Compensatory Brain Mechanisms Research Articles

Adaptive and Compensatory Neural Signatures in Fibromyalgia: An Analysis of Resting-State and Stimulus-Evoked EEG Oscillations.

This study aimed to investigate clinical and physiological predictors of brain oscillatory activity in patients with fibromyalgia (FM), assessing resting-state power, event-related desynchronization (ERD), and event-related synchronization (ERS) during tasks. We performed a cross-sectional analysis, including clinical and neurophysiological data from 78 subjects with FM. Multivariate regression models were built to explore predictors of electroencephalography bands. Our findings show a negative correlation between beta oscillations and pain intensity; fibromyalgia duration is positively associated with increased oscillatory power at low frequencies and in the beta band; ERS oscillations in the theta and alpha bands seem to be correlated with better symptoms of FM; fatigue has a signature in the alpha band-a positive relationship in resting-state and a negative relationship in ERS oscillations. Specific neural signatures lead to potential clusters of neural adaptation, in which beta oscillatory activity in the resting state represents a more adaptive activity when pain levels are low and stimulus-evoked oscillations at lower frequencies are likely brain compensatory mechanisms. These neurophysiological changes may help to understand the impact of long-term chronic pain in the central nervous system and the descending inhibitory system in fibromyalgia subjects.

P157 Neurocognitive insights: functional magnetic resonance imaging of spatial working memory and sustained attention in people with systemic lupus erythematous

Abstract Background/Aims Cognitive impairment (CI) is common in people with systemic lupus erythematosus (pwSLE). Treatment options are limited and the effects upon the brain is unclear. Differences in brain structure seen in SLE do not always associate with CI, however significant associations have been found with functional magnetic resonance imaging (fMRI). Using fMRI, this study aims to further explore potential compensatory brain mechanisms used in SLE that help with cognitive function. Methods Participants were recruited into one of two groups;pwSLE (meeting EULAR/ACR criteria) or healthy controls(HC). Demographic, clinical and psychiatric data and patient reported outcome measures were collected.Cognitive function was assessed using the ACR Neuropsychological Battery. Brain scans included two structural and two fMRI scans done during stage 1 and 2 of a cognitive task. Stage 1 of the task had an encoding, retention and working memory (WM) component. Stage 2 of the task examined long-term memory. Differences between task performances were examined using t-tests. The fMRI data was modelled using SPM12 to look for differences in blood-oxygen-level-dependent (BOLD) brain responses between the study groups during the different stages/components of the task. Results To-date 37 pwSLE and 10 HCs have been recruited. The median ages were 36 (HC) and 40 (pwSLE) years. From the pwSLE group the average disease duration was 15 years, the average SLEDAI-2K score was 5 and percentages of those on antimalarials, corticosteroids, and immunosuppressants and biologics were 66%, 32%, and 54%, respectively. There were no differences on task performance between the two groups. Greater BOLD responses were seen in the HC compared to the pwSLE group during stage 1 encoding and WM phases as well as during stage 2 (long-term memory). pwSLE had less attenuated BOLD signals during the stage 1 retention phase compared to HCs (Table 1). Conclusion We found altered brain responses to our cognitive task between pwSLE and HCs. Predominantly the HC group had greater BOLD responses in cognitive regions during the task compared to the pwSLE group. However, we did not find any difference between the two groups in regards to cognitive performance. This study is still ongoing and additional results are expected. Disclosure M. Barraclough: None. M. McCowen: None. S. McKie: None. A. Kafkas: None. B. Parker: None. J. Diaz-Martinez: None. A. Knight: None. K. Bingham: None. M. Li: None. J. Su: None. M. Kakvan: None. C. Munoz Grajales: None. M. Tartaglia: None. L. Ruttan: None. J. Wither: None. D. Bonilla: None. N. Anderson: None. D. Montaldi: None. R. Elliott: None. P. Katz: None. D. Beaton: None. R. Green: None. I. Bruce: None. Z. Touma: None.

Brain compensatory mechanisms in depression and memory complaints in fibromyalgia: the role of theta oscillatory activity.

The different clinical presentations of fibromyalgia syndrome (FMS) might play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in patients with FMS. Understanding how these clinical presentations are associated with the clinical and neurophysiological aspects of FMS is important for the development of effective treatments. To explore the relationship of memory complaints and depressive symptoms with the different clinical and neurophysiological characteristics of FMS. Cross-sectional data analysis from a randomized clinical trial. Baseline demographics and data on physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) from 63 subjects with FMS were used. Multiple linear and logistic association models were constructed. Final regression models including different sets of predictions were statistically significant (P < .001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poorer sleep quality, lower motor threshold, and higher relative theta power in the central area and were more likely to have clinical depression. Higher anxiety, pain, and theta power were associated with a higher likelihood of memory complaints. Depression symptoms seem to be associated with transcranial magnetic stimulation-indexed motor threshold and psychosocial variables, whereas memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms might be catalyzed or triggered by some behavioral and clinical features, such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests that the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment of FMS. ClinicalTrials.gov ID NCT03371225.

Resting-state electroencephalography delta and theta bands as compensatory oscillations in chronic neuropathic pain: a secondary data analysis.

Chronic neuropathic pain (CNP) remains a significant clinical challenge, with complex neurophysiological underpinnings that are not fully understood. Identifying specific neural oscillatory patterns related to pain perception and interference can enhance our understanding and management of CNP. To analyze resting electroencephalography data from individuals with chronic neuropathic pain to explore the possible neural signatures associated with pain intensity, pain interference, and specific neuropathic pain characteristics. We conducted a secondary analysis from a cross-sectional study using electroencephalography data from a previous study, and Brief Pain Inventory from 36 patients with chronic neuropathic pain. For statistical analysis, we modeled a linear or logistic regression by dependent variable for each model. As independent variables, we used electroencephalography data with such brain oscillations: as delta, theta, alpha, and beta, as well as the oscillations low alpha, high alpha, low beta, and high beta, for the central, frontal, and parietal regions. All models tested for confounding factors such as age and medication. There were no significant models for Pain interference in general activity, walking, work, relationships, sleep, and enjoyment of life. However, the model for pain intensity during the past four weeks showed decreased alpha oscillations, and increased delta and theta oscillations were associated with decreased levels of pain, especially in the central area. In terms of pain interference in mood, the model showed high oscillatory Alpha signals in the frontal and central regions correlated with mood impairment due to pain. Our models confirm recent findings proposing that lower oscillatory frequencies, likely related to subcortical pain sources, may be associated with brain compensatory mechanisms and thus may be associated with decreased pain levels. On the other hand, higher frequencies, including alpha oscillations, may disrupt top-down compensatory mechanisms.

Reorganization of functional brain networks in healthy aging and mild cognitive impairment during the visual motion discrimination task

AbstractBackgroundPreviously, we reported that there was significant decrease in spectral power for eyes‐closed resting state EEG (rsEEG) immediately following a visual motion discrimination task as compared to before task engagement in older adults – the so‐called Task Aftereffect (TA). Further, we have also shown that rsEEG TA differentiated between older adults with mild cognitive impairment (MCI) and healthy controls (HC), with the MCI participants showing more integrated topology in post‐ as compared to pre‐cognitive task rsEEG. We now report EEG topological changes during task performance with regards to: changes in functional network organization from the beginning to the end of the task and evidence for significant differences in topology between MCI patients and HC.MethodWe studied a sample of community dwelling African American older participants over age 60 years, with consensus‐based diagnosis for 51 HC and 39 MCI. EEG epochs extracted for analysis were two‐second epochs before the motion onset of each stimulus at the beginning, middle, and end of the full task. Functional connectivity between channels was assessed by the phase lag index. Minimum spanning tree (MST) was used to characterize network topology.ResultTime effect was confirmed, as network organization in all participants significantly improved with task progression. On average, brain topology became more integrated with higher leaf fraction and smaller average eccentricity. Moreover, our results show differences between groups in MST parameters over the whole task. Most differences were observed at the earliest timepoint at lower frequency range (theta and lower alpha) where average eccentricity was significantly decreased. Leaf fraction and maximal betweenness centrality were significantly increased in the MCI group as compared to HC.ConclusionThe change in network organization suggests that MCI require greater network integration across brain areas before repeated motion onset presentations. This could reflect compensatory brain mechanisms, especially as both groups did not show significant differences in task performance. These findings enhance our understanding of the functional brain network organization immediately prior to repeated responses in a visual perceptual task in MCI compared to HC. This emphasizes the potential for using graph‐theoretic measures as a valid tool for the early detection of cognitive impairment.

Xylazine effects on opioid-induced brain hypoxia.

Xylazine has emerged in recent years as an adulterant in an increasing number of opioid-positive overdose deaths in the United States. Although its exact role in opioid-induced overdose deaths is largely unknown, xylazine is known to depress vital functions and cause hypotension, bradycardia, hypothermia, and respiratory depression. In this study, we examined the brain-specific hypothermic and hypoxic effects of xylazine and its mixtures with fentanyl and heroin in freely moving rats. In the temperature experiment, we found that intravenous xylazine at low, human-relevant doses (0.33, 1.0, 3.0mg/kg) dose-dependently decreases locomotor activity and induces modest but prolonged brain and body hypothermia. In the electrochemical experiment, we found that xylazine at the same doses dose-dependently decreases nucleus accumbens oxygenation. In contrast to relatively weak and prolonged decreases induced by xylazine, intravenous fentanyl (20μg/kg) and heroin (600μg/kg) induce stronger biphasic brain oxygen responses, with the initial rapid and strong decrease, resulting from respiratory depression, followed by a slower, more prolonged increase reflecting a post-hypoxic compensatory phase, with fentanyl acting much quicker than heroin. The xylazine-fentanyl mixture eliminated the hyperoxic phase of oxygen response and prolonged brain hypoxia, suggesting xylazine-induced attenuation of the brain's compensatory mechanisms to counteract brain hypoxia. The xylazine-heroin mixture strongly potentiated the initial oxygen decrease, and the pattern lacked the hyperoxic portion of the biphasic oxygen response, suggesting more robust and prolonged brain hypoxia. These findings suggest that xylazine exacerbates the life-threatening effects of opioids, proposing worsened brain hypoxia as the mechanism contributing to xylazine-positive opioid-overdose deaths.

Compensatory Mechanisms in Early Alzheimer's Disease and Clinical Setting: The Need for Novel Neuropsychological Strategies.

Despite advances in the detection of biomarkers and in the design of drugs that can slow the progression of Alzheimer's disease (AD), the underlying primary mechanisms have not been elucidated. The diagnosis of AD has notably improved with the development of neuroimaging techniques and cerebrospinal fluid biomarkers which have provided new information not available in the past. Although the diagnosis has advanced, there is a consensus among experts that, when making the diagnosis in a specific patient, many years have probably passed since the onset of the underlying processes, and it is very likely that the biomarkers in use and their cutoffs do not reflect the true critical points for establishing the precise stage of the ongoing disease. In this context, frequent disparities between current biomarkers and cognitive and functional performance in clinical practice constitute a major drawback in translational neurology. To our knowledge, the In-Out-test is the only neuropsychological test developed with the idea that compensatory brain mechanisms exist in the early stages of AD, and whose positive effects on conventional tests performance can be reduced in assessing episodic memory in the context of a dual-task, through which the executive auxiliary networks are 'distracted', thus uncover the real memory deficit. Furthermore, as additional traits, age and formal education have no impact on the performance of the In-Out-test.

Improving fMRI in Parkinson’s disease by accounting for brain region-specific activity patterns

In functional magnetic imaging (fMRI) in Parkinson’s disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients’ tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure’s temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop’s structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

Changes in brain response to urgency before and after treatment of urgency urinary incontinence with onabotulinumtoxin A

To better understand the role of the brain in urgency urinary incontinence (UUI), we used onabotulinumtoxin A (BoNTA) as a probe to evaluate changes in the brain's response to urgency in successful and unsuccessful treatment. Because BoNTA acts peripherally, brain changes observed should represent a reaction to changes in bladder function caused by BoNTA, or changes in the brain's compensatory mechanisms, rather than a direct effect of BoNTA on the brain. We recruited 20 women aged over 60 years with nonneurogenic UUI who were to undergo treatment with onabotulinum A toxin injected intravesically. We performed a baseline evaluation which included a 3-day bladder diary and functional magnetic resonance imaging with an urgency provocation task; we repeated this evaluation 6 weeks posttreatment. We performed ananalysis of variance on a priori selected regions of interest and post hoc voxel-wise analysis on responders and nonresponders to treatment. We found a significant interaction in the right insula [F(1,18) = 5.5, p = 0.031]; activity was different during urgency provocation in responders and non-responders to therapy, before and after therapy. The supramarginal gyrus (SMG) and inferior frontal gyrus (IFG) also displayed significant interactions (p &lt; 0.005). Activity in the periaqueductal gray and prefrontal cortex was correlated with number of leakage episodes (p &lt; 0.05). The changes seen in the brain control mechanism after therapy likely reflect reduced bladder sensation caused by BoNTA's peripheral action. We ascribe the SMG and IFG changes to a coping mechanism for urgency which is reduced in those who respond well to treatment.

Brain mapping of emotional prosody in patients with drug-resistant temporal epilepsy: An indicator of plasticity

IntroductionEmotional prosody, a suprasegmental component of language, is predominantly processed by right temporo-frontal areas of the cerebral cortex. In temporal lobe epilepsy (TLE), brain disturbances affecting prosody processing frequently occur. This research assesses compensatory brain mechanisms of prosody processing in refractory TLE using fMRI. MethodsPatients with focal unilateral epilepsy, right (RTLE) (N = 19), left (LTLE) (N = 19), and healthy controls (CTRL) (N = 20) were evaluated during a prosody decoding fMRI task. The stimuli consisted in spoken numbers with different tones of voice (joy, fear, anger, neutral and silent trials). Participants were instructed to label the emotion with a keypad. “Joy” was removed from the analysis due to a high degree of variability. A lateralization index (LI) was used to see individual differences in the interhemispheric activations of each participant. ResultsBehaviorally, The LTLE and RTLE groups did not differ significantly from each other neither from CTRL. In Negative Emotions versus Baseline contrast, the whole sample analysis showed extensive activations in bilateral superior temporal gyrus, bilateral precentral and post–central gyrus, right putamen, and left cerebellar vermis. Compared to the LTLE and CTRL, RTLE activated similar areas, but to a lesser extent. The LI analysis revealed significant differences in hemispheric laterality of the temporal lobe and the parietal lobe between RTLE compared to LTLE and CTRL, being the RTLE group lateralized towards the left, unlike the other two groups. DiscussionThe LI indicated that, since the CTRL and the LTLE groups recruited putative prosodic regions, the RTLE lateralized prosody processing towards the left, recruiting contralateral nodes, homotopic to the putative areas of the prosody. Considering that the groups did not differ in prosody task performance, the findings suggest that, in the RTLE group, alternative brain nodes were recruited for the task, demonstrating plasticity.

Electrophysiology Echoes Brain Dynamics in Children and Adolescents With Tourette Syndrome-A Developmental Perspective.

The development of the complex clinical picture of motor and vocal tics in children and adolescents with Tourette syndrome (TS) must be paralleled by changes in the underlying pathophysiology. Electrophysiological methods such as EEG and event-related potentials (ERPs) are non-invasive, safe and easy to apply and thus seem to provide an adequate means to investigate brain dynamics during this brain maturational period. Also, electrophysiology is characterized by a high time resolution and can reflect motor, sensory and cognitive aspects as well as sleep behavior. Hence, this narrative review focuses on how electrophysiology echoes brain dynamics during development of youngsters with TS and might be useful for the treatment of tics. A comprehensive picture of developmental brain dynamics could be revealed showing that electrophysiological parameters evolve concurrently with clinical characteristics of TS. Specifically, evidence for a maturational delay of motor inhibition related to cortico-spinal hyper-excitability and brain mechanisms for its cognitive compensation could be shown. Moreover, deviant sleep parameters and probably a stronger perception-action binding were reported. For neuromodulatory treatments (e.g., neurofeedback; repetitive transcranial magnetic stimulation, rTMS/transcranial direct current stimulation, tDCS) targeting neuronal deficits and/or strengthening compensatory brain mechanisms, pilot studies support the possibility of positive effects regarding tic reduction. Finally, attention-deficit/hyperactivity disorder (ADHD), as a highly frequent co-existing disorder with TS, has to be considered when using and interpreting electrophysiological measures in TS. In conclusion, application of electrophysiology seems to be promising regarding clinical and research aspects in youngsters with TS.

The brain after COVID-19: Compensatory neurogenesis or persistent neuroinflammation?

Yiping Lu et al. [1] report increased grey matter volumes and changes in MRI-based measures of water diffusion in white matter in the brains of recovered COVID-19 patients three months after acute illness, compared to healthy controls. They propose that neurogenesis and hypertrophy caused volumetric enlargement, and pathway remyelination restricted diffusion in the patients. If valid, these explanations suggest vigorous and counter-intuitive compensatory brain mechanisms during recovery from COVID-19.

Brain compensatory mechanisms enhance the recovery in the Rasmussen encephalitis child patient: a case was followed for 16 years.

Brain compensatory mechanisms enhance the recovery in the Rasmussen encephalitis child patient: a case was followed for 16 years.

BRAIN FUNCTIONAL CONNECTIVITY IN OLDER ADULTS WITH MCI: DO FALLS MATTER?

Older adults with mild cognitive impairment (MCI) are at an elevated risk of falls. We conducted a pilot longitudinal observational study to examine the natural course of brain intrinsic functional connectivity (FC) and cognitive function changes in association to falling history in older adults with MCI. 15 MCI participants (mean age 75.9, range 67-86) included 10 non-fallers and 5 fallers (minimum two falls in the previous 12 months with one in the last 6 months) from Metro Vancouver, BC, Canada. At study entry and 1-year follow-up, participants completed brain scanning session of structural MRI and resting state (RS) functional MRI, the Montreal Cognitive Assessment (MoCA), and the Mini Mental State Examination (MMSE). Results indicated an interaction between time (baseline vs. follow-up) and falls history on RS-FC in individuals with MCI (p<0.001). At 1-year follow-up, MCI non-fallers showed increased FC between frontal, parietal and occipital cortex (from baseline R=0.141 to follow-up R=0.321) and lack of decline on cognitive measures. Meanwhile, MCI fallers showed weakening of FC between those brain regions (from baseline R=0.314 to follow-up R=0.201) with simultaneous cognitive deterioration. Significant relationships between FC strength and cognitive status existed only at follow-up (R=0.525, p<0.05), suggesting that the triggered functional compensatory brain mechanisms in MCI non-fallers are not successfully executed in MCI fallers. Together, our pilot data suggest that older adults with MCI who fall show more advanced brain functional degradation with adjacent cognitive decline as compared to MCI individuals who do not fall.

Adult Mice Lacking Mct8 and Dio2 Proteins Present Alterations in Peripheral Thyroid Hormone Levels and Severe Brain and Motor Skill Impairments.

Background: Mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) lead to peripheral hyperthyroidism and profound psychomotor alterations in humans. Mice lacking Mct8 present peripheral hyperthyroidism but no gross neurological abnormalities due to brain compensatory mechanisms involving the enzyme deiodinase type 2 (Dio2). Methods: Here we have analyzed the endocrine and neurologic phenotype of mice lacking both Mct8 and Dio2 at three and six months of age. Thyroxine (T4) and 3,5,3' triiodothyronine (T3) levels/content were measured by specific radioimmunoassays; motor skill performance was evaluated by the footprint, rotarod, four limb hanging wire, and balance beam tests; and brain histological analysis was performed by immunostaining for neurofilament and parvalbumin. Results: We have found that this mouse model presents peripheral hyperthyroidism and brain hypothyroidism. Interestingly, the severity of the brain hypothyroidism seems permanent and varies across regions, with the striatum being a particularly affected area. We have also found brain alterations at the histological level compatible with TH deficiency and impaired motor skills. Conclusions: These findings indicate the potential of Mct8/Dio2-deficient mice to represent a model for human MCT8 deficiency, to understand the mechanisms underlying its pathophysiology, and ultimately design therapeutic interventions for human patients.

Dissociative changes in gray matter volume following electroconvulsive therapy in major depressive disorder: a longitudinal structural magnetic resonance imaging study.

Electroconvulsive therapy (ECT), has become a widely applied potent treatment in clinical practice for major depressive disorder (MDD) over decades. However, due to its nonspecific and spatially unfocused nature, the underlying mechanisms of ECT remain unclear. In this longitudinal study, 11 patients with MDD underwent magnetic resonance imaging (MRI) before and after ECT at three different time points. A longitudinal voxel-based morphology approach was performed to characterize dynamic changes in brain gray matter volume (GMV). Twelve age- and sex-matched healthy controls were recruited to identify structural brain changes of patients with MDD before and after ECT. The brain GMV was globally found to increase shortly after a series of ECT, and then decrease 1month after ECT treatment exposure. This fluctuating tendency was localized to the bilateral inferior parietal lobes, bilateral insula, and right superior temporal cortex. After the global GMV was corrected, there were only significant global effect increases in GMV in the left anterior hippocampus and right caudate, which were both significantly correlated with the improvement of depression symptoms. However, 1month after ECT treatments, there was still significantly reduced GMV following patients with MDD compared to healthy controls in the left putamen, right anterior cingulate, and left inferior temporal cortex, which was observed before ECT. These findings indicate that ECT in patients with MDD is closely associated with dissociative structural changes. The locally enhanced GMV in limbic areas may reflect that the ECT-related brain compensatory mechanisms contribute to brain structure recovery in MDD.

Influences of age, mental workload, and flight experience on cognitive performance and prefrontal activity in private pilots: a fNIRS study

The effects of aging on cognitive performance must be better understood, especially to protect older individuals who are engaged in risky activities (e.g. aviation). Current literature on executive functions suggests that brain compensatory mechanisms may counter cognitive deterioration due to aging, at least up to certain task load levels. The present study assesses this hypothesis in private pilots engaged in two executive tasks from the standardized CANTAB battery, namely Spatial Working Memory (SWM) and One Touch Stockings of Cambridge (OTS). Sixty-one pilots from three age groups (young, middle-aged, older) performed these two tasks from low to very high difficulty levels, beyond those reported in previous aging studies. A fNIRS headband measured changes in oxyhemoglobin (HbO2) in the prefrontal cortex. Results confirmed an overall effect of the difficulty level in the three age groups, with a decline in task performance and an increase in prefrontal HbO2 signal. Performance of older relative to younger pilots was impaired in both tasks, with the greatest impairment observed for the highest-load Spatial Working Memory task. Consistent with this behavioral deficit in older pilots, a plateau of prefrontal activity was observed at this highest-load level, suggesting that a ceiling in neural resources was reached. When behavioral performance was either equivalent between age groups or only slightly impaired in the older group, there were not any age-related differences in prefrontal activity. Finally, older pilots with extensive flying experience tend to show better preserved spatial working memory performance when compared to mildly-experienced of the same age group. The present findings are discussed in the frames of HAROLD and CRUNCH theoretical models of cognitive and neural aging, evoking the possibility that piloting expertise may contribute to preserve executive functions throughout adulthood.

THE USE OF MULTIMODAL MRI AND COMPUTATIONAL APPROACHES TO INFORM NOVEL INTERVENTIONS FOR AGING AND MOOD DISORDERS: Session 102

Advances in neuroimaging methods and computational approaches provide an unprecedented opportunity to advance our understanding of the role of specific brain networks involved in cognitive and affective expressions of normal aging, major depression and bipolar disorder. In addition, these sophisticated neuroscience approaches can provide distinct targets for novel interventions for cognitive and affective symptoms. This session will present the results of state-of-the-art neuroimaging and computational approaches in normal aging, late-life major depression, and middle-aged and older adults suffering from bipolar disorder. First, Dr. Wang will present results using a novel analytic approach to combine structural and functional MRI data to measure compensatory mechanisms in older adults. In addition, she will relate this measure of brain compensatory mechanisms to exercise. Second, Dr. Victoria will use computational modeling of performance data and task-based fMRI data from a reversal learning task to parse the role of affective salience and reward functions in older adults and older adults with late-life depression. Third, Dr. Gunning will present data using a novel computational approach that is reliant on machine learning of resting state fMRI scans to classify older adults with into neurobiologically-defined subtypes of depression. Next, Dr. Blumberg will present data from multimodal MRI collected in older adults suffering from bipolar disorder and show abnormalities in systems involved in emotion regulation including gray and white matter decreases in ventral prefrontal cortex and in the white matter connections to the amygdala. The session will conclude with a discussion that integrates the findings from the four speakers with a focus on specific ways these approaches can inform novel interventions targeting specific brain network functions to improve cognitive and mood symptoms in older adults.

Unfavourable gender effect of high body mass index on brain metabolism and connectivity

The influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer’s Dementia (AD) (n = 206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by 18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (R = 0.269, p = 0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (p < 0.05 FDR-corrected, k = 100 voxels). This suggests a major vulnerability of neural systems known to be selectively involved in brain compensatory mechanisms in AD females. These findings indicate a strong gender effect of high BMI and obesity in AD, namely reducing the available reserve mechanisms in female patients. This brings to considerations for medical practice and health policy.

S11. BRAIN ABNORMALITIES ASSOCIATED WITH DISEASE-SPECIFIC AND GENETIC RISK FACTORS FOR SCHIZOPHRENIA

BackgroundSchizophrenia is a severe disorder affecting approximately 1% of the population. The disorder is associated with symptoms such as false perceptions and beliefs and disturbances in affect and language production. In 2004 the total direct healthcare and non-healthcare cost in Canada was estimated at $2 billion, with an additional productivity loss estimated at $5 billion.MethodsI will present a program of research into disease-specific and genetic risk factors associated with structural and functional brain abnormalities, including morphology (amount of grey matter), structural connectivity (amount of white matter integrity), and brain functioning (amount of brain activity) in individuals with schizophrenia, their family members, and community controls using magnetic resonance imaging. As healthy relatives share genes with their affected family member, but do not share the disease process, abnormalities present in relatives are likely associated with the genes for schizophrenia.ResultsEvidence was found for disease-specific, genetic risk and compensatory brain mechanisms associated with schizophrenia that were complementary between the results from brain morphology, structural connectivity, and brain functioning.DiscussionIsolating the biological and genetic basis of these deficits could ultimately aid in developing novel psychosocial and pharmacological treatments to facilitate improved day-to-day functioning in schizophrenia.