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.

Local susceptibility variations result in B 0 field inhomogeneities, causing distortions and signal losses in MR imaging. Susceptibility variations become stronger with increasing B 0 magnetic field strength. Active shimming is used to generate corrective magnetic fields, which can be used to improve B 0 field homogeneity. FASTMAP is an effective shimming technique for computing optimal coil currents, which uses data from six projection directions (or columns): this technique is routinely used for shimming cubic volumes of interest (VOIs). In this paper, we propose several improvements to FASTMAP at 4T. For each shim coil, using a modified 3D gradient-echo pulse sequence, we compute B 0 inhomogeneity maps and project them onto eight 1 st and 2 nd order spherical harmonic functions. This process is repeated for shim currents between −15,000 to 15,000 with increments of 5000 Digital to Analog Converter (DAC) units, and is used to compute the gradient between spherical harmonic coefficients and DAC values for all 8 shim coils-along with the R 2 values of linear fits. A method is proposed (based on R 2 values) to further refine optimal shim currents in respective coils. We present an analysis that is numerically robust and completely flexible in the selection of the VOIs for shimming. Performance analyses, phantom results, and in vivo results of a human brain are presented, comparing our methods with the FASTMAP method.

ObjectiveDetermine the neural basis of olfactory impairment in akinetic-rigid (PDAR) and tremor predominant (PDT) Parkinson’s disease subtypes.MethodsWe combined resting-state fMRI (rs-fMRI) with seed based functional connectivity (FC) in order to delineate the olfactory network’s functional connectivity (ON FC) between PDAR and PDT patients. We then contrasted their ON FC patterns with cognitively normal (CN) subjects. All three groups were closely matched in age, demographic variables, and adjusted for relative cognitive performance. Olfactory function was measured using the University of Pennsylvania Smell Identification Test (UPSIT).ResultsUPSIT scores were lower in akinetic-rigid vs tremor subtypes; ON FC values were lower in PDAR compared to PDT and CN, and followed the trend observed in UPSIT scores. UPSIT scores and ON FC values were significantly correlated, reflecting the effects of PD pathologies.ConclusionsThe results show that olfactory function differs between PDAR and PDT suggesting a correlation between PD-related motor symptoms and olfactory deficits. ON FC differences accounts for the impaired olfactory functions observed between PDAR and PDT. PDAR is known to have worse clinical outcomes and faster cognitive decline compared to PDT; therefore, PD-related olfactory dysfunction may serve as a novel metric for enhancing PD prognosis.

Odor-identification is thought to be subserved by a distributed brain network that includes both the medial and inferior temporal lobes, still, its neural substrate remains poorly understood. Odor identification deficits are one of the hallmark symptoms of early Alzheimer’s disease (AD). Here, we propose the development of an oddball olfactory fMRI paradigm to establish the neural basis of odor-identification in healthy subjects. This task may provide a basis for establishing relationships between olfactory deficits, neurodegeneration, and memory impairment for current AD research.