Olfactory-trigeminal integration in the primary olfactory cortex.

Humans naturally integrate signals from the olfactory and intranasal trigeminal systems. A tight interplay has been demonstrated between these two systems, and yet the neural circuitry mediating olfactory-trigeminal (OT) integration remains poorly understood. Using functional magnetic resonance imaging (fMRI), combined with psychophysics, this study investigated the neural mechanisms underlying OT integration. Fifteen participants with normal olfactory function performed a localization task with air-puff stimuli, phenylethyl alcohol (PEA; rose odor), or a combination thereof while being scanned. The ability to localize PEA to either nostril was at chance. Yet, its presence significantly improved the localization accuracy of weak, but not strong, air-puffs, when both stimuli were delivered concurrently to the same nostril, but not when different nostrils received the two stimuli. This enhancement in localization accuracy, exemplifying the principles of spatial coincidence and inverse effectiveness in multisensory integration, was associated with multisensory integrative activity in the primary olfactory (POC), orbitofrontal (OFC), superior temporal (STC), inferior parietal (IPC) and cingulate cortices, and in the cerebellum. Multisensory enhancement in most of these regions correlated with behavioral multisensory enhancement, as did increases in connectivity between some of these regions. We interpret these findings as indicating that the POC is part of a distributed brain network mediating integration between the olfactory and trigeminal systems. PRACTITIONER POINTS: Psychophysical and neuroimaging study of olfactory-trigeminal (OT) integration. Behavior, cortical activity, and network connectivity show OT integration. OT integration obeys principles of inverse effectiveness and spatial coincidence. Behavioral and neural measures of OT integration are correlated.

Default mode network deactivation during odor-visual association.

Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, the DMN's role during olfactory processing was investigated using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation, and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26 ± 4 years, 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor + visual and visual-only trial conditions. During odor + visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the twenty-nine participants (mean age = 27.0 ± 6.0 years, 11 females) also took part in a control no-odor fMRI paradigm that consisted of a visual-only trial condition which was identical to the visual-only trials in the odor-visual association paradigm. Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) were used to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor + visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor + visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights the DMN's role in task-evoked brain activity and behavioral responses during olfactory processing. Hum Brain Mapp 38:1125-1139, 2017. © 2016 Wiley Periodicals, Inc.

Dynamic characteristics of T2*-weighted signal in calf muscles of peripheral artery disease during low-intensity exercise.

PURPOSE: To evaluate the dynamic characteristics of T2* -weighted signal change in exercising skeletal muscle of healthy subjects and peripheral artery disease (PAD) patients under a low-intensity exercise paradigm. MATERIALS AND METHODS: Nine PAD patients and nine age- and sex-matched healthy volunteers underwent a low-intensity exercise paradigm while magnetic resonance imaging (MRI) (3.0T) was obtained. T2*-weighted signal time-courses in lateral gastrocnemius, medial gastrocnemius, soleus, and tibialis anterior were acquired and analyzed. Correlations were performed between dynamic T2*-weighted signal and changes in heart rate, mean arterial pressure, leg pain, and perceived exertion. RESULTS: A significant signal decrease was observed during exercise in soleus and tibialis anterior of healthy participants (P = 0.0007-0.04 and 0.001-0.009, respectively). In PAD, negative signals were observed (P = 0.008-0.02 and 0.003-0.01, respectively) in soleus and lateral gastrocnemius during the early exercise stage. Then the signal gradually increased above the baseline in the lateral gastrocnemius during and after exercise in six of the eight patients who completed the study. This signal increase in patients' lateral gastrocnemius was significantly greater than in healthy subjects' during the later exercise stage (two-sample t-tests, P = 0.001-0.03). Heart rate and mean arterial pressure responses to exercise were significantly higher in PAD than healthy subjects (P = 0.036 and 0.008, respectively) and the patients experienced greater leg pain and exertion (P = 0.006 and P = 0.0014, respectively). CONCLUSION: During low-intensity exercise, there were different dynamic T2*-weighted signal behavior in the healthy and PAD exercising muscles. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:40-48.

Networks involved in olfaction and their dynamics using independent component analysis and unified structural equation modeling.

The study of human olfaction is complicated by the myriad of processing demands in conscious perceptual and emotional experiences of odors. Combining functional magnetic resonance imaging with convergent multivariate network analyses, we examined the spatiotemporal behavior of olfactory-generated blood-oxygenated-level-dependent signal in healthy adults. The experimental functional magnetic resonance imaging (fMRI) paradigm was found to offset the limitations of olfactory habituation effects and permitted the identification of five functional networks. Analysis delineated separable neuronal circuits that were spatially centered in the primary olfactory cortex, striatum, dorsolateral prefrontal cortex, rostral prefrontal cortex/anterior cingulate, and parietal-occipital junction. We hypothesize that these functional networks subserve primary perceptual, affective/motivational, and higher order olfactory-related cognitive processes. Results provided direct evidence for the existence of parallel networks with top-down modulation for olfactory processing and clearly distinguished brain activations that were sniffing-related versus odor-related. A comprehensive neurocognitive model for olfaction is presented that may be applied to broader translational studies of olfactory function, aging, and neurological disease.

Neural correlates of chocolate brand preference: A functional MRI study.

BACKGROUND AND PURPOSE: Preferences can be developed for, or against, specific brands and services. Using two functional magnetic resonance imaging (fMRI) experiments, this study investigated two dissociable aspects of reward processing, craving and liking, in chocolate lovers. The goal was to further delineate the neural basis supporting branding effects using familiar chocolate (FC) and unfamiliar chocolate (UC) brand images. METHODS: In the first experiment, subjects rated their subjective craving and liking on a scale of 1-5 (weak-strong) for each FC and UC image. In the second experiment, they performed a choice task between FC and UC images. RESULTS: Both the craving and liking ratings were significantly greater for FC and were differentially correlated with choice behavior. Craving ratings predicted greater preference for UC, and liking ratings predicted greater preference for FC. A contrast of neural activity for UC versus FC choice trials revealed significantly greater activation for UC choices in the bilateral inferior frontal gyrus and right caudate head. Response times for the FC images were faster than UC images; fMRI activity in the ventromedial prefrontal cortex was significantly correlated with response times during FC trials, but not UC trials. These correlations were significantly different from each other at the group level. CONCLUSIONS: The choices for branded chocolate products are driven by higher subjective reward ratings and lower neural processing demands.

Single-Center In-Hospital and Outpatient Opioid Use for Lower Extremity Arterial Disease.

INTRODUCTION: The pain associated with lower extremity arterial disease is difficult to treat, even with lower extremity revascularization. We sought to evaluate in-hospital and post-operative opioid usage in patients with different disease severities and treatments for lower extremity vascular disease. METHODS: A retrospective review was performed for all hospital encounters for patients with an International Classification of Diseases (ICD) code consistent with lower extremity arterial disease admitted to a single center between January 2018 and March 2023. Cases included patients admitted to the hospital with a primary diagnosis of lower extremity arterial disease. These patients were subdivided based on disease severity, treatment type, and comorbid diagnosis of diabetes mellitus. The analysis focused on in-hospital opioid use frequency and dosage among these patients. The control group (CON) included encounters for patients admitted with a secondary diagnosis of lower extremity atherosclerotic disease. A total of 438 patients represented by all the analyzed encounters were then reviewed for the number and type of vascular procedures performed as well as opioid use in the outpatient setting for one year. RESULTS: Critical limb ischemia (CLI) encounters were more likely to use opioids as compared to the CON and peripheral arterial disease (PAD) without rest pain, ulcer or gangrene groups (CLI 67.9% (95% CI: 63.6%-71.6%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.001 and CLI 67.9% (95% CI: 63.6%-71.6%) versus PAD 50.2% (95% CI: 42.6%-57.4%), p < 0.001). Opioid use was also more common in encounters for gangrene and groups treated with revascularization (REVASC) and amputation (AMP) as compared to CON (gangrene 74.5% (95% CI: 68.5%-82.1%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.01; REVASC 58.3% (95% CI: 57.3%-66.4%) versus CON 52.1% (95% CI: 48.5%-55.7%), p =0.01; and AMP 72.3% (95% CI: 62.1%-74.0%) versus CON 52.1% (95% CI: 48.5%-55.7%), p < 0.01). Significantly increased oral opioid doses per day (MME/day) were not noted for any of the investigated groups as compared to the CON. In the outpatient setting, 186 (42.5% (95% CI: 37.2%-46.4%)) patients were using opioids one month after the most recent vascular intervention. By one year, 31 (7.1% (95% CI: 1.30%-7.70%)) patients were still using opioids. No differences in opioid usage were noted for patients undergoing single versus multiple vascular interventions at one year. Patients undergoing certain vascular surgery procedures were more likely to be using opioids at one year. CONCLUSION: Patients with CLI and gangrene as well as those undergoing vascular treatment have a greater frequency of opioid use during hospital encounters as compared to those patients with less severe disease and undergoing conservative management, respectively. However, these findings do not equate to higher doses of opioids used during hospitalization. Patients undergoing multiple vascular procedures are not more likely to be using opioids long-term (at one year) as compared to those patients treated with single vascular procedures.

BOLD fMRI in infants under sedation: Comparing the impact of pentobarbital and propofol on auditory and language activation.

PURPOSE: To elucidate differences in the disruption of language network function, as measured by blood oxygenation level-dependent (BOLD) contrast functional MRI (fMRI), attributable to two common sedative agents administered to infants under clinical imaging protocols. MATERIALS AND METHODS: The sedatives pentobarbital (Nembutal) and Propofol, administered clinically to infants at 1 year of age, were compared with respect to BOLD activation profiles in response to passive story-listening stimulation. An intermittent event-related imaging protocol was used with which the temporal evolution of language processing resulting from this stimulation was explored. RESULTS: Propofol and Nembutal were found to have distinct and complementary responses to story-listening. Propofol exhibited more activation in higher processing networks with increasing response toward the end of narrative stimulus. Nembutal, in contrast, had much more robust activation of primary and secondary sensory cortices but a decreasing response over time in fronto-parietal default-mode regions. This may suggest a breakdown of top-down feedback for Propofol versus the lack of bottom-up feed-forward processing for Nembutal. CONCLUSION: Two popular sedative agents for use in children for clinical fMRI were found to induce distinct alteration of activation patterns from a language stimulus. This has ramifications for clinical fMRI of sedated infants and encourages further study to build a framework for more confident interpretation.

A review and perspective on the neural basis of radiological expertise.

Radiological expertise requires tremendous time, effort, and training. While there has been a myriad of studies focusing on radiological expertise and error, the precise underlying neural mechanism still remains largely unexplored. In this article, we review potential neural mechanisms, namely, the fusiform face area, working memory, and predictive coding and propose experiments to test the predictive coding framework.

Monorhinal and Birhinal Odor Processing in Humans: an fMRI investigation.

The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. It is still unclear whether these projections also correspond to functional pathways of odor processing. In an olfactory functional magnetic resonance imaging (fMRI) study of twenty young healthy subjects with a normal sense of smell, we tested whether nostril specific stimulation with phenyl ethyl alcohol (PEA), a pure olfactory stimulant, asymmetrically activates primary or secondary olfactory-related brain structures such as primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. The results indicated that without a challenging olfactory task, passive (no sniffing) and active (with sniffing) nostril-specific PEA stimulation did not produce asymmetrical fMRI activation in olfactory cortical structures.

Evidence from an fMRI study that dessert-flavored e-cigarettes engage taste-related, but not smoking-related, brain circuitry for female daily smokers.

Regulations limiting the sale of flavored e-cigarette products are controversial for their potential to interfere with e-cigarette use as a cessation aid in addition to curbing youth use. Limited research suggests that flavor might enhance the addictive potential of e-cigarettes; however, the acute effects of flavored aerosols on brain function among humans have not been assessed. The present study aimed to isolate and compare the neural substrates of flavored and unflavored e-cigarette aerosols on brain function among nine female daily smokers. Participants inhaled aerosolized e-liquid with 36 mg/mL of nicotine with and without a strawberry-vanilla flavor while undergoing functional magnetic resonance imaging. We used general linear modeling to compare whole-brain mean neural activation and seed-to-voxel task-based functional connectivity between the flavored and unflavored inhalation runs. Contrary to our hypothesis, the flavored aerosol was associated with weaker activation than the unflavored aerosol in the brain stem and bilateral parietal-temporal-occipital region of the cortex. Instead, the flavor engaged taste-related brain regions while suppressing activation of the neural circuits typically engaged during smoking and nicotine administration. Alternatively, functional connectivity between subcortical dopaminergic brain seeds and cortical brain regions involved in motivation and reward salience were stronger during the flavored compared to unflavored aerosol run. The findings suggest that fruity and dessert-flavored e-cigarettes may dampen the reward experience of aerosol inhalation for smokers who initiate e-cigarette use by inhibiting activation of dopaminergic brain circuits. These preliminary findings may have implications for understanding how regulations on flavored e-cigarettes might impact their use as cessation aids. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The effects of left or right hemispheric epilepsy on language networks investigated with semantic decision fMRI task and independent component analysis.

Chronic and progressive brain injury, as seen in epilepsy, may alter brain networks that underlie cognitive functions. To evaluate the effect of epilepsy on language functions we investigated the neuroanatomical basis of semantic processing in patients with left (LHE) or right (RHE) hemispheric onset epilepsy using semantic decision fMRI paradigm and group independent component analysis (ICA); we then compared the results of our investigations with language networks in healthy subjects examined with the same language task (Kim K, Karunanayaka P, Privitera M, Holland S, Szaflarski J. Semantic association investigated with fMRI and independent component analysis. In press). Group ICA is a data-driven technique capable of revealing the functional organization of the human brain based on fMRI data. In addition to providing functional connectivity information, ICA can also provide information about the temporal dynamics of underlying networks subserving specific cognitive functions. In this study, we implemented two complementary analyses to investigate group differences in underlying network dynamics based on associated independent component (IC) time courses (a priori defined criterion or a posteriori identified maximum likelihood descriptor). We detected several differences between healthy controls and patients with epilepsy not previously observed with standard fMRI analysis methods. Our analyses confirmed the presence of different effects of LHE or RHE on the behavior of the language network. In particular, a major difference was noted in the nodes subserving verbal encoding and retrieval in the bilateral medial temporal regions. These effects were dependent on the side of the epilepsy onset; that is, effects were different with left or right hemispheric epilepsy. These findings may explain the differences in verbal and nonverbal memory abilities between patients with left and those with right hemispheric epilepsy. Further, although the effects on other nodes of the network were more subtle, several deviations from normal network function were observed in patients with LHE (e.g., alterations in the functions of the primarily left frontotemporal network module) or in patients with RHE (e.g., differences in the medial retrosplenial module responsible for mental imagery or in the anterior cingulate module subserving attention control). These findings not only highlight the negative effects of epilepsy on the main left hemispheric language network nodes in patients with LHE, but also document the effects of epilepsy on other language network nodes whether exerted by LHE or RHE. Further, these results document the advantages of using group ICA for investigating the effects of disease state (e.g., epilepsy) on the network subserving cognitive processing and provide an interesting avenue for further exploration.

Semantic association investigated with functional MRI and independent component analysis.

Semantic association, an essential element of human language, enables discourse and inference. Neuroimaging studies have revealed localization and lateralization of semantic circuitry, making substantial contributions to cognitive neuroscience. However, because of methodological limitations, these investigations have only identified individual functional components rather than capturing the behavior of the entire network. To overcome these limitations, we have implemented group independent component analysis (ICA) to investigate the cognitive modules used by healthy adults performing the fMRI semantic decision task. When compared with the results of a standard general linear modeling (GLM) analysis, ICA detected several additional brain regions subserving semantic decision. Eight task-related group ICA maps were identified, including left inferior frontal gyrus (BA44/45), middle posterior temporal gyrus (BA39/22), angular gyrus/inferior parietal lobule (BA39/40), posterior cingulate (BA30), bilateral lingual gyrus (BA18/23), inferior frontal gyrus (L>R, BA47), hippocampus with parahippocampal gyrus (L>R, BA35/36), and anterior cingulate (BA32/24). Although most of the components were represented bilaterally, we found a single, highly left-lateralized component that included the inferior frontal gyrus and the medial and superior temporal gyri, the angular and supramarginal gyri, and the inferior parietal cortex. The presence of these spatially independent ICA components implies functional connectivity and can be equated with their modularity. These results are analyzed and presented in the framework of a biologically plausible theoretical model in preparation for similar analyses in patients with right- or left-hemispheric epilepsies.

A group independent component analysis of covert verb generation in children: a functional magnetic resonance imaging study.

Semantic language skills are an integral part of early childhood language development. The semantic association between verbs and nouns constitutes an important building block for the construction of sentences. In this large-scale functional magnetic resonance imaging (fMRI) study, involving 336 subjects between the ages of 5 and 18 years, we investigated the neural correlates of covert verb generation in children. Using group independent component analysis (ICA), seven task-related components were identified including the mid-superior temporal gyrus, the most posterior aspect of the superior temporal gyrus, the parahippocampal gyrus, the inferior frontal gyrus, the angular gyrus, and medial aspect of the parietal lobule (precuneus/posterior cingulate). A highly left-lateralized component was found including the medial temporal gyrus, the frontal gyrus, the inferior frontal gyrus, and the angular gyrus. The associated independent component (IC) time courses were analyzed to investigate developmental changes in the neural elements supporting covert verb generation. Observed age effects may either reflect specific local neuroplastic changes in the neural substrates supporting language or a more global transformation of neuroplasticity in the developing brain. The results are analyzed and presented in the framework of two theoretical models for neurocognitive brain development. In this context, group ICA of fMRI data from our large sample of children aged 5-18 years provides strong evidence in support of the regionally weighted model for cognitive neurodevelopment of language networks.

Olfactory Costimulation Influences Intranasal Somatosensory Perception.

Olfactory sensitivity is influenced by intranasal trigeminal sensation. For instance, sniffing is central to how humans and animals perceive odorants. Here, we investigated the influence of olfactory costimulation on the perception of intranasal somatosensory stimulation. In this study, 22 healthy human subjects, with normal olfactory function, performed a localization task for stimulation using weak air puffs, a pure odorant, phenyl ethyl alcohol (PEA; rose odor), or their combination. Visual cues were used to inform participants to briefly hold their breath while weak, poorly localizable, air puffs and/or PEA were delivered to either nostril. Although PEA alone could not be localized to the correct nostril, when it accompanied a weak air puff in the ipsilateral nostril, localization accuracy significantly improved, relative to presentation of the air puff without the odorant. The enhancement of localization was absent when the air puff and PEA were presented to opposite nostrils. Since ipsilateral but not contralateral costimulation with PEA increased the accuracy of weak air puff localization, the results argue against a non-specific alerting effect of PEA. These findings suggest an interaction between olfactory and intranasal somatosensory stimuli leading to their integration.

An Electronic Aerosol Delivery System for Functional Magnetic Resonance Imaging.

BACKGROUND: Public health concerns over the addictive potential of electronic cigarettes (e-cigs) have heightened in recent years. Brain function during e-cig use could provide an objective measure of the addictive potential of new vaping products to facilitate research; however, there are limited methods for delivering e-cig aerosols during functional magnetic resonance imaging (fMRI). The current study describes the development and feasibility testing of a prototype to deliver up to four different e-cig aerosols during fMRI. METHODS: Standardized methods were used to test the devices' air flow variability, nicotine yield, and free radical production. MRI scans were run with and without the device present to assess its safety and effects on MRI data quality. Five daily smokers were recruited to assess plasma nicotine absorption from e-liquids containing nicotine concentrations of 8, 11, 16, 24, and 36 mg/ml. Feedback was collected from participants through a semi-structured interview and computerized questionnaire to assess comfort and subjective experiences of inhaling aerosol from the device. RESULTS: Nicotine yield captured from the aerosol produced by the device was highly correlated with the nicotine concentration of the e-liquids used (R2 = 0.965). Nicotine yield was reduced by a mean of 48% and free radical production by 17% after traveling through the device. The e-liquid containing the highest nicotine concentration tested (36 mg/ml) resulted in the highest plasma nicotine boost (6.6 ng/ml). Overall, participants reported that the device was comfortable to use and inhaling the e-cig aerosols was tolerable. The device was determined to be safe for use during fMRI and had insignificant effects on scan quality. CONCLUSIONS: With the current project, we were able to design a working prototype that safely and effectively delivers e-cig aerosols during fMRI. The device has the potential to be used to assess brain activation during e-cig use and to compare brain reactivity to varying flavors, nicotine concentrations, and other e-cig characteristics.

Language networks in children: evidence from functional MRI studies.

OBJECTIVE: The purpose of our study was to review functional MRI and other neuroimaging studies of language skills in children from infancy to adulthood. CONCLUSION: Functional MRI (fMRI) and other neuroimaging studies show developmental changes in the networks of brain regions supporting language, which can be affected by brain injuries or neurologic disorders. Particular aspects of language rely on networks that lateralize to the dominant hemisphere; others rely on bilateral or nondominant mechanisms. Multiple fMRI tasks for pediatric patients characterize functional brain reorganization that may accompany language deficits.

Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer's Disease.

Olfactory impairment is associated with prodromal Alzheimer's disease (AD) and is a risk factor for the development of dementia. AD pathology is known to disrupt brain regions instrumental in olfactory information processing, such as the primary olfactory cortex (POC), the hippocampus, and other temporal lobe structures. This selective vulnerability suggests that the functional connectivity (FC) between the olfactory network (ON), consisting of the POC, insula and orbital frontal cortex (OFC) (Tobia et al., 2016), and the hippocampus may be impaired in early stage AD. Yet, the development trajectory of this potential FC impairment remains unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to investigate FC changes between the ON and hippocampus in four groups: aged-matched cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. FC was calculated using low frequency fMRI signal fluctuations in the ON and hippocampus (Tobia et al., 2016). We found that the FC between the ON and the right hippocampus became progressively disrupted across disease states, with significant differences between EMCI and LMCI groups. Additionally, there were no significant differences in gray matter hippocampal volumes between EMCI and LMCI groups. Lastly, the FC between the ON and hippocampus was significantly correlated with neuropsychological test scores, suggesting that it is related to cognition in a meaningful way. These findings provide the first in vivo evidence for the involvement of FC between the ON and hippocampus in AD pathology. Results suggest that functional connectivity (FC) between the olfactory network (ON) and hippocampus may be a sensitive marker for Alzheimer's disease (AD) progression, preceding gray matter volume loss.

Disruptions of the olfactory and default mode networks in Alzheimer's disease.

INTRODUCTION: Olfactory deficits are prevalent in early Alzheimer's disease (AD) and are predictive of progressive memory loss and dementia. However, direct neural evidence to relate AD neurodegeneration to deficits in olfaction and memory is limited. METHODS: We combined the University of Pennsylvania Smell Identification Test (UPSIT) with olfactory functional magnetic resonance imaging (fMRI) to investigate links between neurodegeneration, the olfactory network (ON) and the default mode network (DMN) in AD. RESULTS: Behaviorally, olfactory and memory scores showed a strong positive correlation in the study cohorts. During olfactory fMRI, the ON showed reduced task-related activation and the DMN showed reduced task-related suppression in mild cognitive impairment (MCI) and AD subjects compared to age-matched cognitively normal subjects. CONCLUSIONS: The results provide in vivo evidence for selective vulnerability of ON and DMN in AD and significantly improves the viable clinical applications of olfactory testing. A network-based approach, focusing on network integrity rather than focal pathology, seems beneficial to olfactory prediction of dementia in AD.

Long-term neural processing of attention following early childhood traumatic brain injury: fMRI and neurobehavioral outcomes.

Attentional deficits are common and significant sequelae of pediatric traumatic brain injury (TBI). However, little is known about how the underlying neural processes that support different components of attention are affected. The present study examined brain activation patterns using fMRI in a group of young children who sustained a TBI in early childhood (n = 5; mean age = 9.4), and a group of age-matched control children with orthopedic injuries (OI) (n = 8) during a continuous performance task (CPT). Four children in the TBI group had moderate injuries, and one had a severe injury. Performance on the CPT task did not differ between groups. Both TBI and OI children activated similar networks of brain regions relevant to sustained attention processing, but the TBI group demonstrated several areas of significantly greater activation relative to controls, including frontal and parietal regions. These findings of over-activation of the relevant attention network in the TBI group contrast with those obtained in imaging studies of Attention-Deficit/Hyperactivity Disorder where under-activation of the attention network has been documented. This study provides evidence that young children's brains function differently following a traumatic brain injury, and that these differences persist for years after the injury.

Neural substrate differences in language networks and associated language-related behavioral impairments in children with TBI: a preliminary fMRI investigation.

The present study examined whether functional MRI (fMRI) can identify changes in the neural substrates of language in young children following traumatic brain injury (TBI). Eight children with TBI (F/M=3/5, age (Mean +/- SD)=7.98 +/- 1 years, range = 6-9 years) and a comparison group of nine children with orthopedic injuries (OI) (F/M=4/5, age (Mean +/- SD)=7.4 +/- 1 years, range=6-9 years) participated in an fMRI study of covert verb generation (VG). Results revealed significantly different BOLD signal activation in perisylvian language areas between the groups, after accounting for potential confounders such as verbal fluency and executive function. We also found significant associations between the BOLD signal activation and performance on language-specific neuropsychological tests (NEPSY verbal fluency score, Verbal IQ) and Glasgow Coma Scale (GCS) score. This study suggests that children with TBI have significantly different brain activation patterns in language circuitry compared to children with orthopedic injuries. Although we found clear differences in brain activation between the two groups, conventional MR images showed no evidence of structural abnormalities in five of eight children with TBI. Our study demonstrates the feasibility and potential utility of fMRI as a means of quantifying changes associated with language deficits in future pediatric TBI studies.