Parametric Representation of Tactile Numerosity in Working Memory

Estimated numerosity perception is processed in an approximate number system (ANS) that resembles the perception of a continuous magnitude. The ANS consists of a right lateralized frontoparietal network comprising the lateral prefrontal cortex (LPFC) and the intraparietal sulcus. Although the ANS has been extensively investigated, only a few studies have focused on the mental representation of retained numerosity estimates. Specifically, the underlying mechanisms of estimated numerosity working memory (WM) is unclear. Besides numerosities, as another form of abstract quantity, vibrotactile WM studies provide initial evidence that the right LPFC takes a central role in maintaining magnitudes. In the present fMRI multivariate pattern analysis study, we designed a delayed match-to-numerosity paradigm to test what brain regions retain approximate numerosity memoranda. In line with parametric WM results, our study found numerosity-specific WM representations in the right LPFC as well as in the supplementary motor area and the left premotor cortex extending into the superior frontal gyrus, thus bridging the gap in abstract quantity WM literature

Frontoparietal action-oriented codes support novel task set implementation

A key aspect of human cognitive flexibility concerns the ability to rapidly convert complex symbolic instructions into novel behaviors. Previous research proposes that this fast configuration is supported by two differentiated neurocognitive states, namely, an initial declarative maintenance of task knowledge, and a progressive transformation into a pragmatic, action-oriented state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this transformation. However, direct evidence for such frontoparietal formatting of novel task representations is still lacking. Here, we report the results of an fMRI experiment in which participants had to execute novel instructed stimulus-response associations. We then used a multivariate pattern-tracking procedure to quantify the degree of neural activation of instructions in declarative and procedural representational formats. This analysis revealed, for the first time, format-unique representations of relevant task sets in frontoparietal areas, prior to execution. Critically, the degree of procedural (but not declarative) activation predicted subsequent behavioral performance. Our results shed light on current debates on the architecture of cognitive control and working memory systems, suggesting a contribution of frontoparietal regions to output gating mechanisms that drive behavior

Investigation of the multiple-demand network at multiple spatial scales

This dissertation investigates the frontoparietal ‘multiple-demand’ (MD) network that is involved in the processing of diverse cognitive demands. This network is active when the task at hand is made more demanding, in a variety of different tasks including working memory, task switching, inhibition, math, language etc. While the different MD regions have partly different functions, they are highly interconnected allowing them to function together as a network. The experiment in Chapter 2 looked at the interplay between functional differences as well as co-recruitment within this multiple-demand network. Quantitative differences between regions were more prominent in simple tasks. A strong co-recruitment was seen with increased challenge or incentive. In Chapter 3, task preferences were studied at the voxel level. MD regions were equally well localised in single-subjects using any of three task demands. Voxels localised by all three tasks also captured the underlying neural representations to a similar level in a separate criterion task. Chapter 4 investigated if task representations, as measured by multi-voxel patterns, were modified due to external motivation. The effect was limited to the cue phase and did not extend to the stimulus processing phase where the stimulus is integrated with the cue to arrive at the response. Chapter 5 examined neural representations in frontal and parietal regions more directly through single unit activity and local field potentials (LFPs), during a spatial working memory task. While single neurons showed dynamic coding of target information rather than persistent coding, LFPs held this information constant through time. The impact of reference voltages on LFP data was further investigated. Together, these results explore the functional differences between and within the MD regions, and provide evidence for flexible task representations at the voxel and neuronal level.Funded by Gates Cambridg

Representational organization of novel task sets during proactive encoding

Recent multivariate analyses of brain data have boosted our understanding of the organizational principles that shape neural coding. However, most of this progress has focused on perceptual visual regions (Connolly et al., 2012), whereas far less is known about the organization of more abstract, action-oriented representations. In this study, we focused on humans{\textquoteright} remarkable ability to turn novel instructions into actions. While previous research shows that instruction encoding is tightly linked to proactive activations in fronto-parietal brain regions, little is known about the structure that orchestrates such anticipatory representation. We collected fMRI data while participants (both males and females) followed novel complex verbal rules that varied across control-related variables (integrating within/across stimuli dimensions, response complexity, target category) and reward expectations. Using Representational Similarity Analysis (Kriegeskorte et al., 2008) we explored where in the brain these variables explained the organization of novel task encoding, and whether motivation modulated these representational spaces. Instruction representations in the lateral prefrontal cortex were structured by the three control-related variables, while intraparietal sulcus encoded response complexity and the fusiform gyrus and precuneus organized its activity according to the relevant stimulus category. Reward exerted a general effect, increasing the representational similarity among different instructions, which was robustly correlated with behavioral improvements. Overall, our results highlight the flexibility of proactive task encoding, governed by distinct representational organizations in specific brain regions. They also stress the variability of motivation-control interactions, which appear to be highly dependent on task attributes such as complexity or novelty.SIGNIFICANCE STATEMENTIn comparison with other primates, humans display a remarkable success in novel task contexts thanks to our ability to transform instructions into effective actions. This skill is associated with proactive task-set reconfigurations in fronto-parietal cortices. It remains yet unknown, however, how the brain encodes in anticipation the flexible, rich repertoire of novel tasks that we can achieve. Here we explored cognitive control and motivation-related variables that might orchestrate the representational space for novel instructions. Our results showed that different dimensions become relevant for task prospective encoding depending on the brain region, and that the lateral prefrontal cortex simultaneously organized task representations following different control-related variables. Motivation exerted a general modulation upon this process, diminishing rather than increasing distances among instruction representations

Switch-independent task representations in frontal and parietal cortex

Alternating between two tasks is effortful and impairs performance. Previous fMRI studies have found increased activity in frontoparietal cortex when task switching is required. One possibility is that the additional control demands for switch trials are met by strengthening task representations in the human brain. Alternatively, on switch trials, the residual representation of the previous task might impede the buildup of a neural task representation. This would predict weaker task representations on switch trials, thus also explaining the performance costs. To test this, male and female participants were cued to perform one of two similar tasks, with the task being repeated or switched between successive trials. Multivoxel pattern analysis was used to test which regions encode the tasks and whether this encoding differs between switch and repeat trials. As expected, we found information about task representations in frontal and parietal cortex, but there was no difference in the decoding accuracy of task-related information between switch and repeat trials. Using cross-classification, we found that the frontoparietal cortex encodes tasks using a generalizable spatial pattern in switch and repeat trials. Therefore, task representations in frontal and parietal cortex are largely switch independent. We found no evidence that neural information about task representations in these regions can explain behavioral costs usually associated with task switching

Frontoparietal representations of task context support the flexible control of goal-directed cognition.

Cognitive control allows stimulus-response processing to be aligned with internal goals and is thus central to intelligent, purposeful behavior. Control is thought to depend in part on the active representation of task information in prefrontal cortex (PFC), which provides a source of contextual bias on perception, decision making, and action. In the present study, we investigated the organization, influences, and consequences of context representation as human subjects performed a cued sorting task that required them to flexibly judge the relationship between pairs of multivalent stimuli. Using a connectivity-based parcellation of PFC and multivariate decoding analyses, we determined that context is specifically and transiently represented in a region spanning the inferior frontal sulcus during context-dependent decision making. We also found strong evidence that decision context is represented within the intraparietal sulcus, an area previously shown to be functionally networked with the inferior frontal sulcus at rest and during task performance. Rule-guided allocation of attention to different stimulus dimensions produced discriminable patterns of activation in visual cortex, providing a signature of top-down bias over perception. Furthermore, demands on cognitive control arising from the task structure modulated context representation, which was found to be strongest after a shift in task rules. When context representation in frontoparietal areas increased in strength, as measured by the discriminability of high-dimensional activation patterns, the bias on attended stimulus features was enhanced. These results provide novel evidence that illuminates the mechanisms by which humans flexibly guide behavior in complex environments

Individual-subject Functional Localization Increases Univariate Activation but Not Multivariate Pattern Discriminability in the "Multiple-demand" Frontoparietal Network.

The frontoparietal "multiple-demand" (MD) control network plays a key role in goal-directed behavior. Recent developments of multivoxel pattern analysis (MVPA) for fMRI data allow for more fine-grained investigations into the functionality and properties of brain systems. In particular, MVPA in the MD network was used to gain better understanding of control processes such as attentional effects, adaptive coding, and representation of multiple taskrelevant features, but overall low decoding levels have limited its use for this network. A common practice of applying MVPA is by investigating pattern discriminability within a ROI using a template mask, thus ensuring that the same brain areas are studied in all participants. This approach offers high sensitivity but does not take into account differences between individuals in the spatial organization of brain regions. An alternative approach uses independent localizer data for each subject to select the most responsive voxels and define individual ROIs within the boundaries of a group template. Such an approach allows for a refined and targeted localization based on the unique pattern of activity of individual subjects while ensuring that functionally similar brain regions are studied for all subjects. In the current study, we tested whether using individual ROIs leads to changes in decodability of task-related neural representations as well as univariate activity across the MD network compared with when using a group template. We used three localizer tasks to separately define subject-specific ROIs: spatial working memory, verbal working memory, and a Stroop task. We then systematically assessed univariate and multivariate results in a separate rule-based criterion task. All the localizer tasks robustly recruited the MD network and evoked highly reliable activity patterns in individual subjects. Consistent with previous studies, we found a clear benefit of the subject-specific ROIs for univariate results from the criterion task, with increased activity in the individual ROIs based on the localizers' data, compared with the activity observed when using the group template. In contrast, there was no benefit of the subject-specific ROIs for the multivariate results in the form of increased discriminability, as well as no cost of reduced discriminability. Both univariate and multivariate results were similar in the subject-specific ROIs defined by each of the three localizers. Our results provide important empirical evidence for researchers in the field of cognitive control for the use of individual ROIs in the frontoparietal network for both univariate and multivariate analysis of fMRI data and serve as another step toward standardization and increased comparability across studies.This work was funded by a Royal Society Dorothy Hodgkin Research Fellowship (United Kingdom) to Yaara Erez (DH130100). Sneha Shashidhara was supported by a scholarship from the Gates Cambridge Trust, Cambridge, United Kingdom. Floortje Spronkers was supported by an Erasmus+ Traineeship grant and a Stichting A.S.C. Academy grant

Concurrent neuroimaging and neurostimulation reveals a causal role for dlPFC in coding of task-relevant information.

Dorsolateral prefrontal cortex (dlPFC) is proposed to drive brain-wide focus by biasing processing in favour of task-relevant information. A longstanding debate concerns whether this is achieved through enhancing processing of relevant information and/or by inhibiting irrelevant information. To address this, we applied transcranial magnetic stimulation (TMS) during fMRI, and tested for causal changes in information coding. Participants attended to one feature, whilst ignoring another feature, of a visual object. If dlPFC is necessary for facilitation, disruptive TMS should decrease coding of attended features. Conversely, if dlPFC is crucial for inhibition, TMS should increase coding of ignored features. Here, we show that TMS decreases coding of relevant information across frontoparietal cortex, and the impact is significantly stronger than any effect on irrelevant information, which is not statistically detectable. This provides causal evidence for a specific role of dlPFC in enhancing task-relevant representations and demonstrates the cognitive-neural insights possible with concurrent TMS-fMRI-MVPA

Adaptive coding in the human brain: Distinct object features are encoded by overlapping voxels in frontoparietal cortex.

Our ability to flexibly switch between different tasks is a key component of cognitive control. Non-human primate (NHP) studies (e.g., Freedman, Riesenhuber, Poggio, & Miller, 2001) have shown that prefrontal neurons are re-used across tasks, re-configuring their responses to code currently relevant information. In a similar vein, in the human brain, the "multiple demand" (MD) system is suggested to exert control by adjusting its responses, selectively processing information in line with our current goals (Duncan, 2010). However, whether the same or different resources (underlying neural populations) in the human brain are recruited to solve different tasks remains elusive. In the present study, we aimed to bridge the gap between the NHP and human literature by examining human functional imaging data at an intermediate level of resolution: quantifying the extent to which single voxels contributed to multiple neural codes. Participants alternated between two tasks requiring the selection of feature information from two distinct sets of objects. We examined whether neural codes for the relevant stimulus features in the two different tasks depended on the same or different voxels. In line with the electrophysiological literature, MD voxels were more likely to contribute to multiple neural codes than we predicted based on permutation tests. Comparatively, in the visual system the neural codes depended on distinct sets of voxels. Our data emphasise the flexibility of the MD regions to re-configure their responses and adaptively code relevant information across different tasks

Concurrent neuroimaging and neurostimulation reveals a causal role for dlPFC in coding of task-relevant information.

Dorsolateral prefrontal cortex (dlPFC) is proposed to drive brain-wide focus by biasing processing in favour of task-relevant information. A longstanding debate concerns whether this is achieved through enhancing processing of relevant information and/or by inhibiting irrelevant information. To address this, we applied transcranial magnetic stimulation (TMS) during fMRI, and tested for causal changes in information coding. Participants attended to one feature, whilst ignoring another feature, of a visual object. If dlPFC is necessary for facilitation, disruptive TMS should decrease coding of attended features. Conversely, if dlPFC is crucial for inhibition, TMS should increase coding of ignored features. Here, we show that TMS decreases coding of relevant information across frontoparietal cortex, and the impact is significantly stronger than any effect on irrelevant information, which is not statistically detectable. This provides causal evidence for a specific role of dlPFC in enhancing task-relevant representations and demonstrates the cognitive-neural insights possible with concurrent TMS-fMRI-MVPA