Noninvasive brain stimulation techniques can modulate cognitive processing

Recent methods that allow a noninvasive modulation of brain activity are able to modulate human cognitive behavior. Among these methods are transcranial electric stimulation and transcranial magnetic stimulation that both come in multiple variants. A property of both types of brain stimulation is that they modulate brain activity and in turn modulate cognitive behavior. Here, we describe the methods with their assumed neural mechanisms for readers from the economic and social sciences and little prior knowledge of these techniques. Our emphasis is on available protocols and experimental parameters to choose from when designing a study. We also review a selection of recent studies that have successfully applied them in the respective field. We provide short pointers to limitations that need to be considered and refer to the relevant papers where appropriate

Dynamic changes in prefrontal cortex involvement during verbal episodic memory formation

During encoding, the neural activity immediately before or during an event can predict whether that event will be later remembered. The contribution of brain activity immediately after an event to memory formation is however less known. Here, we used repetitive Transcranial Magnetic Stimulation (rTMS) to investigate the temporal dynamics of episodic memory encoding with a focus on post-stimulus time intervals. At encoding, rTMS was applied during the online processing of the word, at its offset, or 100, 200, 300 or 400 ms thereafter. rTMS was delivered to the left ventrolateral (VLPFC) or dorsolateral prefrontal cortex (DLPFC). VLPFC rTMS during the first few hundreds of milliseconds after word offset disrupted subsequent recognition accuracy. We did not observe effects of DLPFC rTMS at any time point. These results suggest that encoding-related VLPFC engagement starts at a relatively late processing stage, and may reflect brain processes related to the offset of the stimulus

FMRI Effective Connectivity and TMS Chronometry: Complementary Accounts of Causality in the Visuospatial Judgment Network

BACKGROUND: While traditionally quite distinct, functional neuroimaging (e.g. functional magnetic resonance imaging: fMRI) and functional interference techniques (e.g. transcranial magnetic stimulation: TMS) increasingly address similar questions of functional brain organization, including connectivity, interactions, and causality in the brain. Time-resolved TMS over multiple brain network nodes can elucidate the relative timings of functional relevance for behavior ("TMS chronometry"), while fMRI functional or effective connectivity (fMRI EC) can map task-specific interactions between brain regions based on the interrelation of measured signals. The current study empirically assessed the relation between these different methods. METHODOLOGY/PRINCIPAL FINDINGS: One group of 15 participants took part in two experiments: one fMRI EC study, and one TMS chronometry study, both of which used an established cognitive paradigm involving one visuospatial judgment task and one color judgment control task. Granger causality mapping (GCM), a data-driven variant of fMRI EC analysis, revealed a frontal-to-parietal flow of information, from inferior/middle frontal gyrus (MFG) to posterior parietal cortex (PPC). FMRI EC-guided Neuronavigated TMS had behavioral effects when applied to both PPC and to MFG, but the temporal pattern of these effects was similar for both stimulation sites. At first glance, this would seem in contradiction to the fMRI EC results. However, we discuss how TMS chronometry and fMRI EC are conceptually different and show how they can be complementary and mutually constraining, rather than contradictory, on the basis of our data. CONCLUSIONS/SIGNIFICANCE: The findings that fMRI EC could successfully localize functionally relevant TMS target regions on the single subject level, and conversely, that TMS confirmed an fMRI EC identified functional network to be behaviorally relevant, have important methodological and theoretical implications. Our results, in combination with data from earlier studies by our group (Sack et al., 2007, Cerebral Cortex), lead to informed speculations on complex brain mechanisms, and TMS disruption thereof, underlying visuospatial judgment. This first in-depth empirical and conceptual comparison of fMRI EC and TMS chronometry thereby shows the complementary insights offered by the two methods

Hemispheric Differences within the Fronto-Parietal Network Dynamics Underlying Spatial Imagery

Spatial imagery refers to the inspection and evaluation of spatial features (e.g., distance, relative position, configuration) and/or the spatial manipulation (e.g., rotation, shifting, reorienting) of mentally generated visual images. In the past few decades, psychophysical as well as functional brain imaging studies have indicated that any such processing of spatially coded information and/or manipulation based on mental images (i) is subject to similar behavioral demands and limitations as in the case of spatial processing based on real visual images, and (ii) consistently activates several nodes of widely distributed cortical networks in the brain. These nodes include areas within both, the dorsal fronto-parietal as well as ventral occipito-temporal visual processing pathway, representing the “what” versus “where” aspects of spatial imagery. We here describe evidence from functional brain imaging and brain interference studies indicating systematic hemispheric differences within the dorsal fronto-parietal networks during the execution of spatial imagery. Importantly, such hemispheric differences and functional lateralization principles are also found in the effective brain network connectivity within and across these networks, with a direction of information flow from anterior frontal/premotor regions to posterior parietal cortices. In an attempt to integrate these findings of hemispheric lateralization and fronto-to-parietal interactions, we argue that spatial imagery constitutes a multifaceted cognitive construct that can be segregated in several distinct mental sub processes, each associated with activity within specific lateralized fronto-parietal (sub) networks, forming the basis of the here proposed dynamic network model of spatial imagery

Dynamic causal modeling of load-dependent modulation of effective connectivity within the verbal working memory network

Neuroimaging studies have consistently shown that working memory (WM) tasks engage a distributed neural network that primarily includes the dorsolateral prefrontal cortex, the parietal cortex, and the anterior cingulate cortex. The current challenge is to provide a mechanistic account of the changes observed in regional activity. To achieve this, we characterized neuroplastic responses in effective connectivity between these regions at increasing WM loads using dynamic causal modeling of functional magnetic resonance imaging data obtained from healthy individuals during a verbal n-back task. Our data demonstrate that increasing memory load was associated with (a) right-hemisphere dominance, (b) increasing forward (i.e., posterior to anterior) effective connectivity within the WM network, and (c) reduction in individual variability in WM network architecture resulting in the right-hemisphere forward model reaching an exceedance probability of 99% in the most demanding condition. Our results provide direct empirical support that task difficulty, in our case WM load, is a significant moderator of short-term plasticity, complementing existing theories of task-related reduction in variability in neural networks

The Role of Posterior Parietal Cortex in Episodic Memory Retrieval: Transcranial Direct Current Stimulation Studies (tDCS)

Neuroimaging studies of recognition memory have shown that greater activity in the lateral posterior parietal cortex (PPC) correlates with successful recognition in a variety of paradigms, but experimental techniques that manipulate brain activity are necessary to determine the specific contribution of the PPC in episodic memory retrieval. Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique that can be used to manipulate cortical excitability. The collection of experiments that comprise this dissertation use tDCS to determine: 1) whether or not the lateral PPC is causally involved in episodic retrieval, and 2) whether the lateral PPC has a direct role in memory accuracy for studied information or an indirect role that can influence retrieval judgments during episodic memory retrieval. We applied tDCS during three memory paradigms that have shown correlated activity in the parietal cortex. Experiments in Chapter 1 used a false memory paradigm to test whether the parietal cortex contributes to the perceived oldness of a memory and showed increased false recognition with tDCS over the PPC compared to sham tDCS. The experiment in Chapter 2 tested whether the parietal cortex is involved in item and source accuracy and showed decreased false recognition with tDCS over the parietal cortex compared to sham tDCS. To resolve these discrepant findings, the experiment in Chapter 3 tested whether the parietal cortex is important for integration of contextual cues and mnemonic information. Results showed greater utilization of cues predicting memoranda as new with tDCS over the parietal cortex compared to sham tDCS. Overall, manipulating activity in the parietal cortex with tDCS led to alterations in memory retrieval responses compared to sham stimulation. Collectively, our results causally link the PPC to aspects of memory retrieval, and are consistent with the idea that the parietal cortex indirectly influences retrieval judgments, particularly for new items

Verbal Fluency in Mild Alzheimer's Disease: Transcranial Direct Current Stimulation over the Dorsolateral Prefrontal Cortex

Background: Recent studies showed that in healthy controls and in aphasic patients inhibitory trains of repetitive transcranial magnetic stimulation (rTMS) over the right prefrontal cortex can improve phonemic fluency performance, while anodal transcranial direct current stimulation (tDCS) over the left prefrontal cortex can improve performance in naming and semantic fluency tasks. Objective: This study aimed at investigating the effects of cathodal tDCS over the left or the right dorsolateral prefrontal cortex (DLPFC) on verbal fluency tasks (VFT) in patients with mild Alzheimer’s Disease (AD). Methods: Forty mild AD patients participated in the study (mean age 73.17 ± 5.61 years). All participants underwent cognitive baseline tasks and a VFT twice. Twenty patients randomly received cathodal tDCS to the left or the right DLPFC, and twenty patients were assigned to a control group in which only the two measures of VFT were taken, without the administration of the tDCS. Results: A significant improvement of performance on the VFT in AD patients was present after tDCS over the right DLPFC (p=.001). Instead, no difference was detected between the two VFTs sessions after tDCS over the left DLPFC (p=.42). Furthermore, these results cannot be related to task learning effects, since no significant difference was found between the two VFT sessions in the control group (p= .73). Conclusions: These data suggest that tDCS over DLPFC can improve VFT performance in AD patients. A hypothesis is that tDCS enhances adaptive patterns of brain activity between functionally connected areas

Functional asymmetries in human working memory

Thesis (Ph.D.)--Boston UniversityWorking memory is the cognitive ability to maintain and manipulate information in mind to guide behavior. This relies on the coordinated activity of a bilateral brain network, which has been modeled as a central executive in control of separate storage systems for verbal and spatial information. Evidence from human and nonhuman primate research demonstrates that the dorsolateral prefrontal cortex (dlPFC) is critical for manipulating information in working memory. However, whether the dlPFC is dissociable by the domain of information remains unsettled. Recent human studies using repetitive transcranial magnetic stimulation (rTMS) suggest the left and right dlPFC may play separable roles in manipulating verbal and spatial information. In the present study, this theory was investigated further with two experiments on healthy right-handed adults. Both experiments utilized the 3-back task of visual working memory with letters and locations serving as verbal and spatial stimuli, respectively. In Experiment 1, tasks were administered during functional neuroimaging in two formats: one using centrally-presented single letters as verbal stimuli, and dots in different locations as spatial stimuli; and another using single letters in different locations for both verbal and spatial tasks. At the whole-brain group-level, letter- and location-specific contrasts did not differ between formats, indicating verbal/spatial differences reflected discrete subsystems in working memory and not simply separate perceptual processing. Nevertheless, in the dlPFC, bilateral activity was observed across versions, suggesting its contributions to working memory are domain-independent. Experiment 2 tested whether this relationship was causal by assessing 3-back performance after applying low-frequency rTMS to the dlPFC. Following rTMS of the right dlPFC, accuracy improved on the letter task, but worsened on the location task, while the opposite was observed after left rTMS. These double-dissociations suggest left and right dlPFC operate as competing subsystems for manipulating verbal and spatial information, respectively. Thus, the observation of equivalent bilateral dlPFC activity during the letter and location tasks might reflect a left-lateralized system for verbally-encoded information and a right-lateralized system for nonverbal representations operating in parallel on all stimuli. Such a functional asymmetry would have implications for therapies aimed at ameliorating working memory impairments in disease and even normal aging

The Role of Working Memory Load in Distractor Suppression

The well-established Load Theory of Attention and Cognitive Control (Load Theory) has sparked research over two decades. There are two integral components of Load Theory, i.e. ‘cognitive load’ and ‘perceptual load’ with the former concept receiving less attention in the literature. The core assumptions of Load Theory, with an emphasis on ‘cognitive load’,have been systematically investigated in this thesis using electroencephalography (EEG) and transcranial magnetic stimulation(TMS). The current research uncovered robust working memory (WM) effects in the healthy youngeradult populationwhich partially supported Load Theory. Experiment 1 revealed that the WM load effect on distractor processing increases when more items were held in WM but can plateau at a certain set-size(i.e.,3 items). In Experiment 2, the direction of distractor interference was inconsistent across the behavioural measures of reaction times and error rates, with the latter in support of Load Theory. In contrast, therewas strong electrophysiological evidence (i.e.,the N2pc and Pd components) for increased susceptibility to peripheral distractors under low WM load conditions (remembering one item). The behavioural effects of Experiments1and 2 which partially supported Load Theory, were not replicated with a TMS protocol (Experiment 3). There were significant effects, partially supporting Load Theory, when the spatial position of distractor and a subsequent target item was considered. Altogether, the findings have contributed to a clearer understanding of WM load effects, especially in terms of the attentional processes involved in distractor processing within a single-task setting. The results have provided recommendations of factors which were omitted in Load Theory such as the distinction of functions (updating and shifting) rather than positing a general executive load. This understanding can inform future research specifically targeting visual processing, WM and selective attention processes which can be extrapolated to everyday situations where attention to detail is crucial