bioRxiv (Cold Spring Harbor Laboratory), Dec 15, 2022
Attention-deficit/hyperactivity disorder (ADHD) is characterized by involuntary fluctuations of a... more Attention-deficit/hyperactivity disorder (ADHD) is characterized by involuntary fluctuations of attention in continuous performance tasks (CPTs) wherein attention must be sustained over long periods of time. The neuronal basis underlying aberrant attentional fluctuations in time scales from seconds to minutes have remained poorly understood. Neuronal alpha-and gammaband oscillations are thought to implement attentional and top-down control of sensorimotor processing. We hypothesized that aberrant behavioral fluctuations in ADHD would be caused by aberrant endogenous brain dynamics in alpha and gamma-band oscillations and specifically by their aberrant long-range temporal correlations (LRTCs). We measured brain activity with magnetoencephalography (MEG) from adult participants diagnosed with ADHD (N = 19) and from healthy control subjects (N = 20) during resting state and two CPTs; a threshold stimulus detection task and a Go/NoGo task. We then estimated LRTCs of neuronal oscillations and behavioral fluctuations with detrended fluctuation analysis (DFA). ADHD was associated with aberrant LRTCs in both behavioral performance and of neuronal oscillations. LRTCs were correlated with symptom severity with a U-shaped correlations indicating that the LRTCs were largest with moderate symptom scores. These data demonstrate the presence of aberrant temporal dynamics of neuronal oscillations in adult ADHD patients, which may underlie involuntary attentional fluctuations in ADHD. Taken that LRTCs are a hallmark of brain critical dynamics, these data show that moderate ADHD symptoms scores maximize brain criticality which is thought to be beneficial for performance.
Chunking language has been proposed to be vital for comprehension enabling the extraction of mean... more Chunking language has been proposed to be vital for comprehension enabling the extraction of meaning from a continuous stream of speech. However, neurocognitive mechanisms of chunking are poorly understood. The present study investigated neural correlates of chunk boundaries intuitively identified by listeners in natural speech drawn from linguistic corpora using magneto- and electroencephalography (MEEG). In a behavioral experiment, subjects marked chunk boundaries in the excerpts intuitively, which revealed highly consistent chunk boundary markings across the subjects. We next recorded brain activity to investigate whether chunk boundaries with high and medium agreement rates elicit distinct evoked responses compared to non-boundaries. Pauses placed at chunk boundaries elicited a closure positive shift with the sources over bilateral auditory cortices. In contrast, pauses placed within a chunk were perceived as interruptions and elicited a biphasic emitted potential with sources located in the bilateral primary and non-primary auditory areas with right-hemispheric dominance, and in the right inferior frontal cortex. Furthermore, pauses placed at stronger boundaries elicited earlier and more prominent activation over the left hemisphere suggesting that brain responses to chunk boundaries of natural speech can be modulated by the relative strength of different linguistic cues, such as syntactic structure and prosody.
Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and atte... more Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and attentional control, respectively, of sensory information maintained in visual working memory (VWM). Within these regions, beta/gamma phase-synchronization supports the integration of sensory functions, while synchronization in theta/alpha bands supports the regulation of attentional functions. A key challenge is to understand which mechanisms integrate neuronal processing across these distinct frequencies and thereby the sensory and attentional functions. We investigated whether such integration could be achieved by cross-frequency phase synchrony (CFS). Using concurrent magneto- and electroencephalography, we found that CFS was load-dependently enhanced between theta and alpha–gamma and between alpha and beta-gamma oscillations during VWM maintenance among visual, FP, and dorsal attention (DA) systems. CFS also connected the hubs of within-frequency-synchronized networks and its strength predicted individual VWM capacity. We propose that CFS integrates processing among synchronized neuronal networks from theta to gamma frequencies to link sensory and attentional functions
The amplitude of a-frequency band (8–14 Hz) activity in the human electroencephalogram is suppres... more The amplitude of a-frequency band (8–14 Hz) activity in the human electroencephalogram is suppressed by eye opening, visual stimuli and visual scanning, whereas it is enhanced during internal tasks, such as mental calculation and working memory. a-Frequency band oscillations have hence been thought to reflect idling or inhibition of task-irrelevant cortical areas. However, recent data on a-amplitude and, in particular, a-phase dynamics posit a direct and active role for a-frequency band rhythmicity in the mechanisms of attention and consciousness. We propose that simultaneous a-, b- (14– 30 Hz) and g- (30–70 Hz) frequency band oscillations are required for unified cognitive operations, and hypothesize that cross-frequency phase synchrony between a, b and g oscillations coordinates the selection and maintenance of neuronal object representations during working memory, perception and consciousness.
This dataset contains results from a study to identify modules in human connectomes of inter-regi... more This dataset contains results from a study to identify modules in human connectomes of inter-regional phase-synchronization, from intra-cerebral stereo-EEG (Electroencephalographic) data. 'Module_assignments.xlsx' contains module assignments, separately for left and right hemispheres, for frequencies from 3 Hz to 320 Hz. Module assignments are provided for different spatial scales, as specified by the 'gamma' parameter of the Louvain community detection method, which we used to identify modules. 'NeurosynthTerms_ConsensusModules.xlsx' contains module assignments for 'consensus modules', i.e. sets of regions consistently assigned to the same module across frequencies and spatial scales. Further, it provides sets of terms related to perceptual, cognitive and motor processing, that are selectively associated to each of the consensus modules.
Background Video gaming is a promising intervention for cognitive and social impairment in patien... more Background Video gaming is a promising intervention for cognitive and social impairment in patients with schizophrenia. A number of gaming interventions have been evaluated in small-scale studies with various patient groups, but studies on patients with schizophrenia remain scarce and rarely include the evaluation of both clinical and neurocognitive outcomes. In this study, we will test the effectiveness of two interventions with gaming elements to improve cognitive and clinical outcomes among persons with schizophrenia. Methods The participants will be recruited from different outpatient units (e.g., outpatient psychiatric units, day hospitals, residential care homes). The controlled clinical trial will follow a three-arm parallel-group design: 1) cognitive training (experimental group, CogniFit), 2) entertainment gaming (active control group, SIMS 4), and 3) treatment as usual. The primary outcomes are working memory function at 3-month and 6-month follow-ups. The secondary outcom...
ABSTRACTAmblyopia is a common visual disorder that is treatable in childhood. However, therapies ... more ABSTRACTAmblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. This phase 2, randomized, double-blind (fluoxetine vs. placebo), multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n=22) or placebo (n=20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. There was no significant difference in treatment efficacy between the groups. Visual acuity at the primary endpoint had significantly improved over baseline in both the fluoxetine (−0.167 logMAR) and placebo (−0.194 l...
Community structure, or ''modularity,'' is a fundamentally important aspect in the organization o... more Community structure, or ''modularity,'' is a fundamentally important aspect in the organization of structural and functional brain networks, but their identification with community detection methods is confounded by noisy or missing connections. Although several methods have been used to account for missing data, the performance of these methods has not been compared quantitatively so far. In this study, we compared four different approaches to account for missing connections when identifying modules in binary and weighted networks using both Louvain and Infomap community detection algorithms. The four methods are ''zeros,'' ''row-column mean,'' ''common neighbors,'' and ''consensus clustering.'' Using Lancichinetti-Fortunato-Radicchi benchmark-simulated binary and weighted networks, we find that ''zeros,'' ''row-column mean,'' and ''common neighbors'' approaches perform well with both Louvain and Infomap, whereas ''consensus clustering'' performs well with Louvain but not Infomap. A similar pattern of results was observed with empirical networks from stereotactical electroencephalography data, except that ''consensus clustering'' outperforms other approaches on weighted networks with Louvain. Based on these results, we recommend any of the four methods when using Louvain on binary networks, whereas ''consensus clustering'' is superior with Louvain clustering of weighted networks. When using Infomap, ''zeros'' or ''common neighbors'' should be used for both binary and weighted networks. These findings provide a basis to accounting for noisy or missing connections when identifying modules in brain networks.
Human cognitive functions are subjectively coherent even though the underlying neuronal processin... more Human cognitive functions are subjectively coherent even though the underlying neuronal processing is achieved in many cortical regions in parallel. A number of animal electrophysiological studies have shown that neuronal synchronization may be a mechanism for the integration of such anatomically distributed neuronal processing as well as for the regulation of neuronal communication within these distributed networks. However, less is known about the functional and behavioral significance of the synchronization of neuronal oscillations in human brains. In recent years, several advancements have been made in source localization of the locally and large-scale synchronized networks by using noninvasive human magneto- and electroencephalography (EEG and MEG). These data have revealed the first glimpses into the structures of cortical networks underlying perceptual, attentional, and working memory functions.
Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have lim... more Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: −0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from ...
SummaryNeuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitu... more SummaryNeuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. However, the genetic underpinnings of oscillatory dynamics have remained poorly understood. We recorded resting-state magnetoencephalography (MEG) from 82 healthy participants and investigated whether oscillation dynamics were influenced by genetic polymorphisms in Catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met. Both COMT and BDNF polymorphisms influenced local oscillation amplitudes and their long-range temporal correlations (LRTCs), while only BDNF polymorphism affected the strength of large-scale synchronization. Our findings demonstrate that COMT and BDNF genetic polymorphisms contribute to inter-individual variability in local and large-scale synchron...
Inter-areal synchronization by phase–phase correlations (PPCs) of cortical oscillations mediates ... more Inter-areal synchronization by phase–phase correlations (PPCs) of cortical oscillations mediates many higher neurocognitive functions, which are often affected by prematurity, a globally prominent neurodevelopmental risk factor. Here, we used electroencephalography to examine brain-wide cortical PPC networks at term-equivalent age, comparing human infants after early prematurity to a cohort of healthy controls. We found that prematurity affected these networks in a sleep state-specific manner, and the differences between groups were also frequency-selective, involving brain-wide connections. The strength of synchronization in these networks was predictive of clinical outcomes in the preterm infants. These findings show that prematurity affects PPC networks in a clinically significant manner, suggesting early functional biomarkers of later neurodevelopmental compromise that may be used in clinical or translational studies after early neonatal adversity.
The capacity of visual attention determines how many visual objects may be perceived at any momen... more The capacity of visual attention determines how many visual objects may be perceived at any moment. This capacity can be investigated with multiple object tracking (MOT) tasks, which have shown that it varies greatly between individuals. The neuronal mechanisms underlying capacity limits have remained poorly understood. Phase synchronization of cortical oscillations coordinates neuronal communication within the fronto-parietal attention network and between the visual regions during endogenous visual attention. We tested a hypothesis that attentional capacity is predicted by the strength of pretarget synchronization within attention-related cortical regions. We recorded cortical activity with magneto- and electroencephalography (M/EEG) while measuring attentional capacity with MOT tasks and identified large-scale synchronized networks from source-reconstructed M/EEG data. Individual attentional capacity was correlated with load-dependent strengthening of theta (3–8 Hz), alpha (8–10 H...
Balance between excitation (E) and inhibition (I) is a key principle for neuronal network organiz... more Balance between excitation (E) and inhibition (I) is a key principle for neuronal network organization and information processing. Consistent with this notion, excitation-inhibition imbalances are considered a pathophysiological mechanism in many brain disorders including autism spectrum disorder (ASD). However, methods to measure E/I ratios in human brain networks are lacking. Here, we present a method to quantify a functional E/I ratio (fE/I) from neuronal oscillations, and validate it in healthy subjects and children with ASD. We define structural E/I ratio in an in silico neuronal network, investigate how it relates to power and long-range temporal correlations (LRTC) of the network’s activity, and use these relationships to design the fE/I algorithm. Application of this algorithm to the EEGs of healthy adults showed that fE/I is balanced at the population level and is decreased through GABAergic enforcement. In children with ASD, we observed larger fE/I variability and stronger...
Stimuli may induce only partial consciousness-an intermediate between null and full consciousness... more Stimuli may induce only partial consciousness-an intermediate between null and full consciousness-where the presence but not identity of an object can be reported. The differences in the neuronal basis of full and partial consciousness are poorly understood. We investigated if evoked and oscillatory activity could dissociate full from partial conscious perception. We recorded human cortical activity with magnetoencephalography (MEG) during a visual perception task in which stimulus could be either partially or fully perceived. Partial consciousness was associated with an early increase in evoked activity and theta/low-alpha-band oscillations while full consciousness was also associated with late evoked activity and beta-band oscillations. Full from partial consciousness was dissociated by stronger evoked activity and late increase in theta oscillations that were localized to higher-order visual regions and posterior parietal and prefrontal cortices. Our results reveal both evoked activity and theta oscillations dissociate partial and full consciousness.
Phase synchronization of neuronal oscillations in specific frequency bands coordinates anatomical... more Phase synchronization of neuronal oscillations in specific frequency bands coordinates anatomically distributed neuronal processing and communication. Typically, oscillations and synchronization take place concurrently in many distinct frequencies, which serve separate computational roles in cognitive functions. While within-frequency phase synchronization has been studied extensively, less is known about the mechanisms that govern neuronal processing distributed across frequencies and brain regions. Such integration of processing between frequencies could be achieved via cross-frequency coupling (CFC), either by phase-amplitude coupling (PAC) or by n:m-cross-frequency phase synchrony (CFS). So far, studies have mostly focused on local CFC in individual brain regions, whereas the presence and functional organization of CFC between brain areas have remained largely unknown. We posit that inter-areal CFC may be essential for large-scale coordination of neuronal activity and investigat...
Sensory-guided actions entail the processing of sensory information, generation of perceptual dec... more Sensory-guided actions entail the processing of sensory information, generation of perceptual decisions, and the generation of appropriate actions. Neuronal activity underlying these processes is distributed into sensory, fronto-parietal, and motor brain areas, respectively. How the neuronal processing is coordinated across these brain areas to support functions from perception to action remains unknown. We investigated whether phase synchronization in large-scale networks coordinate these processes. We recorded human cortical activity with magnetoencephalography (MEG) during a task in which weak somatosensory stimuli remained unperceived or were perceived. We then assessed dynamic evolution of phase synchronization in large-scale networks from source-reconstructed MEG data by using advanced analysis approaches combined with graph theory. Here we show that perceiving and reporting of weak somatosensory stimuli is correlated with sustained strengthening of large-scale synchrony concu...
bioRxiv (Cold Spring Harbor Laboratory), Dec 15, 2022
Attention-deficit/hyperactivity disorder (ADHD) is characterized by involuntary fluctuations of a... more Attention-deficit/hyperactivity disorder (ADHD) is characterized by involuntary fluctuations of attention in continuous performance tasks (CPTs) wherein attention must be sustained over long periods of time. The neuronal basis underlying aberrant attentional fluctuations in time scales from seconds to minutes have remained poorly understood. Neuronal alpha-and gammaband oscillations are thought to implement attentional and top-down control of sensorimotor processing. We hypothesized that aberrant behavioral fluctuations in ADHD would be caused by aberrant endogenous brain dynamics in alpha and gamma-band oscillations and specifically by their aberrant long-range temporal correlations (LRTCs). We measured brain activity with magnetoencephalography (MEG) from adult participants diagnosed with ADHD (N = 19) and from healthy control subjects (N = 20) during resting state and two CPTs; a threshold stimulus detection task and a Go/NoGo task. We then estimated LRTCs of neuronal oscillations and behavioral fluctuations with detrended fluctuation analysis (DFA). ADHD was associated with aberrant LRTCs in both behavioral performance and of neuronal oscillations. LRTCs were correlated with symptom severity with a U-shaped correlations indicating that the LRTCs were largest with moderate symptom scores. These data demonstrate the presence of aberrant temporal dynamics of neuronal oscillations in adult ADHD patients, which may underlie involuntary attentional fluctuations in ADHD. Taken that LRTCs are a hallmark of brain critical dynamics, these data show that moderate ADHD symptoms scores maximize brain criticality which is thought to be beneficial for performance.
Chunking language has been proposed to be vital for comprehension enabling the extraction of mean... more Chunking language has been proposed to be vital for comprehension enabling the extraction of meaning from a continuous stream of speech. However, neurocognitive mechanisms of chunking are poorly understood. The present study investigated neural correlates of chunk boundaries intuitively identified by listeners in natural speech drawn from linguistic corpora using magneto- and electroencephalography (MEEG). In a behavioral experiment, subjects marked chunk boundaries in the excerpts intuitively, which revealed highly consistent chunk boundary markings across the subjects. We next recorded brain activity to investigate whether chunk boundaries with high and medium agreement rates elicit distinct evoked responses compared to non-boundaries. Pauses placed at chunk boundaries elicited a closure positive shift with the sources over bilateral auditory cortices. In contrast, pauses placed within a chunk were perceived as interruptions and elicited a biphasic emitted potential with sources located in the bilateral primary and non-primary auditory areas with right-hemispheric dominance, and in the right inferior frontal cortex. Furthermore, pauses placed at stronger boundaries elicited earlier and more prominent activation over the left hemisphere suggesting that brain responses to chunk boundaries of natural speech can be modulated by the relative strength of different linguistic cues, such as syntactic structure and prosody.
Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and atte... more Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and attentional control, respectively, of sensory information maintained in visual working memory (VWM). Within these regions, beta/gamma phase-synchronization supports the integration of sensory functions, while synchronization in theta/alpha bands supports the regulation of attentional functions. A key challenge is to understand which mechanisms integrate neuronal processing across these distinct frequencies and thereby the sensory and attentional functions. We investigated whether such integration could be achieved by cross-frequency phase synchrony (CFS). Using concurrent magneto- and electroencephalography, we found that CFS was load-dependently enhanced between theta and alpha–gamma and between alpha and beta-gamma oscillations during VWM maintenance among visual, FP, and dorsal attention (DA) systems. CFS also connected the hubs of within-frequency-synchronized networks and its strength predicted individual VWM capacity. We propose that CFS integrates processing among synchronized neuronal networks from theta to gamma frequencies to link sensory and attentional functions
The amplitude of a-frequency band (8–14 Hz) activity in the human electroencephalogram is suppres... more The amplitude of a-frequency band (8–14 Hz) activity in the human electroencephalogram is suppressed by eye opening, visual stimuli and visual scanning, whereas it is enhanced during internal tasks, such as mental calculation and working memory. a-Frequency band oscillations have hence been thought to reflect idling or inhibition of task-irrelevant cortical areas. However, recent data on a-amplitude and, in particular, a-phase dynamics posit a direct and active role for a-frequency band rhythmicity in the mechanisms of attention and consciousness. We propose that simultaneous a-, b- (14– 30 Hz) and g- (30–70 Hz) frequency band oscillations are required for unified cognitive operations, and hypothesize that cross-frequency phase synchrony between a, b and g oscillations coordinates the selection and maintenance of neuronal object representations during working memory, perception and consciousness.
This dataset contains results from a study to identify modules in human connectomes of inter-regi... more This dataset contains results from a study to identify modules in human connectomes of inter-regional phase-synchronization, from intra-cerebral stereo-EEG (Electroencephalographic) data. 'Module_assignments.xlsx' contains module assignments, separately for left and right hemispheres, for frequencies from 3 Hz to 320 Hz. Module assignments are provided for different spatial scales, as specified by the 'gamma' parameter of the Louvain community detection method, which we used to identify modules. 'NeurosynthTerms_ConsensusModules.xlsx' contains module assignments for 'consensus modules', i.e. sets of regions consistently assigned to the same module across frequencies and spatial scales. Further, it provides sets of terms related to perceptual, cognitive and motor processing, that are selectively associated to each of the consensus modules.
Background Video gaming is a promising intervention for cognitive and social impairment in patien... more Background Video gaming is a promising intervention for cognitive and social impairment in patients with schizophrenia. A number of gaming interventions have been evaluated in small-scale studies with various patient groups, but studies on patients with schizophrenia remain scarce and rarely include the evaluation of both clinical and neurocognitive outcomes. In this study, we will test the effectiveness of two interventions with gaming elements to improve cognitive and clinical outcomes among persons with schizophrenia. Methods The participants will be recruited from different outpatient units (e.g., outpatient psychiatric units, day hospitals, residential care homes). The controlled clinical trial will follow a three-arm parallel-group design: 1) cognitive training (experimental group, CogniFit), 2) entertainment gaming (active control group, SIMS 4), and 3) treatment as usual. The primary outcomes are working memory function at 3-month and 6-month follow-ups. The secondary outcom...
ABSTRACTAmblyopia is a common visual disorder that is treatable in childhood. However, therapies ... more ABSTRACTAmblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. This phase 2, randomized, double-blind (fluoxetine vs. placebo), multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n=22) or placebo (n=20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. There was no significant difference in treatment efficacy between the groups. Visual acuity at the primary endpoint had significantly improved over baseline in both the fluoxetine (−0.167 logMAR) and placebo (−0.194 l...
Community structure, or ''modularity,'' is a fundamentally important aspect in the organization o... more Community structure, or ''modularity,'' is a fundamentally important aspect in the organization of structural and functional brain networks, but their identification with community detection methods is confounded by noisy or missing connections. Although several methods have been used to account for missing data, the performance of these methods has not been compared quantitatively so far. In this study, we compared four different approaches to account for missing connections when identifying modules in binary and weighted networks using both Louvain and Infomap community detection algorithms. The four methods are ''zeros,'' ''row-column mean,'' ''common neighbors,'' and ''consensus clustering.'' Using Lancichinetti-Fortunato-Radicchi benchmark-simulated binary and weighted networks, we find that ''zeros,'' ''row-column mean,'' and ''common neighbors'' approaches perform well with both Louvain and Infomap, whereas ''consensus clustering'' performs well with Louvain but not Infomap. A similar pattern of results was observed with empirical networks from stereotactical electroencephalography data, except that ''consensus clustering'' outperforms other approaches on weighted networks with Louvain. Based on these results, we recommend any of the four methods when using Louvain on binary networks, whereas ''consensus clustering'' is superior with Louvain clustering of weighted networks. When using Infomap, ''zeros'' or ''common neighbors'' should be used for both binary and weighted networks. These findings provide a basis to accounting for noisy or missing connections when identifying modules in brain networks.
Human cognitive functions are subjectively coherent even though the underlying neuronal processin... more Human cognitive functions are subjectively coherent even though the underlying neuronal processing is achieved in many cortical regions in parallel. A number of animal electrophysiological studies have shown that neuronal synchronization may be a mechanism for the integration of such anatomically distributed neuronal processing as well as for the regulation of neuronal communication within these distributed networks. However, less is known about the functional and behavioral significance of the synchronization of neuronal oscillations in human brains. In recent years, several advancements have been made in source localization of the locally and large-scale synchronized networks by using noninvasive human magneto- and electroencephalography (EEG and MEG). These data have revealed the first glimpses into the structures of cortical networks underlying perceptual, attentional, and working memory functions.
Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have lim... more Amblyopia is a common visual disorder that is treatable in childhood. However, therapies have limited efficacy in adult patients with amblyopia. Fluoxetine can reinstate early-life critical period-like neuronal plasticity and has been used to recover functional vision in adult rats with amblyopia. We conducted a Phase 2, randomized (fluoxetine vs. placebo), double-blind, multicenter clinical trial examined whether or not fluoxetine can improve visual acuity in amblyopic adults. This interventional trial included 42 participants diagnosed with moderate to severe amblyopia. Subjects were randomized to receive either 20 mg fluoxetine (n = 22) or placebo (n = 20). During the 10-week treatment period, all subjects performed daily computerized perceptual training and eye patching. At the primary endpoint, the mean treatment group difference in visual acuity improvement was only 0.027 logMAR units (95% CI: −0.057 to 0.110; p = 0.524). However, visual acuity had significantly improved from ...
SummaryNeuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitu... more SummaryNeuronal oscillations, their inter-areal synchronization, and scale-free dynamics constitute fundamental mechanisms for cognition by regulating communication in neuronal networks. These oscillatory dynamics have large inter-individual variability that is partly heritable. However, the genetic underpinnings of oscillatory dynamics have remained poorly understood. We recorded resting-state magnetoencephalography (MEG) from 82 healthy participants and investigated whether oscillation dynamics were influenced by genetic polymorphisms in Catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met. Both COMT and BDNF polymorphisms influenced local oscillation amplitudes and their long-range temporal correlations (LRTCs), while only BDNF polymorphism affected the strength of large-scale synchronization. Our findings demonstrate that COMT and BDNF genetic polymorphisms contribute to inter-individual variability in local and large-scale synchron...
Inter-areal synchronization by phase–phase correlations (PPCs) of cortical oscillations mediates ... more Inter-areal synchronization by phase–phase correlations (PPCs) of cortical oscillations mediates many higher neurocognitive functions, which are often affected by prematurity, a globally prominent neurodevelopmental risk factor. Here, we used electroencephalography to examine brain-wide cortical PPC networks at term-equivalent age, comparing human infants after early prematurity to a cohort of healthy controls. We found that prematurity affected these networks in a sleep state-specific manner, and the differences between groups were also frequency-selective, involving brain-wide connections. The strength of synchronization in these networks was predictive of clinical outcomes in the preterm infants. These findings show that prematurity affects PPC networks in a clinically significant manner, suggesting early functional biomarkers of later neurodevelopmental compromise that may be used in clinical or translational studies after early neonatal adversity.
The capacity of visual attention determines how many visual objects may be perceived at any momen... more The capacity of visual attention determines how many visual objects may be perceived at any moment. This capacity can be investigated with multiple object tracking (MOT) tasks, which have shown that it varies greatly between individuals. The neuronal mechanisms underlying capacity limits have remained poorly understood. Phase synchronization of cortical oscillations coordinates neuronal communication within the fronto-parietal attention network and between the visual regions during endogenous visual attention. We tested a hypothesis that attentional capacity is predicted by the strength of pretarget synchronization within attention-related cortical regions. We recorded cortical activity with magneto- and electroencephalography (M/EEG) while measuring attentional capacity with MOT tasks and identified large-scale synchronized networks from source-reconstructed M/EEG data. Individual attentional capacity was correlated with load-dependent strengthening of theta (3–8 Hz), alpha (8–10 H...
Balance between excitation (E) and inhibition (I) is a key principle for neuronal network organiz... more Balance between excitation (E) and inhibition (I) is a key principle for neuronal network organization and information processing. Consistent with this notion, excitation-inhibition imbalances are considered a pathophysiological mechanism in many brain disorders including autism spectrum disorder (ASD). However, methods to measure E/I ratios in human brain networks are lacking. Here, we present a method to quantify a functional E/I ratio (fE/I) from neuronal oscillations, and validate it in healthy subjects and children with ASD. We define structural E/I ratio in an in silico neuronal network, investigate how it relates to power and long-range temporal correlations (LRTC) of the network’s activity, and use these relationships to design the fE/I algorithm. Application of this algorithm to the EEGs of healthy adults showed that fE/I is balanced at the population level and is decreased through GABAergic enforcement. In children with ASD, we observed larger fE/I variability and stronger...
Stimuli may induce only partial consciousness-an intermediate between null and full consciousness... more Stimuli may induce only partial consciousness-an intermediate between null and full consciousness-where the presence but not identity of an object can be reported. The differences in the neuronal basis of full and partial consciousness are poorly understood. We investigated if evoked and oscillatory activity could dissociate full from partial conscious perception. We recorded human cortical activity with magnetoencephalography (MEG) during a visual perception task in which stimulus could be either partially or fully perceived. Partial consciousness was associated with an early increase in evoked activity and theta/low-alpha-band oscillations while full consciousness was also associated with late evoked activity and beta-band oscillations. Full from partial consciousness was dissociated by stronger evoked activity and late increase in theta oscillations that were localized to higher-order visual regions and posterior parietal and prefrontal cortices. Our results reveal both evoked activity and theta oscillations dissociate partial and full consciousness.
Phase synchronization of neuronal oscillations in specific frequency bands coordinates anatomical... more Phase synchronization of neuronal oscillations in specific frequency bands coordinates anatomically distributed neuronal processing and communication. Typically, oscillations and synchronization take place concurrently in many distinct frequencies, which serve separate computational roles in cognitive functions. While within-frequency phase synchronization has been studied extensively, less is known about the mechanisms that govern neuronal processing distributed across frequencies and brain regions. Such integration of processing between frequencies could be achieved via cross-frequency coupling (CFC), either by phase-amplitude coupling (PAC) or by n:m-cross-frequency phase synchrony (CFS). So far, studies have mostly focused on local CFC in individual brain regions, whereas the presence and functional organization of CFC between brain areas have remained largely unknown. We posit that inter-areal CFC may be essential for large-scale coordination of neuronal activity and investigat...
Sensory-guided actions entail the processing of sensory information, generation of perceptual dec... more Sensory-guided actions entail the processing of sensory information, generation of perceptual decisions, and the generation of appropriate actions. Neuronal activity underlying these processes is distributed into sensory, fronto-parietal, and motor brain areas, respectively. How the neuronal processing is coordinated across these brain areas to support functions from perception to action remains unknown. We investigated whether phase synchronization in large-scale networks coordinate these processes. We recorded human cortical activity with magnetoencephalography (MEG) during a task in which weak somatosensory stimuli remained unperceived or were perceived. We then assessed dynamic evolution of phase synchronization in large-scale networks from source-reconstructed MEG data by using advanced analysis approaches combined with graph theory. Here we show that perceiving and reporting of weak somatosensory stimuli is correlated with sustained strengthening of large-scale synchrony concu...
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Papers by Satu Palva