Complexity and 1/f slope jointly reflect brain states.

Characterization of brain states is essential for understanding its functioning in the absence of external stimuli. Brain states differ on their balance between excitation and inhibition, and on the diversity of their activity patterns. These can be respectively indexed by 1/f slope and Lempel-Ziv complexity (LZc). However, whether and how these two brain state properties relate remain elusive. Here we analyzed the relation between 1/f slope and LZc with two in-silico approaches and in both rat EEG and monkey ECoG data. We contrasted resting state with propofol anesthesia, which directly modulates the excitation-inhibition balance. We found convergent results among simulated and empirical data, showing a strong, inverse and non trivial monotonic relation between 1/f slope and complexity, consistent at both ECoG and EEG scales. We hypothesize that differentially entropic regimes could underlie the link between the excitation-inhibition balance and the vastness of the repertoire of brain systems.

A Visuospatial Planning Task Coupled with Eye-Tracker and Electroencephalogram Systems.

The planning process, characterized by the capability to formulate an organized plan to reach a goal, is essential for human goal-directed behavior. Since planning is compromised in several neuropsychiatric disorders, the implementation of proper clinical and experimental tests to examine planning is critical. Due to the nature of the deployment of planning, in which several cognitive domains participate, the assessment of planning and the design of behavioral paradigms coupled with neuroimaging methods are current challenges in cognitive neuroscience. A planning task was evaluated in combination with an electroencephalogram (EEG) system and eye movement recordings in 27 healthy adult participants. Planning can be separated into two stages: a mental planning stage in which a sequence of steps is internally represented and an execution stage in which motor action is used to achieve a previously planned goal. Our protocol included a planning task and a control task. The planning task involved solving 36 maze trials, each representing a zoo map. The task had four periods: i) planning, where the subjects were instructed to plan a path to visit the locations of four animals according to a set of rules; ii) maintenance, where the subjects had to retain the planned path in their working memory; iii) execution, where the subjects used eye movements to trace the previously planned path as indicated by the eye-tracker system; and iv) response, where the subjects reported the order of the visited animals. The control task had a similar structure, but the cognitive planning component was removed by modifying the task goal. The spatial and temporal patterns of the EEG revealed that planning induces a gradual and lasting rise in frontal-midline theta activity (FMθ) over time. The source of this activity was identified within the prefrontal cortex by source analyses. Our results suggested that the experimental paradigm combining EEG and eye-tracker systems was optimal for evaluating cognitive planning.

Dysconnectivity in Schizophrenia Revisited: Abnormal Temporal Organization of Dynamic Functional Connectivity in Patients With a First Episode of Psychosis.

BACKGROUND AND HYPOTHESIS: Abnormal functional connectivity between brain regions is a consistent finding in schizophrenia, including functional magnetic resonance imaging (fMRI) studies. Recent studies have highlighted that connectivity changes in time in healthy subjects. We here examined the temporal changes in functional connectivity in patients with a first episode of psychosis (FEP). Specifically, we analyzed the temporal order in which whole-brain organization states were visited. STUDY DESIGN: Two case-control studies, including in each sample a subgroup scanned a second time after treatment. Chilean sample included 79 patients with a FEP and 83 healthy controls. Mexican sample included 21 antipsychotic-naïve FEP patients and 15 healthy controls. Characteristics of the temporal trajectories between whole-brain functional connectivity meta-states were examined via resting-state functional MRI using elements of network science. We compared the cohorts of cases and controls and explored their differences as well as potential associations with symptoms, cognition, and antipsychotic medication doses. STUDY RESULTS: We found that the temporal sequence in which patients' brain dynamics visited the different states was more redundant and segregated. Patients were less flexible than controls in changing their network in time from different configurations, and explored the whole landscape of possible states in a less efficient way. These changes were related to the dose of antipsychotics the patients were receiving. We replicated the relationship with antipsychotic medication in the antipsychotic-naïve FEP sample scanned before and after treatment. CONCLUSIONS: We conclude that psychosis is related to a temporal disorganization of the brain's dynamic functional connectivity, and this is associated with antipsychotic medication use.

La planificación cognitiva en el contexto de la evaluación neuropsicológica e investigación en neurociencia cognitiva: una revisión sistemática / Cognitive planning in the context of neuropsychological assessment and research in cognitive neuroscience: a systematic review

La planificación es definida como la habilidad de desarrollar un plan secuenciado de pasos conductuales para alcanzar una meta y forma parte de un conjunto de funciones cognitivas de alto orden denominadas funciones ejecutivas. Esta función se ve afectada en diversas situaciones de la vida cotidiana y en una variedad de trastornos neuropsiquiátricos (por ej., depresión, ansiedad, déficit atencional, esquizofrenia, etc.). Tanto el diseño de pruebas cognitivas para evaluar planificación en el contexto clínico, como también el diseño de paradigmas experimentales de evaluación de la planificación en el contexto de investigación, continúa siendo un desafío para la neuropsicología clínica y para las neurociencias. En este artículo de revisión sistemática que sigue las direcciones PRISMA, revisamos la teoría e investigación en relación con la evaluación clínica y la investigación de las bases neurobiológicas de la planificación y los aportes a la comprensión de los mecanismos de su implementación. Se reportan medidas metodológicas comunes y se resumen las aproximaciones teóricas que contribuyen en su comprensión. Nuestros hallazgos muestran la implicancia de la corteza prefrontal en el rendimiento en planificación, en particular el área dorsolateral, corteza cingulada anterior y frontopolar. Mayores estudios clínicos, instrumentales y experimentales son necesarios para comprender mejor la planificación en el contexto de una teoría integrativa de las funciones ejecutivas y del rol de la corteza prefrontal.

Planning is defined as the ability to develop a sequenced plan of behavioral steps to achieve a goal and is part of a set of high-order cognitive functions called executive functions. This function is affected in various daily life situations and in a variety of neuropsychiatric disorders (e.g., depression, anxiety, attention deficit disorder, schizophrenia, etc.). Both the design of cognitive tests to assess planning in the clinical context, as well as the design of experimental paradigms for evaluating planning in research context, continues to be a challenge for clinical neuropsychology and neurosciences. In this PRISMA systematic review article, we review theory and research regarding clinical assessment and research into the neurobiological bases of planning and contributions to understanding the mechanisms of its implementation. Common methodological measures are reported and the theoretical approaches that contribute to their understanding are summarized. Our findings show the involvement of the prefrontal cortex in planning performance, particularly the dorsolateral area, the anterior cingulate cortex, and the frontopolar cortex. Further clinical, instrumental, and experimental studies are needed to better understand planning in the context of an integrative theory of executive functions and the role of the prefrontal cortex.

Brain activity complexity has a nonlinear relation to the level of propofol sedation.

BACKGROUND: Brain activity complexity is a promising correlate of states of consciousness. Previous studies have shown higher complexity for awake compared with deep anaesthesia states. However, little attention has been paid to complexity in intermediate states of sedation. METHODS: We analysed the Lempel-Ziv complexity of EEG signals from subjects undergoing moderate propofol sedation, from an open access database, and related it to behavioural performance as a continuous marker of the level of sedation and to plasma propofol concentrations. We explored its relation to spectral properties, to propofol susceptibility, and its topographical distribution. RESULTS: Subjects who retained behavioural performance despite propofol sedation showed increased brain activity complexity compared with baseline (M=13.9%, 95% confidence interval=7.5-20.3). This was not the case for subjects who lost behavioural performance. The increase was most prominent in frontal electrodes, and correlated with behavioural performance and propofol susceptibility. This effect was positively correlated with high-frequency activity. However, abolishing specific frequency ranges (e.g. alpha or gamma) did not reduce the propofol-induced increase in Lempel-Ziv complexity. CONCLUSIONS: Brain activity complexity can increase in response to propofol, particularly during low-dose sedation. Propofol-mediated Lempel-Ziv complexity increase was independent of frequency-specific spectral power manipulations, and most prominent in frontal areas. Taken together, these results advance our understanding of brain activity complexity and anaesthetics. They do not support models of consciousness that propose a direct relation between brain activity complexity and states of consciousness.

The ascending arousal system promotes optimal performance through mesoscale network integration in a visuospatial attentional task.

Previous research has shown that the autonomic nervous system provides essential constraints over ongoing cognitive function. However, there is currently a relative lack of direct empirical evidence for how this interaction manifests in the brain at the macroscale level. Here, we examine the role of ascending arousal and attentional load on large-scale network dynamics by combining pupillometry, functional MRI, and graph theoretical analysis to analyze data from a visual motion-tracking task with a parametric load manipulation. We found that attentional load effects were observable in measures of pupil diameter and in a set of brain regions that parametrically modulated their BOLD activity and mesoscale network-level integration. In addition, the regional patterns of network reconfiguration were correlated with the spatial distribution of the α2a adrenergic receptor. Our results further solidify the relationship between ascending noradrenergic activity, large-scale network integration, and cognitive task performance.

Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities.

BACKGROUND: Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear. AIMS: We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed. METHOD: This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model. RESULTS: A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (P = 0.006). Controls showed a positive correlation between total grey matter volume and income (R = 0.14, P = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (R = -0.076, P = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure. CONCLUSIONS: Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.

Theta activity from frontopolar cortex, mid-cingulate cortex and anterior cingulate cortex shows different roles in cognitive planning performance.

Cognitive planning, the ability to develop a sequenced plan to achieve a goal, plays a crucial role in human goal-directed behavior. However, the specific role of frontal structures in planning is unclear. We used a novel and ecological task, that allowed us to separate the planning period from the execution period. The spatio-temporal dynamics of EEG recordings showed that planning induced a progressive and sustained increase of frontal-midline theta activity (FMθ) over time. Source analyses indicated that this activity was generated within the prefrontal cortex. Theta activity from the right mid-Cingulate Cortex (MCC) and the left Anterior Cingulate Cortex (ACC) were correlated with an increase in the time needed for elaborating plans. On the other hand, left Frontopolar cortex (FP) theta activity exhibited a negative correlation with the time required for executing a plan. Since reaction times of planning execution correlated with correct responses, left FP theta activity might be associated with efficiency and accuracy in making a plan. Associations between theta activity from the right MCC and the left ACC with reaction times of the planning period may reflect high cognitive demand of the task, due to the engagement of attentional control and conflict monitoring implementation. In turn, the specific association between left FP theta activity and planning performance may reflect the participation of this brain region in successfully self-generated plans.

Transitions between human functional brain networks reveal complex, cost-efficient and behaviorally-relevant temporal paths.

Resting-state functional MRI activity is organized as a complex network. However, this coordinated brain activity changes with time, raising questions about its evolving temporal arrangement. Does the brain visit different configurations through time in a random or ordered way? Advances in this area depend on developing novel paradigms that would allow us to shed light on these issues. We here propose to study the temporal changes in the functional connectome by looking at transition graphs of network activity. Nodes of these graphs correspond to brief whole-brain connectivity patterns (or meta-states), and directed links to the temporal transition between consecutive meta-states. We applied this method to two datasets of healthy subjects (160 subjects and a replication sample of 54), and found that transition networks had several non-trivial properties, such as a heavy-tailed degree distribution, high clustering, and a modular organization. This organization was implemented at a low biological cost with a high cost-efficiency of the dynamics. Furthermore, characteristics of the subjects' transition graphs, including global efficiency, local efficiency and their transition cost, were correlated with cognition and motor functioning. All these results were replicated in both datasets. We conclude that time-varying functional connectivity patterns of the brain in health progress in time in a highly organized and complex order, which is related to behavior.

Perceptual fusion of musical notes by native Amazonians suggests universal representations of musical intervals.

Music perception is plausibly constrained by universal perceptual mechanisms adapted to natural sounds. Such constraints could arise from our dependence on harmonic frequency spectra for segregating concurrent sounds, but evidence has been circumstantial. We measured the extent to which concurrent musical notes are misperceived as a single sound, testing Westerners as well as native Amazonians with limited exposure to Western music. Both groups were more likely to mistake note combinations related by simple integer ratios as single sounds ('fusion'). Thus, even with little exposure to Western harmony, acoustic constraints on sound segregation appear to induce perceptual structure on note combinations. However, fusion did not predict aesthetic judgments of intervals in Westerners, or in Amazonians, who were indifferent to consonance/dissonance. The results suggest universal perceptual mechanisms that could help explain cross-cultural regularities in musical systems, but indicate that these mechanisms interact with culture-specific influences to produce musical phenomena such as consonance.

Human Anterior Insula Encodes Performance Feedback and Relays Prediction Error to the Medial Prefrontal Cortex.

Adaptive behavior requires the comparison of outcome predictions with actual outcomes (e.g., performance feedback). This process of performance monitoring is computed by a distributed brain network comprising the medial prefrontal cortex (mPFC) and the anterior insular cortex (AIC). Despite being consistently co-activated during different tasks, the precise neuronal computations of each region and their interactions remain elusive. In order to assess the neural mechanism by which the AIC processes performance feedback, we recorded AIC electrophysiological activity in humans. We found that the AIC beta oscillations amplitude is modulated by the probability of performance feedback valence (positive or negative) given the context (task and condition difficulty). Furthermore, the valence of feedback was encoded by delta waves phase-modulating the power of beta oscillations. Finally, connectivity and causal analysis showed that beta oscillations relay feedback information signals to the mPFC. These results reveal that structured oscillatory activity in the anterior insula encodes performance feedback information, thus coordinating brain circuits related to reward-based learning.

Semi-Automated and Direct Localization and Labeling of EEG Electrodes Using MR Structural Images for Simultaneous fMRI-EEG.

Electroencephalography (EEG) source reconstruction estimates spatial information from the brain's electrical activity acquired using EEG. This method requires accurate identification of the EEG electrodes in a three-dimensional (3D) space and involves spatial localization and labeling of EEG electrodes. Here, we propose a new approach to tackle this two-step problem based on the simultaneous acquisition of EEG and magnetic resonance imaging (MRI). For the step of spatial localization of electrodes, we extract the electrode coordinates from the curvature of the protrusions formed in the high-resolution T1-weighted brain scans. In the next step, we assign labels to each electrode based on the distinguishing feature of the electrode's distance profile in relation to other electrodes. We then compare the subject's electrode data with template-based models of prelabeled distance profiles of correctly labeled subjects. Based on this approach, we could localize EEG electrodes in 26 head models with over 90% accuracy in the 3D localization of electrodes. Next, we performed electrode labeling of the subjects' data with progressive improvements in accuracy: with ∼58% accuracy based on a single EEG-template, with ∼71% accuracy based on 3 EEG-templates, and with ∼76% accuracy using 5 EEG-templates. The proposed semi-automated method provides a simple alternative for the rapid localization and labeling of electrodes without the requirement of any additional equipment than what is already used in an EEG-fMRI setup.

Universal and Non-universal Features of Musical Pitch Perception Revealed by Singing.

Musical pitch perception is argued to result from nonmusical biological constraints and thus to have similar characteristics across cultures, but its universality remains unclear. We probed pitch representations in residents of the Bolivian Amazon-the Tsimane', who live in relative isolation from Western culture-as well as US musicians and non-musicians. Participants sang back tone sequences presented in different frequency ranges. Sung responses of Amazonian and US participants approximately replicated heard intervals on a logarithmic scale, even for tones outside the singing range. Moreover, Amazonian and US reproductions both deteriorated for high-frequency tones even though they were fully audible. But whereas US participants tended to reproduce notes an integer number of octaves above or below the heard tones, Amazonians did not, ignoring the note "chroma" (C, D, etc.). Chroma matching in US participants was more pronounced in US musicians than non-musicians, was not affected by feedback, and was correlated with similarity-based measures of octave equivalence as well as the ability to match the absolute f0 of a stimulus in the singing range. The results suggest the cross-cultural presence of logarithmic scales for pitch, and biological constraints on the limits of pitch, but indicate that octave equivalence may be culturally contingent, plausibly dependent on pitch representations that develop from experience with particular musical systems. VIDEO ABSTRACT.

A pupil size, eye-tracking and neuropsychological dataset from ADHD children during a cognitive task.

Attention Deficit/Hyperactive Disorder (ADHD) is diagnosed based on observed behavioral outcomes alone. Given that some brain attentional networks involve circuits that control the eye pupil, we monitored pupil size in ADHD- diagnosed children and also in control children during a visuospatial working memory task. We present here the full dataset, consisting of pupil size time series for each trial and subject. There are data from, 22 control, and 28 ADHD-diagnosed children. There are also data from a subset of 17 ADHD children that performed the task twice, on- and off-medication. In addition, our dataset also includes gaze position data from each trial and subject, and also scores from the Weschler Intelligence Scale for Children. In this context, the dataset can serve as a resource to analyze dynamic eye movement and pupil changes as a function of known behavioral changes and scores in neuropsychological tests, which reflect neurocognitive processing.

Imaging Social and Environmental Factors as Modulators of Brain Dysfunction: Time to Focus on Developing Non-Western Societies.

Social and environmental factors are known risk factors and modulators of mental health disorders. We here conducted a nonsystematic review of the neuroimaging literature studying the effects of poverty, urbanicity, and community violence, highlighting the opportunities of studying non-Western developing societies such as those in Latin America. Social and environmental factors in these communities are widespread and have a large magnitude, as well as an unequal distribution, providing a good opportunity for their characterization. Studying the effect of poverty in these settings could help to explore the brain effect of economic improvements, disentangle the effect of absolute and relative poverty, and characterize the modulating impact of poverty on the underlying biology of mental health disorders. Exploring urbanicity effects in highly unequal cities could help identify the specific factors that modulate this effect as well as examine a possible dose-response effect by studying megacities. Studying brain changes in those living among violence, which is particularly high in places such as Latin America, could help to characterize the interplay between brain predisposition and exposure to violence. Furthermore, exploring the brain in an adverse environment should shed light on the mechanisms underlying resilience. We finally provide examples of two methodological approaches that could contribute to this field, namely a big cohort study in the developing world and a consortium-based meta-analytic approach, and argue about the potential translational value of this research on the development of effective social policies and successful personalized medicine in disadvantaged societies.

Brain state-dependent recruitment of high-frequency oscillations in the human hippocampus.

Ripples are high-frequency bouts of coordinated hippocampal activity believed to be crucial for information transfer and memory formation. We used intracortical macroelectrodes to record neural activity in the human hippocampus of awake subjects undergoing surgical treatment for refractory epilepsy and distinguished two populations of ripple episodes based on their frequency spectrum. The phase-coupling of one population, slow ripples (90-110 Hz), to cortical delta oscillations was differentially modulated by cognitive task; whereas the second population, fast ripples (130-170 Hz), was not seemingly correlated to local neural activity. Furthermore, as cognitive tasks changed, the ongoing coordination of neural activity associated to slow ripples progressively augmented along the parahippocampal axis. Thus, during resting states, slow ripples were coordinated in restricted hippocampal territories; whereas during active states, such as attentionally-demanding tasks, high frequency activity emerged across the hippocampus and parahippocampal cortex, that was synchronized with slow ripples, consistent with ripples supporting information transfer and coupling anatomically distant regions. Hence, our results provide further evidence of neural diversity in hippocampal high-frequency oscillations and their association to cognitive processing in humans.

Irrelevant stimulus processing in ADHD: catecholamine dynamics and attentional networks.

A cardinal symptom of attention deficit and hyperactivity disorder (ADHD) is a general distractibility where children and adults shift their attentional focus to stimuli that are irrelevant to the ongoing behavior. This has been attributed to a deficit in dopaminergic signaling in cortico-striatal networks that regulate goal-directed behavior. Furthermore, recent imaging evidence points to an impairment of large scale, antagonistic brain networks that normally contribute to attentional engagement and disengagement, such as the task-positive networks and the default mode network (DMN). Related networks are the ventral attentional network (VAN) involved in attentional shifting, and the salience network (SN) related to task expectancy. Here we discuss the tonic-phasic dynamics of catecholaminergic signaling in the brain, and attempt to provide a link between this and the activities of the large-scale cortical networks that regulate behavior. More specifically, we propose that a disbalance of tonic catecholamine levels during task performance produces an emphasis of phasic signaling and increased excitability of the VAN, yielding distractibility symptoms. Likewise, immaturity of the SN may relate to abnormal tonic signaling and an incapacity to build up a proper executive system during task performance. We discuss different lines of evidence including pharmacology, brain imaging and electrophysiology, that are consistent with our proposal. Finally, restoring the pharmacodynamics of catecholaminergic signaling seems crucial to alleviate ADHD symptoms; however, the possibility is open to explore cognitive rehabilitation strategies to top-down modulate network dynamics compensating the pharmacological deficits.

Functional selectivity in the human occipitotemporal cortex during natural vision: evidence from combined intracranial EEG and eye-tracking.

Eye movements are a constant and essential component of natural vision, yet, most of our knowledge about the human visual system comes from experiments that restrict them. This experimental constraint is mostly in place to control visual stimuli presentation and to avoid artifacts in non-invasive measures of brain activity, however, this limitation can be overcome with intracranial EEG (iEEG) recorded from epilepsy patients. Moreover, the high-frequency components of the iEEG signal (between about 50 and 150Hz) can provide a proxy of population-level spiking activity in any cortical area during free-viewing. We combined iEEG with high precision eye-tracking to study fine temporal dynamics and functional specificity in the fusiform face (FFA) and visual word form area (VWFA) while patients inspected natural pictures containing faces and text. We defined the first local measure of visual (electrophysiological) responsiveness adapted to free-viewing in humans: amplitude modulations in the high-frequency activity range (50-150Hz) following fixations (fixation-related high-frequency response). We showed that despite the large size of receptive fields in the ventral occipito-temporal cortex, neural activity during natural vision of realistic cluttered scenes is mostly dependent upon the category of the foveated stimulus - suggesting that category-specificity is preserved during free-viewing and that attention mechanisms might filter out the influence of objects surrounding the fovea.

Temporal constraints of behavioral inhibition: relevance of inter-stimulus interval in a Go-Nogo task.

The capacity to inhibit prepotent and automatic responses is crucial for proper cognitive and social development, and inhibitory impairments have been considered to be key for some neuropsychiatric conditions. One of the most used paradigms to analyze inhibitory processes is the Go-Nogo task (GNG). This task has been widely used in psychophysical and cognitive EEG studies, and more recently in paradigms using fMRI. However, a technical limitation is that the time resolution of fMRI is poorer than that of the EEG technique. In order to compensate for these temporal constraints, it has become common practice in the fMRI field to use longer inter-stimulus intervals (ISI) than those used in EEG protocols. Despite the noticeable temporal differences between these two techniques, it is currently assumed that both approaches assess similar inhibitory processes. We performed an EEG study using a GNG task with both short ISI (fast-condition, FC, as in EEG protocols) and long ISI (slow-condition, SC, as in fMRI protocols). We found that in the FC there was a stronger Nogo-N2 effect than in the SC. Moreover, in the FC, but not in the SC, the number of preceding Go trials correlated positively with the Nogo-P3 amplitude and with the Go trial reaction time; and negatively with commission errors. In addition, we found significant topographical differences for the Go-P3 elicited in FC and SC, which is interpreted in terms of different neurotransmitter dynamics. Taken together, our results provide evidence that frequency of stimulus presentation in the GNG task strongly modulates the behavioral response and the evoked EEG activity. Therefore, it is likely that short-ISI EEG protocols and long-ISI fMRI protocols do not assess equivalent inhibitory processes.