Neural Mechanisms of Working Memory Cortical Networks

This dissertation is aimed at understanding the cortical networks that maintain working memory information. By leveraging patterns of information degradation in spatial working memory encoding we reveal new neural mechanisms that support working memory function and challenge existing models of working memory circuits. First we examine how interference from previous memoranda influences memory of a currently remembered location. We find that memory for a currently remembered location is biased toward the previously memorized location. This interference is graded, not all-or-none. Interference is strongest when the previous and current targets are close and activate overlapping populations of neurons. Contrary to the attractive behavioral bias, the neural representation of a currently remembered location in the frontal eye fields appears to be biased away from the previous target location, not toward it. We reconcile this discrepancy by proposing a model in which receptive fields of memory cells converge toward memorized locations. This reallocation of neural resources at task-relevant parts of space reduces overall error in the memory network but introduces systematic behavioral biases toward prior memoranda. We also find that attractive behavioral bias asymptotically increases as a function of the memory period length. Critically, the increase in bias depends only on the current trial’s memory period. That is, the effect of the previous target progressively increases in the current trial after that target’s memory has become irrelevant. We modeled this finding using a two-store model with a transient but unbiased visual sensory store and a sustained store with constant bias. Initially behavior is driven by the veridical visual sensory store and is therefore unbiased. As the visual sensory store decays in the current trial, behavioral responses are increasingly driven by the sustained but biased store, leading to an asymptotic increase of behavioral bias with increasing memory period length. Finally, we look at how memory activity is encoded over long (15 second) memory periods. Memory cells tend to turn on early in the memory period and stay active for a fixed amount of time. Most memory cells shut off prior to the end of the memory period. Within each cell, offset times are repeatable from one trial to the next. Across cells, offset times are broadly distributed throughout the entire memory period. Once a cell shuts off, it remains off for the rest of the memory period. On the one hand, these findings challenge the leading model for working memory, the attractor network framework, which predicts a single homogenous time course from all cells. On the other hand, the findings also show that the patterns of activity seen in memory circuits are much more structured than the heterogeneous patterns suggested by the leading competitors to the attractor models. Our findings are not predicted by current models of working memory circuits and indicate that new network models need to be developed

Neural Mechanisms of Working Memory Cortical Networks

This dissertation is aimed at understanding the cortical networks that maintain working memory information. By leveraging patterns of information degradation in spatial working memory encoding we reveal new neural mechanisms that support working memory function and challenge existing models of working memory circuits. First we examine how interference from previous memoranda influences memory of a currently remembered location. We find that memory for a currently remembered location is biased toward the previously memorized location. This interference is graded, not all-or-none. Interference is strongest when the previous and current targets are close and activate overlapping populations of neurons. Contrary to the attractive behavioral bias, the neural representation of a currently remembered location in the frontal eye fields appears to be biased away from the previous target location, not toward it. We reconcile this discrepancy by proposing a model in which receptive fields of memory cells converge toward memorized locations. This reallocation of neural resources at task-relevant parts of space reduces overall error in the memory network but introduces systematic behavioral biases toward prior memoranda. We also find that attractive behavioral bias asymptotically increases as a function of the memory period length. Critically, the increase in bias depends only on the current trial’s memory period. That is, the effect of the previous target progressively increases in the current trial after that target’s memory has become irrelevant. We modeled this finding using a two-store model with a transient but unbiased visual sensory store and a sustained store with constant bias. Initially behavior is driven by the veridical visual sensory store and is therefore unbiased. As the visual sensory store decays in the current trial, behavioral responses are increasingly driven by the sustained but biased store, leading to an asymptotic increase of behavioral bias with increasing memory period length. Finally, we look at how memory activity is encoded over long (15 second) memory periods. Memory cells tend to turn on early in the memory period and stay active for a fixed amount of time. Most memory cells shut off prior to the end of the memory period. Within each cell, offset times are repeatable from one trial to the next. Across cells, offset times are broadly distributed throughout the entire memory period. Once a cell shuts off, it remains off for the rest of the memory period. On the one hand, these findings challenge the leading model for working memory, the attractor network framework, which predicts a single homogenous time course from all cells. On the other hand, the findings also show that the patterns of activity seen in memory circuits are much more structured than the heterogeneous patterns suggested by the leading competitors to the attractor models. Our findings are not predicted by current models of working memory circuits and indicate that new network models need to be developed

Task-Dependent Oscillatory Brain Activity During Oculomotor Delayed Response Task

This study used three Oculomotor Delayed Response (ODR) tasks to investigate the unique cognitive demands during the delay period. Changes in alpha power were used to index cognitive efforts during the delay period. Continuous EEGs from 25 healthy young adults (18-34 years) were recorded using dense electrode array. The data was analyzed by 6-cycle Morlet wavelet decompositions in the frequency range of 2-30 Hz to create time- frequency decompositions for four midline electrode sites. The 99% confidence intervals using the bootstrapped 20% trimmed mean of the 10 Hz frequency were used to examine the differences among conditions. Compared to two Memory conditions (Match and Non-Match), Control condition yielded significant differences in all frequencies over the entire trial period, suggesting a cognitive state difference. Compared to Match condition, the Non–Match condition had lower alpha activity during the delay period at each midline electrode site reflecting the higher cognitive effort required

Age-Related Changes in Visual Spatial Working Memory Cognits: Frontal-Parietal EEG Coherence During Delay

This study explored changes in scalp electrophysiology across two Working Memory (WM) tasks and two age groups. Continuous electroencephalography (EEG) was recorded from 18 healthy adults (18-34 years) and 12 healthy adolescents (14-17) during the performance of two Oculomotor Delayed Response (ODR) WM tasks; (i.e. eye movements were the metric of motor response). Delay-period, EEG data in the alpha frequency was sampled from anterior and parietal scalp sites to achieve a general measure of frontal and parietal activity, respectively. Frontal-parietal, alpha coherence was calculated for each participant for each ODR-WM task. Coherence significantly decreased in adults moving across the two ODR tasks, whereas, coherence significantly increased in adolescents moving across the two ODR tasks. The effects of task in the adolescent and adult groups were large and medium, respectively. Within the limits of this study, the results provide empirical support that WM development during adolescence include complex, qualitative, change

Learning, Arts, and the Brain: The Dana Consortium Report on Arts and Cognition

Reports findings from multiple neuroscientific studies on the impact of arts training on the enhancement of other cognitive capacities, such as reading acquisition, sequence learning, geometrical reasoning, and memory

Visual attention and working memory in action

This doctoral thesis employed a psychophysical approach to investigate the relationship between goal-directed eye and hand movements, visual attention, and visual working memory. To establish a solid methodological basis for investigating visual attention, the first study compared the strengths and weaknesses of a set of discrimination stimuli frequently used in attention research (Chapter 2.1). Based on the results, we used a novel pink noise stimulus for approaching the following research questions concerning visual attention. In the second study, we investigated the dependence of attentional orienting on oculomotor programming (Chapter 2.2). Motivated by the claim that attention can only be allocated to locations reachable by saccadic eye movements, we measured visual sensitivity – a proxy for visual attention – within and beyond the oculomotor range using an eye abduction paradigm. Contrary to previous findings, we found that attention can be shifted without restriction to locations to which saccades cannot be executed, ruling out the necessity to program a saccadic eye movement as a prerequisite for spatial attention. The third study attempted to resolve the longstanding debate as to whether eye and hand movement targets are selected by a single attentional mechanism or by independent, effector-specific systems (Chapter 2.3). Results revealed that during simultaneous eye and hand movements, attention – an index of motor target selection – was allocated in parallel to the saccade and the reach targets. Motor target selection mechanisms moreover did not compete for attentional resources at any time during movement preparation, demonstrating that separate, effector-specific mechanisms attentionally select eye and hand movement targets. The fourth study tested the assumption of effector-specific selection mechanisms in the framework of visual working memory (Chapter 2.4). Participants memorized several locations and performed eye, hand, or simultaneous eye-hand movements during the maintenance interval. When participants performed an eye and a hand movement simultaneously to distinct locations, memory at both motor targets was enhanced with no tradeoff between the two. This suggests that the two effector systems improve working memory at their selected motor targets independently. In the final study, we dissociated the relative contributions of the two highly interdependent parameters, task relevance and oculomotor selection, to the memory benefits consistently observed at eye movement targets (Chapter 2.5). Participants memorized shapes while simultaneously either avoiding or selecting a specific location as a delayed saccade target. While oculomotor selection was consistently associated with an increased working memory performance, mere task relevance was not, indicating that the frequently reported memory benefits for task-relevant items might, in fact, be caused by oculomotor selection. In summary, goal-directed eye and hand movements selectively boost the visual processing of the currently most relevant information, and likewise bias our memory capacities according to behavioral priority. The observed motor-induced enhancements in both the attention and working memory domains appear to be independent and effector-specific, allowing for the most flexible assignment of our limited cognitive resources as we traverse through our crowded environment

READY, STEADY, AND GO. A Transcranial Magnetic Stimulation Study of Set-Related Inhibitory Activity in the Human Dorsal Precentral Region

Successfully acting largely depends on moving at the right time. Consider a member of an orchestra just few instants before starting to play her piece. She should be ready not only to launch the planned movements when appropriate, but also to stop them if required. Action initiation and control are characteristic features of many of our daily life actions. There is a large amount of evidence in monkeys and humans suggesting that the dorsal premotor cortex (PMD) and the supplementary motor areas (SMA) might be critically involved in these features. However, the distinctive role of these areas is still matter of controversy. The aim of the present thesis is to provide some preliminary steps toward a comprehension of whether and how the human dorsal precentral areas may selectively contribute to action initiation and control. In doing this we shall introduce and discuss a series of transcranial magnetic stimulation (TMS) experiments carried out with two different paradigms, namely dual-coil TMS and single pulse TMS paradigm. These experiments were primarily devoted to explore the structural and functional properties of PMD. They also allowed us to assess whether PMD and SMA may be differentially and selectively involved in action control. In more detail, we first investigated the structural connectivity between PMD and the ipsilateral orofacial M1, introducing a novel dual-coil TMS approach. Results displayed the existence of short-latency influences of the left PMD on the ipsilateral orofacial M1, measured by recording motor evoked potentials (MEPs) in the orofacial muscles. Then, taking advantage of this novel approach, we started to explore the functional PMD-M1 connectivity. We tested the short-latency effects of TMS, as measured by changes in orofacial MEPs, during a delayed motor task. The results showed an inhibitory activity in the PMD-M1 module during the SET-period. We also manipulated the duration of the SET-period, to establish whether the effects were time-locked to the start of the delay period or rather time-locked to the predicted GO-signal. Hence, the investigation of the PMD-M1 connectivity paved us the way to explore, first, the role of PMD in initiating action and, then, the differential role of PMD and SMA in controlling and inhibiting action. Indeed, we run a further study, in which we carried out two single pulse TMS experiments. We first stimulated PMD during a stop-signal task, then we contrasted the PMD stimulation with SMA stimulation when participants underwent the same stop-signal task. There are five chapters to come. In Chapter 1 we shall review some key studies exploring anatomical and functional properties of PMD and SMA in both monkeys and humans, with particular emphasis on their putative role in action initiation and control. In Chapter 2 we shall focus on the methodological aspects of our experimental studies. In particular, we shall introduce the so-called twin- or dual-coil TMS paradigm, discuss its main approaches present in the literature and propose a variant of them. In Chapter 3 we shall present and discuss our first dual-coil TMS study exploring, for the first time, the ipsilateral PMD-corticofacial system connectivity. In Chapter 4 we shall examine three dual-coil TMS studies investigating the functional connectivity between PMD and ipsilateral M1 during a motor delayed task. Finally, in Chapter 5 we shall scrutinize two single pulse TMS studies capitalizing on a stop-signal task in order to assess the role of PMD and SMA in action control. Results and future lines of research will be sketched in the Concluding remarks