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.

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.

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).

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.

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.

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.

Different patterns of age-related central olfactory decline in men and women as quantified by olfactory fMRI.

Age-related olfactory decline, or presbyosmia, is a prevalent condition with potentially devastating consequences on both quality of life and safety. Despite clear evidence for this decline, it is unknown whether presbyosmia is sex-dependent and also whether it is due to central or peripheral olfactory system deterioration. Therefore, the goals of this study were to investigate the neurofunctional substrate of olfactory decline and examine its relationship to age and sex in thirty-seven (18 women, 19 men) healthy older participants using olfactory functional MRI (fMRI). The olfactory fMRI paradigm utilized unique odor+visual and visual-only conditions to contrast peripheral-to-central and central-to-central olfactory processing, respectively. Age was negatively correlated with fMRI activation in olfactory-related regions. Significant aging effects were identifiable in male participants in all target regions. Female participants, however, showed a different pattern of functional decline. Extended unified structural equation modeling (euSEM) analysis revealed that the effective functional connectivity profile was drastically different between male and female participants, with females manifesting a top-down mechanism to offset age-related olfactory activation decline. Our results support the hypotheses that the central olfactory system is involved in age-related olfactory decline, and that resilience to age-related olfactory decline in women may be due to their profuse olfactory network effective connectivity.

Age-related resting-state functional connectivity in the olfactory and trigeminal networks.

Brain networks for intranasal chemosensation have been shown to be intrinsically organized in humans . However, little is known about how changes in the intrinsic functional connectivity (FC) in chemosensory networks are related to aging. We, therefore, investigated the impact of age on resting-state FC in the olfactory and trigeminal networks (ON and TN) by combining two freely available resting-state fMRI data sets (obtained from the NITRC.org; Atlanta and New York) with data collected in our lab to generate a large sample size (N=103; 51 women) spanning the age range of 20-61 years. Seed regions were defined using Montreal Neurological Institute's coordinates that anchor ON and TN in activation studies and meta-analyses. The ON included the piriform cortex and the oribtofrontal cortex. The TN included the anterior insula and the cingulate cortex. Scanner site, sex, and age were used as covariates in group-level analyses. The FC between the ON and the parahippocampal gyrus was correlated negatively with age. The FC between the TN and the parahippocampal gyrus, however, was positively correlated. Similarly, age was correlated positively with the ON FC to the ventral striatum and the TN FC to the default mode network. These results reflect divergent age-related alterations in the intrinsic FC of the human chemosensory system.

Lexical-Semantic Search Under Different Covert Verbal Fluency Tasks: An fMRI Study.

Background: Verbal fluency is a measure of cognitive flexibility and word search strategies that is widely used to characterize impaired cognitive function. Despite the wealth of research on identifying and characterizing distinct aspects of verbal fluency, the anatomic and functional substrates of retrieval-related search and post-retrieval control processes still have not been fully elucidated. Methods: Twenty-one native English-speaking, healthy, right-handed, adult volunteers (mean age = 31 years; range = 21-45 years; 9 F) took part in a block-design functional Magnetic Resonance Imaging (fMRI) study of free recall, covert word generation tasks when guided by phonemic (P), semantic-category (C), and context-based fill-in-the-blank sentence completion (S) cues. General linear model (GLM), Independent Component Analysis (ICA), and psychophysiological interaction (PPI) were used to further characterize the neural substrate of verbal fluency as a function of retrieval cue type. Results: Common localized activations across P, C, and S tasks occurred in the bilateral superior and left inferior frontal gyrus, left anterior cingulate cortex, bilateral supplementary motor area (SMA), and left insula. Differential task activations were centered in the occipital, temporal and parietal regions as well as the thalamus and cerebellum. The context-based fluency task, i.e., the S task, elicited higher differential brain activity in a lateralized frontal-temporal network typically engaged in complex language processing. P and C tasks elicited activation in limited pathways mainly within the left frontal regions. ICA and PPI results of the S task suggested that brain regions distributed across both hemispheres, extending beyond classical language areas, are recruited for lexical-semantic access and retrieval during sentence completion. Conclusion: Study results support the hypothesis of overlapping, as well as distinct, neural networks for covert word generation when guided by different linguistic cues. The increased demand on word retrieval is met by the concurrent recruitment of classical as well as non-classical language-related brain regions forming a large cognitive neural network. The retrieval-related search and post-retrieval control processes that subserve verbal fluency, therefore, reverberates across distinct functional networks as determined by respective task demands.

Central Olfactory Dysfunction in Alzheimer's Disease and Mild Cognitive Impairment: A Functional MRI Study.

BACKGROUND: Olfactory deficits are present in early Alzheimer's disease (AD) and mild cognitively impaired (MCI) patients. However, whether these deficits are due to dysfunction of the central or peripheral olfactory nervous system remains uncertain. This question is fundamentally important for developing imaging biomarkers for AD using olfactory testing. OBJECTIVE: This study sought to use olfactory functional magnetic resonance imaging (fMRI) to further demonstrate the involvement of the central olfactory system in olfactory deficits in MCI and AD. METHODS: We investigated the central olfactory system in 27 cognitively normal controls (CN), 21 MCI, and 15 AD subjects using olfactory fMRI with an odor-visual association paradigm during which a visual cue was paired with lavender odorant (odor condition) or odorless air (no-odor condition). RESULTS: The CN subjects had significantly greater activated volume in the primary olfactory cortex during both the odor and no-odor conditions compared to either the MCI or AD groups (p < 0.05). No significant differences were observed between the odor and no-odor conditions within each group. No-odor condition activation in AD and MCI correlated with the cognitive and olfactory assessments. CONCLUSION: The no-odor condition, allowing investigation of activation patterns when the peripheral olfactory system was not directly involved, elicited the same functional response as the odor condition for each of the three groups. Thus, the olfactory activation deficits present in AD and MCI patients are most likely caused by degeneration of the central olfactory nervous system.

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.

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.

Muscle oxygenation during dynamic plantar flexion exercise: combining BOLD MRI with traditional physiological measurements.

Blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) has the potential to quantify skeletal muscle oxygenation with high temporal and high spatial resolution. The purpose of this study was to characterize skeletal muscle BOLD responses during steady-state plantar flexion exercise (i.e., during the brief rest periods between muscle contraction). We used three different imaging modalities (ultrasound of the popliteal artery, BOLD MRI, and near-infrared spectroscopy [NIRS]) and two different exercise intensities (2 and 6 kg). Six healthy men underwent three separate protocols of dynamic plantar flexion exercise on separate days and acute physiological responses were measured. Ultrasound studies showed the percent change in popliteal velocity from baseline to the end of exercise was 151 ± 24% during 2 kg and 589 ± 145% during 6 kg. MRI studies showed an abrupt decrease in BOLD signal intensity at the onset of 2 kg exercise, indicating deoxygenation. The BOLD signal was further reduced during 6 kg exercise (compared to 2 kg) at 1 min (-4.3 ± 0.7 vs. -1.2 ± 0.4%, P < 0.001). Similarly, the change in the NIRS muscle oxygen saturation in the medial gastrocnemius was -11 ± 4% at 2 kg and -38 ± 11% with 6 kg (P = 0.041). In conclusion, we demonstrate that BOLD signal intensity decreases during plantar flexion and this effect is augmented at higher exercise workloads.

Default mode network differences between rigidity- and tremor-predominant Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) traditionally is characterized by tremor, rigidity, and bradykinesia, although cognitive impairment also is a common symptom. The clinical presentation of PD is heterogeneous and associated with different risk factors for developing cognitive impairment. PD patients with primary akinetic/rigidity (PDAR) are more likely to develop cognitive deficits compared to those with tremor-predominant symptoms (PDT). Because cognitive impairment in PD appears to be related to changes in the default mode network (DMN), this study tested the hypothesis that DMN integrity is different between PDAR and PDT subtypes. METHOD: Resting state fMRI (rs-fMRI) and whole brain volumetric data were obtained from 17 PDAR, 15 PDT and 24 healthy controls (HCs) using a 3T scanner. PD patients were matched closely to HCs for demographic and cognitive variables, and showed no symptoms of dementia. Voxel-based morphometry (VBM) was used to examine brain gray matter (GM) volume changes between groups. Independent component analysis (ICA) interrogated differences in the DMN among PDAR, PDT, and HC. RESULTS: There was decreased activity in the left inferior parietal cortex (IPC) and the left posterior cingulate cortex (PCC) within the DMN between PDAR and both HC and PDT subjects, even after controlling for multiple comparisons, but not between PDT and HC. GM volume differences between groups were detected at a lower threshold (p < 0.001, uncorrected). Resting state activity in IPC and PCC were correlated with some measures of cognitive performance in PD but not in HC. CONCLUSION: This is the first study to demonstrate DMN differences between cognitively comparable PDAR and PDT subtypes. The DMN differences between PD and HC appear to be driven by the PDAR subtype. Further studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR and PDT subtypes.

Intrinsic intranasal chemosensory brain networks shown by resting-state functional MRI.

The human brain is organized into functional networks for sensory-motor and cognitive processing. Intrinsic networks are detectable in the absence of stimulation or task demands, whereas extrinsic networks are detectable when stimulated by sensory or cognitive demands. Intranasal chemosensory processing relies on two dissociable networks for processing incoming trigeminal and olfactory stimulation, but it is not known whether these networks are intrinsically organized. The aim of this study was to identify whether brain networks for intranasal chemosensory processing are detectable in functional connectivity resting-state functional MRI (fMRI). Sixteen healthy adults participated in a 5-min resting-state fMRI study. Functional connectivity seeds were defined from coordinates that anchor olfactory (i.e. bilateral piriform and orbitofrontal cortex) and trigeminal (bilateral anterior insula and cingulate cortex) networks in published task activation studies, and the resulting networks were thresholded at P less than 0.001. The olfactory network showed extended functional connectivity to the thalamus, medial prefrontal cortex, caudate, nucleus accumbens, parahippocampal gyrus, and hippocampus. The trigeminal network showed extended functional connectivity to the precuneus, thalamus, caudate, brainstem, and cerebellum. Both networks overlapped in the thalamus, caudate, medial prefrontal cortex, and insula. These results show that brain networks for intranasal chemosensory processing are intrinsically organized, not just extrinsically instantiated in response to task demands, and resemble networks for processing olfactory and trigeminal stimulation. As such, it may be possible to study the functional organization and dynamics of the olfactory network in resting-state fMRI as well as its implications for aging and disease.

Rapidly acquired multisensory association in the olfactory cortex.

BACKGROUND: The formation of an odor percept in humans is strongly associated with visual information. However, much less is known about the roles of learning and memory in shaping the multisensory nature of odor representations in the brain. METHOD: The dynamics of odor and visual association in olfaction was investigated using three functional magnetic resonance imaging (fMRI) paradigms. In two paradigms, a visual cue was paired with an odor. In the third, the same visual cue was never paired with an odor. In this experimental design, if the visual cue was not influenced by odor-visual pairing, then the blood-oxygen-level-dependent (BOLD) signal elicited by subsequent visual cues should be similar across all three paradigms. Additionally, intensity, a major dimension of odor perception, was used as a modulator of associative learning which was characterized in terms of the spatiotemporal behavior of the BOLD signal in olfactory structures. RESULTS: A single odor-visual pairing cue could subsequently induce primary olfactory cortex activity when only the visual cue was presented. This activity was intensity dependent and was also detected in secondary olfactory structures and hippocampus. CONCLUSION: This study provides evidence for a rapid learning response in the olfactory system by a visual cue following odor and visual cue pairing. The novel data and paradigms suggest new avenues to explore the dynamics of odor learning and multisensory representations that contribute to the construction of a unified odor percept in the human brain.

Olfactory cortex degeneration in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Olfactory deficits are prevalent in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). These symptoms precede clinical onset of cognitive and memory deficits and coincide with AD pathology preferentially in the central olfactory structures, suggesting a potential biomarker for AD early detection and progression. OBJECTIVE: Therefore, we tested the hypothesis that structural degeneration of the primary olfactory cortex (POC) could be detected in AD as well as in MCI patients and would be correlated with olfactory functional magnetic resonance imaging (fMRI) alterations, reflecting loss of olfactory cortex activity. METHODS: Total structural volumes and fMRI activation volumes of the POC and hippocampus were measured along with olfactory and cognitive behavioral tests in 27 cognitively normal (CN), 21 MCI, and 15 AD subjects. RESULTS: Prominent atrophy in the POC and hippocampus was found in both AD and MCI subjects and correlated with behavioral measurements. While behavioral and volumetric measurements showed a gradual decline from CN to MCI to AD, olfactory activation volume in the POC and hippocampus showed a steeper decline in the MCI group compared to corresponding tissue volume, resembling the AD group. CONCLUSIONS: Decline in olfactory activity was correlated with the AD structural degeneration in the POC. A more prominent olfactory activity deficit than that of behavioral and tissue volume measurements was shown in the MCI stage. Olfactory fMRI may thus provide an earlier and more sensitive measure of functional neurodegeneration in AD and MCI patients.