Organoids and specifically human cerebral organoids (HCOs) are one of the most relevant novelties in the field of biomedical research. Grown either from embryonic or induced pluripotent stem cells, HCOs can be used as in vitro three-dimensional models, mimicking the developmental process and organization of the developing human brain. Based on that, and despite their current limitations, it cannot be assumed that they will never at any stage of development manifest some rudimentary form of consciousness. In the absence of behavioral (...) indicators of consciousness, the theoretical neurobiology of consciousness being applied to unresponsive brain-injured patients can be considered with respect to HCOs. In clinical neurology, it is difficult to discern a capacity for consciousness in unresponsive brain-injured patients who provide no behavioral indicators of consciousness. In such scenarios, a validated neurobiological theory of consciousness, which tells us what the neural mechanisms of consciousness are, could be used to identify a capacity for consciousness. Like the unresponsive patients that provide a diagnostic difficulty for neurologists, HCOs provide no behavioral indicators of consciousness. Therefore, this article discusses how three prominent neurobiological theories of consciousness apply to human cerebral organoids. From the perspective of the Temporal Circuit Hypothesis, the Global Neuronal Workspace Theory, and the Integrated Information Theory, we discuss what neuronal structures and functions might indicate that cerebral organoids have a neurobiological capacity to be conscious. (shrink)

Depression is vastly heterogeneous in its symptoms, neuroimaging data, and treatment responses. As such, describing how it develops at the network level has been notoriously difficult. In an attempt to overcome this issue, a theoretical “negative prediction mechanism” is proposed. Here, eight key brain regions are connected in a transient, state-dependent, core network of pathological communication that could facilitate the development of depressive cognition. In the context of predictive processing, it is suggested that this mechanism is activated as a response (...) to negative/adverse stimuli in the external and/or internal environment that exceed a vulnerable individual’s capacity for cognitive appraisal. Specifically, repeated activation across this network is proposed to update an individual’s brain so that it increasingly predicts and reinforces negative experiences over time—pushing an individual at-risk for or suffering from depression deeper into mental illness. Within this, the negative prediction mechanism is poised to explain various aspects of prognostic outcome, describing how depression might ebb and flow over multiple timescales in a dynamically changing, complex environment. (shrink)

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of “self” and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate “self,” and employed it to explain some psychopathological symptoms. In those studies, “self” is understood in a minimalist sense, sheer “for-me-ness.” Unfortunately, explication of the “minimal self” (MS) has relied on conceptual analysis, and applications to psychopathology have (...) been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS’s current scientific status is analogous to that of the “atom,” at the time when “atom” was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for “MS.” Discovery of the brain’s Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit “MS” can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that “levels of consciousness” (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation—a bifurcation point—for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness. (shrink)

Categorization and memory for specific items are fundamental processes that allow us to apply knowledge to novel stimuli. This study directly compares categorization and memory using delay match to category (DMC) and delay match to sample (DMS) tasks. In DMC participants view and categorize a stimulus, maintain the category across a delay, and at the probe phase view another stimulus and indicate whether it is in the same category or not. In DMS, a standard item working memory task, participants encode (...) and maintain a specific individual item, and at probe decide if the stimulus is an exact match or not. Constrained Principal Components Analysis was used to identify and compare activity within neural networks associated with these tasks, and we relate these networks to those that have been identified with resting state-fMRI. We found that two frontoparietal networks of particular interest. The first network included regions associated with the dorsal attention network and frontoparietal salience network; this network showed patterns of activity consistent with a role in rapid orienting to and processing of complex stimuli. The second uniquely involved regions of the frontoparietal central executive network; this network responded more slowly following each stimulus and showed a pattern of activity consistent with a general role in role in decision-making across tasks. Additional components were identified that were associated with visual, somatomotor and default mode networks. (shrink)

In 1895 in the Project for a Scientific Psychology Freud tried to integrate psychology and neurology in order to develop a neuroscientific psychology. Since 1880 Freud made no distinction between psychology and physiology. His papers from the end of the 1880s to1890 were very clear on this scientific overlap: as with many of its contemporaries, Freud thought about psychology essentially as the physiology of the brain. Years later he had to surrender, realizing a technological delay, not capable to pursue its (...) ambitious aim, and until that moment psychoanalysis would have to use its more suitable clinical method. Also, he seemed skeptical about the phrenology drift, typical of that time, in which any psychological function needed to be located in its neuroanatomical area. He could not see the progresses of neurosciences and its fruitful dialogue with psychoanalysis, occurred also thanks to the improvements in the field of neuroimaging, which has made possible a remarkable advance in the knowledge of the mind-brain system and a better observation of the psychoanalytical theories. After years of investigations, deriving from research and clinical work of the last century, the discovery of neural networks, together with the free energy principle, we are observing under a new light the psychodynamic neuroscience in its exploration of the mind-brain system. In this narrative review we summarize the important developments of the psychodynamic neuroscience, with particular regard to the free energy principle, the resting state networks, especially the Default Mode Network in its link with the Self; finally we suggest a discussion by approaching the concept of Alpha Function, proposed by the psychoanalyst Wilfred Ruprecht Bion, trying to speculate about the connection with neuroscience. (shrink)

A recent strand in the philosophical literature on addiction emphasizes problems with diachronic self-control. Hanna Pickard, for example, argues that an important aspect of addiction consists in inability to identify with a non-addicted future self. This literature sits alongside another that treats addiction as the product of neural changes that “hijack” mechanisms of reward prediction, habit formation decision making and cognitive control. This hijacking literature originates in accounts that treat the neural changes characteristic of addiction as a brain disease. This (...) paper provides a framework based on predictive processing accounts of self-awareness that integrates the hijacking and diachronic accounts. I discuss a hijacking account proposed to explain disruption of addiction following lesion to the anterior insula cortex. I show how insula activity contributes to the type of identification implicated in diachronic accounts and how deactivation of the anterior insula can disrupt addiction by alienating the subject from her addictive tendencies. This is consistent with neural evidence but also incorporates the personal level features of addiction that are opaque to neural level explanation. (shrink)

Neuroscience has made enormous progress in understanding the brain and its various neuro-sensory and neuro-cognitive functions. However, despite all progress, the model of the brain as well as its ontological characterization remain unclear. The aim in this first paper is the discussion of an empirically plausible model of the brain with the subsequent claim of a neuro-ecological model. Whitehead claimed that he inversed or reversed the Kantian notion of the subject by putting it back into the ecological context of the (...) world, the so-called reformist subjectivist principle. Based on empirical evidence about the experience-dependence of the brain’s spontaneous activity, I argue for an analogous inversion or reversion with regard to the model of brain: empirical evidence is well compatible with a neuro-ecological model which extends beyond and integrates both Humean neuro-sensory and Kantian neuro-cognitive models. I conclude that a neuro-ecological and process-based model of brain and its relationship to the world may offer a novel model of brain that carries major ontological implications as they shall be discussed in the second paper. (shrink)

Recently, interest in the unique pathways linking discrete positive emotions to specific health outcomes has gained increasing attention, but the role of awe is yet to be elucidated. Awe is a complex and transformative emotion that can restructure individuals' mental frames so deeply that it could be considered a therapeutic asset for major mental health major issues, including depression. Despite sparse evidence showing a potential connection between depression and awe, this link has not been combined into a proposal resulting in (...) specific intervention guidelines. The aim of this perspective was three-fold: to provide a new unifying model of awe's functioning—the Matryoshka model; to show systematic and explicit connections between this emotion and depression; and to suggest specific guidelines of intervention utilizing the potential therapeutic role of awe for mental health, specifically for depression. This theoretical endeavor in its entirety has been framed within the health domain. (shrink)

Previous studies have reported abnormal amplitude of low-frequency fluctuation and regional homogeneity in patients with migraine without aura using resting-state functional magnetic resonance imaging. However, how whole brain functional connectivity pattern homogeneity and its corresponding functional connectivity changes in patients with migraine without aura is unknown. In the current study, we employed a recently developed whole brain functional connectivity homogeneity method to identify the voxel-wise changes of functional connectivity patterns in 21 patients with migraine without aura and 21 gender and (...) age matched healthy controls. Moreover, resting-state functional connectivity analysis was used to reveal the changes of corresponding functional connectivities. FcHo analyses identified significantly decreased FcHo values in the posterior cingulate cortex, thalamus, and left anterior insula in patients with migraine without aura compared to healthy controls. Functional connectivity analyses further found decreased functional connectivities between PCC and medial prefrontal cortex, between AI and anterior cingulate cortex, and between THA and left precentral gyrus. The functional connectivities between THA and PCG were negatively correlated with pain intensity. Our findings indicated that whole brain FcHo and connectivity abnormalities of these regions may be associated with functional impairments in pain processing in patients with migraine without aura. (shrink)

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala (...) and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. (shrink)

Occupational therapy often uses craft activities as therapeutic tools, but their therapeutic effectiveness has not yet been adequately demonstrated. The aim of this study was to examine changes in frontal midline theta rhythm (Fmθ) and autonomic nervous responses during craft activities, and to explore the physiological mechanisms underlying the therapeutic effectiveness of occupational therapy. To achieve this, we employed a simple craft activity as a task to induce Fmθ and performed simultaneous EEG and ECG recordings. For participants in which Fmθ (...) activities were provoked, parasympathetic and sympathetic activities were evaluated during the appearance of Fmθ and rest periods using the Lorenz plot analysis. Both parasympathetic and sympathetic indices increased with the appearance of Fmθ compared to during resting periods. This suggests that a relaxed-concentration state is achieved by concentrating on craft activities. Furthermore, the appearance of Fmθ positively correlated with parasympathetic activity, and theta band activity in the frontal area were associated with sympathetic activity. This suggests that there is a close relationship between cardiac autonomic function and Fmθ activity. (shrink)

BackgroundFrontal brain dysfunction is a major challenge in neurorehabilitation. Neurofeedback (NF), as an EEG-based brain training method, is currently applied in a wide spectrum of mental health conditions, including traumatic brain injury.ObjectiveThis study aimed to explore the capacity of Infra-Low Frequency Neurofeedback (ILF-NF) to promote the recovery of brain function in patients with frontal brain injury.Materials and methodsTwenty patients hospitalized at a neurorehabilitation clinic in Switzerland with recently acquired, frontal and optionally other brain lesions were randomized to either receive NF (...) or sham-NF. Cognitive improvement was assessed using the Frontal Assessment Battery (FAB) and the Test of Attentional Performance (TAP) tasks regarding intrinsic alertness, phasic alertness and impulse control.ResultsWith respect to cognitive improvements, there was no significant difference between the two groups after 20 sessions of either NF or sham-NF. However, in a subgroup of patients with predominantly frontal brain lesions, the improvements measured by the FAB and intrinsic alertness were significantly higher in the NF-group.ConclusionThis is the first double-blind controlled study using NF in recovery from brain injury, and thus also the first such study of ILF NF. Although the result of the subgroup has limited significance because of the small number of participants, it accentuates the trend seen in the whole group regarding the FAB and intrinsic alertness (p = 0.068, p = 0.079, respectively). We therefore conclude that NF could be a promising candidate promoting the recoveryfrom frontal brain lesions. Further studies with larger numbers of patients and less lesion heterogeneity are needed to verify the usefulness of NF in the neurorehabilitation of patients with frontal brain injury (NCT02957695 ClinicalTrials.gov). (shrink)

IntroductionNeurofeedback training is increasingly applied as a therapeutic tool in a variety of disorders, with growing scientific and clinical interest in the last two decades. Different Neurofeedback approaches have been developed over time, so it is now important to be able to distinguish between them and investigate the effectiveness and efficiency characteristics of each specific protocol. In this study we intend to examine the effects of Neurofeedback based on slow brain activity, the so-called Infra-Low Frequency training a recently developed methodology (...) that seems promising for the regulation of the central nervous system.AimsWith this review we intend to summarize the currently existing literature on ILF-Neurofeedback, examine its quality and formulate indications about the clinical effectiveness of ILF-Neurofeedback.MethodsLiterature search was first conducted according to PRISMA principles, described, and then assessed using the MMAT appraisal tool. 18 well-documented studies of ILF-Neurofeedback training in human subjects were picked up and analyzed. Reports include group interventions as well as single case studies.ResultsResearch data indicates good potential for ILF-Neurofeedback to influence brain activity and neurovegetative parameters. From the clinical profile, a salient common observation is a high level of individualization as a specific characteristic of ILF-Training: this feature seems to correlate with effectiveness of ILF-Neurofeedback, but also poses a challenge for researchers in terms of producing controlled and comparable findings; according to this point, some recommendation for future research on ILF-Neurofeedback are proposed. In conclusion, ILF-neurofeedback shows great potential for application for all those conditions in which the regulation of brain activity and neurophysiological processes are crucial. Further research will make it possible to complete the available data and to have a broader overview of its possible applications. (shrink)

Migraine is a chronic and idiopathic disorder leading to cognitive and affective problems. However, the neural basis of migraine without aura is still unclear. In this study, dynamic amplitude of low-frequency fluctuations analyses were performed in 21 patients with migraine without aura and 21 gender- and age-matched healthy controls to identify the voxel-level abnormal functional dynamics. Significantly decreased dALFF in the bilateral anterior insula, bilateral lateral orbitofrontal cortex, bilateral medial prefrontal cortex, bilateral anterior cingulate cortex, and left middle frontal cortex (...) were found in patients with migraine without aura. The dALFF values in the anterior cingulate cortex were negatively correlated with pain intensity, i.e., visual analog scale. Finally, support vector machine was used to classify patients with migraine without aura from healthy controls and achieved an accuracy of 83.33%, sensitivity of 90.48%, and specificity of 76.19%. Our findings provide the evidence that migraine influences the brain functional activity dynamics and reveal the neural basis for migraine, which could facilitate understanding the neuropathology of migraine and future treatment. (shrink)

Neurofeedback is a complex learning scenario, as the task consists of trying out mental strategies while processing a feedback signal that signifies activation in the brain area to be self-regulated and acts as a potential reward signal. In an attempt to dissect these subcomponents, we obtained whole-brain networks associated with efficient self-regulation in two paradigms: parallel, where the task was performed concurrently, combining feedback with strategy execution; and serial, where the task was performed consecutively, separating feedback processing from strategy execution. (...) Twenty participants attempted to control their anterior midcingulate cortex using functional magnetic resonance imaging NF in 18 sessions over 2 weeks, using cognitive and emotional mental strategies. We analyzed whole-brain fMRI activations in the NF training runs with the largest aMCC activation for the serial and parallel paradigms. The equal length of the strategy execution and the feedback processing periods in the serial paradigm allows a description of the two task subcomponents with equal power. The resulting activation maps were spatially correlated with functionally annotated intrinsic connectivity brain maps. Brain activation in the parallel condition correlates with the basal ganglia network, the cingulo-opercular network, and the frontoparietal control network ; brain activation in the serial strategy execution condition with the default mode network, the FPCN, and the visual processing network; while brain activation in the serial feedback processing condition predominantly with the CON, the DMN, and the FPCN. Additional comparisons indicate that BG activation is characteristic to the parallel paradigm, while supramarginal gyrus and superior temporal gyrus activations are characteristic to the serial paradigm. The multifaceted view of the subcomponents allows describing the cognitive processes associated with strategy execution and feedback processing independently in the serial feedback task and as combined processes in the multitasking scenario of the conventional parallel feedback task. (shrink)

Voices are a complex and rich acoustic signal processed in an extensive cortical brain network. Specialized regions within this network support voice perception and production and may be differentially affected in pathological voice processing. For example, the experience of hallucinating voices has been linked to hyperactivity in temporal and extra-temporal voice areas, possibly extending into regions associated with vocalization. Predominant self-monitoring hypotheses ascribe a primary role of voice production regions to auditory verbal hallucinations. Alternative postulations view a generalized perceptual salience (...) bias as causal to AVH. These theories are not mutually exclusive as both ascribe the emergence and phenomenology of AVH to unbalanced top-down and bottom-up signal processing. The focus of the current study was to investigate the neurocognitive mechanisms underlying predisposition brain states for emergent hallucinations, detached from the effects of inner speech. Using the temporal voice area localizer task, we explored putative hypersalient responses to passively presented sounds in relation to hallucination proneness. Furthermore, to avoid confounds commonly found in in clinical samples, we employed the Launay-Slade Hallucination Scale for the quantification of HP levels in healthy people across an experiential continuum spanning the general population. We report increased activation in the right posterior superior temporal gyrus during the perception of voice features that positively correlates with increased HP scores. In line with prior results, we propose that this right-lateralized pSTG activation might indicate early hypersensitivity to acoustic features coding speaker identity that extends beyond own voice production to perception in healthy participants prone to experience AVH. (shrink)