Mapping the Dynamic Network Interactions Underpinning Cognition: A cTBS-fMRI Study of the Flexible Adaptive Neural System for Semantics

Higher cognitive function reflects the interaction of a network of multiple brain regions. Previous investigations have plotted out these networks using functional or structural connectivity approaches. While these map the topography of the regions involved, they do not explore the key aspect of this neuroscience principle—namely that the regions interact in a dynamic fashion. Here, we achieved this aim with respect to semantic memory. Although converging evidence implicates the anterior temporal lobes (ATLs), bilaterally, as a crucial component in semantic representation, the underlying neural interplay between the ATLs remains unclear. By combining continuous theta-burst stimulation (cTBS) with functional magnetic resonance imaging (fMRI), we perturbed the left ventrolateral ATL (vATL) and investigated acute changes in neural activity and effective connectivity of the semantic system. cTBS resulted in decreased activity at the target region and compensatory, increased activity at the contralateral vATL. In addition, there were task-specific increases in effective connectivity between the vATLs, reflecting an increased facilitatory intrinsic connectivity from the right to left vATL. Our results suggest that semantic representation is founded on a flexible, adaptive bilateral neural system and reveals an adaptive plasticity-based mechanism that might support functional recovery after unilateral damage in neurological patients

Modulating Brain Networks With Transcranial Magnetic Stimulation Over the Primary Motor Cortex: A Concurrent TMS/fMRI Study

Stimulating the primary motor cortex (M1) using transcranial magnetic stimulation (TMS) causes unique multisensory experience such as the targeted muscle activity, afferent/reafferent sensory feedback, tactile sensation over the scalp and “click” sound. Although the human M1 has been intensively investigated using TMS, the experience of the M1 stimulation has not been elucidated at the whole brain. Here, using concurrent TMS/fMRI, we investigated the acute effect of the M1 stimulation of functional brain networks during task and at rest. A short train of 1 Hz TMS pulses applied to individuals’ hand area in the M1 during motor execution or at rest. Employing the independent component analysis (ICA), we showed the M1 stimulation decreased the motor networks activity when the networks were engaged in the task and increased the deactivation of networks when the networks were not involved in the ongoing task. The M1 stimulation induced the activation in the key networks involved in bodily self-consciousness (BSC) including the insular and rolandic operculum systems regardless of states. The degree of activation in these networks was prominent at rest compared to task conditions, showing the state-dependent TMS effect. Furthermore, we demonstrated that the M1 stimulation modulated other domain-general networks such as the default mode network (DMN) and attention network and the inter-network connectivity between these networks. Our results showed that the M1 stimulation induced the widespread changes in the brain at the targeted system as well as non-motor, remote brain networks, specifically related to the BSC. Our findings shed light on understanding the neural mechanism of the complex and multisensory experience of the M1 stimulation

Vertex Stimulation as a Control Site for Transcranial Magnetic Stimulation: A Concurrent TMS/fMRI Study

AbstractBackgroundA common control condition for transcranial magnetic stimulation (TMS) studies is to apply stimulation at the vertex. An assumption of vertex stimulation is that it has relatively little influence over on-going brain processes involved in most experimental tasks, however there has been little attempt to measure neural changes linked to vertex TMS. Here we directly test this assumption by using a concurrent TMS/fMRI paradigm in which we investigate fMRI blood-oxygenation-level-dependent (BOLD) signal changes across the whole brain linked to vertex stimulation.MethodsThirty-two healthy participants to part in this study. Twenty-one were stimulated at the vertex, at 120% of resting motor threshold (RMT), with short bursts of 1 Hz TMS, while functional magnetic resonance imaging (fMRI) BOLD images were acquired. As a control condition, we delivered TMS pulses over the left primary motor cortex using identical parameters to 11 other participants.ResultsVertex stimulation did not evoke increased BOLD activation at the stimulated site. By contrast we observed widespread BOLD deactivations across the brain, including regions within the default mode network (DMN). To examine the effects of vertex stimulation a functional connectivity analysis was conducted.ConclusionThe results demonstrated that stimulating the vertex with suprathreshold TMS reduced neural activity in brain regions related to the DMN but did not influence the functional connectivity of this network. Our findings provide brain imaging evidence in support of the use of vertex simulation as a control condition in TMS but confirm that vertex TMS induces regional widespread decreases in BOLD activation

The neural bases of resilient cognitive systems: Evidence of variable neuro-displacement in the semantic system

The purpose of this study was to initiate exploration of an equally-important research goal: what are the neurocomputational mechanisms that make these cognitive systems “well engineered” and thus resilient across a range of performance demands and to mild levels of perturbation or even damage? We achieved this aim by investigating the neural dynamics of the semantic network with two task difficulty manipulations. We found that intrinsic resilience-related mechanisms were observed in both the domain-specific semantic representational system and the parallel executive control networks. Functional connectivity between these regions was also increased and these increases were related to better semantic task performance. Our results suggest that higher cognitive functions are made resilient by flexible, dynamic changes (variable neuro-displacement) across both domain-specific and multi-demand networks. Our findings provide strong evidence that the compensatory functional alterations in the impaired brain might reflect intrinsic mechanisms of a well-engineered neural system

Neural correlates of confusability in recognition of morphologically complex Korean words

When people confuse and reject a non-word that is created by switching two adjacent letters from an actual word, is called the transposition confusability effect (TCE). The TCE is known to occur at the very early stages of visual word recognition with such unit exchange as letters or syllables, but little is known about the brain mechanisms of TCE. In this study, we examined the neural correlates of TCE and the effect of a morpheme boundary placement on TCE. We manipulated the placement of a morpheme boundary by exchanging places of two syllables embedded in Korean morphologically complex words made up of lexical morpheme and grammatical morpheme. In the two experimental conditions, the transposition syllable within-boundary condition (TSW) involved exchanging two syllables within the same morpheme, whereas the across-boundary condition (TSA) involved the exchange of syllables across the stem and grammatical morpheme boundary. During fMRI, participants performed the lexical decision task. Behavioral results revealed that the TCE was found in TSW condition, and the morpheme boundary, which is manipulated in TSA, modulated the TCE. In the fMRI results, TCE induced activation in the left inferior parietal lobe (IPL) and intraparietal sulcus (IPS). The IPS activation was specific to a TCE and its strength of activation was associated with task performance. Furthermore, two functional networks were involved in the TCE: the central executive network and the dorsal attention network. Morpheme boundary modulation suppressed the TCE by recruiting the prefrontal and temporal regions, which are the key regions involved in semantic processing. Our findings propose the role of the dorsal visual pathway in syllable position processing and that its interaction with other higher cognitive systems is modulated by the morphological boundary in the early phases of visual word recognition

Establishing the cognitive signature of human brain networks derived from structural and functional connectivity

© 2018, The Author(s). Numerous neuroimaging studies have identified various brain networks using task-free analyses. While these networks undoubtedly support higher cognition, their precise functional characteristics are rarely probed directly. The frontal, temporal, and parietal lobes contain the majority of the tertiary association cortex, which are key substrates for higher cognition including executive function, language, memory, and attention. Accordingly, we established the cognitive signature of a set of contrastive brain networks on the main tertiary association cortices, identified in two task-independent datasets. Using graph-theory analysis, we revealed multiple networks across the frontal, temporal, and parietal cortex, derived from structural and functional connectivity. The patterns of network activity were then investigated using three task-active fMRI datasets to generate the functional profiles of the identified networks. We employed representational dissimilarity analysis on these functional data to quantify and compare the representational characteristics of the networks. Our results demonstrated that the topology of the task-independent networks was strongly associated with the patterns of network activity in the task-active fMRI. Our findings establish a direct relationship between the brain networks identified from task-free datasets and higher cognitive functions including cognitive control, language, memory, visuospatial function, and perception. Not only does this study support the widely held view that higher cognitive functions are supported by widespread, distributed cortical networks, but also it elucidates a methodological approach for formally establishing their relationship

The structural connectivity of higher order association cortices reflects human functional brain networks

AbstractHuman higher cognition arises from the main tertiary association cortices including the frontal, temporal and parietal lobes. Many studies have suggested that cortical functions must be shaped or emerge from the pattern of underlying physical (white matter) connectivity. Despite the importance of this hypothesis, there has not been a large-scale analysis of the white-matter connectivity within and between these associative cortices. Thus, we explored the pattern of intra- and inter-lobe white matter connectivity between multiple areas defined in each lobe. We defined 43 regions of interest on the lateral associative cortex cytoarchitectonically (6 regions of interest – ROIs in the frontal lobe and 17 ROIs in the parietal lobe) and anatomically (20 ROIs in the temporal lobe) on individuals' native space. The results demonstrated that intra-region connectivity for all 3 lobes was dense and graded generally. In contrary, the inter-lobe connectivity was relatively discrete and regionally specific such that only small sub-regions exhibited long-range connections to another lobe. The long-range connectivity was mediated by 6 major associative white matter tracts, consistent with the notion that these higher cognitive functions arises from brain-wide distributed connectivity. Using graph-theory network analysis we revealed five physically-connected sub-networks, which correspond directly to five known functional networks. This study provides strong and direct evidence that core functional brain networks mirror the brain's structural connectivity

Immediate impact of transcranial magnetic stimulation on brain structure: short-term neuroplasticity following one session of cTBS

Recent evidence demonstrates that activation-dependent neuroplasticity on a structural level can occur in a short time (2 hour or less) in humans. However, the exact time scale of structural plasticity in adult human brain remains unclear. Using voxel-based morphometry (VBM), we investigated changes in gray matter (GM) after one session of continuous theta-burst stimulation (cTBS) delivered to the anterior temporal lobe (ATL). Twenty-five participants were received cTBS over the left ATL or occipital pole as a control site outside of the scanner and had structural and functional imaging. During functional imaging, participants performed a semantic association task. VBM result revealed decreased GM in the left ATL and right cerebellum after ATL stimulation compared to the control stimulation. In addition, cTBS over the left ATL induced slower reaction time in sematic task performance, reduced regional activity at the target site, and altered functional connectivity between the left and right ATL during semantic processing. Furthermore, the ATL GM changes were associated with the functional connectivity changes in the ATL-connectivity during semantic processing. These structural alterations are mirrored by functional changes in cortical excitability attributed to the GM changes and demonstrate the rapid dynamics of cortical plasticity. Our findings support fast adjusting neuronal systems, such as postsynaptic morphology changes and neuronal turnover. Our results suggest that TBS is able to produce powerful changes in regional synaptic activity in human adult brain

Enhanced saccadic control in young people with Tourette syndrome despite slowed pro-saccades

Tourette syndrome (TS) is a neurodevelopmental disorder characterised by motor and vocal tics. Tics are repetitive and uncontrolled behaviours that have been associated with basal ganglia dysfunction. We investigated saccadic eye movements in a group of young people with TS but without co-morbid ADHD. Participants performed two tasks. One required them to perform only pro-saccade responses (pure pro-saccade task). The other involved shifting, unpredictably, between executing pro- and anti-saccades (mixed saccade task). We show that in the mixing saccade task, the TS group make significantly fewer errors than an age-matched control group, while responding equally fast. By contrast, on the pure pro-saccade task the TS group were shown to be significantly slower to initiate and to complete the saccades (longer movement duration and decreased peak velocity) than controls, while movement amplitude and direction accuracy were not different. These findings demonstrate enhanced shifting ability despite slower reflexive responding in TS and are discussed with respect to a disorder-related adaptation for increased cognitive regulation of behaviour