Notes from AN INTEGRATIVE THEORY OF PREFRONTAL CORTEX FUNCTION

My notes from: AN INTEGRATIVE THEORY OF PREFRONTAL CORTEX FUNCTION (41 pages)

Earl K. Miller, Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center and Department of Brain and Cognitive Sciences, MIT.
Jonathan D. Cohen, Center for the Study of Brain, Mind, and Behavior and Department of Psychology, Princeton

Abstract ... cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task.

INTRODUCTION ...
Simple behaviors can rely on relatively straightforward interactions between the brain’s input and output systems. Animals with fewer than a hundred thousand neurons (in the human brain there are 100 billion or more neurons) can approach food and avoid predators. For animals with larger brains, behavior is more flexible. ...
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To deal with this multitude of possibilities and to curtail confusion, we have evolved mechanisms that coordinate lower-level sensory and motor processes along a common theme, an internal goal.
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It is well positioned to coordinate a wide range of neural processes: The PFC is a collection of interconnected neocortical areas that sends and receives projections from virtually all cortical sensory systems, motor systems, and many subcortical structures. ...

The Role of the PFC in Top-Down Control of Behavior
The PFC is not critical for performing simple, automatic behaviors, such as our tendency to automatically orient to an unexpected sound or movement. These behaviors can be innate or they can develop gradually with experience as learning mechanisms potentiate existing pathways or form new ones. These “hardwired” pathways are advantageous because they allow highly familiar behaviors to be executed quickly and automatically (i.e. without demanding attention). However,these behaviors are inflexible, stereotyped reactions elicited by just the right stimulus. They do not generalize well to novel situations, and they take extensive time and experience to develop. These sorts of automatic behaviors can be thought of as relying primarily on “bottom-up” processing; that is, they are determined largely by the nature of the sensory stimuli and well-established neural pathways that connect these with corresponding responses.

By contrast, thePFC is important when “top-down” processing is needed; that is, when behavior must be guided by internal states or intentions. The PFC is critical in situations when the mappings between sensory inputs, thoughts, and actions either are weakly established relative to other existing ones or are rapidly changing. This is when we need to use the “rules of the game,” internal representations of goals and the means to achieve them. Several investigators have argued that this is a cardinal function of the PFC...
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This illustrates one of the most fundamental aspects of cognitive control and goal-directed behavior: the ability to select a weaker, task-relevant response (or source of information) in the face of competition from an otherwise stronger, but task-irrelevant one. Patients with frontal impairment have difficulty with this task... ...
Overview of the Theory
We assume that the PFC serves a specific function in cognitive control: the active maintenance of patterns of activity that represent goals and the means to achieve them. They provide bias signals throughout much of the rest of the brain, affecting not only visual processes but also other sensory modalities, as well as systems responsible for response execution, memory retrieval, emotional evaluation, etc.

The aggregate effect of these bias signals is to guide the flow of neural activity along pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. This is especially important whenever stimuli are ambiguous (i.e. they activate more than one input representation), or when multiple responses are possible and the task-appropriate response must compete with stronger alternatives. From this perspective, the constellation of PFC biases...can be viewed as the neural implementation of attentional templates, rules, or goals, depending on the target of their biasing influence.
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When a behavior meets with success, reinforcement signals augment the corresponding pattern of activity by strengthening connections between the PFC neurons activated by that behavior. This process also strengthens connections between these neurons and those whose activity represents the situation in which the behavior was useful, establishing an association between these circumstances and the PFC pattern that supports the correct behavior.
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But we believe that this general notion can explain many of the posited functions of the PFC. The biasing influence of PFC feedback signals on sensory systems may mediate its role in directing attention (Stuss &
Benson 1986; Knight 1984, 1997; Banich et al 2000), signals to the motor system may be responsible for response selection and inhibitory control (Fuster 1980, Diamond 1988), and signals to intermediate systems may support short-term (or working) memory (Goldman-Rakic 1987) and guide retrieval from long-term memory (Schachter 1997, Janowsky et al 1989, Gershberg & Shimamura 1995).

Without the PFC, the most frequently used (and thus best established) neural pathways would predominate or, where these don’t exist, behavior would be haphazard. Such impulsive, inappropriate, or disorganized behavior is a hallmark of PFC dysfunction in humans (e.g. Bianchi 1922, Duncan 1986, Luria 1969, Lhermitte 1983, Shallice & Burgess 1996, Stuss & Benson 1986).

Minimal Requirements for a Mechanism of Top-Down Control
There are several critical features of our theory. First, the PFC must provide a source of activity that can exert the required pattern of biasing signals to other structures. We can thus think of PFC function as “active memory in the service of control.” It follows, therefore, that the PFC must maintain its activity robustly against distractions until a goal is achieved, yet also be flexible enough to update its representations when needed. It must also house the appropriate representations, those that can select the neural pathways needed for the task. In sofar as primates are capable of tasks that involve diverse combinations of stimuli, internal states, and responses, representations in the PFC must have access to and be able to influence a similarly wide range of information in other brain regions. That is, PFC representations must have a high capacity for multimodality and integration. Finally, as we can acquire new goals and means, the PFC must also exhibit a high degree of plasticity. Of course, it must be possible to exhibit all these properties without the need to invoke some other mechanism of control to explain them, lest our theory be subject to perennial concerns of a hidden “homunculus.”
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pattern of deficits following PFC damage as a loss of the ability to acquire and use behavior-guiding rules. ...
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A GUIDED ACTIVATION THEORY OF PFC FUNCTION ...
A Simple Model of PFC Function ...
Guided Activation as a Mechanism of Cognitive Control
...the role of the PFC is modulatory rather than transmissive. That is, the pathway from input to output does not “run through” the PFC. Instead, the PFC guides activity flow along task-relevant pathways in more posterior and/or subcortical areas.
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This distinction between modulation vs transmission is consistent with the classic pattern of neuropsychological deficits associated with frontal lobe damage. The components of a complex behavior are usually left intact, but the subject is not able to coordinate them in a task-appropriate way (for example, a patient who, when preparing coffee, first stirred and then added cream). ...

Active Maintenance in the Service of Control...
another critical feature of our theory: the importance of sustained activity as a mechanism of control...
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executive control involves the active maintenance of a particular type of information: the goals and rules of a task.
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selective attention and behavioral inhibition are two sides of the same coin: Attention is the effect of biasing competition in favor of task-relevant information, and inhibition is the consequence that this has for the irrelevant information.
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In particular, we believe that PFC-mediated control is complemented by another form of control dependent on the hippocampal system. The hippocampus is important for binding together information into a memory of a specific episode (Eichenbaum et al 1999, McClelland et al 1995, Squire 1992, Zola-Morgan & Squire 1993). By contrast, we suggest that the PFC, like other neocortical areas, is more important for extracting the regularities across episodes—in the case of the PFC, those corresponding to goals and task rules, rather than episodic memories of actually performing the task. We further posit that the PFC uses “activity-based” control; that is, its ongoing activity specifies the pattern of neural pathways that are currently needed. If PFC activity changes, so does the selected pattern of pathways.

By contrast, the hippocampus may provide a form of “weighted-based” control; it helps consolidate permanent associative links between the pieces of information that define a long-term memory (Cohen & O’Reilly 1996, O’Reilly et al 1999, O’Reilly 2000). To use the railroad metaphor, the hippocampus is responsible for laying down new tracks and the PFC is responsible for flexibly switching between them. As noted below, interactions between the PFC and the hippocampus may provide a basis for understanding prospective forms of control, such as planning.

Updating of PFC Representations
In the real world, cognitive control is highly dynamic...is highly flexible. So long as suitable representations exist within the PFC, activating them can quickly invoke a goal or rule, which can be flexibly switched to others as circumstances demand. That is, it is easier and faster (and perhaps less costly) to switch between existing tracks than it is to lay new ones down.
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PFC representations are selectively responsive (adaptive) to task-relevant stimuli (Rainer et al 1998b), yet they are resistant to interference (robust) from distractors (Miller et al 1996). Conversely, two hallmarks of damage to the PFC are perseveration (inadequate updating) and increased distractibility (inappropriate updating)
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Recent modeling work suggests that hierarchical updating and the sequencing of actions may rely on interactions between the PFC and the basal ganglia.