Too fast or too slow? Time and neuronal variability in bipolar disorder—A combined theoretical and empirical investigation

Time is an essential feature in bipolar disorder (BP). Manic and depressed BP patients perceive the speed of time as either too fast or too slow. The present article combines theoretical and empirical approaches to integrate phenomenological, psychological, and neuroscientific accounts of abnormal time perception in BP. Phenomenology distinguishes between perception of inner time, ie, self-time, and outer time, ie, world-time, that desynchronize or dissociate from each other in BP: inner time speed is abnormally slow (as in depression) or fast (as in mania) and, by taking on the role as default-mode function, impacts and modulates the perception of outer time speed in an opposite way, ie, as too fast in depression and too slow in mania. Complementing, psychological investigation show opposite results in time perception, ie, time estimation and reproduction, in manic and depressed BP. Neuronally, time speed can be indexed by neuronal variability, ie, SD. Our own empirical data show opposite changes in manic and depressed BP (and major depressive disorder [MDD]) with abnormal SD balance, ie, SD ratio, between somatomotor and sensory networks that can be associated with inner and outer time. Taken together, our combined theoretical-empirical approach demonstrates that desynchronization or dissociation between inner and outer time in BP can be traced to opposite neuronal variability patterns in somatomotor and sensory networks. This opens the door for individualized therapeutic “normalization” of neuronal variability pattern in somatomotor and sensory networks by stimulation with TMS and/or tDCS

Psychoanalysis and the Brain – Why Did Freud Abandon Neuroscience?

Sigmund Freud, the founder of psychoanalysis, was initially a neuroscientist but abandoned neuroscience completely after he made a last attempt to link both in his writing, “Project of a Scientific Psychology,” in 1895. The reasons for his subsequent disregard of the brain remain unclear though. I here argue that one central reason may be that the approach to the brain during his time was simply not appealing to Freud. More specifically, Freud was interested in revealing the psychological predispositions of psychodynamic processes. However, he was not so much focused on the actual psychological functions themselves which though were the prime focus of the neuroscience at his time and also in current Cognitive Neuroscience. Instead, he probably would have been more interested in the brain’s resting state and its constitution of a spatiotemporal structure. I here assume that the resting state activity constitutes a statistically based virtual structure extending and linking the different discrete points in time and space within the brain. That in turn may serve as template, schemata, or grid for all subsequent neural processing during stimulus-induced activity. As such the resting state’ spatiotemporal structure may serve as the neural predisposition of what Freud described as “psychological structure.” Hence, Freud and also current neuropsychoanalysis may want to focus more on neural predispositions, the necessary non-sufficient conditions, rather than the neural correlates, i.e., sufficient, conditions of psychodynamic processes

Genetic prescription for health: The impact of exercise and inflammation on immunugenetics

While inflammation is a central part of our immune defense, excessive inflammation in acute and chronic situations (sepsis; inflammaging) can be very harmful and life shortening. Exercise has been shown to induce and modify gene expression in different tissues. Among the genes strongly activated by exercise, inflammation-related genes are of prime importance. We try to give an overview about the effect of exercise on the activation of genes and pathways involved in inflammation. Activation of inflammatory genes can readily be observed in the muscle, where exercise begins. Other organs can also be influenced by exercise, such as brain, liver and heart, but a mirror of inflammatory regulations by exercise can be found in peripheral blood. The majority of investigations, including ours, thus, have used peripheral blood for analysis. With the advent of microarray technology enormous amounts of data on gene expression following exercise have been generated and a large part of these is related to inflammation. Altogether, it seems that exercise induces both, pro-inflammatory genes (including asthma related genes) but also prominent anti-inflammatory genes. There are differences in gene regulation due to type and duration of exercise, sex and age of the subjects, and the technologies used for analysis. Observations of exercise activity in athletes with solid transplants who are under immunosuppressive medication shows that the vast part of the inflammatory reaction and its anti-inflammatory counter reaction are absent in these patients in spite of performance comparable to healthy subjects. We also present results from a recent study which includes ex vivo stimulation by endotoxin (LPS). They show that exercise can also modify the reaction of peripheral blood cells to TLRs mediated pathogen activation. In special, activation of TNIP3, a negative regulator of TLRs signaling and down-regulation of IFN-β1 through exercise could be observed in these cultures but not in unstimulated cultures. A hypothesis of the interaction of exercise with TLRs signaling will be presented

Interoceptive Awareness and the Insula – Application of Neuroimaging Techniques in Psychotherapy

Interoceptive awareness is defined as the awareness of stimuli originating inside one’s own body such as the heartbeat. The emergence of new brain imaging techniques like functional magnetic resonance imaging (fMRI) or magnetic resonance spectroscopy (MRS) has increased our knowledge of neural substrates underlying interoceptive awareness. In particular, the bilateral brain structure of the insula has been identified as a key region involved in interoceptive processes in healthy populations. In line with prominent theories of human emotion, the insula has an important function in connecting interoceptive awareness with affective experience. This connection hinging on the insula between interoception and emotional processing is suggestive of an involvement of the insula in mood disorders such as major depressive disorder (MDD). Multilayered deficits in the insula cortex of depressed individuals such as abnormal function, biochemistry, and anatomy support this hypothesis. The aim of the present article is a) to describe the importance of the insula for the interplay between interoception and emotional processing and b) how this might be figured into psychotherapeutic treatment of depressed patients using new imaging techniques like real-time fMRI. The article begins with a brief introduction about neuroanatomical settings of the insula (I. Introduction–Neuroanatomical background of the insula). Afterwards, early behavioral studies to investigate interoceptive awareness are described (II. A step Back–First attempts to investigate interoceptive awareness), followed by a description of more recent imaging studies outlining neural mechanisms underlying interoceptive awareness and emotional processing in the insula (III. The insula as key region involved in functional interoception and emotion.) Throughout, the article addresses the question of why the investigation of individuals suffering from depression might provide novel insights into the neural underpinnings of interoceptive awareness and its link to abnormal behavior (IV. Why study interoceptive awareness in depressed participants?). Following the description of a selected study that combines for the first time functional results of interoception (using fMRI) with biochemical results of the insula (using MRS) (V. Neuroimaging in interoceptive awareness combining fMRI and MRS – A specific study), the article concludes with a perspective outlining the potential for using imaging techniques like real-time fMRI to enhance neural activity in the insula during interoceptive awareness. This approach potentially leads to faster recovery in depressed patients and might be the first therapeutic application of functional imaging in psychiatry (VI. Perspectives: Neurofeedback in major depression using real-time fMRI)

First-Person Neuroscience: A new methodological approach for linking mental and neuronal states

Though the brain and its neuronal states have been investigated extensively, the neural correlates of mental states remain to be determined. Since mental states are experienced in first-person perspective and neuronal states are observed in third-person perspective, a special method must be developed for linking both states and their respective perspectives. We suggest that such method is provided by First-Person Neuroscience. What is First-Person Neuroscience? We define First-Person Neuroscience as investigation of neuronal states under guidance of and on orientation to mental states. An empirical example of such methodological approach is demonstrated by an fMRI study on emotions. It is shown that third- and first-person analysis of data yield different results. First-person analysis reveals neural activity in cortical midline structures during subjective emotional experience. Based on these and other results neural processing in cortical midline structures is hypothesized to be crucially involved in generating mental states. Such direct linkage between first- and third-person approaches to analysis of neural data allows insight into the "point of view from within the brain", that is what we call the First-Brain Perspective. In conclusion, First-Person Neuroscience and First-Brain Perspective provide valuable methodological tools for revealing the neuronal correlate of mental states

Is Our Self Related to Personality? A Neuropsychodynamic Model

The concept and the assessment of personality have been extensively discussed in psychoanalysis and in clinical psychology over the years. Nowadays there is large consensus in considering the constructs of the self and relatedness as central criterions to assess the personality and its disturbances. However, the relation between the psychological organization of personality, the construct of the self, and its neuronal correlates remain unclear. Based on the recent empirical data on the neural correlates of the self (and others), on the importance of early relational and attachment experiences, and on the relation with the brain’s spontaneous/resting state activity (rest–self overlap/containment), we propose here a multilayered model of the self with: (i) relational alignment; (ii) self-constitution; (iii) self-manifestation; and (iv) self-expansion. Importantly, these different layers of the self can be characterized by different neuronal correlates—this results in different neuronally grounded configurations or organizations of personality. These layers correspond to different levels of personality organization, such as psychotic (as related to the layer of self-constitution), borderline (as related to the layer of self-manifestation) and neurotic (as related to the layer of self-expansion). Taken together, we provide here for the first time a neurobiologically and clinically grounded model of personality organization, which carries major psychodynamic and neuroscientific implications. The study of the spontaneous activity of the brain, intrinsically related to the self (rest–self overlap/containment) and the interaction with stimuli (rest–stimulus interaction) may represent a further advance in understanding how our default state plays a crucial role in navigating through the internal world and the external reality

Habits: bridging the gap between personhood and personal identity

In philosophy, the criteria for personhood (PH) at a specific point in time (synchronic), and the necessary and sufficient conditions of personal identity (PI) over time (diachronic) are traditionally separated. Hence, the transition between both timescales of a person’s life remains largely unclear. Personal habits reflect a decision-making (DM) process that binds together synchronic and diachronic timescales. Despite the fact that the actualization of habits takes place synchronically, they presuppose, for the possibility of their generation, time in a diachronic sense. The acquisition of habits therefore rests upon PI over time; that is, the temporal extension of personal decisions is the necessary condition for the possible development of habits. Conceptually, habits can thus be seen as a bridge between synchronic and diachronic timescales of a person’s life. In order to investigate the empirical mediation of this temporal linkage, we draw upon the neuronal mechanisms underlying DM; in particular on the distinction between internally and externally guided DM. Externally guided DM relies on external criteria at a specific point in time (synchronic); on a neural level, this has been associated with lateral frontal and parietal brain regions. In contrast, internally guided DM is based on the person’s own preferences that involve a more longitudinal and thus diachronic timescale, which has been associated with the brain’s intrinsic activity. Habits can be considered to reflect a balance between internally and externally guided DM, which implicates a particular temporal balance between diachronic and synchronic elements, thus linking two different timescales. Based on such evidence, we suggest a habit-based neurophilosophical approach of PH and PI by focusing on the empirically-based linkage between the synchronic and diachronic elements of habits. By doing so, we propose to link together what philosophically has been described and analyzed separately as PH and PI

Identifying a Network of Brain Regions Involved in Aversion-Related Processing: A Cross-Species Translational Investigation

The ability to detect and respond appropriately to aversive stimuli is essential for all organisms, from fruit flies to humans. This suggests the existence of a core neural network which mediates aversion-related processing. Human imaging studies on aversion have highlighted the involvement of various cortical regions, such as the prefrontal cortex, while animal studies have focused largely on subcortical regions like the periaqueductal gray and hypothalamus. However, whether and how these regions form a core neural network of aversion remains unclear. To help determine this, a translational cross-species investigation in humans (i.e., meta-analysis) and other animals (i.e., systematic review of functional neuroanatomy) was performed. Our results highlighted the recruitment of the anterior cingulate cortex, the anterior insula, and the amygdala as well as other subcortical (e.g., thalamus, midbrain) and cortical (e.g., orbitofrontal) regions in both animals and humans. Importantly, involvement of these regions remained independent of sensory modality. This study provides evidence for a core neural network mediating aversion in both animals and humans. This not only contributes to our understanding of the trans-species neural correlates of aversion but may also carry important implications for psychiatric disorders where abnormal aversive behavior can often be observed