Neurological basis for the feeling of meaning

After coming up with these two theories of what I think the feeling of meaning or purpose is, the neuronal basis of the feeling was still unclear to me. I thought it might be a different mechanism than reward prediction (dopamine), or at least a different neurotransmitter, which causes a "rush of meaning" rather than the more hedonic "dopamine rush". However, I now think it may be much simpler, and reading more about dopamine (mainly Getting Formal with Dopamine and Reward (Wolfram Schultz, 2002). Pretty much all the basic claims below are from that paper) really convinced me: Both are dopamine, but in different brain regions!

Dopaminergic pathways

(What is a dopaminergic pathway? A bunch of axons which send electrical signals from area A to B and release dopamine in B (the cell bodies are in A, their axonal projections go all the way to B))

The brain uses dopamine in different ways. Dopamine release in one area will not do the same thing as dopamine release in another area. The following dopaminergic pathways exist, ordered from most boring to most interesting:  

• The retina has some neurons which release dopamine, indicating contrast. We do not conscioussly observe dopamine release here, so probably no meaning-making happens in the eyes. 
• Hypothalamus --> pituitory gland: Some of the neuronal cell bodies in the hypothalamus project their axons into the pituitory gland and release dopamine there. Here,  dopamine inhibits prolactine release (prolactine causes milk production and the sexual refractory period). We also cannot consciously feel the dopamine release in the pituitory gland. 
• Nigrostriatal pathway (substantia nigra --> dorsal striatum (basal ganglia): Reduced number of dopamine-releasing neurons in the substantia nigra are what causes pakinsons. Symptoms include difficulty initiating motor tasks. Motor control is one of the jobs of the basal ganglia. The basal ganglia do not make any consciousness though, so probably no meaning is make here either. 
•  Mesolimbic pathway (ventral tegmental area (VTA) --> nucleus accumbens (NA) (NA is in the ventral striatum, which is part of the limbic loop): We do feel the dopamine here! That the limbic system is where emotions are thought to be created, and dopamine here is thought to cause the classic feeling of a dopamine-rush: A rush of motivation. NA dopamine transmission lesions cause "motivational deficits in approach behavior, reward-directed learning, and attentional responses" 
• Mesocortical pathway (VTA --> prefrontal cortex (PFC)): The same area whose neurons release dopamine in the striatum also has neurons which send their electrical signals all the way to the PFC in the very front of the brain. dopamine release here is thought to cause a "sense of priority", "planning the next move" and a "sharpening of thought/clarity", which is quite similar to the Mesolimbic pathway (or maybe we just haven't figured out the differences too well). 

Now the Mesocortical pathway is really interesting because the PFC is the area where top-down planning happens according the amount of subjective value which things and actions hold for the subject. This is in contrast to the primary cortical areas, which process low-level inputs (eg. for vision: detect the angles and locations of edges etc.) or outputs (motor commands). One can see the PFC as the most high-level motor planning area: Signals from here make their way to the secondary motor cortex, the motor cortex and finally the spinal cord and muscles, and on their way there, they become more and more concrete. So that sounds to me like dopamine in the PFC is a pretty good candidate for a neural meaning-making mechanism! I should also add that in schizophrenia (specifically acute psychosis) dopamine levels are thought to be too high (or at least interpreted as too high), and I am guessing the PFC-part of this pathology is exactly what causes a schizophrenic's finding of deep meaning in even the most mundane things. 

So I think the situation is this: Low dopamine in the basal ganglia causes incapability to initiate movement. Low dopamine in the limbic system causes low motivation. Low dopamine in the PFC causes lack of meaning. They all are the same thing, namely motivation. Just on different timescales (ordered from fast to slow). Maybe this could roughly correspond to the following division: 

 Timescales of dopamine

• Fast (100-300ms): This is the time it takes dopamine to act as a reinforcement-learning teaching signal. 
• Medium (seconds/minutes): In this timescale, it induces goal-oriented behavior like chasing sex, food or other rewards.  
• Tonic: Constantly low levels of dopamine in the dorsal striatum cause movement inhibition, in the cortex they probably cause depression. This is because then, the phasic (more short term) dopamine increases will not increase dopamine levels enough to cause action (which, in combination with the global nature of dopamine releases (see below), probably explains why eating while working helps me focus!)

Dopamine is broadcast

 It is also worth noting that dopamine is released rather globally (it is "broadcast" to everywhere), rather than being targeted at specific neurons at a time. A dopamine rush carries little information about the nature of the event which caused it, just that what happened was a good thing. A hypothesis here is that it is a fast signal which later has to be interpreted by cognitive processing in order to figure out what actually caused the dopamine rush. Emotions might then be generated through the combination of dopamine and the specific "stimulus-attribution" signals. 

 

My argument

The most important observations are:  

• The VTA sends dopaminergic projections to two brain areas, the striatum and the PFC. Both are felt similarly, both feelings have something to do with motivation. The difference seems not clear. 
• If you ask humans, they tend to confuse meaning and happiness, indicating that they feel simlar or are highly correlated (maybe meaning is needed for reward to kick in)
• The PFC encodes extremely high-level concepts (long-term value) 
• Meaning is extremely high-level/long-term version of motivation  
•  Dopamine causes motivation in the ventral striatum, but movement initiation in the dorsal striatum, because the ventral striatum holds more high-level concepts than the dorsal striatum. 
•  Schizophrenia and Depressions are (amongst other things) over and under-regulations of dopamine, and also meaning. 

So I would argue that it seems quite likely that 

1) Motivation is created by dopamine in the ventral striatum

2) Meaning is created by Dopamine release in the PFC.