on these areas. Perhaps these changes are due to neurotoxic effects of low sleep duration. Alternatively, low sleep duration and chronic pain may be caused by these structural differences. Evidently, further research is still needed to identify the directionality of these changes and their functional implications through longitudinal functional brain imaging studies, to identify the underlying cause of these structural differences. Disclosure N.W.I.L. Silva: None. A. Soni: None. V. Wanigasekera: None. S. Zhang: None. A.J.W. Wall: None. I. Tracey: None.

Neuroanatomical correlations of visuospatial processing in primary progressive aphasia.

Clinical phenotyping of primary progressive aphasia has largely focused on speech and language presentations, leaving other cognitive domains under-examined. This study investigated the diagnostic utility of visuospatial profiles and examined their neural basis among the three main primary progressive aphasia variants. We studied the neuropsychological performances of 118 primary progressive aphasia participants and 30 cognitively normal controls, across 11 measures of visuospatial cognition, and investigated their neural correlates via voxel-based morphometry analysis using visuospatial composite scores derived from principal component analysis. The principal component analysis identified three main factors: visuospatial-executive, visuospatial-memory and visuomotor components. Logopenic variant primary progressive aphasia performed significantly worst across all components; nonfluent/agrammatic variant primary progressive aphasia showed deficits in the visuospatial-executive and visuomotor components compared with controls; and the semantic variant primary progressive aphasia scored significantly lower than nonfluent/agrammatic variant primary progressive aphasia and control in the visuospatial-memory component. Grey matter volumes over the right parieto-occipital cortices correlated with visuospatial-executive performance; volumetric changes in the right anterior parahippocampal gyrus and amygdala were associated with visuospatial-memory function, and visuomotor composite scores correlated significantly with the grey matter volume at the right precentral gyrus. Discriminant function analysis identified three visuospatial measures: Visual Object and Space Perception and Benson figure copy and recall test, which classified 79.7% (94/118) of primary progressive aphasia into their specific variant. This study shows that each primary progressive aphasia variant also carries a distinctive visuospatial cognitive profile that corresponds with grey matter volumetric changes and in turn can be largely represented by their performance on the visuomotor, visuospatial-memory and executive functions.

Structural and Functional Correlates of Hallucinations and Illusions in Parkinson's Disease.

Visual illusions (VI) in Parkinson's disease (PD) are generally considered as an early feature of the psychosis spectrum leading to fully formed visual hallucinations (VH), although this sequential relationship has not been clearly demonstrated. We aimed to determine whether there are any overlapping, potentially graded patterns of structural and functional connectivity abnormalities in PD with VI and with VH. Such a finding would argue for a continuum between these entities, whereas distinct imaging features would suggest different neural underpinnings for the phenomena. In this case control study, we compared structural and resting state functional MRI brain patterns of PD patients with VH (PD-H, n = 20), with VI (PD-I, n = 19), and without VH or VI (PD-C, n = 23). 1) PD-H had hypo-connectivity between the ILO and anterior cingulate precuneus and parahippocampal gyrus compared to PD-C and PD-I; 2) In contrast, PD-I had hyper-connectivity between the inferior frontal gyrus and the postcentral gyrus compared to PD-C and PD-H. Moreover, PD-I had higher levels of functional connectivity between the amygdala, hippocampus, insula, and fronto-temporal regions compared to PD-H, together with divergent patterns toward the cingulate. 3) Both PD-I and PD-H had functional hypo-connectivity between the lingual gyrus and the parahippocampal region vs. PD-C, and no significant grey matter volume differences was observed between PD-I and PD-H. Distinct patterns of functional connectivity characterized VI and VH in PD, suggesting that these two perceptual experiences, while probably linked and driven by at least some similar mechanisms, could reflect differing neural dysfunction.

In vivo exploration of synaptic projections in frontotemporal dementia

The purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer’s disease (AD). Loss of synaptic projections was assessed with [18F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, [18F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in [18F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes.

Anhedonia in Semantic Dementia-Exploring Right Hemispheric Contributions to the Loss of Pleasure.

Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right temporal regions. How lateralisation of temporal lobe pathology impacts the hedonic experience in SD remains largely unknown yet has important implications for understanding socioemotional and functional impairments in this syndrome. Here, we explored how lateralisation of temporal lobe atrophy impacts anhedonia severity on the Snaith–Hamilton Pleasure Scale in 28 SD patients presenting with variable right- (SD-R) and left-predominant (SD-L) profiles of temporal lobe atrophy compared to that of 30 participants with Alzheimer’s disease and 30 healthy older Control participants. Relative to Controls, SD-R but not SD-L or Alzheimer’s patients showed clinically significant anhedonia, representing a clear departure from premorbid levels. Overall, anhedonia was more strongly associated with functional impairment on the Frontotemporal Dementia Functional Rating Scale and motivational changes on the Cambridge Behavioural Inventory in SD than in Alzheimer’s disease patients. Voxel-based morphometry analyses revealed that anhedonia severity correlated with reduced grey matter intensity in a restricted set of regions centred on right orbitofrontal and temporopolar cortices, bilateral posterior temporal cortices, as well as the anterior cingulate gyrus and parahippocampal gyrus, bilaterally. Finally, regression and mediation analysis indicated a unique role for right temporal lobe structures in modulating anhedonia in SD. Our findings suggest that degeneration of predominantly right-hemisphere structures deleteriously impacts the capacity to experience pleasure in SD. These findings offer important insights into hemispheric lateralisation of motivational disturbances in dementia and suggest that anhedonia may emerge at different timescales in the SD disease trajectory depending on the integrity of the right hemisphere.

Posterior Precuneus is Highly Connected to Medial Temporal Lobe Revealed by Tractography and White Matter Dissection

The precuneus, involved in various cognitive processes, is considered to form the midline core of the default mode network (DMN), while the medial temporal lobe (MTL) is a subsystem of the DMN. Until now, the anatomical study of the precuneus-MTL connection is limited in humans. One possible reason is the precuneus’ territory of the posteromedial cortex (PMC) is inconsistent across studies. The primary purpose of this study is to investigate the structural connectivity (SC) of precuneus-MTL, focusing on its anatomical organization using the Human Connectome Project Multi-modal Parcellation (HCP MMP) atlas. We first conducted the quantitative tractography analyses using the HCP dataset. The major streamlines originated from the posterior precuneus and were projected to the MTL extensively. Next, to complement the tractography data, we conducted the white matter dissection in the post-mortem human brain. We observed the major fiber bundles arise from the posterior precuneus extending to the anterior parahippocampal gyrus, which could support our tractography results. Then we analyzed the relationship between SC and resting-state functional connectivity (rsFC) of the precuneus-MTL. Although the SC-rsFC correlation was scarce on the whole, the posterior precuneus (POS2, 7Pm, 7m) showed a relatively high correlation (r = 0.38349, p < 0.05) with the posterior MTL (PreS, H, ProS, PHA1, PHA2). Our findings suggest the posterior precuneus is highly connected to MTL structurally, which could have an effect on the resting-state functional connectivity. In addition, the precuneus might consist of the heterogeneous connectivity-based subdivisions.

Functional Brain Imaging During Rest and Pain: Differences According to Race and Knee Osteoarthritis

Considerable evidence suggests that knee osteoarthritis (OA)-related clinical pain and disability significantly differs according to racial background. However, brain mechanisms underlying these differences are not well understood. We investigated altered central pain processing in a sample comprised of Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) adults with and without knee OA. NHB and NHW participants with knee OA (n = 123) and without knee OA (N = 41) were recruited to complete a brain imaging protocol using Arterial Spin Labeling (ASL) on a 3T fMRI scanner. Participant's regional cerebral blood flow (rCBF), a measure of brain activation, was examined at rest and during pressure pain stimulation. Aim 1 was to examine altered central processing in people with knee OA compared to people without knee OA. Aim 2 assessed racial group differences in central processing among NHB and NHW adults with knee OA. People with knee OA showed significant differences in rCBF at rest and during pain in the anterior cingulate cortex, sensory-motor cortex, para-hippocampal gyrus, and amygdala in comparison to people without knee OA. For people with knee OA, ethnic differences between NHWs (n = 52) and NHBs (n = 71) were present in the cingulate gyrus, amygdala, thalamus, sensory-motor cortex, and cerebellum. Comparing people with knee OA to people without knee OA at rest while controlling for race, we found a significant effect in the thalamus (p = .036) and amygdala (p = .046). For people with knee OA, NHBs vs NHWs showed a significant effect for the difference score (pain - rest) in the cerebellum (p = .012) when controlling for age and education. These results indicate that knee OA and racial background may be important contributors to altered central nervous system processing of pain. Supported in part by NIH/NIA grant AG033906 and the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 T64) and the University of Alabama at Birmingham (ULITR000165).

Changes in Temporal and Spatial Patterns of Intrinsic Brain Activity and Functional Connectivity in Upper-Limb Amputees: An fMRI Study.

Background Amputation in adults is a serious procedure or traumatic outcome, one that leads to a possible “remapping” of limb representations (somatotopy) in the motor and sensory cortex. The temporal and spatial extent underlying reorganization of somatotopy is unclear. The aim of this study was to better understand how local and global structural plasticity in sensory-motor cortical networks changes temporally and spatially after upper-limb amputation. Methods We studied 8 healthy nonamputee control subjects and 16 complete upper-limb amputees. Resting-state MRI (rs-fMRI) was used to measure local and large-scale relative differences (compared to controls) in both the amplitude of low-frequency fluctuations (ALFF) and degree of centrality (DC) at 2 months, 6 months, and 12 months after traumatic amputation. Results In amputees, rs-fMRI scans revealed differences in spatial patterns of ALFF and DC among brain regions over time. Significant relative increases in ALFF and DC were detected not only in the sensory and motor cortex but also in related cortical regions believed to be involved in cognition and motor planning. We observed changes in the magnitude of ALFFs in the pre- and postcentral gyrus and primary sensory cortex, as well as in the anterior cingulate, parahippocampal gyrus, and hippocampus, 2 months after the amputation. The regional distribution of increases/decreases in ALFFs and DC documented at 2-month postamputation was very different from those at 6 and 12-month postamputation. Conclusion Local and wide-spread changes in ALFFs in the sensorimotor cortex and cognitive-related brain regions after upper-limb amputation may imply dysfunction not only in sensory and motor function but also in areas responsible for sensorimotor integration and motor planning. These results suggest that cortical reorganization after upper extremity deafferentation is temporally and spatially more complicated than previously appreciated, affecting DC in widespread regions.

Increased links between language and motor areas: A proof-of-concept study on resting-state functional connectivity following Personalized Observation, Execution and Mental imagery therapy in chronic aphasia

A tight coupling of language and motor processes has been established, which is consistent with embodied cognition theory. However, very few therapies have been designed to exploit the synergy between motor and language processes to help rehabilitate people with aphasia (PWA). Moreover, the underlying mechanisms supporting the efficacy of such approaches remain unknown.Previous work in our laboratory has demonstrated that personalized observation, execution, and mental imagery therapy (POEM)—a new therapy using three sensorimotor strategies to trigger action verb naming—leads to significant improvements in verb retrieval in PWA. Moreover, these improvements were supported by significant activations in language and sensorimotor processing areas, which further reinforce the role of both processes in language recovery (Durand et al., 2018). The present study investigates resting state functional connectivity (rsFC) changes following POEM in a pre-/post-POEM therapy design. A whole brain network functional connectivity approach was used to assess and describe changes in rsFC in a group of four PWA, who were matched and compared with four healthy controls (HC).Results showed increased rsFC in PWA within and between visuo-motor and language areas (right cuneal cortex—left supracalcarin (SCC) cortex/right precentral gyrus (PreCG)—left lingual gyrus (LG)) and between areas involved in action processing (right anterior parahippocampal gyrus (aPaHC)—left superior parietal lobule (SPL). In comparison to HC, the PWA group showed increased rsFC between the right inferior frontal gyrus (IFG) and left thalamus, which are areas involved in lexico-semantic processing. This proof-of-concept study suggests that the sensorimotor and language strategies used in POEM may induce modifications in large-scale networks, probably derived from the integration of visual and sensorimotor systems to sustain action naming, which is consistent with the embodied cognition theory.

White matter microstructural impairments in amyotrophic lateral sclerosis: A mean apparent propagator MRI study

BackgroundWhite matter (WM) impairment is a hallmark of amyotrophic lateral sclerosis (ALS). This study evaluated the capacity of mean apparent propagator magnetic resonance imaging (MAP-MRI) for detecting ALS-related WM alterations. MethodsDiffusion images were obtained from 52 ALS patients and 51 controls. MAP-derived indices [return-to-origin/-axis/-plane probability (RTOP/RTAP/RTPP) and non-Gaussianity (NG)/perpendicular/parallel NG (NG⊥/NG||)] were computed. Measures from diffusion tensor/kurtosis imaging (DTI/DKI) and neurite orientation dispersion and density imaging (NODDI) were also obtained. Voxel-wise analysis (VBA) was performed to determine differences in these parameters. Relationship between MAP parameters and disease severity (assessed by the revised ALS Functional Rating Scale (ALSFRS-R)) was evaluated by Pearson’s correlation analysis in a voxel-wise way. ALS patients were further divided into two subgroups: 29 with limb-only involvement and 23 with both bulbar and limb involvement. Subgroup analysis was then conducted to investigate diffusion parameter differences related to bulbar impairment. ResultsThe VBA (with threshold of P < 0.05 after family-wise error correction (FWE)) showed that ALS patients had significantly decreased RTOP/RTAP/RTPP and NG/ NG⊥/NG|| in a set of WM areas, including the bilateral precentral gyrus, corona radiata, posterior limb of internal capsule, midbrain, middle corpus callosum, anterior corpus callosum, parahippocampal gyrus, and medulla. MAP-MRI had the capacity to capture WM damage in ALS, which was higher than DTI and similar to DKI/NODDI. RTOP/RTAP/NG/NG⊥/NG|| parameters, especially in the bilateral posterior limb of internal capsule and middle corpus callosum, were significantly correlated with ALSFRS-R (with threshold of FWE-corrected P < 0.05). The VBA (with FWE-corrected P < 0.05) revealed the significant RTAP reduction in subgroup with both bulbar and limb involvement, compared with those with limb-only involvement. ConclusionsMicrostructural impairments in corticospinal tract and corpus callosum represent the consistent characteristic of ALS. MAP-MRI could provide alternative measures depicting ALS-related WM alterations, complementary to the common diffusion imaging methods.

PET‐[18F]UCB‐H for assessing synaptic density in FTD

AbstractBackgroundThe behavioural variant of fronto‐temporal dementia (FTD) is characterized by clinical symptoms including behavioural and cognitive changes and by neurodegenerative involvement of the anterior part of the brain. The objective was to study the in vivo distribution of synaptic loss.Method12 patients with possible FTD and frontotemporal hypometabolism on FDG‐PET (mean disease duration of 4 years) were compared to 12 control participants and 12 patients with Alzheimer’s disease, matched for age, sex and education. Measures of verbal fluency, episodic memory and awareness of cognitive impairment did not differ between patients groups. We used [18F]UCBH‐PET to assess the regional loss of synaptic density. Total distribution volume was obtained with Logan method and carotid artery derived input function. SPM12 was used to analyze pve‐corrected PET and MRI images.ResultA significant decrease of [18F]UCBH uptake was observed in the right anterior parahippocampal gyrus of FTD patients, while atrophy was observed in the ventromedial prefrontal cortex. Loss of synaptic density was observed in the right hippocampus of AD participants, while atrophy extended from the right hippocampus to bilateral posterior associative cortices. AD patients showed lower [18F]UCBH uptake in the precuneus that FTD patients. Anosognosia for clinical symptoms was correlated with synaptic density in caudate nucleus and prefrontal cortex in FTD, and with synaptic density in posterior hippocampus in AD.ConclusionSynaptic loss was predominant in the anterior parahippocampal gyrus of our bvFTD patients. This region is part of the limbic network and the perceptive social brain. A validated measure of anosognosia (a characteristic but variable symptom in bvFTD) was related to synaptic density in two interconnected regions, caudate nucleus and anteromedial prefrontal cortex, the later being involved in self‐reference.

Functional connectivity changes of nucleus Accumbens Shell portion in left mesial temporal lobe epilepsy patients.

Growing evidence has supported that the nucleus accumbens (NAc), especially its shell portion, has been involved in epileptogenesis. However, relevant studies on vivo human brain are quite limited. In this study, we investigated left mesial temporal lobe epilepsy (MTLE) related function connectivity (FC) changes of NAc subregions using resting-state functional magnetic resonance imaging. We calculated functional connectivity from two NAc subregions to both whole brain and 16 related targets. Two-sample t-test (Alphasim multiple comparisons corrected) was performed to identify the effect of the disease on each seed's whole brain network. Repeated-measures ANOVA and Post hoc pairwise t test (Bonferroni corrections) were performed to visualize the seed to target FC group differences in each subdivision. In whole brain FC networks, neither the left or right core show different FC changes. The left shell showed decreased FC with a cluster located around the right inferior frontal gyrus. The right shell portion showed increased FC with a cluster located around the left inferior temporal gyrus. The seed to targets results showed that the left shell of LTLE group exhibited lower FC with left posterior-parahippocampal gyrus and right caudate, putamen, thalamus, paracingulate gyrus but higher FC with right subcallosal cortex. The right core of LTLE group exhibited higher FC with right frontal pole and the right shell exhibited lower FC with left thalamus and left anterior-parahippocampal gyrus. This is the first study to investigate the functional connectivity changes of NAc subdivisions of epilepsy in vivo human brain. Our results showed that the left MTLE related FC changes on NAc are mainly on shell portion rather than core. The decrease FC between the left shell and right frontal area and the decrease FC between the right shell and left temporal area suggested they serve vital roles for MTLE.