Taraz G. Lee

The Dynamic Nature of Top-Down Signals Originating from Prefrontal Cortex: A Combined fMRI–TMS Study

The prefrontal cortex (PFC) is proposed to be the source of top-down signals that can modulate extrastriate visual processing in accordance with behavioral goals, yet little direct causal evidence for this hypothesis exists. Using theta burst transcranial magnetic stimulation, we disrupted PFC function in human participants before performing a working memory task during fMRI scanning. PFC disruption decreased the tuning of extrastriate cortex responses, coinciding with decrements in working memory performance. We also found that activity in the homologous PFC region in the nonstimulated hemisphere predicted performance following disruption. Specifically, those participants with greater homologous PFC activity and greater connectivity between this region and extrastriate cortex were the most resistant to PFC disruption. These findings provide evidence for a compensatory mechanism following insults to the brain, and insight into the dynamic nature of top-down signals originating from the PFC.

Quantifying the Reconfiguration of Intrinsic Networks during Working Memory

Rapid, flexible reconfiguration of connections across brain regions is thought to underlie successful cognitive control. Two intrinsic networks in particular, the cingulo-opercular (CO) and fronto-parietal (FP), are thought to underlie two operations critical for cognitive control: task-set maintenance/tonic alertness and adaptive, trial-by-trial updating. Using functional magnetic resonance imaging, we directly tested whether the functional connectivity of the CO and FP networks was related to cognitive demands and behavior. We focused on working memory because of evidence that during working memory tasks the entire brain becomes more integrated. When specifically probing the CO and FP cognitive control networks, we found that individual regions of both intrinsic networks were active during working memory and, as expected, integration across the two networks increased during task blocks that required cognitive control. Crucially, increased integration between each of the cognitive control networks and a task-related, non-cognitive control network (the hand somatosensory-motor network; SM) was related to increased accuracy. This implies that dynamic reconfiguration of the CO and FP networks so as to increase their inter-network communication underlies successful working memory.

The effects of lateral prefrontal transcranial magnetic stimulation on item memory encoding.

Previous neuroimaging research has established that the left ventrolateral prefrontal cortex (VLPFC) is involved in long-term memory (LTM) encoding for individual items. Dorsolateral prefrontal cortex (DLPFC) is implicated less frequently, and one theory that has gained support to explain this discrepancy is that DLPFC is involved in forming item-item relational but not item LTM. Given that neuroimaging results are correlational, complimentary methods such as repetitive transcranial magnetic stimulation (TMS) have been used to test causal hypotheses generated from imaging data. Most TMS studies of LTM encoding have found that disruption of lateral PFC activity impairs subsequent memory. However these studies have lacked methods to precisely localize and directly compare TMS effects from frontal subregions implicated by the neuroimaging literature. Here, we target specific subregions of lateral PFC with TMS to test the prediction from the item/relational framework that temporary disruption of VLPFC during encoding will impair subsequent memory whereas TMS to DLPFC during item encoding will not. Frontal TMS was administered prior to a LTM encoding task in which participants were presented with a list of individual nouns and asked to judge whether each noun was concrete or abstract. After a 40 min delay period, item recognition memory was tested. Results indicate that VLPFC and DLPFC TMS have differential effects on subsequent item memory. VLPFC TMS reliably disrupted subsequent item memory whereas DLPFC TMS led to numerical enhancement in item memory, relative to TMS to a control region.

Disruption of Dorsolateral But Not Ventrolateral Prefrontal Cortex Improves Unconscious Perceptual Memories

Attentive encoding often leads to more accurate responses in recognition memory tests. However, previous studies have described conditions under which taxing explicit memory resources by attentional distraction improved perceptual recognition memory without awareness. These findings lead to the hypothesis that explicit memory processes mediated by the prefrontal cortex (PFC) can interfere with memory processes necessary for implicit recognition memory. The present study directly tested this hypothesis by applying transcranial magnetic stimulation separately over either dorsolateral (DLPFC) or ventrolateral PFC (VLPFC) in humans before performance of a visual memory task. Disruption of DLPFC function led to improvement in recognition accuracy only in responses in which the participants awareness of memory retrieval was absent. However, disruption of VLPFC function led to subtle shifts in recollection and familiarity accuracy. We conclude that explicit memory processes mediated by the DLPFC can indirectly interfere with implicit recognition memory.

When it hurts (and helps) to try: the role of effort in language learning.

Compared to children, adults are bad at learning language. This is counterintuitive; adults outperform children on most measures of cognition, especially those that involve effort (which continue to mature into early adulthood). The present study asks whether these mature effortful abilities interfere with language learning in adults and further, whether interference occurs equally for aspects of language that adults are good (word-segmentation) versus bad (grammar) at learning. Learners were exposed to an artificial language comprised of statistically defined words that belong to phonologically defined categories (grammar). Exposure occurred under passive or effortful conditions. Passive learners were told to listen while effortful learners were instructed to try to 1) learn the words, 2) learn the categories, or 3) learn the category-order. Effortful learners showed an advantage for learning words while passive learners showed an advantage for learning the categories. Effort can therefore hurt the learning of categories.

Perfusion MRI Indexes Variability in the Functional Brain Effects of Theta-Burst Transcranial Magnetic Stimulation

Transcranial Magnetic Stimulation (TMS) is an important tool for testing causal relationships in cognitive neuroscience research. However, the efficacy of TMS can be variable across individuals and difficult to measure. This variability is especially a challenge when TMS is applied to regions without well-characterized behavioral effects, such as in studies using TMS on multi-modal areas in intrinsic networks. Here, we examined whether perfusion fMRI recordings of Cerebral Blood Flow (CBF), a quantitative measure sensitive to slow functional changes, reliably index variability in the effects of stimulation. Twenty-seven participants each completed four combined TMS-fMRI sessions during which both resting state Blood Oxygen Level Dependent (BOLD) and perfusion Arterial Spin Labeling (ASL) scans were recorded. In each session after the first baseline day, continuous theta-burst TMS (TBS) was applied to one of three locations: left dorsolateral prefrontal cortex (L dlPFC), left anterior insula/frontal operculum (L aI/fO), or left primary somatosensory cortex (L S1). The two frontal targets are components of intrinsic networks and L S1 was used as an experimental control. CBF changes were measured both before and after TMS on each day from a series of interleaved resting state and perfusion scans. Although TBS led to weak selective increases under the coil in CBF measurements across the group, individual subjects showed wide variability in their responses. TBS-induced changes in rCBF were related to TBS-induced changes in functional connectivity of the relevant intrinsic networks measured during separate resting-state BOLD scans. This relationship was selective: CBF and functional connectivity of these networks were not related before TBS or after TBS to the experimental control region (S1). Furthermore, subject groups with different directions of CBF change after TBS showed distinct modulations in the functional interactions of targeted networks. These results suggest that CBF is a marker of individual differences in the effects of TBS.

The Effect of Disruption of Prefrontal Cortical Function with Transcranial Magnetic Stimulation on Visual Working Memory

It is proposed that feedback signals from the prefrontal cortex (PFC) to extrastriate cortex are essential for goal-directed processing, maintenance, and selection of information in visual working memory (VWM). In a previous study, we found that disruption of PFC function with transcranial magnetic stimulation (TMS) in healthy individuals impaired behavioral performance on a face/scene matching task and decreased category-specific tuning in extrastriate cortex as measured with functional magnetic resonance imaging (fMRI). In this study, we investigated the effect of disruption of left inferior frontal gyrus (IFG) function on the fidelity of neural representations of two distinct information codes: (1) the stimulus category and (2) the goal-relevance of viewed stimuli. During fMRI scanning, subjects were presented face and scene images in pseudo-random order and instructed to remember either faces or scenes. Within both anatomical and functional regions of interest (ROIs), a multi-voxel pattern classifier was used to quantitatively assess the fidelity of activity patterns representing stimulus category: whether a face or a scene was presented on each trial, and goal relevance, whether the presented image was task relevant (i.e., a face is relevant in a “Remember Faces” block, but irrelevant in a “Remember Scenes” block). We found a reduction in the fidelity of the stimulus category code in visual cortex after left IFG disruption, providing causal evidence that lateral PFC modulates object category codes in visual cortex during VWM. In addition, we found that IFG disruption caused a reduction in the fidelity of the goal relevance code in a distributed set of brain regions. These results suggest that the IFG is involved in determining the task-relevance of visual input and communicating that information to a network of regions involved in further processing during VWM. Finally, we found that participants who exhibited greater fidelity of the goal relevance code in the non-disrupted right IFG after TMS performed the task with the highest accuracy.

Coupling between Theta Oscillations and Cognitive Control Network during Cross-Modal Visual and Auditory Attention: Supramodal vs Modality-Specific Mechanisms.

Cortical theta band oscillations (4–8 Hz) in EEG signals have been shown to be important for a variety of different cognitive control operations in visual attention paradigms. However the synchronization source of these signals as defined by fMRI BOLD activity and the extent to which theta oscillations play a role in multimodal attention remains unknown. Here we investigated the extent to which cross-modal visual and auditory attention impacts theta oscillations. Using a simultaneous EEG-fMRI paradigm, healthy human participants performed an attentional vigilance task with six cross-modal conditions using naturalistic stimuli. To assess supramodal mechanisms, modulation of theta oscillation amplitude for attention to either visual or auditory stimuli was correlated with BOLD activity by conjunction analysis. Negative correlation was localized to cortical regions associated with the default mode network and positively with ventral premotor areas. Modality-associated attention to visual stimuli was marked by a positive correlation of theta and BOLD activity in fronto-parietal area that was not observed in the auditory condition. A positive correlation of theta and BOLD activity was observed in auditory cortex, while a negative correlation of theta and BOLD activity was observed in visual cortex during auditory attention. The data support a supramodal interaction of theta activity with of DMN function, and modality-associated processes within fronto-parietal networks related to top-down theta related cognitive control in cross-modal visual attention. On the other hand, in sensory cortices there are opposing effects of theta activity during cross-modal auditory attention.

Human perception-motor decision-making is not optimal

Abstract From financial choice to movement planning, many human behaviors can be understood as the outcomes of decision processes. Results from studies of decision making under risk in behavioral economics, where risk is manifest in varying probabilities of payoffs in presented options, are taken to indicate that humans fail to maximize expected objective value. In contrast to this research, a recent line of work in psychophysics argues that when such decisions are framed as risky visuomotor decisions, where payoff probabilities in part depend on the variance of reaching end points, people make approximately optimal decisions which maximize expected objective value. We rigorously test this claim by formally comparing three computational models in terms of their ability to predict human behavior in incentivized reaching tasks. Across two experiments, we find that human reaching outcomes are better described by a simple satisficing heuristic than objective or subjective expected-value-maximizing strategies that are optimally adapted each individual’s variance in reaching end points, especially when the risk of financial loss is high. The present work provides evidence against the claim that human visuomotor decision making under risk is optimal given the bounds imposed by motor variance, and demonstrates the fruitfulness of including alternative models in analyses of human behavior.Economic decision-making under risk often fails to maximize expected value, perhaps reflecting cognitive biases and heuristics. A line of recent work argues that when economic decisions are reformulated as decisions about where to aim rapid reaching movements, the resulting decisions are optimal (i.e. maximize expected value), in dramatic contrast to the standard findings obtained with decisions among gambles. These arguments for optimality rely on a comparison between human performance and the performance of an ideal agent in a reaching task with a narrow range of incentive values. Here, we improve on this methodology, both empirically and analytically, by devising a task with a wider range of incentive values, and by performing trial-level comparisons of participant behavior to the Ideal Model and two plausible alternative models. The first alternative, the Loss-averse Model, incorporates participant-level loss aversion, and the second alternative, the Heuristic Model, embodies a simple satisficing heuristic that is invariant to incentive magnitudes. Across two experiments, we find that participants’ movement outcomes are more likely under the Heuristic Model than the Ideal or Loss-averse models, especially when the risk of financial loss is high. The present work provides evidence against the claim that perceptuo-motor decision making is optimal and demonstrates the fruitfulness of including alternative models in analyses of human behavior.Abstract The rationality of human behavior has been a major problem in philosophy for centuries. The pioneering work of Kahneman and Tversky provides strong evidence that people are not rational. Recent work in psychophysics argues that incentivized sensorimotor decisions (such as deciding where to reach to get a reward) maximizes expected gain, suggesting that it may be impervious to cognitive biases and heuristics. We rigorously tested this hypothesis using multiple experiments and multiple computational models. We obtained strong evidence that people deviated from the objectively rational strategy when potential losses were large. They instead appeared to follow a strategy in which they simplify the decision problem and satisfice rather than optimize. This work is consistent with the framework known as bounded rationality, according to which people behave rationally given their computational limitations.

Multivariate fMRI Approaches to Flexible Sensorimotor Maps in Parietal Cortex

The posterior parietal cortex (PPC) is uniquely suited to coordinate goal-related action because of its rich connectivity with frontal motor regions and posterior sensory regions. Among other functions, PPC is essential for computing sensorimotor transformations that require perceptual