Decision-Making in the Primate Brain

Making decisions is fundamental to everything we do, yet it can be impaired in various disorders and conditions. While research into the neural basis of decision-making has flourished in recent years, many questions remain about how decisions are instantiated in the brain. Here we explored how primates make abstract decisions and decisions in social contexts, as well as one way to non-invasively modulate the brain circuits underlying decision-making. We used rhesus macaques as our model organism. First we probed numerical decision-making, a form of abstract decision-making. We demonstrated that monkeys are able to compare discrete ratios, choosing an array with a greater ratio of positive to negative stimuli, even when this array does not have a greater absolute number of positive stimuli. Monkeys’ performance in this task adhered to Weber’s law, indicating that monkeys—like humans—treat proportions as analog magnitudes. Next we showed that monkeys’ ordinal decisions are influenced by spatial associations; when trained to select the fourth stimulus from the bottom in a vertical array, they subsequently selected the fourth stimulus from the left—and not from the right—in a horizontal array. In other words, they begin enumerating from one side of space and not the other, mirroring the human tendency to associate numbers with space. These and other studies confirmed that monkeys’ numerical decision-making follows similar patterns to that of humans, making them a good model for investigations of the neurobiological basis of numerical decision-making.

We sought to develop a system for exploring the neuronal basis of the cognitive and behavioral effects observed following transcranial magnetic stimulation, a relatively new, non-invasive method of brain stimulation that may be used to treat clinical disorders. We completed a set of pilot studies applying offline low-frequency repetitive transcranial magnetic stimulation to the macaque posterior parietal cortex, which has been implicated in numerical processing, while subjects performed a numerical comparison and control color comparison task, and while electrophysiological activity was recorded from the stimulated region of cortex. We found tentative evidence in one paradigm that stimulation did selectively impair performance in the number task, causally implicating the posterior parietal cortex in numerical decisions. In another paradigm, however, we manipulated the subject’s reaching behavior but not her number or color comparison performance. We also found that stimulation produced variable changes in neuronal firing and local field potentials. Together these findings lay the groundwork for detailed investigations into how different parameters of transcranial magnetic stimulation can interact with cortical architecture to produce various cognitive and behavioral changes.

Finally, we explored how monkeys decide how to behave in competitive social interactions. In a zero-sum computer game in which two monkeys played as a shooter or a goalie during a hockey-like “penalty shot” scenario, we found that shooters developed complex movement trajectories so as to conceal their intentions from the goalies. Additionally, we found that neurons in the dorsolateral and dorsomedial prefrontal cortex played a role in generating this “deceptive” behavior. We conclude that these regions of prefrontal cortex form part of a circuit that guides decisions to make an individual less predictable to an opponent.

Gaussian Process Kernels for Cross-Spectrum Analysis in Electrophysiological Time Series

Multi-output Gaussian processes provide a convenient framework for multi-task problems. An illustrative and motivating example of a multi-task problem is multi-region electrophysiological time-series data, where experimentalists are interested in both power and phase coherence between channels. Recently, the spectral mixture (SM) kernel was proposed to model the spectral density of a single task in a Gaussian process framework. This work develops a novel covariance kernel for multiple outputs, called the cross-spectral mixture (CSM) kernel. This new, flexible kernel represents both the power and phase relationship between multiple observation channels. The expressive capabilities of the CSM kernel are demonstrated through implementation of 1) a Bayesian hidden Markov model, where the emission distribution is a multi-output Gaussian process with a CSM covariance kernel, and 2) a Gaussian process factor analysis model, where factor scores represent the utilization of cross-spectral neural circuits. Results are presented for measured multi-region electrophysiological data.

Control of radiative processes using tunable plasmonic nanopatch antennas.

The radiative processes associated with fluorophores and other radiating systems can be profoundly modified by their interaction with nanoplasmonic structures. Extreme electromagnetic environments can be created in plasmonic nanostructures or nanocavities, such as within the nanoscale gap region between two plasmonic nanoparticles, where the illuminating optical fields and the density of radiating modes are dramatically enhanced relative to vacuum. Unraveling the various mechanisms present in such coupled systems, and their impact on spontaneous emission and other radiative phenomena, however, requires a suitably reliable and precise means of tuning the plasmon resonance of the nanostructure while simultaneously preserving the electromagnetic characteristics of the enhancement region. Here, we achieve this control using a plasmonic platform consisting of colloidally synthesized nanocubes electromagnetically coupled to a metallic film. Each nanocube resembles a nanoscale patch antenna (or nanopatch) whose plasmon resonance can be changed independent of its local field enhancement. By varying the size of the nanopatch, we tune the plasmonic resonance by ∼ 200 nm, encompassing the excitation, absorption, and emission spectra corresponding to Cy5 fluorophores embedded within the gap region between nanopatch and film. By sweeping the plasmon resonance but keeping the field enhancements roughly fixed, we demonstrate fluorescence enhancements exceeding a factor of 30,000 with detector-limited enhancements of the spontaneous emission rate by a factor of 74. The experiments are supported by finite-element simulations that reveal design rules for optimized fluorescence enhancement or large Purcell factors.

Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity.

The reliable neuroimaging finding that older adults often show greater activity (over-recruitment) than younger adults is typically attributed to compensation. Yet, the neural mechanisms of over-recruitment in older adults (OAs) are largely unknown. Rodent electrophysiology studies have shown that as number of afferent fibers within a circuit decreases with age, the fibers that remain show higher synaptic field potentials (less wiring, more firing). Extrapolating to system-level measures in humans, we proposed and tested the hypothesis that greater activity in OAs compensates for impaired white-matter connectivity. Using a neuropsychological test battery, we measured individual differences in executive functions associated with the prefrontal cortex (PFC) and memory functions associated with the medial temporal lobes (MTLs). Using event-related functional magnetic resonance imaging, we compared activity for successful versus unsuccessful trials during a source memory task. Finally, we measured white-matter integrity using diffusion tensor imaging. The study yielded 3 main findings. First, low-executive OAs showed greater success-related activity in the PFC, whereas low-memory OAs showed greater success-related activity in the MTLs. Second, low-executive OAs displayed white-matter deficits in the PFC, whereas low-memory OAs displayed white-matter deficits in the MTLs. Finally, in both prefrontal and MTL regions, white-matter decline and success-related activations occurred in close proximity and were negatively correlated. This finding supports the less-wiring-more-firing hypothesis, which provides a testable account of compensatory over-recruitment in OAs.

A widespread chromosomal inversion polymorphism contributes to a major life-history transition, local adaptation, and reproductive isolation.

The role of chromosomal inversions in adaptation and speciation is controversial. Historically, inversions were thought to contribute to these processes either by directly causing hybrid sterility or by facilitating the maintenance of co-adapted gene complexes. Because inversions suppress recombination when heterozygous, a recently proposed local adaptation mechanism predicts that they will spread if they capture alleles at multiple loci involved in divergent adaptation to contrasting environments. Many empirical studies have found inversion polymorphisms linked to putatively adaptive phenotypes or distributed along environmental clines. However, direct involvement of an inversion in local adaptation and consequent ecological reproductive isolation has not to our knowledge been demonstrated in nature. In this study, we discovered that a chromosomal inversion polymorphism is geographically widespread, and we test the extent to which it contributes to adaptation and reproductive isolation under natural field conditions. Replicated crosses between the prezygotically reproductively isolated annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatus, revealed that alternative chromosomal inversion arrangements are associated with life-history divergence over thousands of kilometers across North America. The inversion polymorphism affected adaptive flowering time divergence and other morphological traits in all replicated crosses between four pairs of annual and perennial populations. To determine if the inversion contributes to adaptation and reproductive isolation in natural populations, we conducted a novel reciprocal transplant experiment involving outbred lines, where alternative arrangements of the inversion were reciprocally introgressed into the genetic backgrounds of each ecotype. Our results demonstrate for the first time in nature the contribution of an inversion to adaptation, an annual/perennial life-history shift, and multiple reproductive isolating barriers. These results are consistent with the local adaptation mechanism being responsible for the distribution of the two inversion arrangements across the geographic range of M. guttatus and that locally adaptive inversion effects contribute directly to reproductive isolation. Such a mechanism may be partially responsible for the observation that closely related species often differ by multiple chromosomal rearrangements.

Towards a field-compatible optical spectroscopic device for cervical cancer screening in resource-limited settings: effects of calibration and pressure.

Quantitative optical spectroscopy has the potential to provide an effective low cost, and portable solution for cervical pre-cancer screening in resource-limited communities. However, clinical studies to validate the use of this technology in resource-limited settings require low power consumption and good quality control that is minimally influenced by the operator or variable environmental conditions in the field. The goal of this study was to evaluate the effects of two sources of potential error: calibration and pressure on the extraction of absorption and scattering properties of normal cervical tissues in a resource-limited setting in Leogane, Haiti. Our results show that self-calibrated measurements improved scattering measurements through real-time correction of system drift, in addition to minimizing the time required for post-calibration. Variations in pressure (tested without the potential confounding effects of calibration error) caused local changes in vasculature and scatterer density that significantly impacted the tissue absorption and scattering properties Future spectroscopic systems intended for clinical use, particularly where operator training is not viable and environmental conditions unpredictable, should incorporate a real-time self-calibration channel and collect diffuse reflectance spectra at a consistent pressure to maximize data integrity.

The incidence of unacceptable movement with motor evoked potentials during craniotomy for aneurysm clipping.

OBJECTIVE: To review the experience at a single institution with motor evoked potential (MEP) monitoring during intracranial aneurysm surgery to determine the incidence of unacceptable movement. METHODS: Neurophysiology event logs and anesthetic records from 220 craniotomies for aneurysm clipping were reviewed for unacceptable patient movement or reason for cessation of MEPs. Muscle relaxants were not given after intubation. Transcranial MEPs were recorded from bilateral abductor hallucis and abductor pollicis muscles. MEP stimulus intensity was increased up to 500 V until evoked potential responses were detectable. RESULTS: Out of 220 patients, 7 (3.2%) exhibited unacceptable movement with MEP stimulation-2 had nociception-induced movement and 5 had excessive field movement. In all but one case, MEP monitoring could be resumed, yielding a 99.5% monitoring rate. CONCLUSIONS: With the anesthetic and monitoring regimen, the authors were able to record MEPs of the upper and lower extremities in all patients and found only 3.2% demonstrated unacceptable movement. With a suitable anesthetic technique, MEP monitoring in the upper and lower extremities appears to be feasible in most patients and should not be withheld because of concern for movement during neurovascular surgery.

Division of labor in frontal eye field neurons during presaccadic remapping of visual receptive fields.

Our percept of visual stability across saccadic eye movements may be mediated by presaccadic remapping. Just before a saccade, neurons that remap become visually responsive at a future field (FF), which anticipates the saccade vector. Hence, the neurons use corollary discharge of saccades. Many of the neurons also decrease their response at the receptive field (RF). Presaccadic remapping occurs in several brain areas including the frontal eye field (FEF), which receives corollary discharge of saccades in its layer IV from a collicular-thalamic pathway. We studied, at two levels, the microcircuitry of remapping in the FEF. At the laminar level, we compared remapping between layers IV and V. At the cellular level, we compared remapping between different neuron types of layer IV. In the FEF in four monkeys (Macaca mulatta), we identified 27 layer IV neurons with orthodromic stimulation and 57 layer V neurons with antidromic stimulation from the superior colliculus. With the use of established criteria, we classified the layer IV neurons as putative excitatory (n = 11), putative inhibitory (n = 12), or ambiguous (n = 4). We found that just before a saccade, putative excitatory neurons increased their visual response at the RF, putative inhibitory neurons showed no change, and ambiguous neurons increased their visual response at the FF. None of the neurons showed presaccadic visual changes at both RF and FF. In contrast, neurons in layer V showed full remapping (at both the RF and FF). Our data suggest that elemental signals for remapping are distributed across neuron types in early cortical processing and combined in later stages of cortical microcircuitry.

Frontal eye field neurons assess visual stability across saccades.

The image on the retina may move because the eyes move, or because something in the visual scene moves. The brain is not fooled by this ambiguity. Even as we make saccades, we are able to detect whether visual objects remain stable or move. Here we test whether this ability to assess visual stability across saccades is present at the single-neuron level in the frontal eye field (FEF), an area that receives both visual input and information about imminent saccades. Our hypothesis was that neurons in the FEF report whether a visual stimulus remains stable or moves as a saccade is made. Monkeys made saccades in the presence of a visual stimulus outside of the receptive field. In some trials, the stimulus remained stable, but in other trials, it moved during the saccade. In every trial, the stimulus occupied the center of the receptive field after the saccade, thus evoking a reafferent visual response. We found that many FEF neurons signaled, in the strength and timing of their reafferent response, whether the stimulus had remained stable or moved. Reafferent responses were tuned for the amount of stimulus translation, and, in accordance with human psychophysics, tuning was better (more prevalent, stronger, and quicker) for stimuli that moved perpendicular, rather than parallel, to the saccade. Tuning was sometimes present as well for nonspatial transaccadic changes (in color, size, or both). Our results indicate that FEF neurons evaluate visual stability during saccades and may be general purpose detectors of transaccadic visual change.

Reversible inactivation of macaque frontal eye field.

The macaque frontal eye field (FEF) is involved in the generation of saccadic eye movements and fixations. To better understand the role of the FEF, we reversibly inactivated a portion of it while a monkey made saccades and fixations in response to visual stimuli. Lidocaine was infused into a FEF and neural inactivation was monitored with a nearby microelectrode. We used two saccadic tasks. In the delay task, a target was presented and then extinguished, but the monkey was not allowed to make a saccade to its location until a cue to move was given. In the step task, the monkey was allowed to look at a target as soon as it appeared. During FEF inactivation, monkeys were severely impaired at making saccades to locations of extinguished contralateral targets in the delay task. They were similarly impaired at making saccades to locations of contralateral targets in the step task if the target was flashed for < or =100 ms, such that it was gone before the saccade was initiated. Deficits included increases in saccadic latency, increases in saccadic error, and increases in the frequency of trials in which a saccade was not made. We varied the initial fixation location and found that the impairment specifically affected contraversive saccades rather than affecting all saccades made into head-centered contralateral space. Monkeys were impaired only slightly at making saccades to contralateral targets in the step task if the target duration was 1000 ms, such that the target was present during the saccade: latency increased, but increases in saccadic error were mild and increases in the frequency of trials in which a saccade was not made were insignificant. During FEF inactivation there usually was a direct correlation between the latency and the error of saccades made in response to contralateral targets. In the delay task, FEF inactivation increased the frequency of making premature saccades to ipsilateral targets. FEF inactivation had inconsistent and mild effects on saccadic peak velocity. FEF inactivation caused impairments in the ability to fixate lights steadily in contralateral space. FEF inactivation always caused an ipsiversive deviation of the eyes in darkness. In summary, our results suggest that the FEF plays major roles in (1) generating contraversive saccades to locations of extinguished or flashed targets, (2) maintaining contralateral fixations, and (3) suppressing inappropriate ipsiversive saccades.

Beyond the Convent Walls: The Local and Japan-wide Activities of Daihongan’s Nuns in the Early Modern Period (c. 1550–1868)

This dissertation examines the social and financial activities of Buddhist nuns to demonstrate how and why they deployed Buddhist doctrines, rituals, legends, and material culture to interact with society outside the convent. By examining the activities of the nuns of the Daihongan convent (one of the two administrative heads of the popular pilgrimage temple, Zenkōji) in Japan’s early modern period (roughly 1550 to 1868) as documented in the convent’s rich archival sources, I shed further light on the oft-overlooked political and financial activities of nuns, illustrate how Buddhist institutions interacted with the laity, provide further nuance to the discussion of how Buddhist women navigated patriarchal sectarian and secular hierarchies, and, within the field of Japanese history, give voice to women who were active outside of the household unit around which early modern Japanese society was organized.

Zenkōji temple, surrounded by the mountains of Nagano, has been one of Japan’s most popular pilgrimage sites since the medieval period. The abbesses of Daihongan, one Zenkōji’s main sub-temples, traveled widely to maintain connections with elite and common laypeople, participated in frequent country-wide displays of Zenkōji’s icon, and oversaw the creation of branch temples in Edo (now Tokyo), Osaka, Echigo (now Niigata), and Shinano (now Nagano). The abbesses of Daihongan were one of only a few women to hold the imperially sanctioned title of eminent person (shōnin 上人) and to wear purple robes. While this means that this Pure Land convent was in some ways not representative of all convents in early modern Japan, Daihongan’s position is particularly instructive because the existence of nuns and monks in a single temple complex allows us to see in detail how monastics of both genders interacted in close quarters.

This work draws heavily from the convent’s archival materials, which I used as a guide in framing my dissertation chapters. In the Introduction I discuss previous works on women in Buddhism. In Chapter 1, I briefly discuss the convent’s history and its place within the Zenkōji temple complex. In Chapter 2, I examine the convent’s regular economic bases and its expenditures. In Chapter 3, I highlight Daihongan’s branch temples and discuss the ways that they acted as nodes in a network connecting people in various areas to Daihongan and Zenkōji, thus demonstrating how a rural religious center extended its sphere of influence in urban settings. In Chapter 4, I discuss the nuns’ travels throughout the country to generate new and maintain old connections with the imperial court in Kyoto, confraternities in Osaka, influential women in the shogun’s castle, and commoners in Edo. In Chapter 5, I examine the convent’s reliance upon irregular means of income such as patronage, temple lotteries, loans, and displays of treasures, and how these were needed to balance irregular expenditures such as travel and the maintenance or reconstruction of temple buildings. Throughout the dissertation I describe Daihongan’s inner social structure comprised of abbesses, nuns, and administrators, and its local emplacement within Zenkōji and Zenkōji’s temple lands.

Exploring these themes sheds light on the lives of Japanese Buddhist nuns in this period. While the tensions between freedom and agency on the one hand and obligations to patrons, subordination to monks, or gender- and status-based restrictions on the other are important, and I discuss them in my work, my primary focus is on the nuns’ activities and lives. Doing so demonstrates that nuns were central figures in ever-changing economic and social networks as they made and maintained connections with the outside world through Buddhist practices and through precedents set centuries before. This research contributes to our understanding of nuns in Japan’s early modern period and will participate in and shape debates on the roles of women in patriarchal religious hierarchies.

The Influence of Household Economic Status and Food Consumption Patterns on Obesity Rates in Peru – Evidence from a Field Study in 11 Communities of Madre de Dios

The globalization contributes to rapid economic developments and great changes of lifestyle in Madre de Dios of Peru, both of which have influenced the health status of local people in direct and indirect ways. The high overweight and obesity rate has become one of the biggest health challenges in this region. This study quantitatively analyzed the impact of household economic status and food consumption patterns on overweight and obesity, and tried to establish their relationship with local economic activities. People living in mining communities are more likely to be overweight or obese. Increased family incomes and lacks of health knowledge are two important reasons. The large consumption of soda and alcohol are positively associated with overweight and obesity. In addition, lack of physical activities is also one of the risk factors of overweight and obesity.