Multiple Cortical Networks Research Articles

P211. Long-Term Effects of Maternal Stress and Depression on Within-Network Functional Connectivity in Young Adult Offspring

Maternal stress and depression during pregnancy and early postnatal period have been associated with depressive symptoms and altered brain structure in young adult offspring, but their impact on functional connectivity (FC) is less well-understood. Here, we set out to identify multivariate relationships between FC within multiple cortical networks and maternal adverstiy (stress and depression) assessed at multiple timepoints.

The Dying Forward Hypothesis of ALS: Tracing Its History

The site of origin of amyotrophic lateral sclerosis (ALS), although unsettled, is increasingly recognized as being cortico-fugal, which is a dying-forward process primarily starting in the corticomotoneuronal system. A variety of iterations of this concept date back to over 150 years. Recently, the hallmark TAR DNA-binding protein 43 (TDP-43) pathology, seen in >95% of patients with ALS, has been shown to be largely restricted to corticofugal projecting neurons (“dying forward”). Possibly, soluble but toxic cytoplasmic TDP-43 could enter the axoplasm of Betz cells, subsequently causing dysregulation of nuclear protein in the lower brainstem and spinal cord anterior horn cells. As the disease progresses, cortical involvement in ALS becomes widespread, including or starting with frontotemporal dementia, implying a broader view of ALS as a brain disease. The onset at the motor and premotor cortices should be considered a nidus at the edge of multiple cortical networks which eventually become disrupted, causing failure of a widespread cortical connectome.

Selective changes in moral judgment by noninvasive brain stimulation of the medial prefrontal cortex.

Multiple cortical networks intervene in moral judgment, among which the dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal structures (medial PFC) emerged as two major territories, which have been traditionally attributed, respectively, to cognitive control and affective reactions. However, some recent theoretical and empirical accounts disputed this dualistic approach to moral evaluation. In the present study, to further assess the functional contribution of the medial PFC in moral judgment, we modulated its cortical excitability by means of transcranial direct current stimulation (tDCS) and tracked the change in response to different types of moral dilemmas, including switch-like and footbridge-like moral dilemmas, with and without personal involvement. One hundred participants (50 males) completed a questionnaire to assess the baseline levels of deontology. Next, participants were randomly assigned to receive anodal, sham, or cathodal tDCS over the medial prefrontal structures and then were asked to address a series of dilemmas. The results showed that participants who received anodal stimulation over the medial PFC provided more utilitarian responses to switch-like (but not footbridge-like) dilemmas than those who received cathodal tDCS. We also found that neurostimulation modulated the influence that deontology has on moral choices. Specifically, in the anodal tDCS group, participants' decisions were less likely to be influenced by their baseline levels of deontology compared with the sham or cathodal groups. Overall, our results seem to refute a functional role of the medial prefrontal structures purely restricted to affective reactions for moral dilemmas, providing new insights on the functional contribution of the medial PFC in moral judgment.

Temporal Dynamics of the Default Mode Network Characterize Meditation-Induced Alterations in Consciousness.

Current research suggests that human consciousness is associated with complex, synchronous interactions between multiple cortical networks. In particular, the default mode network (DMN) of the resting brain is thought to be altered by changes in consciousness, including the meditative state. However, it remains unclear how meditation alters the fast and ever-changing dynamics of brain activity within this network. Here we addressed this question using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to compare the spatial extents and temporal dynamics of the DMN during rest and meditation. Using fMRI, we identified key reductions in the posterior cingulate hub of the DMN, along with increases in right frontal and left temporal areas, in experienced meditators during rest and during meditation, in comparison to healthy controls (HCs). We employed the simultaneously recorded EEG data to identify the topographical microstate corresponding to activation of the DMN. Analysis of the temporal dynamics of this microstate revealed that the average duration and frequency of occurrence of DMN microstate was higher in meditators compared to HCs. Both these temporal parameters increased during meditation, reflecting the state effect of meditation. In particular, we found that the alteration in the duration of the DMN microstate when meditators entered the meditative state correlated negatively with their years of meditation experience. This reflected a trait effect of meditation, highlighting its role in producing durable changes in temporal dynamics of the DMN. Taken together, these findings shed new light on short and long-term consequences of meditation practice on this key brain network.

The neurobiology of mammalian parenting and the biosocial context of human caregiving

This article is part of a Special Issue “Parental Care”. Research on the neurobiology of attachment, pioneered by scholars in the generation that followed the discovery of social bonding, examined the biological basis of mammalian parenting through systematic experiments in animal models and their application to theories on human attachment. This paper argues for the need to construct a theory on the neurobiology of human attachment that integrates findings in animal models with human neuroscience research to formulate concepts based on experimental, not only extrapolative data. Rosenblatt's (2003) three characteristics of mammalian parenting – rapid formation of attachment, behavioral synchrony, and mother-offspring attachment as basis of social organization – are used to guide discussion on mammalian-general versus human-specific attributes of parental care. These highlight specific components of attachment in rodents, primates, and humans that chart the evolution from promiscuous, nest-bound, olfactory-based bonds to exclusive, multi-sensory, and representation-based attachments. Following, three continua are outlined in parental behavior, hormones, and brain, each detailing the evolution from rodents to humans. Parental behavior is defined as a process of trophallaxis – the reciprocal multisensory exchange that supports approach orientation and enables collaboration in social species – and includes human-specific features that enable behavioral synchrony independent of tactile contact. The oxytocin system incorporates conserved and human-specific components and is marked by pulsatile activity and dendritic release that reorganize neural networks on the basis of species-specific attachment experiences. Finally, the subcortical limbic circuit underpinning mammalian mothering extends in humans to include multiple cortical networks implicated in empathy, mentalizing, and emotion regulation that enable flexible, goal-directed caregiving. I conclude by presenting a philosophical continuum from Hobbes to Lorenz, which illustrates how research on the neurobiology of attachment can put in the forefront the social-collaborative elements in human nature and afford a new perspective on the mind-brain polarity.

Functional connectivity change across multiple cortical networks relates to episodic memory changes in aging

A major task of contemporary cognitive neuroscience of aging is to explain why episodic memory declines. Change in resting-state functional connectivity (rsFC) could be a mechanism accounting for reduced function. We addressed this through 3 studies. In study 1, 119 healthy participants (20–83 years) were followed for 3.5 years with verbal recall testing and magnetic resonance imaging. Independent of atrophy, recall change was related to change in rsFC in anatomically widespread areas. Striking age-effects were observed in that a positive relationship between rsFC and memory characterized older participants while a negative relationship was seen among the younger and middle-aged. This suggests that cognitive consequences of rsFC change are not stable across age. In study 2 and 3, the age-dependent differences in rsFC-memory relationship were replicated by use of a simulation model (study 2) and by a cross-sectional experimental recognition memory task (study 3). In conclusion, memory changes were related to altered rsFC in an age-dependent manner, and future research needs to detail the mechanisms behind age-varying relationships.

Functional topography of the thalamocortical system in human.

Various studies have indicated that the thalamus is involved in controlling both cortico-cortical information flow and cortical communication with the rest of the brain. Detailed anatomy and functional connectivity patterns of the thalamocortical system are essential to understanding the cortical organization and pathophysiology of a wide range of thalamus-related neurological and neuropsychiatric diseases. The current study used resting-state fMRI to investigate the topography of the human thalamocortical system from a functional perspective. The thalamus-related cortical networks were identified by performing independent component analysis on voxel-based thalamic functional connectivity maps across a large group of subjects. The resulting functional brain networks were very similar to well-established resting-state network maps. Using these brain network components in a spatial regression model with each thalamic voxel's functional connectivity map, we localized the thalamic subdivisions related to each brain network. For instance, the medial dorsal nucleus was shown to be associated with the default mode, the bilateral executive, the medial visual networks; and the pulvinar nucleus was involved in both the dorsal attention and the visual networks. These results revealed that a single nucleus may have functional connections with multiple cortical regions or even multiple functional networks, and may be potentially related to the function of mediation or modulation of multiple cortical networks. This observed organization of thalamocortical system provided a reference for studying the functions of thalamic sub-regions. The importance of intrinsic connectivity-based mapping of the thalamocortical relationship is discussed, as well as the applicability of the approach for future studies.

Functional Connectivity in Multiple Cortical Networks Is Associated with Performance Across Cognitive Domains in Older Adults.

Intrinsic functional connectivity MRI has become a widely used tool for measuring integrity in large-scale cortical networks. This study examined multiple cortical networks using Template-Based Rotation (TBR), a method that applies a priori network and nuisance component templates defined from an independent dataset to test datasets of interest. A priori templates were applied to a test dataset of 276 older adults (ages 65–90) from the Harvard Aging Brain Study to examine the relationship between multiple large-scale cortical networks and cognition. Factor scores derived from neuropsychological tests represented processing speed, executive function, and episodic memory. Resting-state BOLD data were acquired in two 6-min acquisitions on a 3-Tesla scanner and processed with TBR to extract individual-level metrics of network connectivity in multiple cortical networks. All results controlled for data quality metrics, including motion. Connectivity in multiple large-scale cortical networks was positively related to all cognitive domains, with a composite measure of general connectivity positively associated with general cognitive performance. Controlling for the correlations between networks, the frontoparietal control network (FPCN) and executive function demonstrated the only significant association, suggesting specificity in this relationship. Further analyses found that the FPCN mediated the relationships of the other networks with cognition, suggesting that this network may play a central role in understanding individual variation in cognition during aging.

Large-scale microelectrode recordings of high-frequency gamma oscillations in human cortex during sleep.

Gamma oscillations (40-120 Hz), usually associated with waking functions, can be recorded in the deepest stages of sleep in animals. The full details of their large-scale coordination across multiple cortical networks are still unknown. Furthermore, it is not known whether oscillations with similar characteristics are also present in the human brain. In this study, we examined the existence of gamma oscillations during polysomnographically defined sleep-wake states using large-scale microelectrode recordings (up to 56 channels), with single-cell and spike-time precision, in epilepsy patients. We report that low (40-80 Hz) and high (80-120 Hz) gamma oscillations recurrently emerged over time windows of several hundreds of milliseconds in all investigated cortical areas during slow-wave sleep. These patterns were correlated with positive peaks of EEG slow oscillations and marked increases in local cellular discharges, suggesting that they were associated with cortical UP states. These gamma oscillations frequently appeared at approximately the same time in many different cortical areas, including homotopic regions, forming large spatial patterns. Coincident firings with millisecond precision were strongly enhanced during gamma oscillations but only between cells within the same cortical area. Furthermore, in a significant number of cases, cortical gamma oscillations tended to occur within 100 ms after hippocampal ripple/sharp wave complexes. These data confirm and extend earlier animal studies reporting that gamma oscillations are transiently expressed during UP states during sleep. We speculate that these high-frequency patterns briefly restore "microwake" activity and are important for consolidation of memory traces acquired during previous awake periods.

Dorsolateral prefrontal cortex specifically processes general – but not personal – knowledge deception: Multiple brain networks for lying

Despite intensive research into ways of detecting deception in legal, moral and clinical contexts, few experimental data are available on the neural substrate for the different types of lies. We used transcranial direct current stimulation (tDCS) to modulate dorsolateral prefrontal cortex (DLPFC) function and to assess its influence on various types of lies. Twenty healthy volunteers were tested before and after tDCS (anodal and sham). In each session the Guilty Knowledge Task and Visual Attention Task were administered at baseline and immediately after tDCS ended. A computer-controlled task was used to evaluate truthful responses and lie responses to questions referring to personal information and general knowledge. Dependent variables collected were reaction times (RTs) and accuracy. At baseline the RTs were significantly longer for lies than for truthful responses. After sham stimulation, lie responses remained unchanged ( p = 0.24) but after anodal tDCS, RTs decreased significantly only for lies involving general knowledge ( p = 0.02). tDCS left the Visual Attention Task unaffected. These findings show that manipulating DLPFC function with tDCS specifically modulates deceptive responses for general information leaving those on personal information unaffected. Multiple cortical networks intervene in deception involving general and personal knowledge. Deception referring to general and personal knowledge probably involves multiple cortical networks.

Differential activation patterns of occipital and prefrontal cortices during motion processing: Evidence from normal and schizophrenic brains

Visual motion perception is normally mediated by neural processing in the posterior cortex. Focal damage to the middle temporal area (MT), a posterior extrastriate region, induces motion perception impairment. It is unclear, however, how more broadly distributed cortical dysfunction affects this visual behavior and its neural substrates. Schizophrenia manifests itself in a variety of behavioral and perceptual abnormalities that have proved difficult to understand through a dysfunction of any single brain system. One of these perceptual abnormalities involves impaired motion perception. Motion processing provides an opportunity to clarify the roles of multiple cortical networks in both healthy and schizophrenic brains. Using fMRI, we measured cortical activation while participants performed two visual motion tasks (direction discrimination and speed discrimination) and one nonmotion task (contrast discrimination). Normal controls showed robust cortical activation (BOLD signal changes) in MT during the direction and speed discrimination tasks, documenting primary processing of sensory input in this posterior region. In patients with schizophrenia, cortical activation was significantly reduced in MT and significantly increased in the inferior convexity of the prefrontal cortex, an area that is normally involved in higher level cognitive processing. This shift in cortical responses from posterior to prefrontal regions suggests that motion perception in schizophrenia is associated with both deficient sensory processing and compensatory cognitive processing. Furthermore, this result provides evidence that in the context of broadly distributed cortical dysfunction, the usual functional specificity of the cortex becomes modified, even across the domains of sensory and cognitive processing.

Dynamic interaction of attractors across multiple cortical networks as a neural basis for intersensory facilitation

I propose a neural network model for intersensory facilitation and investigate its essential neuronal mechanisms. The model consists of sensory networks (SI, SII) and an integration network (IT). The integration network binds information derived from the sensory networks and sends feedback signals to them. Through a Hebbian learning process, point attractors representing individual features and objects are created in the dynamics of the sensory networks and integration network, respectively. The ongoing state of each network is a randomly itinerant state among these point attractors. When the SI network is stimulated with a feature (I_ n ) belonging to an object (O_ n ) with suprathreshold intensity, the point attractor corresponding to I_ n emerges in the SI network, but does not when stimulated with subthreshold intensity. Intersensory facilitation occurs when associate feature II_ n derived from the other modality belonging to the same object (O_ n ) is simultaneously presented to other sensory network SII, where the point attractor corresponding to feature I_ n emerges even when the sensory networks are stimulated with subthreshold intensity. I suggest here that the dynamic interaction of relevant point attractors across multiple neural networks is essential for intersensory facilitation, and that self-organized synaptic modulation effectively contributes to intersensory facilitation when crossmodal stimuli are separated in time.