In the blink of an eye: Value and novelty drive saccades

Evidence accumulation is an essential component of value-based decisions. Recent human studies suggest that overt attention correlates with evidence accumulation necessary for optimal decisions. However, the influence of covert attention on decision-making remains relatively unexplored. To investigate this issue, two monkeys were trained to perform a decision-making task where they chose between two stimuli, which were either ‘Overtrained’ or learned that day (‘Novel’). Subjects could freely saccade during choice evaluation and indicated their decision by moving a joystick. Saccades were made within 170 ms of stimulus presentation and were strongly driven by both value and novelty, implying covert stimulus evaluation prior to saccade. This effect was strongest for ‘Overtrained’ choices, but rapidly emerged during learning of ‘Novel’ choices. Though novel stimuli attracted initial saccades, final decisions were guided only by value; implying attentional value comparison processes are at least partially dissociable from value comparison processes that govern final decisions. While subjects made highly optimal decisions, they frequently viewed only one stimulus; final choice was thus best explained by assuming covert evidence accumulation. Our results suggest that the primate brain contains multiple value comparison systems for guiding attention toward highly valuable or novel information while simultaneously optimizing final decision value

Decision Making and Reward in Frontal Cortex: Complementary Evidence From Neurophysiological and Neuropsychological Studies

Patients with damage to the prefrontal cortex (PFC)—especially the ventral and medial parts of PFC—often show a marked inability to make choices that meet their needs and goals. These decision-making impairments often reflect both a deficit in learning concerning the consequences of a choice, as well as deficits in the ability to adapt future choices based on experienced value of the current choice. Thus, areas of PFC must support some value computations that are necessary for optimal choice. However, recent frameworks of decision making have highlighted that optimal and adaptive decision making does not simply rest on a single computation, but a number of different value computations may be necessary. Using this framework as a guide, we summarize evidence from both lesion studies and single-neuron physiology for the representation of different value computations across PFC areas

Coupling between gamma-band power and cerebral blood volume during recurrent acute neocortical seizures

Characterization of neural and hemodynamic biomarkers of epileptic activity that can be measured using non-invasive techniques is fundamental to the accurate identification of the epileptogenic zone (EZ) in the clinical setting. Recently, oscillations at gamma-band frequencies and above (>30 Hz) have been suggested to provide valuable localizing information of the EZ and track cortical activation associated with epileptogenic processes. Although a tight coupling between gamma-band activity and hemodynamic-based signals has been consistently demonstrated in non-pathological conditions, very little is known about whether such a relationship is maintained in epilepsy and the laminar etiology of these signals. Confirmation of this relationship may elucidate the underpinnings of perfusion-based signals in epilepsy and the potential value of localizing the EZ using hemodynamic correlates of pathological rhythms. Here, we use concurrent multi-depth electrophysiology and 2-dimensional optical imaging spectroscopy to examine the coupling between multi-band neural activity and cerebral blood volume (CBV) during recurrent acute focal neocortical seizures in the urethane-anesthetized rat. We show a powerful correlation between gamma-band power (25-90 Hz) and CBV across cortical laminae, in particular layer 5, and a close association between gamma measures and multi-unit activity (MUA). Our findings provide insights into the laminar electrophysiological basis of perfusion-based imaging signals in the epileptic state and may have implications for further research using non-invasive multi-modal techniques to localize epileptogenic tissue

Neural Signatures of Value Comparison in Human Cingulate Cortex during Decisions Requiring an Effort-Reward Trade-off

UNLABELLED: Integrating costs and benefits is crucial for optimal decision-making. Although much is known about decisions that involve outcome-related costs (e.g., delay, risk), many of our choices are attached to actions and require an evaluation of the associated motor costs. Yet how the brain incorporates motor costs into choices remains largely unclear. We used human fMRI during choices involving monetary reward and physical effort to identify brain regions that serve as a choice comparator for effort-reward trade-offs. By independently varying both options' effort and reward levels, we were able to identify the neural signature of a comparator mechanism. A network involving supplementary motor area and the caudal portion of dorsal anterior cingulate cortex encoded the difference in reward (positively) and effort levels (negatively) between chosen and unchosen choice options. We next modeled effort-discounted subjective values using a novel behavioral model. This revealed that the same network of regions involving dorsal anterior cingulate cortex and supplementary motor area encoded the difference between the chosen and unchosen options' subjective values, and that activity was best described using a concave model of effort-discounting. In addition, this signal reflected how precisely value determined participants' choices. By contrast, separate signals in supplementary motor area and ventromedial prefrontal cortex correlated with participants' tendency to avoid effort and seek reward, respectively. This suggests that the critical neural signature of decision-making for choices involving motor costs is found in human cingulate cortex and not ventromedial prefrontal cortex as typically reported for outcome-based choice. Furthermore, distinct frontal circuits seem to drive behavior toward reward maximization and effort minimization. SIGNIFICANCE STATEMENT: The neural processes that govern the trade-off between expected benefits and motor costs remain largely unknown. This is striking because energetic requirements play an integral role in our day-to-day choices and instrumental behavior, and a diminished willingness to exert effort is a characteristic feature of a range of neurological disorders. We use a new behavioral characterization of how humans trade off reward maximization with effort minimization to examine the neural signatures that underpin such choices, using BOLD MRI neuroimaging data. We find the critical neural signature of decision-making, a signal that reflects the comparison of value between choice options, in human cingulate cortex, whereas two distinct brain circuits drive behavior toward reward maximization or effort minimization

Investigation of cell movement and the associated cytoskeleton during chick gastrulation and somitogenesis

Cell migration involves dynamic and spatially regulated changes to the cytoskeleton. During avian gastrulation, cells ingress through the primitive streak. Previous characterisation of microtubule organisation during this process revealed the distribution of cells with polarised and radial arrays across different regions of the embryo. Interestingly, many cells organised into groups arranged in rosette-like structures. As the primitive streak regresses and the neural folds gather at the centre of the embryo, bands of paraxial mesoderm that lie either side of the neural tube separate into somites. As new somites form caudally, the more rostral somites undergo a process of morphogenesis. Each somite divides into two regions: the dermomyotome and the sclerotome. Little is known about the cytoskeletonduring this process. Signalling by the Wnt family of secreted proteins influences the fate of cells during early embryonic patterning, cell movement, and cell polarity, processes in which the cytoskeleton is noticeably modified. The microtubule and actin crosslinking factor-1/actin crosslinking factor-7 (MACF1/ACF7) protein has been implicated in Wnt signalling and, additionally, its regulation has been shown to be important in cell migration. This thesis concentrates on cellular dynamics and organisation (and the associated cytoskeleton) during chick gastrulation and somitogenesis. The aims of this project were to a) further characterise the cytoskeleton in cells that ingress into the avian primitive streak. b) Establish a published electroporation technique, which permits the targeting of different regions of the somite and subsequently observe cells (and their associated cytoskeleton) in real time. c) Determine the expression pattern for MACF1/ACF7 in chick. d) To ascertain if there is a direct role for canonical Wnt signalling in somitic myofibre orientation/organisation

Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7T

Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in ‘arterial’ and ‘venous’ blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between ‘arterial’ and ‘venous’ contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms