Elsevier

Journal of Affective Disorders

Volume 190, 15 January 2016, Pages 854-866
Journal of Affective Disorders

Spatiotemporal psychopathology I: No rest for the brain’s resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms

https://doi.org/10.1016/j.jad.2015.05.007Get rights and content

Highlights

  • Various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure.

  • 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.

  • 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

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.

Introduction

Major depressive disorder (MDD) is a complex disturbance showing a wide variety of symptoms that cover most brain functions, including sensorimotor, affective, cognitive, and social functions. For instance, patients with major depressive disorder (MDD) show a wide variety of symptoms: cognitive changes are manifest in ruminations and increased self-focus, affective changes predominate here with anhedonia, sensorimotor changes are manifest in terms of psychomotor agitation or retardation, and social functions are affected in the often observed social withdrawal and isolation.

This suggests a close link between psychopathological symptoms on the one hand and sensorimotor, affective, social, and cognitive functions on the other. For that reason, neuroimaging often focuses on searching the neural correlates underlying the abnormalities in the sensorimotor, affective, cognitive, and social functions. Various kinds of affective, sensorimotor, cognitive, and social tasks are applied to probe abnormal changes in the brain’s extrinsic activity, otherwise known as stimulus-induced or task-evoked activity (see Northoff, 2014a, Northoff, 2014b, Northoff, 2014c, Northoff, 2014d, Raichle, 2009). These studies yielded novel and important insights into the relationship between extrinsic activity and psychopathological symptoms, and has led to what one may wish to describe as cognitive (Frith, 1992, Kahn and Keefe, 2013) and affective (Panksepp, 2004) approaches to psychopathology.

For all the progress in investigating the brain’s extrinsic activity and its various functions, diagnostic or therapeutic markers still remain nevertheless, elusive in both affective and cognitive psychopathology. In its search for these specific markers, recent neuroimaging in psychiatry has shifted to the brain’s intrinsic activity, its so-called resting state activity. Roughly, the brain’s resting state activity describes the brain’s neural activity in the absence of any specific tasks or stimuli (Logothetis et al., 2009). The brain’s intrinsic activity can spatially be characterized by various neural networks consisting of regions showing close functional connectivity thus yielding a particular spatial structure (see below for details). The same applies to the temporal domain, where fluctuations in different frequency ranges are coupled with each other, providing ‘neural synchrony’ (see below). One should be aware, however, that the understanding of the resting state activity’s spatial and temporal structure is in its infancy. It shall be pointed out that the concepts of spatial and temporal structure do not refer to merely anatomical and structural features but rather to physiological and functional features; the resting state’s spatiotemporal structure may therefore not be directly observable as such but rather existing in a virtual (and statistically-based) sense (see Northoff, 2014a, Northoff, 2014c).

Neuroimaging reports a variety of changes in both functional connectivity and neural synchrony (see below) in various psychiatric disorders. Both the origin of the resting state abnormalities, as well as their relevance for yielding psychiatric symptoms such as cognitive deficits, however, remains unclear. Setting aside their origin for future discussion, I argue that spatiotemporal abnormalities in resting state activity lead to abnormal spatiotemporal organization of the various internal and external cognitive contents. This, in turn, produces various cognitive deficits and psychopathological symptoms as they can be observed in MDD.

Without conducting a thorough literature review, this will be paradigmatically illustrated by linking cognitive symptoms, such as ruminations in depression and thought disorder, to specific spatial and temporal abnormalities in resting state activity as recently reported. I conclude that such a spatiotemporal approach may lead to a novel psychopathological one, namely a spatiotemporal psychopathology to MDD that, unlike its cognitive and affective siblings, may be able to bridge the gap between the brain and psychopathological symptoms. Finally, I will touch upon the potential diagnostic and therapeutic implications of such a spatiotemporal approach to MDD.

Section snippets

Determination of intrinsic activity

How can we determine the brain’s resting state activity? The term resting state is often used interchangeable with the ones intrinsic activity or spontaneous activity. Moreover, one should be aware that the concept of the brain’s intrinsic or resting state activity is a rather heterogenous one and raises methodological and physiological issues (see also Northoff, 2014a, Northoff, 2014c). Resting state activity can be measured in different ways: metabolic investigations using PET focus on

Spatial dysbalance between medial/DMN and lateral/CEN networks in resting state activity

Major depressive disorder (MDD) is a psychiatric disorder that is characterized by extremely negative emotions, suicidal thoughts, hopelessness, diffuse bodily symptoms, lack of pleasure, i.e., anhedonnia, ruminations, and enhanced stress sensitivity (see Hasler and Northoff, 2011 as well as Northoff et al., 2011 for a recent overview and Kuhn and Gallinat, 2013 as well as Northoff, 2014c, Northoff, 2014b, Northoff, 2014c, Northoff, 2014d). We here focus only on MDD while leaving aside bipolar

Temporal dysbalance between slow and fast oscillations in resting state activity

The temporal structure of the resting state activity can be measured using EEG. EEG is predominantly used to measure event-related potentials (ERP) in response to specific stimuli thus targeting stimulus-induced or task-evoked activity. Additionally, EEG can also measure the power in different frequency oscillations including delta (1–4 Hz), theta (5–8 Hz), alpha (8–12 Hz), beta (12–30 Hz), and gamma (30–180 Hz) in resting state as during eyes open and closed. Resting state investigations in MDD

Conclusion: Why do we need “Spatiotemporal Psychopathology”?

How can we characterize the approach taken here? I traced back psychopathological symptoms in MDD (and also in schizophrenia; see Northoff, 2014a, Northoff, 2014c, Northoff, 2015a) to underlying spatial and temporal abnormalities which in turn are supposed to be based on abnormalities in the resting state’s spatial and temporal structure. One may consequently want to speak of what I describe as “Spatiotemporal Psychopathology”. Put in a nutshell (and awaiting future more detailed development),

Acknowledgments

I am thankful to Benedetta Conio, Annemarie Wolf, Francesca Ferri, and Wendy Carter who commented in a very helpful way on prior versions of this paper. I am also grateful to the CIHR No 4566, the ISAN-HDRF No 462, the EJLB-CIHR 05, and the Michael Smith Foundation for their generous financial support.

References (100)

  • M. Ganzetti et al.

    Functional connectivity and oscillatory neuronal activity in the resting human brain

    Neuroscience

    (2013)
  • B.J. He et al.

    The fMRI signal, slow cortical potential and consciousness

    Trends Cogn. Sci.

    (2009)
  • P. Khader et al.

    On the relationship between slow cortical potentials and BOLD signal changes in humans

    Int. J. Psychophysiol.

    (2008)
  • D.-J. Kim et al.

    Disturbed resting state EEG synchronization in bipolar disorder: a graph-theoretic analysis

    NeuroImage: Clin.

    (2013)
  • W. Klimesch

    Alpha-band oscillations, attention, and controlled access to stored information

    Trends Cogn. Sci.

    (2012)
  • T.-W. Lee et al.

    The implication of functional connectivity strength in predicting treatment response of major depressive disorder: a resting EEG study

    Psychiatry Res.: NeuroImaging

    (2011)
  • C. Lemogne et al.

    Medial prefrontal cortex and the self in major depression

    J. Affect. Disord.

    (2012)
  • N.K. Logothetis et al.

    How not to study spontaneous activity

    NeuroImage

    (2009)
  • R. Mahlberg et al.

    Evaluation of time memory in acutely depressed patients, manic patients, and healthy controls using a time reproduction task

    Eur. Psychiatry

    (2008)
  • V. Menon

    Large-scale brain networks and psychopathology: a unifying triple network model

    Trends Cogn. Sci.

    (2011)
  • G. Northoff

    Psychopathology and pathophysiology of the self in depression—neuropsychiatric hypothesis

    J. Affect. Disord.

    (2007)
  • G. Northoff

    Do cortical midline variability and low frequency fluctuations mediate William James’ “Stream of Consciousness”? “Neurophenomenal Balance Hypothesis” of “Inner Time Consciousness

    Conscious Cogn.

    (2014)
  • G. Northoff et al.

    How can the brain’s resting state activity generate hallucinations? A ‘resting state hypothesis’ of auditory verbal hallucinations

    Schizophr. Res.

    (2011)
  • G. Northoff et al.

    The ‘resting-state hypothesis’ of major depressive disorder—a translational subcortical–cortical framework for a system disorder

    Neurosci. Biobehav. Rev.

    (2011)
  • S. Olbrich et al.

    Functional connectivity in major depression: increased phase synchronization between frontal cortical EEG-source estimates

    Psychiatry Res.: NeuroImaging

    (2014)
  • M.E. Raichle

    A brief history of human brain mapping

    Trends Neurosci.

    (2009)
  • P. Sauseng et al.

    What does phase information of oscillatory brain activity tell us about cognitive processes?

    Neurosci. Biobehav. Rev.

    (2008)
  • J. Savitz et al.

    Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide

    Neurosci. Biobehav. Rev.

    (2009)
  • J. Savitz et al.

    Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide

    Neurosci. Biobehav. Rev.

    (2009)
  • J.B. Savitz et al.

    Imaging phenotypes of major depressive disorder: genetic correlates

    Neuroscience

    (2009)
  • G. Stanghellini et al.

    The bodily self: a qualitative study of abnormal bodily phenomena in persons with schizophrenia

    Comprehen. Psychiatry

    (2014)
  • C. Wiebking et al.

    Are emotions associated with activity during rest or interoception? An exploratory fMRI study in healthy subjects

    Neurosci. Lett.

    (2011)
  • C. Wiebking et al.

    GABA in the insula—a predictor of the neural response to interoceptive awareness

    NeuroImage

    (2014)
  • X. Zhu et al.

    Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients

    Biol. Psychiatry

    (2012)
  • X.-N. Zuo et al.

    Reliable intrinsic connectivity networks: test–retest evaluation using ICA and dual regression approach

    NeuroImage

    (2010)
  • A. Abou Elseoud et al.

    Altered resting‐state activity in seasonal affective disorder

    Hum. Brain Mapp.

    (2014)
  • A. Arieli et al.

    Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses

    Science

    (1996)
  • T. Bschor et al.

    Time experience and time judgment in major depression, mania and healthy subjects. A controlled study of 93 subjects

    Acta Psychiatr. Scand.

    (2004)
  • R.L. Buckner et al.

    The brain’s default network: anatomy, function, and relevance to disease

    Ann. N.Y. Acad. Sci.

    (2008)
  • G. Buzsaki

    Rhythms of the Brain

    (2006)
  • G. Buzsaki et al.

    Neuronal oscillations in cortical networks

    Science

    (2004)
  • J. Cabral et al.

    Exploring the network dynamics underlying brain activity during rest

    Prog. Neurobiol.

    (2013)
  • R.L. Carhart-Harris et al.

    Functional connectivity measures after psilocybin inform a novel hypothesis of early psychosis

    Schizophr. Bull.

    (2013)
  • A.C. Chen et al.

    Causal interactions between fronto-parietal central executive and default-mode networks in humans

    Proc. Natl. Acad. Sci. U.S.A.

    (2013)
  • B.N. Cuthbert et al.

    Toward the future of psychiatric diagnosis: the seven pillars of RDoC

    BMC Med.

    (2013)
  • J. Fell et al.

    The role of phase synchronization in memory processes

    Nat. Rev. Neurosci.

    (2011)
  • Fingelkurts, A.A., Fingelkurts, A.A., 2014a. Altered structure of dynamic ‘EEG Oscillatory Pattern’in major depression....
  • A.A. Fingelkurts et al.

    EEG oscillatory states: universality, uniqueness and specificity across healthy-normal, altered and pathological brain conditions

    PLoS One

    (2014)
  • A.A. Fingelkurts et al.

    Impaired functional connectivity at EEG alpha and theta frequency bands in major depression

    Hum. Brain Mapp.

    (2007)
  • P.B. Fitzgerald et al.

    A functional magnetic resonance imaging study of the effects of low frequency right prefrontal transcranial magnetic stimulation in depression

    J. Clin. Psychopharmacol.

    (2007)
  • Cited by (104)

    • Spatiotemporal Psychopathology – An integrated brain-mind approach and catatonia

      2024, Schizophrenia Research
      Citation Excerpt :

      It extends and specifies experience-based approaches by introducing a hierarchical structure of experience with differentiation of its constitution through space-time and manifestation in first-person experience of body, self and world. At the same time, STPP provides a more holistic and thereby more comprehensive framework for function-based approaches as the various functions are now considered within the broader framework of the four-layer hierarchy of space-time, self-world-body, and functions, and symptoms (Northoff, 2016a,b). More precisely, STPP aims to integrate both approaches (phenomenological psychopathology and function-based approach) and also plausibly relate them to aberrant neurobiological processes, i.e.; alterations of respective brain dynamics and topography.

    View all citing articles on Scopus
    View full text