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