Theoretical Model

The following provides a scientific explanation behind Dr. Langenecker's theoretical resarch model.

Salience/Valence Processing and Executive Control Model of Depression. There appears to be a dynamic interplay between resources devoted to emotion processing and to those devoted towards cognitive problem solving and control. There is a dorso-lateral fronto-parietal network (the Problem Solving and Control Circuit, PSCC) that is important for executive functioning processes, which includes inhibitory control. A distinct, medial fronto-subcortical-temporal circuit is devoted towards classifying and processing emotional, salient, or novel stimuli, further divided into Approach (AppC) and Avoidance (AvC) circuits [108-110].

Salience and Valence Circuits. Models of the purpose and function of the limbic system include the concepts of salience and valence processing [108]. In some sense, emotion has once again been relegated to an epiphenomenon describing the individual experience and intimating the scope of response contingencies present to the individual (e.g., fear = freezing or flight). The limbic system determines the salience of a stimulus or situation to the organism, and depending upon the relevance and intensity of the stimulus, and the valence, appropriate response contingencies are recalled from short and long term memory [111]. After the valence of a stimulus is determined, approach and/or avoidance specific responses are prepared [72;112]. While avoidance and approach circuits traverse through similar brain regions, they are distinct processing streams [108;113] within the limbic system [114-116]. Frontal circuits modulate limbic circuits and engage in self-direction and problem-solving.

Avoidance Circuit. This circuit is primarily comprised of ventral and lateral amygdala structures and orbito-frontal cortex, and is likely related to serotonin and/or norepinephrine dys/function. The posterior aspect of the nucleus accumbens may be more responsive to negative stimuli [113]. The avoidance circuit (AvC) is a rapid response circuit with low signal discrimination ability [48;49;117;118] that relies on preprogrammed response contingencies (e.g., memory and procedural escape/avoidance strategies). A large, unrestrained carnivore in close proximity would powerfully engage the AvC and divert attention and resources away from other circuits (e.g., AppC and PSCC) [47;49;69;119-126].

Approach Circuit. A primary disruption in the neural systems supporting the approach circuit (AppC) can result in anhedonia, which may include anergia, abulia and psychomotor retardation. These symptoms are typified in melancholic depression [31;73;127-129] [82;129;130]. Existing activation, lesion, and animal studies suggest that the approach circuit (AppC) may be comprised of subcortical areas such as the nucleus accumbens, ventral pallidum and basal ganglia, and may be related to dopamine dys/function [113;131;132]. There is some debate about whether under-activation in this circuit results in left frontal hypometabolism [133;134]. This system has been assessed using positive emotion-laden stimuli and providing the context for reward anticipation [98;111;135-137]. The AppC circuit is also a fairly rapid response circuit, with low signal discrimination ability (e.g., black/white discrimination), which relies largely on “preprogrammed” response contingencies. This circuit is a subordinate circuit in strength to the AvC and is slightly slower [137]. This circuit may engage in exploration, whereby novelty, and or reward anticipation might play prominent roles unless it is suppressed by the AvC or PSCC [111;138].

Problem Solving and Control Circuit. One of the primary roles of the prefrontal cortex is to sort out response contingencies based upon prior knowledge, including expectations and computations from cost-benefit analyses. The effectiveness of this circuit is limited by time-to-decision and preprogrammed genetic response contingencies. The prefrontal cortex has been subdivided based upon the interconnectivity with five fronto-subcortical circuits[139;140]. The circuits thought to be relevant to depression include the dorsal anterior cingulate-dorsal prefrontal circuit (PSCC), and the ventral cingulate-medial prefrontal circuit [141]. Damage to these areas often reveal the types of behavior/emotion expression that were previously better regulated [142-146]. The PSCC is much slower in processing information compared to the more primitive circuits which it controls, has high signal-discriminability, and in ideal situations, is capable of balancing current goals with past memories of similar experiences and future expectations [123;147;148].

Neural basis of the PSCC using Stroop Interference and Response Inhibition. Thirty-eight healthy younger adults were recruited for performance of a GNG test (10, [6]), a revised GNG test (10, see [8], and a manual-response, computer-based Stroop Interference Test (18,[7, 237]. Event-related analysis was conducted for both GNG groups, whereby functional activation related to response inhibition was assessed. Two separate conjunction analyses were conducted for the Stroop Interference test; Incongruent-Congruent and Incongruent-Neutral. As such, 56 functional datasets were tested with the null hypothesis of no activation change during response inhibition or interference resolution. Each of these tasks share a common inhibitory control component that, when combined into one omnibus analysis, illustrates the functional architecture of cortical, “top-down” cognitive and behavioral inhibition. Results support a bilateral, distributed fronto-parietal, dorso-lateral circuit that is active during successful response inhibition [3, 6-8, 237, 238]. As data were analyzed differently for each study (eg, GNG = event-related, Stroop = block design), individual datasets were converted to Z-scores based upon the mean and standard deviation of activation for each individual in the condition or comparison of interest. What emerged from this omnibus analysis is a nicely delineated cortical circuit for the PSCC (purple and blue). Additionally deactivation was observed in structures identified as part of the AvC and AppC (orange). PSCC activation during response inhibition/interference resolution results in reciprocal deactivation in the AvC and AppC.