Anatomical and Functional Organization of Domain-General Brain Regions

How does complex brain activity organize thought and behaviour? Theoretical proposals have long emphasized that intelligent behaviour must be supported by a flexible control system. Numerous brain imaging studies identified a domain-general or “multiple-demand” (MD) brain system co-activated accompanying many tasks and is hypothesised to play a central role in cognitive control. However, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding its anatomy and physiology. To address these limitations, the experiments in chapters 2 and 3 capitalize on novel multi-modal magnetic resonance imaging (MRI) methods developed by the Human Connectome Project. Chapter 2 delineated nine cortical MD patches per hemisphere and subdivided them into 10 regions forming a core of most strongly activated and functionally interconnected regions, surrounded by a penumbra of 17 additional regions. MD activations were also identified in specific subcortical and cerebellar regions. Chapter 3 investigated the relation between the newly defined MD regions and previously identified sensory-biased cortical regions. Contrasting auditory and visual low working memory demands revealed the strongest sensory-biases are localized just outside of MD regions. And additional working memory demands revealed MD activations showed no sensory biases. Chapter 4 used human electrophysiological recordings from the lateral frontal cortex to functionally map cognitive control regions during awake neurosurgeries. By contrasting a hard vs easy cognitive demand, spectral analysis revealed localized power increases in the gamma range (>30 Hz) that overlap with a canonical mask of the fronto-parietal control network. These findings contrast with spatially non-specific power decreases in the beta range (12-30 Hz). Thus, using similar task difficulty manipulations, electrophysiology and MRI functional signals converged on localizing lateral frontal regions related to cognitive control and support their clinical potential for intraoperative mapping of cognitive control. All together, the distributed anatomical organization, mosaic functional preferences, and strong functional interconnectivity of MD regions, suggest a skeleton for integrating and organizing the diverse components of cognitive operations. The precise anatomical delineation of MD regions provides the groundwork for refined analyses of their functions

Who is that? Brain networks and mechanisms for identifying individuals

Social animals can identify conspecifics by many forms of sensory input. However, whether the neuronal computations that support this ability to identify individuals rely on modality-independent convergence or involve ongoing synergistic interactions along the multiple sensory streams remains controversial. Direct neuronal measurements at relevant brain sites could address such questions, but this requires better bridging the work in humans and animal models. Here, we overview recent studies in nonhuman primates on voice and face identity-sensitive pathways and evaluate the correspondences to relevant findings in humans. This synthesis provides insights into converging sensory streams in the primate anterior temporal lobe (ATL) for identity processing. Furthermore, we advance a model and suggest how alternative neuronal mechanisms could be tested

An interoceptive predictive coding model of conscious presence

We describe a theoretical model of the neurocognitive mechanisms underlying conscious presence and its disturbances. The model is based on interoceptive prediction error and is informed by predictive models of agency, general models of hierarchical predictive coding and dopaminergic signaling in cortex, the role of the anterior insular cortex (AIC) in interoception and emotion, and cognitive neuroscience evidence from studies of virtual reality and of psychiatric disorders of presence, specifically depersonalization/derealization disorder. The model associates presence with successful suppression by top-down predictions of informative interoceptive signals evoked by autonomic control signals and, indirectly, by visceral responses to afferent sensory signals. The model connects presence to agency by allowing that predicted interoceptive signals will depend on whether afferent sensory signals are determined, by a parallel predictive-coding mechanism, to be self-generated or externally caused. Anatomically, we identify the AIC as the likely locus of key neural comparator mechanisms. Our model integrates a broad range of previously disparate evidence, makes predictions for conjoint manipulations of agency and presence, offers a new view of emotion as interoceptive inference, and represents a step toward a mechanistic account of a fundamental phenomenological property of consciousness

Task-load-dependent activation of dopaminergic midbrain areas in the absence of reward

Dopamine release in cortical and subcortical structures plays a central role in reward-related neural processes. Within this context, dopaminergic inputs are commonly assumed to play an activating role, facilitating behavioral and cognitive operations necessary to obtain a prospective reward. Here, we provide evidence from human fMRI that this activating role can also be mediated by task-demand-related processes and thus extendsbeyondsituationsthatonlyentailextrinsicmotivatingfactors. Using a visual discrimination task in which varying levels of task demands were precued, we found enhanced hemodynamic activity in the substantia nigra (SN) for high task demands in the absence of reward or similar extrinsic motivating factors. This observation thus indicates that the SN can also be activated in an endogenous fashion. In parallel to its role in reward-related processes, reward-independent activation likely serves to recruit the processing resources needed to meet enhanced task demands. Simultaneously, activity in a wide network of cortical and subcortical control regions was enhanced in response to high task demands, whereas areas of the default-mode network were deactivated more strongly. The present observations suggest that the SN represents a core node within a broader neural network that adjusts the amount of available neural and behavioral resources to changing situational opportunities and task requirements, which is often driven by extrinsic factors but can also be controlled endogenously

A Putative Multiple-Demand System in the Macaque Brain.

UNLABELLED: In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. SIGNIFICANCE STATEMENT: In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex

Supraspinal characterization of the thermal grill illusion with fMRI.

BackgroundSimultaneous presentation of non-noxious warm (40°C) and cold (20°C) stimuli in an interlacing fashion results in a transient hot burning noxious sensation (matched at 46°C) known as the thermal grill (TG) illusion. Functional magnetic resonance imaging and psychophysical assessments were utilized to compare the supraspinal events related to the spatial summation effect of three TG presentations: 20°C/20°C (G2020), 20°C/40°C (G2040) and 40°C/40°C (G4040) with corresponding matched thermode stimuli: 20°C (P20), 46°C (P46) and 40°C (P40) and hot pain (HP) stimuli.ResultsFor G2040, the hot burning sensation was only noted during the initial off-line assessment. In comparison to P40, G4040 resulted in an equally enhanced response from all supraspinal regions associated with both pain sensory/discriminatory and noxious modulatory response. In comparison to P20, G2020 presentation resulted in a much earlier diminished/sedative response leading to a statistically significantly (P < 0.01) higher degree of deactivation in modulatory supraspinal areas activated by G4040. Granger Causality Analysis showed that while thalamic activation in HP may cast activation inference in all hot pain related somatosensory, affective and modulatory areas, similar activation in G2040 and G2020 resulted in deactivation inference in the corresponding areas.ConclusionsIn short, the transient TG sensation is caused by a dissociated state derived from non-noxious warm and cold spatial summation interaction. The observed central dissociated state may share some parallels in certain chronic neuropathic pain states

A Domain-General Cognitive Core Defined in Multimodally Parcellated Human Cortex.

Numerous brain imaging studies identified a domain-general or "multiple-demand" (MD) activation pattern accompanying many tasks and may play a core role in cognitive control. Though this finding is well established, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding the precise anatomy, functional differentiation, and connectivity of the MD system. To address these limitations, we used data from 449 subjects from the Human Connectome Project, with the cortex of each individual parcellated using neurobiologically grounded multimodal MRI features. The conjunction of three cognitive contrasts reveals a core of 10 widely distributed MD parcels per hemisphere that are most strongly activated and functionally interconnected, surrounded by a penumbra of 17 additional areas. Outside cerebral cortex, MD activation is most prominent in the caudate and cerebellum. Comparison with canonical resting-state networks shows MD regions concentrated in the fronto-parietal network but also engaging three other networks. MD activations show modest relative task preferences accompanying strong co-recruitment. With distributed anatomical organization, mosaic functional preferences, and strong interconnectivity, we suggest MD regions are well positioned to integrate and assemble the diverse components of cognitive operations. Our precise delineation of MD regions provides a basis for refined analyses of their functions

Die Rolle der Zielnähe und der investierten Anstrengung für den erwarteten Wert einer Handlung

In human neuroscientific research, there has been an increasing interest in how the brain computes the value of an anticipated outcome. However, evidence is still missing about which valuation related brain regions are modulated by the proximity to an expected goal and the previously invested effort to reach a goal. The aim of this dissertation is to investigate the effects of goal proximity and invested effort on valuation related regions in the human brain. We addressed this question in two fMRI studies by integrating a commonly used reward anticipation task in differential versions of a Multitrial Reward Schedule Paradigm. In both experiments, subjects had to perform consecutive reward anticipation tasks under two different reward contingencies: in the delayed condition, participants received a monetary reward only after successful completion of multiple consecutive trials. In the immediate condition, money was earned after every successful trial. In the first study, we could demonstrate that the rostral cingulate zone of the posterior medial frontal cortex signals action value contingent to goal proximity, thereby replicating neurophysiological findings about goal proximity signals in a homologous region in non-human primates. The findings of the second study imply that brain regions associated with general cognitive control processes are modulated by previous effort investment. Furthermore, we found the posterior lateral prefrontal cortex and the orbitofrontal cortex to be involved in coding for the effort-based context of a situation. In sum, these results extend the role of the human rostral cingulate zone in outcome evaluation to the continuous updating of action values over a course of action steps based on the proximity to the expected reward. Furthermore, we tentatively suggest that previous effort investment invokes processes under the control of the executive system, and that posterior lateral prefrontal cortex and the orbitofrontal cortex are involved in an effort-based context representation that can be used for outcome evaluation that is dependent on the characteristics of the current situation.Derzeit besteht im Bereich der Neurowissenschaften ein großes Interesse daran aufzuklären, auf welche Weise verschiedene Variablen die Wertigkeit eines erwarteten Handlungsziels beeinflussen bzw. welche Hirnregionen an der Repräsentation der Wertigkeit eines Handlungsziels beteiligt sind. Die meisten Untersuchungen beziehen sich dabei auf Einflussgrößen wie die erwartete Belohnungshöhe, die Wahrscheinlichkeit, mit der ein bestimmtes Ereignis eintritt, oder die Dauer bis zum Erhalt einer Belohnung. Bisher liegen jedoch kaum Untersuchungen vor bezüglich zweier anderer Variablen, die ebenfalls den erwarteten Wert eines Handlungsergebnisses beeinflussen. Das sind (a) die Nähe zu dem erwarteten Ziel und (b) die bisher investierte Anstrengung, um ein Ziel zu erreichen. Das Ziel der vorliegenden Dissertation ist zu untersuchen, wie die Nähe zum Ziel und die bisher investierte Anstrengung Gehirnregionen beeinflussen, die mit der Repräsentation von Wertigkeit im Zusammenhang stehen. Dazu führten wir zwei fMRT-Studien durch, in denen wir eine klassische Belohnungs-Antizipationsaufgabe in unterschiedliche Versionen eines „Multitrial Reward Schedule“ Paradigmas integriert haben. Das bedeutet, dass die Probanden Belohnungs-Antizipationsaufgaben unter zwei unterschiedlichen Belohnungskontingenzen bearbeiteten: In der verzögerten Bedingung erhielten die Probanden einen Geldbetrag nach der erfolgreichen Bearbeitung von mehreren aufeinanderfolgenden Aufgaben, in der direkten Bedingung dagegen nach jeder korrekt ausgeführten Aufgabe. In der ersten Studie konnte eine sukzessiv ansteigende Aktivität in Abhängigkeit zur Zielnähe in der rostralen cingulären Zone identifiziert werden. Das deutet darauf hin, dass dieses Areal den Wert einer Handlung in Abhängigkeit zur Nähe zum Ziel kodiert. Die Ergebnisse der zweiten Studie zeigten, dass die bisher investierte Anstrengung kortikale Regionen moduliert, die klassischerweise mit kognitiven Kontrollfunktionen in Zusammenhang gebracht werden. Außerdem repräsentierten der posteriore laterale präfrontale Cortex und der orbitofrontale Cortex den motivationalen Kontext eines Trials anhand des Risikos des Verlustes von bisher investierter Anstrengung. Insgesamt weisen diese Befunde darauf hin, dass die rostrale cinguläre Zone eine entscheidende Rolle spielt für die Kontrolle sequenzieller Handlungsstufen, die auf eine verzögerte Belohnung ausgerichtet sind. Diese Kontrollfunktion scheint auf der kontinuierlichen Aktualisierung des Wertes einer Handlungsstufe zu basieren, der von der aktuellen Zielnähe bestimmt wird. Die Befunde der zweiten Studie lassen darauf schließen, dass sich die bisher investierte Anstrengung zur Erreichung eines Handlungsziels auf die Bereitstellung von allgemeinen kognitiven Ressourcen auswirkt. Das Risiko des Verlustes von bisher investierter Anstrengung kann außerdem ein kontextuelles Merkmal der Situation darstellen, das als Bezugsrahmen für die Evaluation des erwarteten Wertes dienen kann

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

Response of the multiple-demand network during simple stimulus discriminations

The multiple-demand (MD) network is sensitive to many aspects of task difficulty, including such factors as rule complexity, memory load, attentional switching and inhibition. Many accounts link MD activity to top-down task control, raising the question of response when performance is limited by the quality of sensory input, and indeed, some prior results suggest little effect of sensory manipulations. Here we examined judgments of motion direction, manipulating difficulty by either motion coherence or salience of irrelevant dots. We manipulated each difficulty type across six levels, from very easy to very hard, and additionally manipulated whether difficulty level was blocked, and thus known in advance, or randomized. Despite the very large manipulations employed, difficulty had little effect on MD activity, especially for the coherence manipulation. Contrasting with these small or absent effects, we observed the usual increase of MD activity with increased rule complexity. We suggest that, for simple sensory discriminations, it may be impossible to compensate for reduced stimulus information by increased top-down control