The effect of early trauma on suicidal vulnerability depends on fronto-insular sulcation.

Improving our understanding of pathophysiology of suicidal behavior (SB) is an important step for prevention. Assessment of suicide risk is based on socio-demographic and clinical risk factors with a poor predictivity. Current understanding of SB is based on a stress-vulnerability model, whereby early-life adversities are predominant. SB may thus result from a cascade of developmental processes stemming from early-life abuse and/or neglect. Some cerebral abnormalities, particularly in fronto-limbic regions, might also provide vulnerability to develop maladaptive responses to stress, leading to SB. We hypothesized that SB is associated with interactions between early trauma and neurodevelopmental deviations of the frontal and insular cortices. We recruited 86 euthymic women, including 44 suicide attempters (history of depression and SB) and 42 affective controls (history of depression without SB). The early development of prefrontal cortex (PFC) and insula was inferred using 3D magnetic resonance imaging-derived regional sulcation indices, which are indirect markers of early neurodevelopment. The insula sulcation index was higher in emotional abused subjects; among those patients, PFC sulcation index was reduced in suicide attempters, but not in affective controls. Such findings provide evidence that SB likely traced back to early stages of brain development in interaction with later environmental factors experienced early in life.

Cerebral Vasoreactivity as an Indirect MRI Marker of White Matter Tracts Alterations in Multiple Sclerosis.

Patients with multiple sclerosis (MS) show a diffuse cerebral perfusion decrease, presumably related to multiple metabolism and vascular alterations. It is assumed that white matter fiber alterations cause a localized cerebral vasoreactivity (CVR) disruption through astrocytes metabolism alteration, leading to hypoperfusion. We proposed to (1) evaluate the CVR disruptions in MS, (2) in relation to white matter lesions and (3) compare CVR disruptions maps with standard imaging biomarkers. Thirty-five MS patients (10 progressive, 25 relapsing-remitting) and 22 controls underwent MRI with hypercapnic challenge, DTI imaging and neuropsychological assessment. Areas with disrupted CVR were assessed using a general linear model. Resulting maps were associated with clinical scores, compared between groups, and related to DTI metrics and white matter lesions. MS patients showed stronger disrupted CVR within supratentorial white matter, linking the left anterior insula to both the precentral gyrus and the right middle and superior frontal gyrus through the corpus callosum (P < 0.05, FWE corrected). Patient's verbal intellectual quotient was negatively associated with a pathway linking both hippocampi to the ispilateral prefrontal cortex (P < 0.05, FWE corrected). Disrupted CVR maps unrelated to DTI metrics and white matter lesions. We have demonstrated for the first time that white matter alterations can be indirectly identified through surrounding vessel alterations, and are related to clinical signs of MS. This offers a new, likely independent marker to monitor MS and supports a mediator role of the astrocytes in the fibers/vessels relationship.

Phase Contrast MRI Suggests an Internal Carotid Vascular Tone Alteration in Migraines.

INTRODUCTION: Migraine is the most common neurological disorder and the third most common disease worldwide. However, the underlying mechanisms contributing to its development are not completely understood. Symptoms may arise from a combination of dilation-independent vascular events and neurogenic mechanisms interacting throughout the brain and within the trigeminovascular system in the meninges MATERIALS AND METHOD: We report here a case of a patient with a suspected familial hemiplegic migraine who presented an increased recurrence of events from one per month to one every other day. Three magnetic resonance imaging (MRI) acquisitions were performed after the appearance of a strong crisis which included a paresthesia and aphasia along with headaches. Two MRIs were performed close to the crisis, while the last one was done 1 month later. RESULTS: During the crisis, cerebral perfusion exhibits incoherent results. Blood velocity measurements highlight a strong phase lag between left internal carotid artery (ICA) and basilar artery and more importantly right ICA. After a month, parameters came back to standard values. CONCLUSION: The transitory nature of the observed modifications suggests a reversible alteration of the vascular tone of the ICA in patients with migraine. This alteration seems to follow recovery pattern of the patient.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

OBJECTIVE: The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. METHODS: Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. RESULTS: Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. CONCLUSIONS: Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. KEY POINTS: • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

IDH mutation and 1p19q codeletion distinguish two radiological patterns of diffuse low-grade gliomas.

Diffuse low-grade gliomas (DLGG) prognosis is variable, depending on several factors, including the isocitrate dehydrogenase (IDH) mutation and the 1p19q codeletion. A few studies suggested associations between these parameters and tumor radiological characteristics including topography. Our aim was analyzing the correlations between the IDH and 1p19q statuses and the tumor intracerebral distribution (at the lobar and voxel levels), volume, and borders. We conducted a retrospective, monocentric study on a consecutive series of 198 DLGG patients. The IDH and 1p19q statuses were recorded. The pre-treatment magnetic resonance FLAIR imagings were reviewed for determination of lobar topography, tumor volume, and characterisation of tumor borders (sharp or indistinct). We conducted a voxel-based lesion-symptom mapping analysis to investigate the correlations between the IDH and 1p19q statuses and topography at the voxel level. The IDH mutation and 1p19q statuses were correlated with the tumor topography defined using lobar anatomy (p < 0.001 and p = 0.004, respectively). Frontal tumors were more frequently IDH-mutant (87.1 vs. 57.4%) and 1p19q codeleted (45.2 vs. 17.0%) than temporo-insular lesions. At the voxel level, these associations were not found. Tumors with sharp borders were more frequently IDH-mutant (p = 0.001) while tumors with indistinct borders were more frequently IDH wild-type and 1p19q non-codeleted (p < 0.001). Larger tumors at diagnosis (possibly linked to a slower growth rate) were more frequently IDH-mutant (p < 0.001). IDH wild-type, 1p19q non-codeleted temporo-insular tumors are distinct from IDH-mutant, 1p19q codeleted frontal tumors. Further studies are needed to determine whether the therapeutic strategy should be adapted to each pattern.

Validation of a quantitative susceptibility mapping acquisition and reconstruction pipeline using a new iron sucrose based MR susceptibility phantom.

PURPOSE: Quantitative susceptibility mapping is a new technique and its processing pipeline has to be validated before clinical practice. We described an easy to build magnetic resonance (MR) susceptibility phantom based on iron sucrose. MATERIALS AND METHODS: In a plastic container, Eppendorf tubes containing increasing iron sucrose concentration ranging from 0 to 60µg Fe/mL were inserted in an agarose gel. To estimate susceptibility, multiple coronal gradient echo acquisitions were performed with varying angle of the phantom relative to the B0 field, ranging from 30 to 90°. Quantitative susceptibility maps were reconstructed using the l1 and l2 norm of total variation using Split Bregman approach. Iron concentration was finally estimated from the susceptibility in the tubes. RESULTS: In l1norm susceptibility and estimated iron concentration were not different from the real values while l2norm underestimated the susceptibility. A correlation was found between the angle of the phantom and the difference between real and estimated iron concentrations. The results highlight the importance of this validation by emphasizing the effects of various reconstruction parameters as well as acquisition conditions. Using optimal parameters, the quantitative susceptibility mapping provides a very good estimation of the iron concentrations in the phantom.

Comparison between resting state fMRI networks and responsive cortical stimulations in glioma patients.

OBJECTIVES: To validate the functional relevance of resting state networks (RSNs) by means of a comparison of resting state connectivity (RSC) between language regions elicited by direct cortical stimulation versus RSC between random regions; and to evaluate the accuracy of resting state fMRI in surgical planning by assessing the overlap between RSNs and intraoperative functional mapping results. METHODS: Sensorimotor and language eloquent sites were identified by direct electrical cortical stimulation in 98 patients with a diffuse low-grade glioma. A seed to voxel analysis with inter-language stimulation point connectivity versus inter-random ROIs connectivity was performed (19 patients). An independant component analysis (ICA) was also applied to rsfMRI data. Language and sensorimotor components were selected over 20 independent components and compared to the corresponding stimulation points and resected cortex masks (31 and 90 patients, respectively). RESULTS: Mean connectivity value between language seeds was significantly higher than the one between random seeds (0.68 ± 0.39 and 0.12 ± 0.21 respectively, P < 10-10 ). 96 ± 11% of sensorimotor stimulation points were located within 10 mm from sensorimotor ICA maps versus 92 ± 21% for language. 3.1 and 15% of resected cortex overlapped sensorimotor and language networks, respectively. Mean sensorimotor stimulation points and resected cortex z-scores were 2.0 ± 1.2 and -0.050 ± 0.60, respectively (P < 10-10 ). Mean language stimulation points and resected cortex z-scores were 1.6 ± 1.9 and 0.68 ± 0.91, respectively, P < 0.005. CONCLUSION: The significantly higher RSC between language seeds than between random seeds validated the functional relevance of RSC. ICA partly succeeded to distinguish eloquent versus surgically removable areas and may be possibly used as a complementary tool to intraoperative mapping. Hum Brain Mapp 37:3721-3732, 2016. © 2016 Wiley Periodicals, Inc.

Working memory performance is related to intrinsic resting state functional connectivity changes in community-dwelling elderly cohort.

Characterization of normal age-related changes in resting state brain networks associated with working memory performance is a major prerequisite for studying neurodegenerative diseases. The aim of this study was to investigate the relationship between performing a working memory task (under MRI) and resting-state brain networks in a large cohort of healthy elderly subjects (n=337). Functional connectivity and interactions between networks were assessed within the default mode (DMN), salience (SN), and right and left central executive (CEN) networks in two groups of subjects classed by their performance (low and high). The low performance group showed lower functional connectivity in both the DMN and SN, and higher functional connectivity in the right and left CEN compared to the high performance group. Overall the functional connectivity within the DMN and the CEN were correlated. The lower functional connectivity within the DMN and SN in the low performance group is suggestive of altered attentional and memory processes and/or altered motivation. The higher functional connectivity within the CEN could be related to compensatory mechanisms, without which the subjects would have even lower performances. The correlation between the DMN and CEN suggests a modulation between the lower functional connectivity within the DMN and the higher functional connectivity within the CEN when performance is reduced. Finally, this study suggests that performance modifications in healthy elderly subjects are associated with reorganization of functional connectivity within the DMN, SN, and CEN.

Longitudinal Changes in Cerebellar and Thalamic Spontaneous Neuronal Activity After Wide-Awake Surgery of Brain Tumors: a Resting-State fMRI Study.

Hypometabolism has been observed in the contralesional cerebellar hemisphere after various supratentorial cortical lesions. It is unknown whether the consequences of the dee- and deafferentation subsequent to wide-awake surgery for brain diffuse low-grade glioma can be assessed within remote and unresected subcortical structures such as the cerebellum or thalamus. To answer this question, we have conducted several regional analyses. More specifically, we have performed amplitude of low-frequency fluctuations (neuronal activity magnitude) and regional homogeneity (local temporal correlations) analyses on resting state functional magnetic resonance imaging (rs-fMRI) data and at different time points, before and after surgery. Our main results demonstrated that it is possible to evaluate subtle subcortical changes using these tools dedicated to the analysis of rs-fMRI data. The observed variations of spontaneous neuronal activity were particularly significant within the cerebellum which showed altered regional homogeneity and neuronal activity intensity in very different, specialized and non-overlapping subregions, in accordance to its neuro-anatomo-functional topography. These variations were moreover observed in the immediate postoperative period and recovered after 3 months.

Working memory activation of neural networks in the elderly as a function of information processing phase and task complexity.

Changes in working memory are sensitive indicators of both normal and pathological brain aging and associated disability. The present study aims to further understanding of working memory in normal aging using a large cohort of healthy elderly in order to examine three separate phases of information processing in relation to changes in task load activation. Using covariance analysis, increasing and decreasing neural activation was observed on fMRI in response to a delayed item recognition task in 337 cognitively healthy elderly persons as part of the CRESCENDO (Cognitive REServe and Clinical ENDOphenotypes) study. During three phases of the task (stimulation, retention, probe), increased activation was observed with increasing task load in bilateral regions of the prefrontal cortex, parietal lobule, cingulate gyrus, insula and in deep gray matter nuclei, suggesting an involvement of central executive and salience networks. Decreased activation associated with increasing task load was observed during the stimulation phase, in bilateral temporal cortex, parietal lobule, cingulate gyrus and prefrontal cortex. This spatial distribution of decreased activation is suggestive of the default mode network. These findings support the hypothesis of an increased activation in salience and central executive networks and a decreased activation in default mode network concomitant to increasing task load.

Education modulates the impact of white matter lesions on the risk of mild cognitive impairment and dementia.

OBJECTIVES: Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia. METHODS: We followed 500 healthy subjects from a cohort of community-dwelling persons aged 65 years and over (ESPRIT Project). At baseline, WML volume was measured using a semi-automatic method on T2-weighted MRI. Standardized cognitive and neurological evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized according to education level into low (≤8 years) and high (>8 years) education groups. Cox proportional hazard models were constructed to study the association between WML and risk of MCI/dementia. RESULTS: The interaction between education level and WML volume reached significance (p = 0.017). After adjustment for potential confounders, the association between severe WML and increased MCI/dementia risk was significant in the low education group (≤8 years) (p = 0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). CONCLUSIONS: Severe WML significantly increases the risk of developing MCI/dementia over a 7-year period in low educated participants. Subjects with higher education levels were seen to be more likely to be resilient to the deleterious effects of severe WML. The CR hypothesis suggests several avenues for dementia prevention.

Safety and efficacy of transvenous embolization of cerebrospinal fluid-venous fistula in patients with spontaneous intracranial hypotension.

BACKGROUND: Transvenous embolization is a recent treatment strategy for cerebrospinal fluid-venous fistulas (CSFVF), which are associated with spontaneous intracranial hypotension (SIH). METHODS: Participants were selected from a prospective database on patients with CSFVF that received transvenous Onyx embolization. All patients underwent a brain magnetic resonance imaging (MRI) before and after embolization with MRI follow-up performed at least 3 months after treatment. Clinical and MRI results after treatment were described. RESULTS: Twenty-one consecutive patients (median age 63 years, IQR = 58-71; females: 15/21 = 71.5%) with 30 CSFVF were included. Most lesions were situated between T9 and L1 (19/30 = 63%), 70% were right-sided, and 38% of the patients had multiples fistulas. Embolization was successful in all cases. The mean MRI SIH score before and after treatment was 6 (±2.5) and 1.4 (±1.6), respectively (p < 0.0001). Twenty patients (90%) experienced improvement of their initial condition, of which 67% reported complete clinical recovery. The mean HIT-6 score decreased from 67 (±15) to 38 (±9) (p < 0.0001), the mean amount of monthly headache days from 23.5 (±10) and 3.2 (±6.6) (p < 0.0001), the visual assessment scale (VAS) for headache severity from 8 (±1.9) to 1.2 (±2) (p < 0.0001), and the mean VAS for perception quality of life improved from 2.6 (±2.5) to 8.6 (±1.8) (p < 0.0001). There were no major complications. The suspected rebound headache rate after treatment was 33%. CONCLUSION: Transvenous embolization of CSFVF allowed high rates of clinical improvement with no morbidity related to the treatment.

Functional PET Neuroimaging in Consciousness Evaluation: Study Protocol.

Ensuring a robust and reliable evaluation of coma deepness and prognostication of neurological outcome is challenging. We propose to develop PET neuroimaging as a new diagnostic and prognosis tool for comatose patients using a recently published methodology to perform functional PET (fPET). This exam permits the quantification of task-specific changes in neuronal metabolism in a single session. The aim of this protocol is to determine whether task-specific changes in glucose metabolism during the acute phase of coma are able to predict recovery at 18 months. Participation will be proposed for all patients coming for a standard PET-CT in our center in order to evaluate global cerebral metabolism during the comatose state. Legally appointed representative consent will be obtained to slightly modify the exam protocol: (1) 18F-fluorodeoxyglucose (18F-FDG) bolus plus continuous infusion instead of a simple bolus and (2) more time under camera to perform dynamic acquisition. Participants will undergo a 55-min fPET session with a 20% bolus + 80% infusion protocol. Two occurrences of three block (5-min rest, 10-min auditory stimulation and 10-min emotional auditory stimulation) will be performed after reaching equilibrium of FDG arterial concentration. We will compare the regional brain metabolism at rest and during the sessions of auditory and emotional auditory stimulation to search for a determinant of coma recovery (18 months of follow-up after the exam). Emotional auditory stimulation should induce an activation of: the auditory cortex, the consciousness areas and the neural circuitry for emotion (function to coma deepness). An activation analysis will be carried out to highlight regional brain activation using dedicated custom-made software based on Python statistical and image processing toolboxes. The association between activation levels and the Coma Recovery Scale-Revisited (CRS-R) will be assessed using multivariate analysis. If successful, the results from this study will help improve coma prognosis evaluation based on the pattern of neuronal metabolism at the onset of the pathology. The study protocol, rationale and methods are described in this paper.

Low levels of peripheral blood activated and senescent T cells characterize people with HIV-1-associated neurocognitive disorders.

Background: HIV infection induces a 75% increase in the risk of developing neurocognitive impairment (NCI), which has been linked to immune activation. We therefore looked for immune activation markers correlating with NCI. Method: Sixty-five people aged 55-70 years living with controlled HIV-1 infection were enrolled in the study and their neurocognitive ability was assessed according to the Frascati criteria. Fifty-nine markers of T4 cell, T8 cell, NK cell, and monocyte activation, inflammation and endothelial activation were measured in their peripheral blood. White matter hyperintensities (WMH) were identified by magnetic resonance imaging. Double hierarchical clustering was performed for the activation markers and 240 patients including the 65 whose neurocognitive performance had been evaluated. Results: Thirty-eight percent of volunteers presented NCI. Twenty-four percent of them were asymptomatic and fourteen percent had a mild disorder. Strikingly, activated (HLA-DR+) as well as senescent (CD57+CD28-CD27±) T4 cells and T8 cells were less prevalent in the peripheral blood of participants with NCI than in participants without the disorder. Accordingly, the percentage of HLA-DR+ T4 cells was lower in volunteers with periventricular and deep WMH. The double hierarchical clustering unveiled six different immune activation profiles. The neurocognitive performances of participants with two of these six profiles were poor. Here again, these two profiles were characterized by a low level of T4 and T8 cell activation and senescence. Conclusion: Our observation of low circulating levels of activated and senescent T cells in HIV-1 patients with NCI raises the interesting hypothesis that these lymphocytes may be recruited into the central nervous system.

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

OBJECTIVE: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. METHOD: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA-Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. RESULTS: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15-0.97; r range: 0.21-0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. CONCLUSIONS: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Perfusion-weighted MR imaging in persistent hemiplegic migraine.

INTRODUCTION: Hemiplegic migraine is a rare type of migraine that has an aura characterized by the presence of motor weakness, which may occasionally last up to several days, and then resolve without sequela. Pathogenesis of migraine remains unclear and, recently, perfusion-weighted imaging (PWI) has provided a non-invasive method to study hemodynamic changes during acute attacks. METHODS: Two female patients were admitted in our hospital suffering from prolonged hemiparesis. In both cases, they underwent MRI examination using a 1.5 T magnet including axial diffusion-weighted and perfusion sequences. From each perfusion MRI acquisition two regions of interest were delineated on each hemisphere and, the index of flow, cerebral blood volume, mean transit time, and time to peak were recorded and asymmetry indices from each perfusion parameter were calculated. RESULTS: Perfusion alterations were detected during the attacks. In one case, we observed, after 3 h of left hemiparesia, hypoperfusion of the right hemisphere. In the other case, who presented a familial hemiplegic migraine attack, on the third day of a persistent aura consisting of right hemiplegia and aphasia, PWI revealed hyperperfusion of the left hemisphere. Asymmetry indices for temporal parameters (mean transit time and time to peak) were the most sensitive. These findings resolved spontaneously after the attacks without any permanent sequel or signs of cerebral ischemia on follow-up MRI. CONCLUSIONS: PWI should be indicated for patients with migraine attacks accompanied by auras to assess the sequential changes in cerebral perfusion and to better understand its pathogenesis.

Effects of preventive interventions on neuroimaging biomarkers in subjects at-risk to develop Alzheimer's disease: A systematic review.

Alzheimer's Disease (AD) is a multifactorial and complex neurodegenerative disorder. Some modifiable risk factors have been associated with an increased risk of appearance of the disease and/or cognitive decline. Preventive clinical trials aiming at reducing one or combined risk factors have been implemented and their potential effects assessed on cognitive trajectories and on AD biomarkers. However, the effect of interventions on surrogate markers, in particular imaging biomarkers, remains poorly understood. We conducted a review of the literature and analyzed 43 interventional studies that included physical exercise, nutrition, cognitive training or multidomain interventions, and assessed various brain imaging biomarkers, to determine the effects of preventive interventions on imaging biomarkers for subjects at-risk to develop AD. Deciphering the global and regional brain effect of each and combined interventions will help to better understand the interplay relationship between multimodal interventions, cognition, surrogate brain markers, and to better design primary and secondary outcomes for future preventive clinical trials. Those studies were pondered using generally-admitted quality criteria to reveal that interventions may affect the brain of patients with cognitive impairment rather than those without cognitive impairment thus indicating that particular care should be taken when selecting individuals for interventions. Additionally, a majority of the studies concurred on the effect of the interventions and particularly onto the frontal brain areas.

Glucometabolic Changes Are Associated with Structural Gray Matter Alterations in Prodromal Dementia.

BACKGROUND: Glucometabolic changes, such as high glycemic load (GL) diet and insulin resistance (IR), are potential risk factor of Alzheimer's disease (AD). Yet, the effect of these factors on brain alterations that contribute to AD pathology has not been clearly demonstrated. OBJECTIVE: We aimed to assess the relationship of GL and IR with gray matter volumes involved in prodromal dementia. METHODS: GL and Triglyceride-Glucose (TyG) index, an IR surrogate marker, were calculated in 497 participants who underwent magnetic resonance imaging (MRI). The gray matter volumes most related to prodromal dementia/mild cognitive impairment (diagnosed in 18/158 participants during the 7-year follow-up) were identified using a data-driven machine learning algorithm. RESULTS: Higher GL diet was associated with reduced amygdala volume. The TyG index was negatively associated with the hippocampus, amygdala, and putamen volumes. CONCLUSION: These results suggest that GL and IR are associated with lower gray matter volumes in brain regions involved in AD pathology.

Impact of multidomain preventive strategies on functional brain connectivity in older adults with cognitive complaint: Subset from the Montpellier center of the ancillary MAPT-MRI study.

Introduction: The impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC). Methods: To determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints. Results: No global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden. Discussion: These results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Task- and Rest-based Functional Brain Connectivity in Food-related Reward Processes among Healthy Adolescents.

It is known that the nucleus accumbens, orbitofrontal cortex and insula play a role in food-related reward processes. Although their interconnectedness would be an ideal topic for understanding food intake mechanisms, it nevertheless remains unclear especially in adolescent. Therefore, this study aims to investigate the effect of hunger on functional connectivity in healthy adolescents using task- and rest-based imaging. Fifteen participants underwent two MRI sessions, pre-lunch (hunger) and post-lunch (satiety), including food cue task and resting-state. During task- and rest-based imaging, functional connectivity was greater when hungry as opposed to satiated between the right posterior insula/nucleus accumbens, suggesting involvement of salient interoceptive stimuli signals. During task-based imaging, an increase was observed in functional connectivity when hungry as opposed to satiated between the medial and lateral orbitofrontal cortex which contributes to the perception of food deprivation as a frustration. A decrease was identified when hungry as opposed to satiated in functional connectivity in the right anterior orbitofrontal/accumbens and posterior insula/medial orbitofrontal cortices reflecting suppression of the affective and sensorial information. Conversely, functional connectivity was increased during aversive stimuli between the right medial orbitofrontal cortex and right posterior insula when hungry as opposed to satiated. This suggests that the value of valence could occur in the shift in connectivity between these two regions. In addition, during rest-based imaging, a left-sided lateralization was reported (accumbens/lateral orbitofrontal and accumbens/posterior insula) when hungry as opposed to satiated which may represent changes in internal state due to focus on the benefit of an upcoming meal.