Network organization of sensory-biased and multi-sensory working memory and attention in human cortex with fMRI

The ability to attentively filter sensory information and manipulate it in working memory is critical for our ability to interact with the world. Although primary and secondary sensory cortical areas have been well-studied, frontal lobe contributions to sensory attention and working memory remain under-investigated. This dissertation investigates the topography and network organization of sensory-biased and multi-sensory regions in the healthy human brain using functional magnetic resonance imaging (fMRI). First, this research developed a series of functional connectivity analyses of data from the Human Connectome Project to validate and extend recently localized auditory-biased network structures, transverse gyrus intersecting the precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS), and visual-biased network structures, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), in lateral frontal cortex (LFC). Results replicated the original findings and extended them by revealing five additional bilateral LFC regions, including middle inferior frontal sulcus (midIFS) and frontal operculum (FO), differentially connected to either the visual- or auditory-biased networks. Due to inter-subject anatomical variability, identification of sPCS, tgPCS, iPCS and cIFS depends critically on within-subject analyses. Next, this work demonstrated that an individual’s unique pattern of resting-state functional connectivity can accurately identify their specific pattern of working memory (WM) and attention task activation in LFC using “connectome fingerprinting” (CF). CF predictions were superior to group-average predictions and matched the accuracy of within-subject task-based functional localization. This research developed and validated methods that use intrinsic functional connectivity information to perform functional brain analyses on highly idiosyncratic brain regions. Finally, a combined auditory, tactile and visual WM study revealed the joint organization of sensory-biased and multi-sensory regions within individual subjects. Hypothesized visual-biased midIFS and auditory-biased FO regions were functionally confirmed for the first time. Several bilateral tactile-biased regions, premotor dorsal, premotor ventral, anterior middle frontal gyrus, middle insula, postcentral sulcus, posterior middle temporal gyrus and pre-supplemental motor area, abutting previously described visual- and auditory-biased regions were identified. Several multi-sensory WM regions, recruited in each stimulus modality, were observed to partially overlap with visual-biased regions. Intrinsic functional connectivity analyses revealed that regions segregate into networks largely based upon their modality preferences.2020-06-14T00:00:00

Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study

Objective: To study the association between hormonal exposures and disease onset in a cohort of women with neuromyelitis optica spectrum disorder (NMOSD). Methods: Reproductive history and hormone use were assessed using a standardized reproductive survey administered to women with NMOSD (82% aquaporin-4 antibody positive) at 8 clinical centers. Using multivariable regression, we examined the association between reproductive exposures and age at first symptom onset (FS). Results: Among 217 respondents, the mean age at menarche was 12.8 years (SD 1.7). The mean number of pregnancies was 2.1 (SD 1.6), including 0.3 (SD 0.7) occurring after onset of NMOSD symptoms. In the 117 participants who were postmenopausal at the time of the questionnaire, 70% reported natural menopause (mean age: 48.9 years [SD 3.9]); fewer than 30% reported systemic hormone therapy (HT) use. Mean FS age was 40.1 years (SD 14.2). Ever-use of systemic hormonal contraceptives (HC) was marginally associated with earlier FS (39 vs 43 years, p = 0.05). Because HC use may decrease parity, when we included both variables in the model, the association between HC use and FS age became more significant (estimate = 2.7, p = 0.007). Among postmenopausal participants, 24% reported NMOSD onset within 2 years of (before or after) menopause. Among these participants, there was no association between age at menopause or HT use and age at NMOSD onset. Conclusions: Overall, age at NMOSD onset did not show a strong relationship with endogenous hormonal exposures. An earlier onset age did appear to be marginally associated with systemic HC exposure, an association that requires confirmation in future studies

Cooperative interactions between hippocampal and striatal systems support flexible navigation

Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually dependent navigation

Corpus callosum axon diameter relates to cognitive impairment in multiple sclerosis

Abstract Objective To evaluate alterations in apparent axon diameter and axon density obtained by high‐gradient diffusion MRI in the corpus callosum of MS patients and the relationship of these advanced diffusion MRI metrics to neurologic disability and cognitive impairment in MS. Methods Thirty people with MS (23 relapsing‐remitting MS [RRMS], 7 progressive MS [PMS]) and 23 healthy controls were scanned on a human 3‐tesla (3T) MRI scanner equipped with 300 mT/m maximum gradient strength using a comprehensive multishell diffusion MRI protocol. Data were fitted to a three‐compartment geometric model of white matter to estimate apparent axon diameter and axon density in the midline corpus callosum. Neurologic disability and cognitive function were measured using the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Minimal Assessment of Cognitive Function in MS battery. Results Apparent axon diameter was significantly larger and axon density reduced in the normal‐appearing corpus callosum (NACC) of MS patients compared to healthy controls, with similar trends seen in PMS compared to RRMS. Larger apparent axon diameter in the NACC of MS patients correlated with greater disability as measured by the EDSS (r = 0.555, P = 0.007) and poorer performance on the Symbol Digits Modalities Test (r = ‐0.593, P = 0.008) and Brief Visuospatial Memory Test–Revised (r = −0.632, P < 0.01), tests of interhemispheric processing speed and new learning and memory, respectively. Interpretation Apparent axon diameter in the corpus callosum obtained from high‐gradient diffusion MRI is a potential imaging biomarker that may be used to understand the development and progression of cognitive impairment in MS