Differential Intrinsic Coupling Modes in Psychological and Physical Trauma

摘要

Introduction Despite each disorder having a distinct etiology, post-traumatic stress disorder (PTSD), and mild traumatic brain injury (mTBI) often exhibit overlapping symptomatology that makes clinical diagnosis difficult. Furthermore, identification using structural imaging is impractical because anatomical alterations, if they exist at all, can be subtle, or lie beyond the resolution of current technology. Functional MRI, which relies on an indirect measure of brain function (that of blood hemodynamics), has revealed that aberrant functional connectivity (FC) is prevalent in these disorders ( 1 , 2 ), and machine learning/pattern classification shows promise that these injuries can be objectively classified on certain feature parameters within the spontaneous fluctuations of these signals ( 3 ). Although these analyses could potentially aid diagnosis, theories of how these disorders impact underlying neurophysiological interactions and neural network function remain scant. Generating the questions driving answers to this knowledge gap, basic neuroscience research is increasingly revealing the critical role that neurophysiological networks and their dynamics play in cognition and behavior ( 4 ). From a philosophical viewpoint, there has been a Kuhnian epistemological paradigm shift from a reductionist, and historically segregative approach toward, or at least combined with, an integrative neural doctrine ( 5 ). In other words, ontological standpoints are being driven by neuroscience moving toward the view that mental states are the population-level interactions of neurons, rather than simply the activity of “independent” neurophysiological units; the emergent properties of these networks ultimately give rise to our inner mental life. Understanding how perturbations to these networks results in psychiatric and neurological disorders will be crucial in future explanations, and ultimately the efficacy of diagnostics, intervention, and prognostication. In this short opinion piece, I discuss some of the Taylor and Pang laboratory’s recent exploratory studies using resting-state paradigms with magnetoencephalography (MEG) that have investigated FC and spontaneous networks in two groups of these patients by examining “intrinsic coupling modes” [ICMs ( 6 )]. These putative types of network interactions comprise distinct mechanisms that facilitate the spatiotemporal organization of ongoing and spontaneous brain activity that defines our psychological state (these modes also subserve goal-directed action, but this is outside the scope of the current piece). I will describe the phenomenology of discrete neurophysiological connectivity profiles evident in the specific cohorts we tested with these disorders, and how they differ in subtle but important ways as well as theorize on the underlying alterations to connectivity that drive these macroscopic markers of disease. Coincidence of Symptomatology in Psychological and Physical Trauma Psychological and physical trauma can give rise to severe psychiatric (PTSD) and neurological (mTBI) disorders that severely affect a patient’s quality of life and impart a huge burden on a healthcare system. These disorders are defined by symptomatology that is often distinct, but in some cases, at the interface between these conditions, overlapping features occur that makes diagnosis difficult for clinicians. A non-exhaustive list of coincident symptoms includes anxiety, depression, cognitive deficits (including attention, memory, and cognitive control), irritability, and insomnia (Figure 1 A). Compounding the difficulty of this differentiation is that physical trauma can often lead to PTSD, or mTBI, or a combination of the two; this is especially prevalent in the military. Correct diagnosis is important due to differences in treatment required for these disorders, and this is where delineation based on profiles of brain FC is starting to show promise in both health science and objective assessment. Before the findings are described, I will first explain the types of ICMs [for an in-depth review, see Ref. ( 6 )]. Figure 1 (A) Interface of PTSD and mTBI symptomatology, and empirical evidence of altered spontaneous functional connectivity patterns in a resting-state paradigm. Both patient groups show elevated connectivity compared to their respective control groups, with increased coupling in PTSD mediated by high-frequency (high gamma-range, 80–150?Hz) oscillatory synchronization; in the mTBI group connectivity is enhanced in the low-frequency range (delta–theta range, 1–3 and 3–7?Hz), and is typified by envelope amplitude cross-correlations/temporal covariations. (B) Hypothesized role of coupled oscillators in interregional brain communication, and the distinct mechanisms of “intrinsic coupling modes.” These are divided into phase ICMs (facilitating communication between regions 1 and 2, described in I), and envelope ICMs (regulating temporally coordinated activity between regions 2 an