Abnormal functional connectivity in women with urgency urinary incontinence: Can we predict disease presence and severity in individual women using Rs-fcMRI/.

AIMS: To identify atypical brain functional connectivity in women with UUI and detrusor overactivity (DO) and to predict the presence/severity of UUI in individual women using connectivity features. METHODS: This is a cross-sectional study comparing brain functional connectivity in women with and without UUI. Validated symptom/quality of life questionnaires were used for phenotyping. Participants are females between ages 40 and 85 with daily UUI with DO (Cases, N = 16) and without UUI (Controls, N = 24). Functional MRI and Resting state connectivity MRI were obtained at empty/ full bladder. Multivariate pattern analysis (MVPA) was used to predict the presence and severity of UUI from connectivity data. RESULTS: There are significant differences in brain activation between cases and controls in eighteen brain regions irrespective of empty or full bladder. These include regions involved in attention (inferior partietal), decision making (inferior and superior frontal gyrus), primary motor and sensory (precentral and postcentral gyrus) functions. Women with UUI showed no change in connectivity with bladder filling in regions involved in interoception (insula), integration of afferent function (anterior cingulate), and decision making (middle frontal). MVPA of connectivity data showed robust classification of an individual woman as case or control (89% sensitivity, 83% specificity). Six connectivity features accurately predicted disease severity (R(2) = 0.81). CONCLUSION: We identified two mechanisms of abnormal bladder control, one involving atypical activation of brain regions, and another atypical functional integration across sensory, emotional, cognitive and motor regions. Connectivity information is robust enough to classify an individual as having UUI or not and to predict symptom severity. Neurourol. Urodynam. 35:564-573, 2016. © 2015 Wiley Periodicals, Inc.

Examining mechanisms of brain control of bladder function with resting state functional connectivity MRI.

AIMS: This aim of this study is to identify the brain mechanisms involved in bladder control. METHODS: We used fMRI to identify brain regions that are activated during bladder filling. We then used resting state connectivity fMRI (rs-fcMRI) to assess functional connectivity of regions identified by fMRI with the rest of the brain as the bladder is filled to capacity. RESULTS: Female participants (n = 20) were between ages 40 and 64 with no significant history of symptomatic urinary incontinence. Main effect of time (MET) fMRI analysis resulted in 20 regions of interest (ROIs) that have significant change in BOLD signal (z = 3.25, P <0.05) over the course of subtle bladder filling and emptying regardless of full versus empty bladder state. Bladder-state by time (BST) fMRI analysis resulted in three ROIs that have significant change in BOLD signal (z = 3.25, P <0.05) over the course of bladder runs comparing full versus empty bladder state. Rs-fcMRI fixed effects analysis identified significant changes in connectivity between full and empty bladder states in seven brain regions (z = 4.0) using the three BST ROIs and sixteen brain regions (z = 7) using the twenty MET ROIs. Regions identified include medial frontal gyrus, posterior cingulate (PCC), inferiolateral temporal and post-central gyrus, amygdale, the caudate, inferior parietal lobe as well as anterior and middle cingulate gyrus. CONCLUSIONS: There is significant and vast changes in the brain's functional connectivity when bladder is filled suggesting that the central process responsible for the increased control during the full bladder state appears to largely rely on the how distributed brain systems are functionally integrated.

Intrahepatic lipid, not visceral or muscle fat, is correlated with insulin resistance in older, female rhesus macaques.

OBJECTIVE: Little is known of the effect of body composition on glucose metabolism in the aging female non-human primate. These variables in older female Rhesus macaques were studied. DESIGN AND METHODS: Female Rhesus macaques (Macaca mulatta, n = 19, age range 23-30 years) underwent magnetic resonance imaging and (1) H spectroscopy to quantify total abdominal fat, visceral fat (VF), subcutaneous fat (SF) area, extramyocellular lipid (EMCL), intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content, and DEXA scan for whole body composition. A subgroup (n = 12) underwent a fasting blood draw and intravenous glucose tolerance test. RESULTS: SF correlated with homeostatic model assessment of insulin resistance (HOMAIR ) and quantitative insulin sensitivity check index (QUICKI), but not after adjustment for fat mass. IHL demonstrated the strongest correlation with HOMAIR , QUICKI and calculated insulin sensitivity index (CSI ), and remained significant after adjustment for fat mass. VF, IMCL, and EMCL did not correlate with any of our measures of insulin sensitivity. CONCLUSIONS: Despite a greater amount of VF compared to SF, VF was not associated with markers of insulin resistance (IR) in the older female monkey. Instead, IHL is a marker for IR in the fasting and post-prandial state in these animals.

Changes in fMRI activation following rehabilitation of reading and visual processing deficits in subjects with traumatic brain injury.

In this case series fMRI was used to examine activation patterns during presentation of a reading comprehension (RC) task in three adult subjects with a history of severe traumatic brain injury (TBI). These subjects received cognitive rehabilitation therapy (CRT) for visual processing and acquired reading deficits. fMRI and neuropsychological testing occurred pre- and post-rehabilitation. The study's objective was to evaluate the neurobiological changes using fMRI occurring with CRT and to compare these results to repeat fMRI in matched controlsubjects. While improvements in neuropsychologicaltesting occurred post-CRT, diffuse and variable activation patterns in the subjects with TBI were still demonstrated when compared to the control subjects repeat imaging. Multiple networks exist to accomplish the complex task of sentence reading and rehabilitation of the cognitive components of reading, such as visual processing; in subjects with TBI, can alter the activation pattern demonstrated during reading comprehension in subjects many years post-injury. This is the first demonstration of changes in network activation patterns post-CRT in patients with severe, chronic TBI on an fMRI task shown to have imaging stability in a normal control sample.

Functional neuroanatomy of anticipatory behavior: dissociation between sensory-driven and memory-driven systems.

The ability to anticipate predictable stimuli allows faster responses. The predictive saccade (PRED) task has been shown to quickly induce such anticipatory behavior in humans. In a PRED task subjects track a visual target jumping back and forth between fixed positions at a fixed time interval. During this task, saccade latencies drop from approximately 200 ms to <80 ms as subjects anticipate target appearance. This change in saccade latency indicates that subjects' behavior shifts from being sensory driven to being memory driven. We conducted functional magnetic resonance imaging studies with 10 healthy adults performing the PRED task using a standard block design. We compared the PRED task with a visually guided saccade (VGS) task using unpredictable targets matched for number, direction and amplitude of required saccades. Our results show greater activation during the PRED task in the prefrontal, pre-supplementary motor and anterior cingulate cortices, hippocampus, mediodorsal thalamus, striatum and cerebellum. The VGS task elicited greater activation in the cortical eye fields and occipital cortex. These results demonstrate the important dissociation between sensory and predictive neural control of similar saccadic eye movements. Anticipatory behavior induced by the PRED task required less sensory-related processing activity and was subserved by a distributed cortico-subcortical memory system including prefronto-striatal circuitry.

Pursuit eye movement deficits in autism.

Oculomotor studies provide a novel strategy for evaluating the functional integrity of multiple brain systems and cognitive processes in autism. The current study compared pursuit eye movements of 60 high-functioning individuals with autism and 94 intelligence quotient, age and gender matched healthy individuals using ramp and oscillating target tasks. Individuals with autism had normal pursuit latency, but reduced closed-loop pursuit gain when tracking both oscillating and ramp targets. This closed-loop deficit was similar for leftward and rightward pursuit, but the difference between individuals with autism and their age-matched peers was more apparent after mid-adolescence, suggesting reduced maturational achievement of the pursuit system in autism. Individuals with autism also had lower open-loop pursuit gain (initial 100 ms of pursuit) and less accurate initial catch-up saccades during a foveofugal step-ramp task, but these deficits were only seen when targets moved into the right visual field. Pursuit performance in both open- and closed-loop phases was correlated with manual praxis in individuals with autism. Bilateral disturbances in the ability to use internally generated extraretinal signals for closed-loop pursuit implicate frontostriatal or cerebellar circuitry. The hemifield specific deficit in open-loop pursuit demonstrates a lateralized disturbance in the left extrastriate areas that extract visual motion information, or in the transfer of visual motion information to the sensorimotor areas that transform visual information into appropriate oculomotor commands.

Frequency and metrics of square-wave jerks: influences of task-demand characteristics.

PURPOSE: Square-wave jerks (SWJs) during visual fixation and pursuit tracking of targets of varying speed and predictability were investigated in the present study. METHODS: SWJs were measured in 91 subjects as they fixated a target or a remembered target location and tracked targets that varied in velocity and predictability. RESULTS: Percentages of subjects making SWJ and mean SWJ frequency per minute in the high- and low-predictability conditions were 99% and 9.34 and 91% and 2.78, respectively. SWJ rates were significantly lower when observers fixated remembered target locations rather than visual targets and during tracking of faster-moving and less predictable targets. Differences in task conditions cannot be explained by volitional influences to control the first saccade in the SWJ. There was also no influence of age on SWJ rate. CONCLUSIONS: Reduced SWJ rates after manipulations that increased task demands on visual pursuit of targets suggest an inverse relationship between current demands imposed by visual tasks and rates of intrusive saccades. These findings suggest that signals from cortical attentional systems may suppress inappropriate saccades that would divert the eyes from objects of interest during conditions imposing high task demands on the visual system.

Pursuit and saccadic eye movement subregions in human frontal eye field: a high-resolution fMRI investigation.

Recent positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in humans have localized the frontal eye field (FEF) to the precentral sulcus (PCS). In macaque monkeys, low-threshold microstimulation and single unit recording studies have located a saccadic subregion of FEF in a restricted area along the anterior wall of the arcuate sulcus and a pursuit subregion located deeper in the sulcus close to the fundus. The functional organization and anatomical location of these two FEF subregions are still to be defined in humans. In the present study, we used fMRI with high spatial resolution image acquisition at 3.0 Tesla to map the saccade- and pursuit-related areas of FEF within the two walls of the PCS in 11 subjects. We localized the saccade-related area to the upper portion of the anterior wall of the precentral sulcus and the pursuit-related area to a deeper region along the anterior wall, extending in some subjects to the fundus or deep posterior wall. These findings localize distinct pursuit and saccadic subregions of FEF in humans and demonstrate a high degree of homology in the organization of these FEF subregions in the human and the macaque monkey.