Faculty Bibliography

Responses of sensory neurons represent stimulus information, but are also influenced by internal state. For example, when monkeys direct their attention to a visual stimulus, the response gain of specific subsets of neurons in visual cortex changes. Here, we develop a functional model of population activity to investigate the structure of this effect. We fit the model to the spiking activity of bilateral neural populations in area V4, recorded while the animal performed a stimulus discrimination task under spatial attention. The model reveals four separate time-varying shared modulatory signals, the dominant two of which each target task-relevant neurons in one hemisphere. In attention-directed conditions, the associated shared modulatory signal decreases in variance. This finding provides an interpretable and parsimonious explanation for previous observations that attention reduces variability and noise correlations of sensory neurons. Finally, the recovered modulatory signals reflect previous reward, and are predictive of choice behavior.

Synaptic plasticity serves as a cellular substrate for information storage in the central nervous system. The entorhinal cortex (EC) and hippocampus are interconnected brain areas supporting basic cognitive functions important for the formation and retrieval of declarative memories. Here, we discuss how information flow in the EC-hippocampal loop is organized through circuit design. We highlight recently identified corticohippocampal and intrahippocampal connections and how these long-range and local microcircuits contribute to learning. This review also describes various forms of activity-dependent mechanisms that change the strength of corticohippocampal synaptic transmission. A key point to emerge from these studies is that patterned activity and interaction of coincident inputs gives rise to associational plasticity and long-term regulation of information flow. Finally, we offer insights about how learning-related synaptic plasticity within the corticohippocampal circuit during sensory experiences may enable adaptive behaviors for encoding spatial, episodic, social, and contextual memories.

PURPOSE: Strict regulations are imposed on the amount of radiofrequency (RF) energy that devices can emit to prevent excessive deposition of RF energy into the body. In this study, we investigated the application of MR temperature mapping and 10-g average specific absorption rate (SAR) computation for safety evaluation of RF-emitting devices. METHODS: Quantification of the RF power deposition was shown for an MRI-compatible dipole antenna and a non-MRI-compatible mobile phone via phantom temperature change measurements. Validation of the MR temperature mapping method was demonstrated by comparison with physical temperature measurements and electromagnetic field simulations. MR temperature measurements alongside physical property measurements were used to reconstruct 10-g average SAR. RESULTS: The maximum temperature change for a dipole antenna and the maximum 10-g average SAR were 1.83 degrees C and 12.4 W/kg, respectively, for simulations and 1.73 degrees C and 11.9 W/kg, respectively, for experiments. The difference between MR and probe thermometry was <0.15 degrees C. The maximum temperature change and the maximum 10-g average SAR for a cell phone radiating at maximum output for 15 min was 1.7 degrees C and 0.54 W/kg, respectively. CONCLUSION: Information acquired using MR temperature mapping and thermal property measurements can assess RF/microwave safety with high resolution and fidelity. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

Patients with familial dysautonomia (FD) have afferent baroreflex failure and often experience extremely low blood pressure when upright, but rarely complain of symptoms of hypoperfusion. This suggests that patients either fail to recognize cerebral ischemia or have a better than normal cerebrovascular auto-regulatory capacity. Our aim was to examine the relationship between blood pressure, cerebral blood flow, and orthostatic symptoms in FD patients. We measured continuous blood pressure, RR intervals, end-tidal carbon dioxide and middle cerebral artery blood flow velocity (transcranial Doppler) supine, sitting, and standing in eleven patients with FD (age 27+/-2 years, 5males) and seven age-matched controls. Subjects were asked to report the presence or absence of symptoms at one-minute intervals. In patients with FD, systolic blood pressure fell significantly from 137+/-8 mmHg to 105 +/- 9 mmHg after 3 minutes of standing (p < 0.006, range 55 to 149 mmHg). Despite the fall in blood pressure none of the patients reported symptoms of orthostatic hypotension. Changes in cerebral blood flow were minimal (mean DELTA-6+/-3%), and not statistically different to controls (DELTA-3+/- 2%, p=0.39), which maintained their blood pressure well on standing. The results show that patients with FDhave an excellent auto-regulatory capacity and maintain cerebral blood flow within the normal range despite severe hypotension. This study highlights the usefulness of cerebral blood flow recordings to understand the relationship between symptoms and blood pressure in patients with abnormal baroreflex function

Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure due to baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD, and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and RR intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach with a percutaneous endoscopic gastrostomy (PEG) tube feeding (n = 9). Responses were compared to those of normal controls (n = 10) and of patients with autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked, but transient pressor response (p<0.0001) and additional signs of sympathetic activation including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in controls (p = 0.0001), but was absent in patients with autonomic failure. In patients with FD distending the stomach with a PEG tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic activation. The increase in blood pressure that is exaggerated in patients with FD due to blunted afferent baroreceptor signalling. The chewing pressor response may be useful as a counter-manoeuvre to raise blood pressure and prevent symptomatic orthostatic hypotension in patients with FD

In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal-regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

C.H. Vanderwolf described motor correlates of hippocampal theta oscillations and uncovered two broad classes: atropine-sensitive and atropine-resistant rhythm with likely different behavioral and cognitive significance. (c) 2015 Wiley Periodicals, Inc.

A fundamental theoretical result for diffusion MRI is the formula by Stejskal showing that the diffusion NMR signal is proportional to the Fourier transform of the diffusion displacement probability density function. Here this result is extended to multiple-pulsed diffusion MRI (MP-dMRI) by using a higher dimensional q-space formalism to express the diffusion-weighted signal for a sequence with N diffusion wave vectors in terms of a Fourier transform of a diffusion displacement probability density function in a 3N-dimensional space. As an illustration of the application of this extended version of Stejskal's formula, it is used to analyze the cumulant expansion of the signal magnitude for MP-dMRI.

Reduced parasympathetic modulation of heart rate is an independent predictor of mortality in heart failure. It is not known whether enhancing parasympathetic outflow to the heart impacts survival in these patients. Our aim was to evaluate whether the neck collar technique, a noninvasive method of stimulating the carotid baroreceptors, was a reliable and reproducible means to evaluate baroreflex control of heart rate in patients with heart failure. Twenty-five patients (20 males, mean age 54 +/-10-years) with symptomatic heart failure (NYHA class II-III) were studied on two separate days, one week apart. All were free of cholesterol plaques in the carotid arteries. Blood pressure and RR intervals were measured continuously in the seated position. Graded pressure (-70 to +70 mmHg) was administered to the neck during a held expiration using a custom-designed collar. Maximum change in RR intervals was determined during the onset of neck pressure. Stimulus response curves were plotted for changes in RR intervals against estimated-carotid sinus pressure. The technique was well tolerated and there were no adverse events. The maximal differential, used to estimate baroreflex gain, was tightly correlated between visits 1 and 2 (R2= 0.8063, p < 0.0001). The corresponding "set point" of the reflex was also significantly correlated between visits (R2=0.3324 p=0.049). To our knowledge, this is the first time the neck collar technique has been validated in a medically fragile population. The technique is safe and reproducible and maybe useful to help understand whether strategies that enhance parasympathetic activity change outcomes in heart failure

OBJECTIVE: This study aimed to demonstrate feasibility of free-breathing radial acquisition with respiratory motion-resolved compressed sensing reconstruction [extra-dimensional golden-angle radial sparse parallel imaging (XD-GRASP)] for multiphase dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced liver imaging, and to compare image quality to compressed sensing reconstruction with respiratory motion-averaging (GRASP) and prior conventional breath-held Cartesian-sampled data sets [BH volume interpolated breath-hold examination (VIBE)] in same patients. SUBJECTS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, 16 subjects underwent free-breathing continuous radial acquisition during Gd-EOB-DTPA injection and had prior BH-VIBE available. Acquired data were reconstructed using motion-averaging GRASP approach in which consecutive 84 spokes were grouped in each contrast-enhanced phase for a temporal resolution of approximately 14 seconds. Additionally, respiratory motion-resolved reconstruction was performed from the same k-space data by sorting each contrast-enhanced phase into multiple respiratory motion states using compressed sensing algorithm named XD-GRASP, which exploits sparsity along both the contrast-enhancement and respiratory-state dimensions.Contrast-enhanced dynamic multiphase XD-GRASP, GRASP, and BH-VIBE images were anonymized, pooled together in a random order, and presented to 2 board-certified radiologists for independent evaluation of image quality, with higher score indicating more optimal examination. RESULTS: The XD-GRASP reconstructions had significantly (all P < 0.05) higher overall image quality scores compared to GRASP for early arterial (reader 1: 4.3 +/- 0.6 vs 3.31 +/- 0.6; reader 2: 3.81 +/- 0.8 vs 3.38 +/- 0.9) and late arterial (reader 1: 4.5 +/- 0.6 vs 3.63 +/- 0.6; reader 2: 3.56 +/- 0.5 vs 2.88 +/- 0.7) phases of enhancement for both readers. The XD-GRASP also had higher overall image quality score in portal venous phase, which was significant for reader 1 (4.44 +/- 0.5 vs 3.75 +/- 0.8; P = 0.002). In addition, the XD-GRASP had higher overall image quality score compared to BH-VIBE for early (reader 1: 4.3 +/- 0.6 vs 3.88 +/- 0.6; reader 2: 3.81 +/- 0.8 vs 3.50 +/- 1.0) and late (reader 1: 4.5 +/- 0.6 vs 3.44 +/- 0.6; reader 2: 3.56 +/- 0.5 vs 2.94 +/- 0.9) arterial phases. CONCLUSION: Free-breathing motion-resolved XD-GRASP reconstructions provide diagnostic high-quality multiphase images in patients undergoing Gd-EOB-DTPA-enhanced liver examination.