Dependent Functional Magnetic Resonance Imaging Research Articles

Considerations for implanting speech brain computer interfaces based on functional magnetic resonance imaging

Objective. Brain-computer interfaces (BCIs) have the potential to reinstate lost communication faculties. Results from speech decoding studies indicate that a usable speech BCI based on activity in the sensorimotor cortex (SMC) can be achieved using subdurally implanted electrodes. However, the optimal characteristics for a successful speech implant are largely unknown. We address this topic in a high field blood oxygenation level dependent functional magnetic resonance imaging (fMRI) study, by assessing the decodability of spoken words as a function of hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal-axis. Approach. Twelve subjects conducted a 7T fMRI experiment in which they pronounced 6 different pseudo-words over 6 runs. We divided the SMC by hemisphere, gyrus, sulcal depth, and position along the ventral/dorsal axis. Classification was performed on in these SMC areas using multiclass support vector machine (SVM). Main results. Significant classification was possible from the SMC, but no preference for the left or right hemisphere, nor for the precentral or postcentral gyrus for optimal word classification was detected. Classification while using information from the cortical surface was slightly better than when using information from deep in the central sulcus and was highest within the ventral 50% of SMC. Confusion matrices where highly similar across the entire SMC. An SVM-searchlight analysis revealed significant classification in the superior temporal gyrus and left planum temporale in addition to the SMC. Significance. The current results support a unilateral implant using surface electrodes, covering the ventral 50% of the SMC. The added value of depth electrodes is unclear. We did not observe evidence for variations in the qualitative nature of information across SMC. The current results need to be confirmed in paralyzed patients performing attempted speech.

300 Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: An fMRI pilot study

OBJECTIVES/GOALS: This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). METHODS/STUDY POPULATION: Participants were recruited from a phase II, randomized, double-blind, placebo-controlled clinical trial investigating psilocybin-assisted therapy (PAT) for the treatment of AUD (NCT02061293). Eleven adult patients completed task-based blood oxygen dependent functional magnetic resonance imaging (fMRI) approximately 3 days before and 2 days after receiving 25 mg of psilocybin (n = 5) or 50 mg of diphenhydramine (n = 6). Visual alcohol and emotionally valanced (positive, negative, or neutral) stimuli were presented in block design. RESULTS/ANTICIPATED RESULTS: Across both alcohol and emotional cues, psilocybin increased activity in the medial and lateral prefrontal cortex (PFC) and left caudate, and decreased activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. Unique to negative cues, psilocybin increased supramarginal gyrus activity; unique to positive cues, psilocybin increased right hippocampus activity and decreased left hippocampus activity. DISCUSSION/SIGNIFICANCE: Greater PFC and caudate engagement and concomitant insula, motor, and cerebellar disengagement suggests enhanced goal-directed action, improved emotional regulation, and diminished craving. The robust changes in brain activity observed in this pilot study warrant larger neuroimaging studies to elucidate neural mechanisms of PAT.

Psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder: an fMRI pilot study

This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants were recruited from a phase II, randomized, double-blind, placebo-controlled clinical trial investigating psilocybin-assisted therapy (PAT) for the treatment of AUD (NCT02061293). Eleven adult patients completed task-based blood oxygen dependent functional magnetic resonance imaging (fMRI) approximately 3 days before and 2 days after receiving 25 mg of psilocybin (n = 5) or 50 mg of diphenhydramine (n = 6). Visual alcohol and emotionally valanced (positive, negative, or neutral) stimuli were presented in block design. Across both alcohol and emotional cues, psilocybin increased activity in the medial and lateral prefrontal cortex (PFC) and left caudate, and decreased activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. Unique to negative cues, psilocybin increased supramarginal gyrus activity; unique to positive cues, psilocybin increased right hippocampus activity and decreased left hippocampus activity. Greater PFC and caudate engagement and concomitant insula, motor, and cerebellar disengagement suggests enhanced goal-directed action, improved emotional regulation, and diminished craving. The robust changes in brain activity observed in this pilot study warrant larger neuroimaging studies to elucidate neural mechanisms of PAT.Trial registration: NCT02061293.

Atopic dermatitis and stress: A functional magnetic resonance imaging study of female patients with atopic dermatitis using an arithmetic task

AbstractBackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by eczematous lesions, dry skin and persistent itch. AD may worsen due to psychological stress. However, little is known about the neural correlates that mediate the interaction between psychological stress and AD.ObjectivesTo identify the possible difference in brain activation during arithmetic‐task induced stress in patients with AD versus healthy controls (HC) as well as the link between the brain response and clinical and psychodemographic parameters.MethodsA cohort of 29 AD female patients and 23 matched HC were recruited to investigate the potential difference in functional magnetic resonance imaging (fMRI) response to a block‐designed arithmetic paradigm. Both the HC and AD subjects were evaluated regarding their psychological traits, and for the AD subjects also their clinical characteristics, including stress indicators such as heart rate and salivary cortisol. We employed both univariate and multivariate statistical methods to analyse the blood oxygen level dependent (BOLD) fMRI response of the subjects to the block‐designed arithmetic paradigm.Results(1) Compared with HC subjects, the AD patients depict less deactivation in the default mode network including right angular gyrus, bilateral temporal pole and temporal lobe in response to the arithmetic task. (2) The BOLD fMRI response amplitude in the right postcentral gyrus and inferior parietal lobule is positively correlated with the stress susceptibility scores in the AD subjects, whereas the trend was the opposite of this for the HC subjects. (3) The activation in the postcentral gyrus also shows a correlation with the degree of itch in the AD patients.ConclusionsThe BOLD fMRI measurements based on an arithmetic paradigm can provide useful insight into altered brain processing and its association with psychological traits and clinical characteristics in subjects with AD. Psychological stress exacerbates brain activities for the AD subjects in the motor, somatosensory association cortex, perception and sensory integration processing. The postcentral gyrus might be of particular interest for itch and stress.

Adaptive smoothing of retinotopic maps based on Teichmüller parametrization

Retinotopic mapping, the mapping between visual inputs on the retina and neural responses on the cortical surface, is one of the fundamental topics in visual neuroscience. In human studies, retinotopic maps are conventionally constructed and processed by decoding blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to designed visual stimuli on the cortical surface. However, these methods frequently generate retinotopic maps that do not preserve topology, contradicting a fundamental property of retinotopic maps observed in neurophysiology. To address this problem, we propose an integrated approach to simultaneously refine the flattening from the 3D cortical surface to the 2D parametric space and adaptively smooth retinotopic perception centers in the visual space to make the retinotopic maps topological. One key element of the approach is the enhanced error tolerant Teichmüller mapping, which refines the parametrization by minimizing angle distortions and maximizing alignment to noisy landmarks. We validated our overall approach with synthetic and real retinotopic mapping datasets and applied it to compute cortical magnification factor (CMF). The results showed that the proposed approach was superior to other conventional retinotopic mapping methods in predicting BOLD fMRI time series and preserving topology.

Generalized Calibrated BOLD fMRI for the Relationship between Cerebral Metabolism and Hypertensive Status

AbstractBackgroundElevated blood pressure levels during mid‐life have been found to be associated with an increased susceptibility to developing dementia later in life, particularly vascular dementia. Quantitative imaging biomarkers, such as Oxygen Extraction Fraction (OEF) and Cerebral Metabolism Rate of Oxygen (CMRO2), can be indicators of impaired cerebral metabolism. Calibrated Blood Oxygen Level Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) is a multi‐parametric approach utilizing hyperoxic and hypercapnic gas challenges (Figure 1). The impact of hypertension on OEF and CMRO2 has been investigated.MethodA cohort of 84 participants was recruited from the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core (Table 1). Among all the covariates, participants with prediabetes and diabetes were considered diabetic, and those who exhibited high blood pressure or were using medication to manage hypertension were classified as hypertensive. The MRI was conducted using a 3T Siemens Skyra MRI scanner with a 32‐channel head coil. Dynamic Pseudocontinuous Arterial Spin Labeling (PCASL) was used to acquire cerebral blood flow (CBF) and BOLD images during respiratory challenges with an end‐tidal forcing system. The ROI values in the frontal lobe, temporal lobe, parietal lobe, and occipital lobe regions were chosen. The correlation between hypertensive status and OEF and CMRO2 in the ROI was analyzed with a linear mixed model, with covariates of age, sex, cognitive status, APOE genotype, diabetic status, and hypertensive status.ResultA negative correlation was found between CBF, OEF, and CMRO2 with hypertensive status in frontal lobe region (Figure 2). Statistical significance was observed for OEF and CMRO2 (p = 0.049 and p = 0.028, respectively), indicating the potential influence of hypertensive status on these biomarkers.ConclusionThe study concludes that there is a significant negative association between hypertensive status and both OEF and CMRO2, particularly in the frontal lobe region. The observed reduction in OEF and CMRO2 is not solely due to decreased CBF, but rather complex and multifactorial processes involving vascular remodeling and altered oxygen metabolism. Additional research is necessary to fully understand the underlying pathophysiological mechanisms that link hypertension to decreased OEF and CMRO2, particularly in the context of regional specificity.

Assessment of brainstem function and haemodynamics by MRI: challenges and clinical prospects.

MRI offers techniques for non-invasively measuring a range of aspects of brain tissue function. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used to assess neural activity, based on the brain's haemodynamic response, while arterial spin labelling (ASL) MRI is a non-invasive method of quantitatively mapping cerebral perfusion. Both techniques can be applied to measure cerebrovascular reactivity (CVR), an important marker of the health of the cerebrovascular system. BOLD, ASL and CVR have been applied to study a variety of disease processes and are already used in certain clinical circumstances. The brainstem is a critical component of the central nervous system and is implicated in a variety of disease processes. However, its function is difficult to study using MRI because of its small size and susceptibility to physiological noise. In this article, we review the physical and biological underpinnings of BOLD and ASL and their application to measure CVR, discuss the challenges associated with applying them to the brainstem and the opportunities for brainstem MRI in the research and clinical settings. With further optimisation, functional MRI techniques could feasibly be used to assess brainstem haemodynamics and neural activity in the clinical setting.

Is the Brainstem Activation Different Between Healthy Young Male and Female Volunteers at Initiation of Voiding? A High Definition 7-Tesla Magnetic Resonance Imaging Study.

Assessing brainstem function in humans through typical neuroimaging modalities has been challenging. Our objective was to evaluate brain and brainstem activation patterns during initiation of voiding in healthy males and females utilizing a 7 Tesla magnetic resonance imaging (MRI) scanner and a noninvasive brain-bladder functional MRI (fMRI) protocol. Twenty healthy adult volunteers (10 males and 10 females) with no history of urinary symptoms were recruited. Each volunteer underwent a clinic uroflow and postvoid residual assessment and was asked to consume water prior to entering the scanner. Anatomical and diffusion tensor images were obtained first, followed by a blood oxygenation level dependent (BOLD) resting-state fMRI (rs-fMRI) during the empty bladder. Subjects indicated when they felt the urge to void, and a full bladder rs-fMRI was obtained. Once completed, the subjects began 5 voiding cycles, where the first 7.5 seconds of each voiding cycle was identified as "initiation of voiding." BOLD activation maps were generated, and regions of interests with a t-value greater than 2.1 were deemed statistically significant. We present 5 distinct regions within the periaqueductal gray (PAG) and pontine micturition center (PMC) with statistically significant activation associated with an initiation of voiding in both men and women, 3 within the PAG and 2 within the PMC. Several additional areas in the brain also demonstrated activation as well. When comparing males to females, there was an overall lower BOLD activation seen in females throughout all regions, with the exception of the caudate lobe. Our study effectively defines regions within the PAG and PMC involved in initiation of voiding in healthy volunteers. To our knowledge, this is the first study investigating differences between male and female brainstem activation utilizing an ultra-high definition 7T MRI.

Enhanced activity of the left precuneus as a predictor of visuospatial dysfunction correlates with disease activity in rheumatoid arthritis

ObjectiveTo identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and assess the relation between visuospatial dysfunction and disease activity in RA patients using mental rotation task (MRT)-based functional magnetic resonance imaging (fMRI).MethodsA total of 27 RA patients (11 in remission, 16 in active) and 27 well-matched controls were enrolled. The visuospatial function of the subjects was measured by MRT. Brain activity data were collected using blood oxygen level dependent fMRI technique under MRT. Disease activity score 28 (DAS28) was used to evaluate the disease severity of RA patients. An analysis of the correlations between abnormal visuospatial-related brain regions, MRT performance, and DAS28 was conducted.ResultsRA patients performed worse on MRT than controls. Compared to the control group, RA patients showed enhanced activation in the left precuneus, left superior frontal gyrus and right cingulate gyrus during the rotation task, with left hemisphere dominance. RA patients in active showed enhanced activation in the left precuneus, left middle frontal gyrus and right cingulate gyrus compared to the patients in remission. The left precuneus activation was negatively correlated with MRT accuracy (r = −0.621, p = 0.01) and positively correlated with DAS28 (r = 0.710, p = 0.002), and MRT accuracy was negatively correlated with DAS28 in RA patients (r = −0.702, p = 0.002).ConclusionEnhanced activation of the left precuneus in RA patients affects visuospatial function and is closely related to disease activity. These changes may provide a valuable diagnostic neuroimaging biomarker of RA.

Functional Network of Neurocognitive Development in Correlations of BOLD Signals

Blood Oxygen Level Dependent (BOLD) fMRI is widely used for non-invasive brain mapping and neuroimaging. Despite the challenges, significant advancements have been made in empirically explaining several (BOLD) signal features. Before applying functional connectivity measures to assess the (BOLD) signal, preprocessing is required. Different stimuli produced by a regular periodic oscillation pulse and propagation loops were applied to generate the (BOLD) signal. The fundamentals of the brain and cognitive development are being highlighted through functional connectivity in a unique approach. In this work, we present an approach that analyzes variations in (BOLD) connectivity over time. Our approach emphasizes the temporal or spatial aspects however, simultaneous co-activation events may trigger (BOLD). Our findings show the measures to assess Functional Connectivity (FC) through Pearson’s correlation to describe FC. (BOLD) responses are used in a voxel-wise linear model with an estimation of the maximum likelihood to get the regressors’ correlated components.

Hyperlocal Spatial Flows in BOLD fMRI Expose Novel Brain-Based Correlates of Schizophrenia.

While analysis of temporal signal fluctuations has long been a fixture of blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) research, the role of spatially localized directional diffusion in both signal propagation and emergent large-scale functional integration remains almost entirely neglected. We are proposing an extensible framework to capture and analyze spatially localized fMRI directional signal flow dynamics. The approach is validated in a large resting-state fMRI schizophrenia study where it uncovers significant and novel relationships between hyperlocal spatial dynamics and subject diagnostic status.

Evaluation of T2-prepared blood oxygenation level dependent functional magnetic resonance imaging with an event-related task: Hemodynamic response function and reproducibility.

T2-prepared (T2prep) blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an alternative fMRI approach developed to mitigate the susceptibility artifacts that are typically observed in brain regions near air-filled cavities, bleeding and calcification, and metallic objects in echo-planar-imaging (EPI) based fMRI images. Here, T2prep BOLD fMRI was evaluated in an event-related paradigm for the first time. Functional experiments were performed using gradient-echo (GRE) EPI, spin-echo (SE) EPI, and T2prep BOLD fMRI during an event-related visual task in 10 healthy human subjects. Each fMRI method was performed with a low (3.4 × 3.4 × 4 mm3) and a high (1.5 mm isotropic) spatial resolution on 3T and a high resolution (1.5 mm isotropic) on 7T. Robust activation were detected in the visual cortex with all three fMRI methods. In each group of fMRI scans (3T low resolution, 3T high resolution, and 7T high resolution), GRE EPI showed the highest signal change (ΔS/S), largest full-width-at-half-maximum (FWHM) and longest time-to-peak (TTP) extracted from the hemodynamic response functions (HRF), indicating substantial signal contribution from large draining veins which have longer response times than microvessels. In contrast, T2prep BOLD showed the lowest ΔS/S, smallest FWHM, and shortest TTP, suggesting that T2prep BOLD may have a purer T2-weighted BOLD contrast that is more sensitive to microvessels compared to GRE/SE EPI BOLD. This trend was more obvious in fMRI scans performed with a lower spatial resolution on a lower field (3T with a 3.4 × 3.4 × 4 mm3 voxel). Scan-rescan reproducibility in the same subjects was comparable among the three fMRI methods. The results from the current study are expected to be useful to establish T2prep BOLD as a useful alternative fMRI approach for event-related fMRI in brain regions with large susceptibility artifacts.

Using carpet plots to analyze blood transit times in the brain during hypercapnic challenge magnetic resonance imaging.

Blood arrival time and blood transit time are useful metrics in characterizing hemodynamic behaviors in the brain. Functional magnetic resonance imaging in combination with a hypercapnic challenge has been proposed as a non-invasive imaging tool to determine blood arrival time and replace dynamic susceptibility contrast (DSC) magnetic resonance imaging, a current gold-standard imaging tool with the downsides of invasiveness and limited repeatability. Using a hypercapnic challenge, blood arrival times can be computed by cross-correlating the administered CO2 signal with the fMRI signal, which increases during elevated CO2 due to vasodilation. However, whole-brain transit times derived from this method can be significantly longer than the known cerebral transit time for healthy subjects (nearing 20s vs. the expected 5-6s). To address this unrealistic measurement, we here propose a novel carpet plot-based method to compute improved blood transit times derived from hypercapnic blood oxygen level dependent fMRI, demonstrating that the method reduces estimated blood transit times to an average of 5.32s. We also investigate the use of hypercapnic fMRI with cross-correlation to compute the venous blood arrival times in healthy subjects and compare the computed delay maps with DSC-MRI time to peak maps using the structural similarity index measure (SSIM). The strongest delay differences between the two methods, indicated by low structural similarity index measure, were found in areas of deep white matter and the periventricular region. SSIM measures throughout the remainder of the brain reflected a similar arrival sequence derived from the two methods despite the exaggerated spread of voxel delays computed using CO2 fMRI.

Cerebral neurovascular alterations in stable chronic obstructive pulmonary disease: a preliminary fMRI study.

Cognitive impairment (CI) is very common in patients with chronic obstructive pulmonary disease (COPD). Cerebral structural and functional abnormalities have been reported in cognitively impaired patients with COPD, and the neurovascular coupling changes are rarely investigated. To address this issue, arterial spin labeling (ASL) and resting-state blood oxygenation level dependent (BOLD) fMRI techniques were used to determine whether any neurovascular changes in COPD patients. Forty-five stable COPD patients and forty gender- and age-matched healthy controls were recruited. Furthermore, resting-state BOLD fMRI and ASL were acquired to calculate degree centrality (DC) and cerebral blood flow (CBF) respectively. The CBF-DC coupling and CBF/DC ratio were compared between the two groups. COPD patients showed abnormal CBF, DC and CBF/DC ratio in several regions. Moreover, lower CBF/DC ratio in the left lingual gyrus negatively correlated with naming scores, lower CBF/DC ratio in medial frontal cortex/temporal gyrus positively correlated with the Montreal Cognitive Assessment (MoCA), visuospatial/executive and delayed recall scores. These findings may provide new potential insights into neuropathogenesis of cognition decline in stable COPD patients.

The many layers of BOLD. The effect of hypercapnic and hyperoxic stimuli on macro- and micro-vascular compartments quantified by CVR, M, and CBV across cortical depth

Ultra-high field functional magnetic resonance imaging (fMRI) offers the spatial resolution to measure neuronal activity at the scale of cortical layers. However, cortical depth dependent vascularization differences, such as a higher prevalence of macro-vascular compartments near the pial surface, have a confounding effect on depth-resolved blood-oxygen-level dependent (BOLD) fMRI signals. In the current study, we use hypercapnic and hyperoxic breathing conditions to quantify the influence of all venous vascular and micro-vascular compartments on laminar BOLD fMRI, as measured with gradient-echo (GE) and spin-echo (SE) scan sequences, respectively. We find that all venous vascular and micro-vascular compartments are capable of comparable theoretical maximum signal intensities, as represented by the M-value parameter. However, the capacity for vessel dilation, as reflected by the cerebrovascular reactivity (CVR), is approximately two and a half times larger for all venous vascular compartments combined compared to the micro-vasculature at superficial layers. Finally, there is roughly a 35% difference in estimates of CBV changes between all venous vascular and micro-vascular compartments, although this relative difference was approximately uniform across cortical depth. Thus, our results suggest that fMRI BOLD signal differences across cortical depth are likely caused by differences in dilation properties between macro- and micro-vascular compartments.

Recognition and Processing of Visual Information after Neuronavigated Transcranial Magnetic Stimulation Session

Background: Transcranial magnetic stimulation (TMS) is a method of noninvasive and painless stimulation of the nervous system, which is based on Faraday’s law of electromagnetic induction. Over the past twenty years, the TMS technique has been deployed as a tool for the diagnosis and therapy of neurodegenerative diseases, as well as in the treatment of mental disorders (e.g., depression). Methods: We tested the inhibitory effects of repetitive TMS (rTMS) on reaction times to militarily relevant visual stimuli amidst distractors and on accompanying blood oxygenation level dependent (BOLD) signal functional magnetic resonance imaging (fMRI) in 20 healthy people. rTMS was applied over the visual cortices, V1, on both hemispheres with the inhibitory theta burst paradigm with the intensity of 70% of the active motor threshold fMRI in 20 healthy people. Results: Analysis of the reaction time to visual stimuli after using TMS to the V1 visual cortex revealed an increase in the number of incorrect recognitions, and the reaction time was from 843 to 910 ms. In the subgroup of participants (n = 15), after the stimulation, there were significant reductions of BOLD signal in blood flow within V1 cortices. Conclusions: The studies of reaction times after the rTMS revealed the inhibitory effect of rTMS on the reaction times and recognition performance of significant (military) objects in the visual field.

Robust group- but limited individual-level (longitudinal) reliability and insights into cross-phases response prediction of conditioned fear.

Here, we follow the call to target measurement reliability as a key prerequisite for individual-level predictions in translational neuroscience by investigating (1) longitudinal reliability at the individual and (2) group level, (3) internal consistency and (4) response predictability across experimental phases. One hundred and twenty individuals performed a fear conditioning paradigm twice 6 months apart. Analyses of skin conductance responses, fear ratings and blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) with different data transformations and included numbers of trials were conducted. While longitudinal reliability was rather limited at the individual level, it was comparatively higher for acquisition but not extinction at the group level. Internal consistency was satisfactory. Higher responding in preceding phases predicted higher responding in subsequent experimental phases at a weak to moderate level depending on data specifications. In sum, the results suggest that while individual-level predictions are meaningful for (very) short time frames, they also call for more attention to measurement properties in the field.

Intracranial recordings show evidence of numerosity tuning in human parietal cortex.

Numerosity is the set size of a group of items. Numerosity perception is a trait shared across numerous species. Numerosity-selective neural populations are thought to underlie numerosity perception. These neurons have been identified primarily using electrical recordings in animal models and blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) in humans. Here we use electrical intracranial recordings to investigate numerosity tuning in humans, focusing on high-frequency transient activations. These recordings combine a high spatial and temporal resolution and can bridge the gap between animal models and human recordings. In line with previous studies, we find numerosity-tuned responses at parietal sites in two out of three participants. Neuronal populations at these locations did not respond to other visual stimuli, i.e. faces, houses, and letters, in contrast to several occipital sites. Our findings further corroborate the specificity of numerosity tuning of in parietal cortex, and further link fMRI results and electrophysiological recordings.

The enigma of infra-slow fluctuations in the human EEG.

Spontaneous Infra-Slow Fluctuations (ISFs) of the human EEG (EEG-ISFs) were discovered 60 years ago when appropriate amplifiers for their recordings were designed. To avoid skin-related artifacts the recording of EEG-ISFs required puncturing the skin under the electrode. In the beginning of the 21st century the interest in EEG-ISFs was renewed with the appearance of commercially available DC-coupled amplified and by observation of ISFs of the blood oxygen level–dependent (BOLD) functional magnetic resonance imaging signal at a similar frequency. The independent components of irregular EEG-ISFs were shown to correlate with BOLD signals which in turn were driven by changes in arousal level measured by galvanic skin response (GSR), pupil size and HRV. There is no consensus regarding the temporal organization of EEG-ISFs: some studies emphasize the absence of peaks on EEG-ISFs spectra, some studies report prominent oscillations with frequency around 0.1 or 0.02 Hz, while some emphasize multiple discrete infraslow oscillations. No studies used parameters of EEG-ISFs as neuromarkers to discriminate psychiatric patients from healthy controls. Finally, a set of working hypotheses is suggested that must be tested in future research to solve the enigma of EEG-ISFs.

219-OR: Intranasal Insulin Enhanced Resting-State Functional Connectivity of Medio-Prefrontal Cortex in Type 2 Diabetes: A Substudy of the Memory Advancement with Type 2 Diabetes (MemAID) Randomized Control Trial

Type 2 diabetes mellitus (T2DM) is associated with impairment of resting-state functional connectivity (rsFC) and cognition. Intranasal insulin (INI) has emerged as potential treatment for T2DM-related cognitive decline. INI treatment has increased perfusion and low-frequency fluctuations in medio-prefrontal cortex (mPFC) . We aimed to evaluate the effect of INI treatment on mPFC rsFC.MemAIDs trial consisted of 24-week of treatment with 40 IU of intranasal insulin (Novolin® R, off label use) or placebo (sterile saline) once daily and 24-week follow-up period. Of 244 randomized participants (115 T2DM and 129 controls, > 50 years old) , T2DM participants (eight INI, three placebo, > 50 years old) completed the baseline and end-of-treatment blood oxygen level dependent (BOLD) fMRI scans.INI treatment increased resting state mPFC-postcentral rsFC (p=0.005) and decreased mPFC-cerebellum rsFC (p<0.001) . The mPFC rsFC changes after INI treatment were different from those from placebo (Figure 1) .INI treatment can modulate resting state connectivity between pre-frontal and sensorimotor cortex and cerebellum, indicating its potential effects on decision making and goal-oriented behaviors. These findings warrant further investigation. Disclosure Z.Zhang: None. V.Novak: None. P.Novak: Stock/Shareholder; Moderna, Inc., Novavax, Pfizer Inc., Prothena. C.Mantzoros: Advisory Panel; Novo Nordisk. L.H.Ngo: None. V.Lioutas: None. W.Dai: None. Funding Funded by NIH-NIDDK (1R01DK103902) , FDA (IND#107690) , Novo Nordisk, Inc. (ISS-001063) , Medtronic Inc. (NERP15-0310) and registered on www.clinicaltrials.gov (NCT02415556.)