Dynamic regulation of interregional cortical communication by slow brain oscillations during working memory.
ABSTRACT: Transiently storing information and mentally manipulating it is known as working memory. These operations are implemented by a distributed, fronto-parietal cognitive control network in the brain. The neural mechanisms controlling interactions within this network are yet to be determined. Here, we show that during a working memory task the brain uses an oscillatory mechanism for regulating access to prefrontal cognitive resources, dynamically controlling interactions between prefrontal cortex and remote neocortical areas. Combining EEG with non-invasive brain stimulation we show that fast rhythmical brain activity at posterior sites are nested into prefrontal slow brain waves. Depending on cognitive demand this high frequency activity is nested into different phases of the slow wave enabling dynamic coupling or de-coupling of the fronto-parietal control network adjusted to cognitive effort. This mechanism constitutes a basic principle of coordinating higher cognitive functions in the human brain.
Project description:Demands on visuospatial working memory are a ubiquitous part of everyday life. As such, significant efforts have been made to understand how the brain responds to these demands in real-world environments. Multiple brain imaging studies have highlighted a fronto-parietal cortical network that underlies visuospatial working memory, is modulated by cognitive load, and that appears to respond uniquely to encoding versus retrieval components. Furthermore, multiple studies have identified functional connectivity in regions of the fronto-parietal network during working memory tasks. Together, these findings have helped outline important aspects of the neural architecture that underlies visuospatial working memory. Here, we provide results from the first fNIRS-based investigation of fronto-parietal signatures of cortical activation and functional connectivity during a computer-based visuospatial working memory task. Our results indicate that the local maxima of cortical activation and functional coherence do not necessarily overlap spatially, and that cortical activation is significantly more susceptible to task-specific demands compared to functional connectivity. These results highlight important and novel information regarding neurotypical signatures of cortical activation and functional connectivity during visuospatial working memory. Our findings also demonstrate the utility of fNIRS for interrogating these cognitive processes.
Project description:<h4>Background</h4>Imaging studies help to understand the evolution of key cognitive processes related to aging, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to WM processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition.<h4>Methods</h4>We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects.<h4>Results</h4>During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parietal network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas.<h4>Conclusion</h4>Successful WM processes in the elderly population are accompanied by an activation pattern that involves cerebellar regions working together with a fronto-parietal network.
Project description:Lateral prefrontal and posterior parietal cortical areas exhibit task-dependent activation during working memory tasks in humans and monkeys. Neurons in these regions become synchronized during attention-demanding tasks, but the contribution of these interactions to working memory is largely unknown. Using simultaneous recordings of neural activity from multiple areas in both regions, we find widespread, task-dependent, and content-specific synchronization of activity across the fronto-parietal network during visual working memory. The patterns of synchronization are prevalent among stimulus-selective neurons and are governed by influences arising in parietal cortex. These results indicate that short-term memories are represented by large-scale patterns of synchronized activity across the fronto-parietal network.
Project description:Schizophrenia (SZ) is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC). Utilizing linked independent component analysis (LICA), a data-driven multimodal analysis approach, we investigated structure-function associations in a large sample of SZ (n = 96) and HC (n = 142). We tested for associations between task-positive (fronto-parietal) and task-negative (default-mode) brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p < .05, corrected for multiple comparisons) was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure-function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.
Project description:Although research shows that working memory improves during early childhood, it remains unclear how the fronto-parietal network of cortical regions, known to support this ability in adults, relates to changes in young children. Measures of cortical thickness may be useful in investigating this association as they reflect age-related differences in gray matter and have been proposed to support age-related improvements in other cognitive abilities, but have only sparingly been tested empirically in early childhood. The present study sought to investigate relations between cortical thickness and performance on a digit span task in 200 4- to 8-year-old children using both a priori defined regions of interest related to working memory (superior frontal cortex, middle frontal cortex, anterior cingulate cortex, superior parietal cortex) and whole brain analyses. Results indicated a significant association between cortical thickness in each a priori defined fronto-parietal region and performance on digit span, such that those with a thinner cortex recalled more items than those with a thicker cortex. Similar regions emerged from the whole brain analyses, as did several other regions not typically included in the fronto-parietal network. Results of a mediation analysis indicated that age-related differences in behavior were partially explained by variations in thickness of anterior cingulate cortex, suggesting a potentially important role for this structure during early childhood. Overall, these results suggest that in children as young as 4 years of age there are associations between working memory abilities and thickness in cortical areas known to support working memory in adults.
Project description:Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and controls (CON group; n = 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.
Project description:Working memory is a limited capacity system that integrates and manipulates information across brief periods of time, engaging a network of prefrontal, parietal and subcortical brain regions. Genetic control of these heritable brain processes have been suggested by functional genetic variations influencing dopamine signalling, which affect prefrontal activity during complex working memory tasks. However, less is known about genetic control over component working memory cortical-subcortical networks in humans, and the pharmacogenetic implications of dopamine-related genes on cognition in patients receiving anti-dopaminergic drugs. Here, we examined predictions from basic models of dopaminergic signalling in cortical and cortical-subcortical circuitries implicated in dissociable working memory maintenance and manipulation processes. We also examined pharmacogenetic effects on cognition in the context of anti-dopaminergic drug therapy. Using dynamic causal models of functional magnetic resonance imaging in normal subjects (n?=?46), we identified differentiated effects of functional polymorphisms in COMT, DRD2 and AKT1 genes on prefrontal-parietal and prefrontal-striatal circuits engaged during maintenance and manipulation, respectively. Cortical synaptic dopamine monitored by the COMT Val158Met polymorphism influenced prefrontal control of both parietal processing in working memory maintenance and striatal processing in working memory manipulation. DRD2 and AKT1 polymorphisms implicated in DRD2 signalling influenced only the prefrontal-striatal network associated with manipulation. In the context of anti-psychotic drugs, the DRD2 and AKT1 polymorphisms altered dose-response effects of anti-psychotic drugs on cognition in schizophrenia (n?=?111). Thus, we suggest that genetic modulation of DRD2-AKT1-related prefrontal-subcortical circuits could at least in part influence cognitive dysfunction in psychosis and its treatment.
Project description:Brain dysfunction in prefrontal cortex (PFC) and dorsal striatum (DS) contributes to habitual drug use. These regions are constituents of brain networks thought to be involved in drug addiction. To investigate whether networks containing these regions differ between nicotine dependent female smokers and age-matched female non-smokers, we employed functional MRI (fMRI) at rest.Data were processed with independent component analysis (ICA) to identify resting state networks (RSNs). We identified a subcortical limbic network and three discrete PFC networks: a medial prefrontal cortex (mPFC) network and right and left lateralized fronto-parietal networks common to all subjects. We then compared these RSNs between smokers and non-smokers using a dual regression approach.Smokers had greater coupling versus non-smokers between left fronto-parietal and mPFC networks. Smokers with the greatest mPFC-left fronto-parietal coupling had the most DS smoking cue reactivity as measured during an fMRI smoking cue reactivity paradigm. This may be important because the DS plays a critical role in maintaining drug-cue associations. Furthermore, subcortical limbic network amplitude was greater in smokers.Our results suggest that prefrontal brain networks are more strongly coupled in smokers, which could facilitate drug-cue responding. Our data also are the first to document greater reward-related network fMRI amplitude in smokers. Our findings suggest that resting state PFC network interactions and limbic network amplitude can differentiate nicotine-dependent smokers from controls, and may serve as biomarkers for nicotine dependence severity and treatment efficacy.
Project description:Organisms operate within both a perceptual domain of objects and events, and a mnemonic domain of past experiences and future goals. Each domain requires a deliberate selection of task-relevant information, through deployments of external (perceptual) and internal (mnemonic) attention, respectively. Little is known about the control of attention shifts in working memory, or whether voluntary control of attention in these two domains is subserved by a common or by distinct functional networks. We used human fMRI to examine the neural basis of cognitive control while participants shifted attention in vision and in working memory. We found that these acts of control recruit in common a subset of the dorsal fronto-parietal attentional control network, including the medial superior parietal lobule, intraparietal sulcus, and superior frontal sulcus/gyrus. Event-related multivoxel pattern classification reveals, however, that these regions exhibit distinct spatio-temporal patterns of neural activity during internal and external shifts of attention, respectively. These findings constrain theoretical accounts of selection in working memory and perception by showing that populations of neurons in dorsal fronto-parietal network regions exhibit selective tuning for acts of cognitive control in different cognitive domains.
Project description:In this study, we used model-based functional MRI (fMRI) to locate two functions of the fronto-parietal network: declarative memory retrievals and updating of working memory. Because regions in the fronto-parietal network are by definition coherently active, locating functions within this network is difficult. To overcome this problem, we applied model-based fMRI, an analysis method that uses predictions of a computational model to inform the analysis. We applied model-based fMRI to five previously published datasets with associated computational cognitive models, and subsequently integrated the results in a meta-analysis. The meta-analysis showed that declarative memory retrievals correlated with activity in the inferior frontal gyrus and the anterior cingulate, whereas updating of working memory corresponded to activation in the inferior parietal lobule, as well as to activation around the inferior frontal gyrus and the anterior cingulate.