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Changes in EEG have been reported in both major depressive disorder (MDD) and bipolar disorder (BD). Specifically, power changes in EEG alpha and theta frequency bands during rest and task are known in both disorders. This leaves open whether there are changes in yet another component of the electrophysiological EEG signal, namely phase-related processes that may allow for distinguishing MDD and BD. For that purpose, we investigate EEG-based spontaneous phase in the resting state of MDD, BD and healthy controls. Our main findings show: (i) decreased spontaneous phase variability in frontal theta of both MDD and BD compared to HC; (ii) decreased spontaneous phase variability in central-parietal alpha in MDD compared to both BD and HC; (iii) increased delays or lags of alpha phase cycles in MDD (but not in BD), which (iv) correlate with the decreased phase variability in MDD. Together, we show similar (decreased frontal theta variability) and distinct (decreased central-parietal alpha variability with increased lags or delays) findings in the spontaneous phase dynamics of MDD and BD. This suggests potential relevance of theta and alpha phase dynamics in distinguishing MDD and BD in clinical differential-diagnosis. • Resting state EEG shows decreased variability in major depressive disorder • Frontal theta phase variability is decreased in both depression and bipolar disorder • Centro-parietal phase variability is decreased in depression but not bipolar disorder • Depressed but not bipolar patients show phase lag in centro-parietal alpha The alpha lag correlated with decreased variability in depression [ABSTRACT FROM AUTHOR]

How can we characterize psychopathological symptoms and connect them to the brain? Current psychopathological symptoms only focus on either the symptoms themselves or predominantly on the brain. This leaves open their intimate connection. A novel approach, Spatiotemporal Psychopathology, proposes that the brain inner spatiotemporal organisation of its neural activity provides the spatiotemporal organization of the psychopathological symptoms. Specifically, the brains' neuronal topography and dynamic is manifest in a more or less analogous spatiotemporal organisation on the mental level, i.e., mental topography and dynamic. This is strongly supported by various examples including major depressive disorder, bipolar disorder, schizophrenia, and autism. We therefore conclude that Spatiotemporal Psychopathology provides a promising approach to intimately connect brain and symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Depression can be characterized by rumination that is featured by spontaneity and perseveration of internally oriented thoughts. At the same time, depressed subjects complain about abnormal slowness and lack of power/energy in their thoughts, suggesting abnormal "thought dynamics." The relationship between rumination and thought dynamics in depression remains unclear, though. Method: We investigated thought dynamics and rumination in healthy control, major depressive disorder (MDD), and depressed bipolar disorder (BD) subjects. The dynamics in the spontaneous shift between internally and externally oriented thoughts were measured by a novel method of continuous experience sampling whose time series was subjected to power and frequency analyses. Subjects filled out the Beck Depression Inventory-II and Ruminative Response Scale questionnaires to evaluate current depressive symptoms and ruminative responses to negative affect. The methods used to analyze data included χ2, Pearson correlation, ANOVA, and partial correlation. Results: Our main findings are: (i) increased number and longer duration of internally oriented thought contents in MDD and BD; (ii) reduced thought dynamics with slower frequency (calculated in Hz) and decreased power (power spectral density) in shifting between internally and externally oriented thoughts, especially in MDD and, less strongly, in BD subjects; and (iii) power spectral density as a dimension of thought dynamics is related to brooding rumination with depression severity explaining high degrees of their variance. Conclusion: Our results show slow frequency and low power in the internal-external thought dynamic of acute MDD and depressed BD. Together with its close relation to depression severity and rumination, our findings highlight the key importance of abnormal dynamics on the cognitive level of depression. [ABSTRACT FROM AUTHOR]

Childhood trauma is one of the most prominent risk factors in developing major depressive disorder (MDD) and may lead to unfavorable outcomes of pharmacotherapy and psychotherapy in MDD. While how it modulates the treatment outcome of the repetitive transcranial magnetic stimulation (rTMS) and how sex difference may play a role in mediating this relationship remain unknown. To evaluate this question, 51 (37 women) MDD patients were treated with 10 Hz rTMS to the left dorsolateral prefrontal cortex (lDLPFC). The experience of childhood trauma was quantified by the Childhood Traumatic Questionnaire (CTQ). The depressive severity was assessed by Hamilton Depression Scale (HAMD) and Beck Depression Inventory (BDI) as the primary and secondary assessments. Beck Hopelessness Scale (BHS) and Hamilton Anxiety Scale (HAMA) were also assessed for further confirmation. Thirty-six (70.6%) participants showed a response including 17 (33.3%) achieving remission to the rTMS treatment. The alleviation of depressive symptoms was negatively correlated with the CTQ scores, specifically in women but not men, in subjective BDI and BHS, but not objective HAMD or HAMA. We demonstrate that childhood trauma negatively affects the subjective perception of rTMS-lDLPFC treatment outcomes in female MDD patients. This highlights the importance of measuring childhood trauma-related symptoms in routine clinical rTMS treatment, as they may impact perceived efficacy. [ABSTRACT FROM AUTHOR]

Objective Manic and depressive phases of bipolar disorder (BD) show opposite symptoms in psychomotor, thought, and affective dimensions. Neuronally, these may depend on distinct patterns of alterations in the functional architecture of brain intrinsic activity. Therefore, the study aimed to characterize the spatial and temporal changes of resting-state activity in mania and depression, by investigating the regional homogeneity (ReHo) and degree of centrality (DC), in different frequency bands. Methods Using resting-state functional magnetic resonance imaging (fMRI), voxel-wise ReHo and DC were calculated—in the standard frequency band (SFB: 0.01–0.10 Hz), as well as in Slow5 (0.01–0.027 Hz) and Slow4 (0.027–0.073 Hz)—and compared between manic (n = 36), depressed (n = 43), euthymic (n = 29) patients, and healthy controls (n = 112). Finally, clinical correlations were investigated. Results Mania was mainly characterized by decreased ReHo and DC in Slow4 in the medial prefrontal cortex (as part of the default-mode network [DMN]), which in turn correlated with manic symptomatology. Conversely, depression was mainly characterized by decreased ReHo in SFB in the primary sensory-motor cortex (as part of the sensorimotor network [SMN]), which in turn correlated with depressive symptomatology. Conclusions Our data show a functional reconfiguration of the spatiotemporal structure of intrinsic brain activity to occur in BD. Mania might be characterized by a predominance of sensorimotor over associative networks, possibly driven by a deficit of the DMN (reflecting in internal thought deficit). Conversely, depression might be characterized by a predominance of associative over sensorimotor networks, possibly driven by a deficit of the SMN (reflecting in psychomotor inhibition). [ABSTRACT FROM AUTHOR]

Objective Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. Method In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. Results (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. Conclusions These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a complex psychiatric disorder characterized by changes in both resting state and stimulus-evoked activity. Whether resting state changes are carried over to stimulus-evoked activity, however, is unclear. We conducted a combined rest (3 min) and task (three-stimulus auditory oddball paradigm) EEG study in n =28 acute depressed MDD patients, comparing them with n =25 healthy participants. Our focus was on the temporal dynamics of both resting state and stimulus-evoked activity for which reason we measured peak frequency (PF), coefficient of variation (CV), Lempel-Ziv complexity (LZC), and trial-to-trial variability (TTV). Our main findings are: i) atypical temporal dynamics in resting state, specifically in the alpha and theta bands as measured by peak frequency (PF), coefficient of variation (CV) and power; ii) decreased reactivity to external deviant stimuli as measured by decreased changes in stimulus-evoked variance and complexity—TTV, LZC, and power and frequency sliding (FS and PS); iii) correlation of stimulus related measures (TTV, LZC, PS, and FS) with resting state measures. Together, our findings show that resting state dynamics alone are atypical in MDD and, even more important, strongly shapes the dynamics of subsequent stimulus-evoked activity. We thus conclude that MDD can be characterized by an atypical temporal dynamic of its rest–stimulus interaction; that, in turn, makes it difficult for depressed patients to react to relevant stimuli such as the deviant tone in our paradigm. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Phenomenological psychopathology, through theoretical and idiographic studies, conceptualizes major depressive disorder (MDD) as a disorder of time experience. Investigations on abnormal time experience (ATE) in MDD adopting methodologies requested by the standards of empirical sciences are still lacking. Our study aimed to provide a qualitative analysis, on an empirical ground and on a large scale, of narratives of temporal experiences of persons affected by MDD. Methods: We interviewed 550 consecutive patients affected by affective and schizophrenic disorders. Clinical files were analysed by means of consensual qualitative research. Results: Out of 100 MDD patients, 96 reported at least 1 ATE. The principal categories of ATE are vital retardation- the experience of a stagnation of endogenous vital processes (37 patients), the experience of present and future dominated by the past (29 patients) and the experience of the slackening of the flow of time (25 patients). A comparison with ATE in schizophrenia patients showed that in MDD, unlike in schizophrenia, there is no disarticulation of time experience (disorder of temporal synthesis ) but rather a disorder of conation or inhibition of becoming. Limitations: The interview style was not meant to make a quantitative assessment ("false negatives" cannot be excluded). Conclusions: Our findings confirm the relevance of distinctive features of ATE in MDD, support the hypothesis of an intrinsic disordered temporal structure in depressive symptoms and may have direct implications in clinical practice, especially in relation to differential diagnosis, setting the boundaries between "true" and milder forms of depression and neurobiological research. [ABSTRACT FROM AUTHOR]

Psychopathology as the investigation and classification of experience, behavior and symptoms in psychiatric patients is an old discipline that ranges back to the end of the 19th century. Since then different approaches to psychopathology have been suggested. Recent investigations showing abnormalities in the brain on different levels raise the question how the gap between brain and psyche, between neural abnormalities and alteration in experience and behavior can be bridged. Historical approaches like descriptive (Jaspers) and structural (Minkoswki) psychopathology as well as the more current phenomenological psychopathology (Paarnas, Fuchs, Sass, Stanghellini) remain on the side of the psyche giving detailed description of the phenomenal level of experience while leaving open the link to the brain. In contrast, the recently introduced Research Domain Classification (RDoC) aims at explicitly linking brain and psyche by starting from so-called 'neuro-behavioral constructs'. How does Spatiotemporal Psychopathology, as demonstrated in the first paper on depression, stand in relation to these approaches? In a nutshell, Spatiotemporal Psychopathology aims to bridge the gap between brain and psyche. Specifically, as demonstrated in depression in the first paper, the focus is on the spatiotemporal features of the brain's intrinsic activity and how they are transformed into corresponding spatiotemporal features in experience on the phenomenal level and behavioral changes, which can well account for the symptoms in these patients. This second paper focuses on some of the theoretical background assumptions in Spatiotemporal Psychopathology by directly comparing it to descriptive, structural, and phenomenological psychopathology as well as to RDoC. [ABSTRACT FROM AUTHOR]

Despite intense neurobiological investigation in psychiatric disorders like major depressive disorder (MDD), the basic disturbance that underlies the psychopathological symptoms of MDD remains, nevertheless, unclear. Neuroimaging has focused mainly on the brain's extrinsic activity, specifically task-evoked or stimulus-induced activity, as related to the various sensorimotor, affective, cognitive, and social functions. Recently, the focus has shifted to the brain's intrinsic activity, otherwise known as its resting state activity. While various abnormalities have been observed during this activity, their meaning and significance for depression, along with its various psychopathological symptoms, are yet to be defined. Based on findings in healthy brain resting state activity and its particular spatial and temporal structure - defined in a functional and physiological sense rather than anatomical and structural - I claim that the various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure. This is supported by recent findings that link ruminations and increased self-focus in depression to abnormal spatial organization of resting state activity. Analogously, affective and cognitive symptoms like anhedonia, suicidal ideation, and thought disorder can be traced to an increased focus on the past, increased past-focus as basic temporal disturbance o the resting state. Based on these findings, I conclude that the various depressive symptoms must be conceived as spatiotemporal disturbances of the brain's resting state's activity and its spatiotemporal structure. Importantly, this entails a new form of psychopathology, "Spatiotemporal Psychopathology" that directly links the brain and psyche, therefore having major diagnostic and therapeutic implications for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN).The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. Methods: Sixteen medication-free women with BN (age=23±5 years) and 18 matched controls (age=23±3 years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms.Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. Results: Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t =9.0, df=1, P =0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P =0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r =-0.4; P =0.02) and interoceptive awareness (r =-0.4; P =0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. Conclusion: Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size. [ABSTRACT FROM AUTHOR]

The article discusses the psychopathology and pathophysiology of depression. It presents the case of an executive assistant who was hospitalized with a severe episode of depression when her boss, a chief executive officer of a major company, shouted at her due to the allegedly bad tasting coffee that she prepared. The work of A. Vanhaudenhuyse and colleagues on the condition is also cited.

The concept of SEEKING describes a predisposition to search enthusiastically for rewards in the environment. While SEEKING and its underlying functional anatomy have been extensively investigated in animals, such processes in humans, especially brain-damaged individuals, remain understudied. We therefore conducted an exploratory behavioral study in stroke patients to investigate the effects of brain lesions that anatomically could be interpreted to impact the SEEKING system and predicted relationships to depression. Patients with lesions in anterior, medial, and/or subcortical lesions showed significantly lower SEEKING scores and higher depression scores than nonlesioned subjects in the control group. Based on our data and related work on animals, we propose central involvement of the anterior subcortical–cortical midline system as core of the limbic system in SEEKING in humans. [ABSTRACT FROM PUBLISHER]

Depression, conceptualized as major depressive disorder (MDD), is a complex psychiatric disorder with multiple behavioral changes and alterations in various brain regions. Biochemically, serotonin and others substances like GABA, glutamate, norepinephrin, adrenaline/noradrenaline play an essential role in the pathogenesis of MDD. The paper reviews recent human neuroimaging findings on how the genes underlying these biochemical substances modulate neural activity, behavior, and ultimately clinical symptoms. Current data provide solid evidence that genes related to serotonin impact emotion-related neural activity in the amygdala and the anterior cingulate cortex. By contrast, evidence is not as strong for genes related to biochemical substances other than serotonin and other regions of the brain. The review concludes with discussing future genetic, neural, and clinical challenges that point out the central role of gene×environment and brain×environment interactions as genetic and neural predispositions of depression. [ABSTRACT FROM AUTHOR]

Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resting state neural activity and negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network (DMN). Methods. Since activity in DMN regions has been associated with self-relatedness, we investigated neural activity in these regions during self-related emotional judgement and passive picture viewing in 25 patients with MDD and 25 healthy controls in an event-related fMRI design. Results. Behaviourally, MDD subjects showed significantly higher ratings of self-relatedness that also correlated with depression symptoms such as hopelessness. Neuroimaging results in MDD patients showed significantly lower negative BOLD responses (NBRs) in anterior medial cortical regions during judgement of self-relatedness while posterior medial regions showed increased NBRs. Unlike in healthy subjects, the anterior medial cortical NBRs were no longer parametrically modulated by the degree of self-relatedness in MDD patients. Conclusions. Our findings suggest that reduced NBRs in the anterior regions of the default-mode network may signify decoupling from self-relatedness in MDD patients with the consecutive abnormal increase of self-focus. [ABSTRACT FROM AUTHOR]

Abstract: Major depressive disorder (MDD) has traditionally been characterized by various psychological symptoms, involvement of diverse functional systems (e.g., somatic, affect, cognition, reward, etc.), and with progress in neuroscience, an increasing number of brain regions. This has led to the general assumption that MDD is a stress–responsive brain ‘system disorder’ where either one or several alterations infiltrate a large number of functional systems in the brain that control the organism''s somatic, affective, and cognitive life. However, while the effects or consequences of the abnormal changes in the functional systems of, for instance affect, cognition or reward have been investigated extensively, the underlying core mechanism(s) underlying MDD remain unknown. Hypotheses are proliferating rapidly, though. Based on recent findings, we will entertain an abnormality in the resting-state activity in MDD to be a core feature. Based on both animal and human data, we hypothesize that abnormal resting-state activity levels may impact stimulus-induced neural activity in medially situated core systems for self-representation as well as external stimulus (especially stress, specifically separation distress) interactions. Moreover, due to nested hierarchy between subcortical and cortical regions, we assume ‘highjacking’ of higher cortical affective and cognitive functions by lower subcortical primary-process emotional systems. This may account for the predominance of negative affect in somatic and cognitive functional system operations with the consecutive generation of the diverse symptoms in MDD. We will here focus on the neuroanatomical and biochemical basis of resting-state abnormalities in MDD including their linkage to the diverse psychopathological symptoms in depression. However, our ‘resting-state hypothesis’ may go well beyond that by being sufficiently precise to be linked to genetic, social, immunological, and endocrine dimensions and hypotheses as well as to clinical dimensions like endophenotypes and various diagnostic-prognostic biomarkers. Taken together, our ‘resting-state hypothesis’ may be considered a first tentative framework for MDD that integrates translational data, the various dimensions, and subcortical–cortical systems while at the same time providing the link to the clinical level of symptoms, endophenotypes and biomarkers. [Copyright &y& Elsevier]

Abstract: Despite all the recent progress in neuroscience, we still do not understand the basic principles according to which the brain functions. This may be due, at least in part, to our lack of knowledge how the brain''s intrinsic activity, the brain''s input, impacts stimulus-induced changes in the brain. We here discuss the neuronal, experimental and methodological relevance of the brain''s resting state activity for future studies. Furthermore, we make several suggestions how to best define and include the brain''s resting state into our experimental designs. We conclude that experimental consideration of the brain''s resting state has major implications for setting up experimental designs and methodological strategies. This may also shed new light on some hitherto unresolved questions like the neuroscientific mechanisms underlying consciousness and psychiatric disorders. [Copyright &y& Elsevier]

Heinzel A, Northoff G, Boeker H, Boesiger P, Grimm S. Emotional processing and executive functions in major depressive disorder: dorsal prefrontal activity correlates with performance in the intra-extra dimensional set shift. Major depressive disorder (MDD) is characterised by predominately negatively valenced emotional symptoms that are often accompanied by cognitive impairments. We posited that cognitive impairments in MDD are related to altered emotional processing in prefrontal cortex. We compared 20 medication-free patients with MDD and 29 matched healthy controls. Both groups performed an emotional task during functional magnetic resonance imaging (fMRI). Furthermore, they completed the intra-extra dimensional set shift (IED) test probing for cognitive impairments. Then we correlated the results of the IED with the changes in fMRI BOLD signal in MDD patients and healthy subjects. The subcategory of the IED applying extradimensional shift (EDS) showed a divergent performance of the MDD group committing significantly more errors than the control group. Correlating the EDS errors with fMRI signal changes, the healthy subjects showed a positive correlation with the right ventrolateral prefrontal cortex and the right orbitofrontal cortex. MDD subjects, in contrast, showed a positive correlation in right dorsolateral prefrontal cortex (DLPFC) and a negative correlation in the left dorsomedial prefrontal cortex (DMPFC). We hypothesise that the differential correlation in healthy controls and MDD patients may reflect the use of different strategies in their performance. The impaired executive functions, as reflected by altered processing in right DLPFC and left DMPFC, may implicitly influence emotional processing in patients suffering from MDD. [ABSTRACT FROM AUTHOR]

Objectives. In addition to affective-cognitive symptoms, patients with major depressive disorder (MDD) suffer from somato-vegetative symptoms, suggesting abnormal interoceptive awareness of their “material me”. While recent imaging studies have extensively investigated affective-cognitive symptoms in MDD, the neural correlates of somato-vegetative symptoms and abnormal interoception remain unclear. Since the “material me” has been especially associated with the anterior insula in healthy subjects, we hypothesized abnormalities in this region during interoceptive awareness in MDD. Methods. We therefore investigated behavioural and neural correlates of interoception in healthy and depressed subjects using the Body Perception Questionnaire (BPQ) and a well established heartbeat perception task in fMRI. Results. MDD patients showed significantly higher scores in the BPQ and reduced neural activity during rest periods, particularly in the bilateral anterior insula. In contrast to healthy subjects, BPQ scores no longer correlated with activity during rest periods in the anterior insula. Both BPQ scores and left anterior insula signal changes correlated with depression severity. Conclusions. We demonstrate for the first time abnormal body perception and altered activity in the insula during rest in MDD. Our results suggest that these behavioural and neural abnormalities are closely related to these patients’ somato-vegetative abnormalities and their abnormal “material me”. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the relationship among aberrant neuronal activation, pregenual anterior cingulate (pgACC), altered glutamatergic metabolism and anhedonia in major depressive disorder (MDD). The study aims to contextualize metabolic, functional and clinical parameters to reveal cellular mechanisms related to anhedonia. Meanwhile, the results show that patients with highly anhedonic MDD have a decreased glutamine but normal glutamate and y-aminobutyric acid concentrations. Moreover, deficits of glutamergic metabolism can be related with the aberrant neuronal activation patterns of the pgACC in anhedonic depression.

Studies using functional magnetic resonance imaging (fMRI) show predominant negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network such as the pregenual anterior cingulate cortex, the ventromedial prefrontal cortex, and the posterior cingulate cortex. Patients with major depressive disorder (MDD) show emotional–cognitive disturbances, which have been associated with alterations within the default-mode network. However, it remains unclear whether these default-mode network alterations are related to abnormalities in NBRs. We therefore investigated neural activity in the default-mode network during different emotional tasks in patients with MDD in an event-related fMRI design. MDD patients showed significantly reduced NBRs in several regions of the default-mode network. Decreased NBRs in MDD patients correlated with depression severity and feelings of hopelessness. In sum, our findings demonstrate that default-mode network NBRs are reduced in MDD and modulate these patients' abnormally negative emotions.Neuropsychopharmacology (2009) 34, 932–943; doi:10.1038/npp.2008.81; published online 4 June 2008 [ABSTRACT FROM AUTHOR]

Abstract: Background: The question of the self has intrigued philosophers and psychologists for a long time. More recently distinct concepts of self have also been suggested in neuroscience more specifically in neuroimaging. Aims: The aim here is to apply these findings to abnormalities of the self in depression and to develop neuropsychiatric hypothesis. Methods and results: Patients with depression suffer from an increased self-focus, attribution of negative emotions to the self, and increased cognitive processing of the own self. We assume that in major depressive disorder (MDD), the abnormal self-focus may be related to altered neural activity in the ventral cortical midline structures (CMS), the one-sided attribution of negative emotions to the self with neural activity in the amygdala and the ventral striatum/N. accumbens, and the abnormal cognitive processing of one''s self with reciprocal modulation between ventral CMS and lateral prefrontal cortical regions. Conclusions: It is concluded that the transdisciplinary investigation of the self between neuroscience, psychiatry and philosophy yields novel insights into the psychopathology and pathophysiology of the self in depression as well as into the neurophilosophical concept of the self in general. [Copyright &y& Elsevier]

Anxiety is a pervasive emotional state where, phenomenologically, subjects often report changes in their experience of time and space. However, a systematic and quantified examination of time and space experience in terms of a self-report scale is still missing which eventually could also be used for clinical differential diagnosis. Based on historical phenomenological literature and patients' subjective reports, we here introduce, in a first step, the Scale for Time and Space Experience of Anxiety (STEA) in a smaller sample of 19 subjects with anxiety disorders and, in a second step, validate its shorter clinical version (cSTEA) in a larger sample of 48 anxiety subjects. The main findings are (i) high convergent and divergent validity of STEA with both Beck Anxiety Inventory (BAI) (r = 0.7325; p < 0.001) and Beck Depression Inventory (BDI) (r = 0.7749; p < 0.0001), as well as with spontaneous mind wandering (MWS) (r = 0.7343; p < 0.001) and deliberate mind wandering (MWD) (r = 0.1152; p > 0.05), (ii) statistical feature selection shows 8 key items for future clinical usage (cSTEA) focusing on the experience of temporal and spatial constriction, (iii) the effects of time and space experience (i.e., for both STEA and cSTEA scores) on the level of anxiety (BAI) are mediated by the degree of spontaneous mind wandering (MWS), (iv) cSTEA allows for differentiating high levels of anxiety from the severity of comorbid depressive symptoms, and (v) significant reduction in the cSTEA scores after a therapeutic intervention (breathing therapy). Together, our study introduces a novel fully quantified and highly valid self-report instrument, the STEA, for measuring time-space experiences in anxiety. Further we develop a shorter clinical version (cSTEA) which allows assessing time space experience in a valid, quick, and simple way for diagnosis, differential diagnosis, and therapeutic monitoring of anxiety. • Anxiety is closely related to constricted time and space experiences. • The dynamic of thoughts, i.e., mind wandering, may serve as the mediator between the time and space experiences and anxiety. • cSTEA allow a valid and simple way to assess clinical phenomenology of anxiety. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) at left dorsolateral prefrontal cortex (lDLPFC) is commonly used in major depressive disorder (MDD), even though its therapeutic efficacy is limited. Given that many MDD patients show psychomotor retardation, we aim to examine whether the left motor cortex (lMC) as a novel rTMS target would provide effective and well-tolerated treatment as being comparable to lDLPFC-rTMS. In this prospective double-blind randomized single-center study, 131 MDD patients were randomly assigned to the lDLPFC or lMC group and were treated with 10 Hz rTMS (90 % motor threshold) applied twice daily for 4000 pulses continuously over five days. The primary endpoint was the Hamilton Depression Scale (HAMD) total score change after treatment. After the five-day rTMS treatment, there was no significant difference in both HAMD reduction rate (lDLPFC 59.3 % ± 20.4 %, lMC 51.3 % ± 26.3 %, P = 0.10) and adverse effects (P = 0.79) between 48 (73.8 %) lMC subjects and 51 (77.3 %) lDLPFC subjects. Furthermore, the lMC study group showed stable HAMD scores at follow-up compared to their endpoint scores (P = 0.08). Sham-control group was not included and the sample size was small. Therefore, our results should be seen as exploratory and preliminary. The preliminary good therapeutic response, comparability, and tolerability of lMC-rTMS suggest lMC a potential and more easily accessible rTMS target. Together, our findings raise the possibility of symptom-specific rTMS in motor cortex (psychomotor retardation) or lDLPFC (cognitive deficits). This warrants larger clinical trials of rTMS in MDD with symptom-specific stimulation targets. • lMC-rTMS yields a good therapeutic response in MDD patients. • lMC-rTMS shows non-inferior therapeutic effects compared to lDLPFC-rTMS. • lMC-rTMS is well tolerated showing no major side effects. [ABSTRACT FROM AUTHOR]

Background: Altered global signal (GS) topography features in the resting-state fMRI of major depressive disorder (MDD), showing abnormally strong global signal representation in the default-mode network (DMN). Whether the abnormal local to global change also shapes activity during task states, and how it relates to psychopathological symptoms, e.g., abnormally slow time speed of motor, cognitive, and affective symptoms, remains unknown.Methods: We investigated fMRI-based GS with its topographical representation during task states in unmedicated 51 MDD subjects and 28 healthy subjects. Task-related global signal correlation (GSCORR) was probed by a novel paradigm testing the processing of negative/neutral emotions during different time speeds, i.e., slow and fast.Results: We observed a significant interaction between time speed and emotion of GSCORR in various DMN regions in healthy subjects. Next, we showed that MDD exhibits reduced task-related GSCORR in various DMN regions during specifically the fast processing of negative emotions. Finally, we demonstrated that GSCORR in DMN and other brain regions (motor-related regions, inferior frontal cortex) correlated with the degree of psychomotor retardation especially during the fast emotional stimuli.Limitations: The measurement of interoceptive variables like respiration rate or heart rate were not included in our fMRI acquisition.Conclusion: Together, we demonstrated the functional relevance of GS topography by showing reduced GSCORR in DMN during specifically the fast processing of negative emotions in MDD, suggesting the abnormal slowness, i.e., reduced time speed, to be a key feature of both brain and symptoms in MDD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a multifaceted mental disorder where participants, in addition to various symptoms, often suffer from increased focus on past time perspective and higher incidence of childhood trauma. Whether the abnormal time perspective is a result of the depressive symptoms or, alternatively, mediates between childhood trauma and depression remains unclear. To examine the triangular relationship between early life trauma, time perspective, and depressive symptoms. We investigated a large-scale MDD sample (n = 93) and healthy subject sample (n = 69) with Beck depression inventory-II (BDI-II), Beck hopelessness scale (BHS), childhood traumatic questionnaire-Short Form (CTQ-SF), and the Zimbardo time perspective inventory (ZTPI). The MDD patients reported more childhood trauma experiences, and were featured by abnormal time perspectives on past and future when compared to healthy control. By applying two alternative mediation models, we observed that the time perspective acted as a mediator between childhood trauma and depressive symptom severity, rather than as a consequence of depressive symptom. Furthermore, this abnormal time perspective was a risk factor to MDD, as the childhood trauma only mediated the time perspective in MDD. Finally, we showed that time perspective was a long-term personal trait and unchanged after the remission of depression symptoms under five-day transcranial magnetic stimulation. Abnormal time perspective mediates the impact of early childhood trauma on depressive symptomatology. Besides better understanding of the temporal basis of depressive symptoms, we highlight the importance of preventive time perspective therapy in subjects with childhood trauma. [ABSTRACT FROM AUTHOR]

Abstract: The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero- and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear. In order to investigate these, a well-established fMRI task targeting interoceptive awareness (heartbeat counting) and exteroceptive awareness (tone counting) was combined with magnetic resonance spectroscopy (MRS). Controlling for physiological noise, neural activity in the insula during intero- and exteroceptive awareness was confirmed in an independent data sample using the same fMRI design. Focussing on MRS values from the left insula and combining them with neural activity during intero- and exteroceptive awareness in the same healthy individuals, we demonstrated that GABA concentration in a region highly involved in interoceptive processing is correlated with neural responses to interoceptive stimuli, as opposed to exteroceptive stimuli. In addition, both GABA and interoceptive signal changes in the insula predicted the degree of depressed affect, as measured by the Beck Hopelessness Scale. On the one hand, the association between GABA concentration and neural activity during interoceptive awareness provides novel insight into the biochemical underpinnings of insula function and interoception. On the other, through the additional association of both GABA and neural activity during interoception with depressed affect, these data also bear potentially important implications for psychiatric disorders like depression and anxiety, where GABAergic deficits, altered insula function and abnormal affect coincide. [Copyright &y& Elsevier]

Abstract: Imaging studies investigating the default-mode network (DMN) of the brain revealed the phenomenon of elevated neural responses during periods of rest. This effect has been shown to be abnormally elevated in regions of the DMN concerning mood disorders like major depressive disorder (MDD). Since these disorders are accompanied by impaired emotional functioning, this leads to the suggestion of an association between activity during rest conditions and emotions, which remains to be demonstrated in a healthy and clinical population. Controlling for interoceptive processing, a process often closely connected to emotional functioning, we here demonstrate in an fMRI study of 30 healthy subjects the connection between activity during rest conditions in regions of the DMN and emotions in a psychologically, regionally, and stimulus specific way. Our findings provide further insight into the psychological functions underlying rest activity. Our findings in healthy subjects may also have future implications for a better understanding of mood disorders. [Copyright &y& Elsevier]

Abstract: Major depressive disorder has recently been characterized by abnormal resting state hyperactivity in anterior midline regions. The neurochemical mechanisms underlying resting state hyperactivity remain unclear. Since animal studies provide an opportunity to investigate subcortical regions and neurochemical mechanisms in more detail, we used a cross-species translational approach comparing a meta-analysis of human data to animal data on the functional anatomy and neurochemical modulation of resting state activity in depression. Animal and human data converged in showing resting state hyperactivity in various ventral midline regions. These were also characterized by abnormal concentrations of glutamate and γ-aminobutyric acid (GABA) as well as by NMDA receptor up-regulation and AMPA and GABA receptor down-regulation. This cross-species translational investigation suggests that resting state hyperactivity in depression occurs in subcortical and cortical midline regions and is mediated by glutamate and GABA metabolism. This provides insight into the biochemical underpinnings of resting state activity in both depressed and healthy subjects. [Copyright &y& Elsevier]

Abstract: Objective: The Beck Depression Inventory (BDI) is probably the most widely used depression scale. It has been suggested that it contains a two-factor structure measuring cognitive-affective (i.e. psychological) and somatic-vegetative depressive symptoms. In this study we aim to evaluate these factors by probing for their neural correlates. Methods: Neural responses evoked by emotional perception, relative to an emotional judgment task, were measured using functional magnetic resonance imaging (fMRI) in 20 medication-free patients with severe MDD. Psychological and somatic-vegetative symptoms were evaluated with the BDI. Results: Psychological symptoms correlated with signal changes in the dorsomedial and right ventrolateral prefrontal cortex, while somatic-vegetative symptoms correlated with signal changes in the pre-genual anterior cingulate cortex. Conclusions: These preliminary findings demonstrate segregated neural representation of psychological and somatic-vegetative symptoms of MDD in different cortical regions. Thus, our results indicate that the two-factor structure of the BDI is related to distinct neural correlates. [Copyright &y& Elsevier]

• The self is the fundamental core of our mental life. • The self is the psychological counterpart of the default mode functionality of the brain. • The self serves as "psychological baseline" for its inner thoughts and cognition. • Self, ruminative thought, spontaneous mindwandering and depressive symptoms are closely related. • The self's ruminative spontaneous thought act as a "magnet" exacerbating depression symptoms. Self-consciousness is neuronally associated with the brain's default mode network as its "neuronal baseline" while, psychologically the self is characterized by different thought modes and dynamics. We here raise the question whether they reflect the "psychological baseline" of the self. We investigate the psychological relationship of the self with thought modes (rumination, reflection) and mind-wandering dynamics (spontaneous, deliberate), as well as with depressive symptomatology. Our findings show a relationship between self-consciousness and i) mind-wandering dynamics, and ii) thought functional modes, in their respective forms. At the same time, self-consciousness is more related to spontaneous mind-wandering than deliberate and to rumination than reflection. Furthermore, iii) rumination acts as a mediator between self-consciousness and spontaneous mind-wandering dynamics; and iv) the relationship between high levels of self-consciousness and depressive symptoms is mediated by ruminative modes and spontaneous mind-wandering dynamics. Together, these findings support the view of the self as "psychological baseline". [ABSTRACT FROM AUTHOR]

Background: Although recent neuroimaging and therapeutic transcranial magnetic cortex stimulation (TMS) studies suggest imbalance between left and right dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD) the fundamental neuropsychological characterization of left DLPFC hypoactivity and right DLPFC hyperactivity in MDD remains poorly understood. Methods: We used event-related functional magnetic resonance imaging (fMRI) to investigate neural activity in left and right DLPFC related to unattended (unexpected) and attended (expected) judgment of emotions. Participating in the study were 20 medication-free patients with MDD and 30 healthy subjects. Results: The MDD patients showed hypoactivity in the left DLPFC during both unattended and attended emotional judgment and hyperactivity in the right DLPFC during attended emotional judgment. In contrast to healthy subjects, left DLPFC activity during emotional judgment was not parametrically modulated by negative emotional valence and was inversely modulated by positive emotional valence in MDD patients. Hyperactivity in the right DLPFC correlated with depression severity. Conclusions: Results demonstrate that left DLPFC hypoactivity is associated with negative emotional judgment rather than with emotional perception or attention while right DLPFC hyperactivity is linked to attentional modulation. Left–right DLPFC imbalance is characterized in neuropsychological regard, which bridges the gap from resting metabolism and therapeutic repetitive transcranial magnetic stimulation effects to functional neuroanatomy of altered emotional–cognitive interaction in MDD. [Copyright &y& Elsevier]

Abstract: Repetitive transcranial magnetic stimulation (rTMS) holds promise as a therapeutic tool in major depression. However, a means to assess the effects of a single rTMS session on mood to guide subsequent sessions would be desirable. The present study examined the effects of a single rTMS session on an affective go/no-go task known to measure emotional–cognitive deficits associated with major depression. Ten patients with an acute episode of unipolar major depression and eight partially or completely remitted (improved) patients underwent 1 Hz rTMS over the left and right dorsolateral prefrontal cortex prior to task performance. TMS over the mesial occipital cortex was used as a control. We observed significantly improved performance in depressed patients following right prefrontal rTMS. This beneficial effect declined with decreasing depression severity and tended to reverse in the improved group. Left prefrontal rTMS had no significant effect in the depressed group, but it resulted in impaired task performance in the improved group. Our findings indicate that the acute response of depressed patients to rTMS varies with the stimulation site and depression severity. Further studies are needed to determine whether the present paradigm could be used to predict antidepressant treatment success or to individualize stimulation parameters according to specific pathology. [Copyright &y& Elsevier]