Since the “Decade of the Brain,” neuroscientists and clinical psychologists have been particularly interested in understanding how the brain contributes to psychopathology (commonly referred to as mental illness or mental disorder). However, despite all the resources poured into pursuing questions along these lines, there is little overlap in research findings between studies; it remains difficult to effectively translate neuroscience research into clinical practice, arguably the ultimate goal in studying the brain basis of psychopathology. One reason for these limitations may be that the predominant neuroscientific framework used to study the influence of the brain on these complicated clinical phenomena largely do not align with how the brain actually contributes to behavior, including psychopathology.
The brain is organized in multiple levels, which I will refer to as parcel, network, and global levels. The parcel level is comprised of specific brain regions that have their own anatomical and functional boundaries. Two common parcels studied in psychopathology research are the amygdala and prefrontal cortex given their roles in coordinating specific emotional and cognitive processes, such as identifying threatening stimuli and inhibiting an impulse, respectively. Moving up a step, the network level consists of different sets of parcels that typically co-activate together. Common networks studied in psychopathology research include, among many others, the salience network and executive network, also given their roles in emotion and cognition (albeit at a larger scale). For example, the salience network organizes the behavioral response to stress and the executive network integrates different cognitive processes to promote some behavior. The global level reflects interactions among all the different networks and parcels. When studying the global level and its relation to psychopathology, researchers are often interested in properties of the brain like efficiency (how well information can travel throughout the brain), modularity (how well the brain can be split into different subnetworks while maintaining integrity), or all possible interactions among levels. The brain, then, is organized in a hierarchical fashion. The global level subsumes the network level, which subsumes the parcel level. As they relate to complex behavior like psychopathology, each level is necessary and neither level in isolation is sufficient.
How, then, does the brain and its complex organization contribute to psychopathology? It is often assumed that the parcel level carries the most weight in influencing behavior given specific brain regions affect specific behaviors. For example, the prefrontal cortex largely contributes to cognitive functions like being able to inhibit some response, whereas the amygdala is important in functions like detecting emotional stimuli. Damage to these parcels is reflected in observable changes in their accompanying behaviors. However, damage to these parcels doesn’t completely prevent someone from engaging in some behavior or impact all cognitive or emotional functions, suggesting other parcels are picking up some of the slack.
This recognition has been accompanied by the growing appreciation that perhaps it isn’t parcels themselves, but rather the networks they are part of, that primarily influence behavior. Indeed, different networks contribute to different behaviors. For example, the executive network and salience network are involved in a range of cognitive and affective functions, respectively. Distributed-but-interconnected parcels being involved in shared and unique behavior allows the brain (and its owner) to flexibly adapt to changing environments. There is also evidence that the global brain properties are critical for behavior above and beyond the network level. Global brain organization constrains other levels, so if the brain is not efficient or cannot delegate different tasks to different networks, behavior will be affected. In this sense, their hierarchical organization of the brain discussed above is critical for manifesting complex day-to-day behaviors.
To date, the neuroscientific framework most commonly used by clinical scientists interested in the neural basis of psychopathology has been to focus on interactions among specific parcels of the brain. While this framework has proved useful for understanding specific, isolated behaviors like emotion detection, it does not align with how the brain is organized and contributes to complex, multidimensional behavior like psychopathology. To see just how quickly the current brain-behavior framework (that is, a framework focusing on interactions at the parcel level) falls apart when considering a complex behavior like a symptom of some psychopathology, let us consider a theoretical example.
The neural basis of anxiety disorders, a class of mental disorders characterized in large part by uncontrollable worry or fear, is often attributed to interactions between two specific parcels, the prefrontal cortex and the amygdala. This attribution is defended by the experimentally-supported idea that the amygdala contributes to the expression of fear/worry and the prefrontal cortex inhibits this amygdala-mediated response in situations where fear/worry is not adaptive. It follows, then, that anxiety disorders may result in part from reduced communication between the two regions (that is, the prefrontal cortex is less able to inhibit amygdala-dependent fear/worry). However, it is unlikely that fear/worry and amygdala-prefrontal interactions occur in isolation from other neural and psychological processes. An individual might only begin to experience fear or worry when they notice their heart rate speed up or palms begin to sweat, the perception of which is mediated by another brain region not incorporated in traditional brain models of anxiety, the insula. These signals might then integrate with other percepts in the sensorimotor cortex to promote fight-or-flight behavior. If individual circuits and regions cannot adequately explain specific symptoms, how could they explain entire psychopathologies?
In this example, the single symptom of fear/worry is regulated by five different parcels spanning at least three different networks. But anxiety is not just fear and worry. To meet clinical criteria to be diagnosed with Generalized Anxiety Disorder, you must find it difficult to control the worry. Plus, you must have at least three more symptoms from a laundry list of options: restlessness or feeling keyed up, being fatigued easily, trouble concentrating, irritability, muscle tension, sleep difficulties. Very quickly, it becomes clear that one would realistically need more than the two parcels (amygdala and prefrontal cortex), and the two networks they’re a part of, to understand how the brain contributes to psychopathology. One would also need more than one level of brain organization to understand these behaviors. To better elucidate brain-behavior relationships, then, a framework that considers the brain as a hierarchically organized interacting feedback system may be poised to advance research and the translation of neuroscience to clinical practice.
Understanding and characterizing how the brain relates to psychopathology will require a different outlook on how the brain contributes to complex behaviors and how the socioecological factors (for example, socioeconomic status or trauma exposure) influence brain organization. Future research will need to integrate theories and frameworks from clinical neuroscience with diverse fields, including developmental, social, and cognitive psychology, to incorporate contextual factors into our brain-behavior models.
Focusing on the contributions of individuals parcels will only take our developmental models of psychopathology so far and I believe we have about reached its limit. As technology and conceptualizations of mental disorders continue to evolve and advance, so too must our assumptions about the brain and behavior. Instead of considering how isolated brain regions relate to complicated, multidimensional behaviors, particularly psychopathology, perhaps clinical neuroscience should shift towards treating the brain as what it is – a hierarchically-organized complex system.
Edited by Joe Vuletich and Taylor Woodward
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