Klaartje Heinen

Causal evidence for frontal involvement in memory target maintenance by posterior brain areas during distracter interference of visual working memory

Dorsolateral prefrontal cortex (DLPFC) is recruited during visual working memory (WM) when relevant information must be maintained in the presence of distracting information. The mechanism by which DLPFC might ensure successful maintenance of the contents of WM is, however, unclear; it might enhance neural maintenance of memory targets or suppress processing of distracters. To adjudicate between these possibilities, we applied time-locked transcranial magnetic stimulation (TMS) during functional MRI, an approach that permits causal assessment of a stimulated brain regions influence on connected brain regions, and evaluated how this influence may change under different task conditions. Participants performed a visual WM task requiring retention of visual stimuli (faces or houses) across a delay during which visual distracters could be present or absent. When distracters were present, they were always from the opposite stimulus category, so that targets and distracters were represented in distinct posterior cortical areas. We then measured whether DLPFC-TMS, administered in the delay at the time point when distracters could appear, would modulate posterior regions representing memory targets or distracters. We found that DLPFC-TMS influenced posterior areas only when distracters were present and, critically, that this influence consisted of increased activity in regions representing the current memory targets. DLPFC-TMS did not affect regions representing current distracters. These results provide a new line of causal evidence for a top-down DLPFC-based control mechanism that promotes successful maintenance of relevant information in WM in the presence of distraction.

Connectivity-based neurofeedback: Dynamic causal modeling for real-time fMRI

Neurofeedback based on real-time fMRI is an emerging technique that can be used to train voluntary control of brain activity. Such brain training has been shown to lead to behavioral effects that are specific to the functional role of the targeted brain area. However, real-time fMRI-based neurofeedback so far was limited to mainly training localized brain activity within a region of interest. Here, we overcome this limitation by presenting near real-time dynamic causal modeling in order to provide feedback information based on connectivity between brain areas rather than activity within a single brain area. Using a visual–spatial attention paradigm, we show that participants can voluntarily control a feedback signal that is based on the Bayesian model comparison between two predefined model alternatives, i.e. the connectivity between left visual cortex and left parietal cortex vs. the connectivity between right visual cortex and right parietal cortex. Our new approach thus allows for training voluntary control over specific functional brain networks. Because most mental functions and most neurological disorders are associated with network activity rather than with activity in a single brain region, this novel approach is an important methodological innovation in order to more directly target functionally relevant brain networks.

Figure-ground segregation requires two distinct periods of activity in V1: A transcranial magnetic stimulation study

Discriminating objects from their surroundings by the visual system is known as figure–ground segregation. This process entails two different subprocesses: boundary detection and subsequent surface segregation or ‘filling in’. In this study, we used transcranial magnetic stimulation to test the hypothesis that temporally distinct processes in V1 and related early visual areas such as V2 or V3 are causally related to the process of figure–ground segregation. Our results indicate that correct discrimination between two visual stimuli, which relies on figure–ground segregation, requires two separate periods of information processing in the early visual cortex: one around 130–160u2009ms and the other around 250–280u2009ms.

Parietal Stimulation Decouples Spatial and Feature-Based Attention

Everyday visual scenes contain a vast quantity of information, only a fraction of which can guide our behavior. Properties such as the location, color and orientation of stimuli help us extract relevant information from complex scenes (Treisman and Gelade, 1980; Livingstone and Hubel, 1987). But how does the brain coordinate the selection of such different stimulus characteristics? Neuroimaging studies have revealed significant regions of overlapping activity in frontoparietal cortex during attention to locations and features, suggesting a global component to visual selection (Vandenberghe et al., 2001; Corbetta and Shulman, 2002; Giesbrecht et al., 2003; Slagter et al., 2007). At the same time, the neural consequences of spatial and feature-based attention differ markedly in early visual areas (Treue and Martinez-Trujillo, 2007), implying that selection may rely on more specific top-down processes. Here we probed the balance between specialized and generalized control by interrupting preparatory attention in the human parietal cortex with transcranial magnetic stimulation (TMS). We found that stimulation of the supramarginal gyrus (SMG) impaired spatial attention only, whereas TMS of the anterior intraparietal sulcus (aIPS) disrupted spatial and feature-based attention. The selection of different stimulus characteristics is thus mediated by distinct top-down mechanisms, which can be decoupled by cortical interference.

Neuronal integration in visual cortex elevates face category tuning to conscious face perception

The human brain has the extraordinary capability to transform cluttered sensory input into distinct object representations. For example, it is able to rapidly and seemingly without effort detect object categories in complex natural scenes. Surprisingly, category tuning is not sufficient to achieve conscious recognition of objects. What neural process beyond category extraction might elevate neural representations to the level where objects are consciously perceived? Here we show that visible and invisible faces produce similar category-selective responses in the ventral visual cortex. The pattern of neural activity evoked by visible faces could be used to decode the presence of invisible faces and vice versa. However, only visible faces caused extensive response enhancements and changes in neural oscillatory synchronization, as well as increased functional connectivity between higher and lower visual areas. We conclude that conscious face perception is more tightly linked to neural processes of sustained information integration and binding than to processes accommodating face category tuning.

Concurrent TMS-fMRI reveals dynamic interhemispheric influences of the right parietal cortex during exogenously cued visuospatial attention.

We used concurrent transcranial magnetic stimulation and functional MRI (TMS‐fMRI) during a visuospatial cueing paradigm in humans, to study the causal role of the right angular gyrus (AG) as a source of attentional control. Our findings show that TMS over the right AG (high vs. low intensity) modulates neural responses interhemispherically, in a manner that varies dynamically with the current attentional condition. The behavioural impact of such TMS depended not only on the target hemifield but also on exogenous cue validity, facilitating spatial reorienting to invalidly cued right visual targets. On a neural level, right AG TMS had corresponding interhemispheric effects in the left AG and left retinotopic cortex, including area V1. We conclude that the direction of covert visuospatial attention can involve dynamic interplay between the right AG and remote interconnected regions of the opposite left hemisphere, whereas our findings also suggest that the right AG can influence responses in the retinotopic visual cortex.

Direct Evidence for Attention-Dependent Influences of the Frontal Eye-Fields on Feature-Responsive Visual Cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for “spatial” attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level–dependent (BOLD) signals in visual areas processing “target feature” but not in “distracter feature”–processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial “feature”-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

Cathodal transcranial direct current stimulation over posterior parietal cortex enhances distinct aspects of visual working memory

In this study, we investigated the effects of tDCS over the posterior parietal cortex (PPC) during a visual working memory (WM) task, which probes different sources of response error underlying the precision of WM recall. In two separate experiments, we demonstrated that tDCS enhanced WM precision when applied bilaterally over the PPC, independent of electrode configuration. In a third experiment, we demonstrated with unilateral electrode configuration over the right PPC, that only cathodal tDCS enhanced WM precision and only when baseline performance was low. Looking at the effects on underlying sources of error, we found that cathodal stimulation enhanced the probability of correct target response across all participants by reducing feature-misbinding. Only for low-baseline performers, cathodal stimulation also reduced variability of recall. We conclude that cathodal- but not anodal tDCS can improve WM precision by preventing feature-misbinding and hereby enhancing attentional selection. For low-baseline performers, cathodal tDCS also protects the memory trace. Furthermore, stimulation over bilateral PPC is more potent than unilateral cathodal tDCS in enhancing general WM precision.

TMS and the functional neuroanatomy of attention

Coordinated behaviour depends on selective attention: the ability to select a limited subset of stimuli for detailed analysis, while suppressing the stream of irrelevant information continuously received by our senses. Over the past three decades, converging evidence from neurophysiology, neuropsychology and cognitive neuroscience has suggested that selection modulates brain activity at sensory cortical levels ( [Desimone and Duncan, 1995], [Kastner and Ungerleider, 2000] and [Saalman et al., 2007]), and that potential sources of control are distributed across a frontoparietal network of brain regions ( [Corbetta and Shulman, 2002] and [Corbetta et al., 2008]). More recently, TMS studies have provided insights into the functional neuroanatomy of selective processes, revealing not only which areas of the healthy human brain are crucial for attention, but also when they are engaged during the timecourse of information processing.

Functional connectivity between prefrontal and parietal cortex drives visuo-spatial attention shifts

ABSTRACT It is well established that the frontal eye‐fields (FEF) in the dorsal attention network (DAN) guide top‐down selective attention. In addition, converging evidence implies a causal role for the FEF in attention shifting, which is also known to recruit the ventral attention network (VAN) and fronto‐striatal regions. To investigate the causal influence of the FEF as (part of) a central hub between these networks, we applied thetaburst transcranial magnetic stimulation (TBS) off‐line, combined with functional magnetic resonance (fMRI) during a cued visuo‐spatial attention shifting paradigm. We found that TBS over the right FEF impaired performance on a visual discrimination task in both hemifields following attention shifts, while only left hemifield performance was affected when participants were cued to maintain the focus of attention. These effects recovered ca. 20 min post stimulation. Furthermore, particularly following attention shifts, TBS suppressed the neural signal in bilateral FEF, right inferior and superior parietal lobule (IPL/SPL) and bilateral supramarginal gyri (SMG). Immediately post stimulation, functional connectivity was impaired between right FEF and right SMG as well as right putamen. Importantly, the extent of decreased connectivity between right FEF and right SMG correlated with behavioural impairment following attention shifts. The main finding of this study demonstrates that influences from right FEF on SMG in the ventral attention network causally underly attention shifts, presumably by enabling disengagement from the current focus of attention. HIGHLIGHTSThetaburst stimulation to the right FEF temporarily impairs bilateral attention shifts.Lateralised behavioural deficits in the contralateral hemifield are observed when cued to maintain attention.These effects recover ca. 20 min post stimulation.During shifts, neural activity is suppressed following right FEF TBS in the dorsal attention network and supramarginal gyri.Influences from right FEF to SMG causally underlie attention shifts, presumably by enabling disengagement from current focus.