Beyond Antidepressants Plasticity Bayesian Brain Emergence

Abraham Peled M.D.

SSRI are known to be antidepressants and they receive their names from their receptor-level activity. Such activity happens in 8 hours but the antidepressant effect takes 6 weeks;

Thus, their antidepressant effect is probably related to the events that take 6 weeks after the serotoninergic receptor blockade the second neurotransmitter activity

And the ensuing plasticity effect, plasticity being synaptogenetic activity as in Figure 3

Plasticity is not just a random activity it is guided by the Hebbian law, fire together wire together.

This mechanism spans multiple levels of brain activity for example fast ‘chemical’ neuronal interactions as in Figure 5

Or even structural permanent connections actually shaping connectivity morphology in the brain. As in figure 6

Off course these changes have their underlying molecular-level machinery shown in Figure 7

The BIG QUESTION is how plasticity relates to MOOD to understand this we need to surpass the molecular neural level and understand global brain network dynamics. As mood is an emergent phenomenon from whole-brain dynamic optimization. Let as look at a simple schematic fully connected network as in Figure 8

We can describe the changing neuronal activity in the network as states, and the dynamics of the network as a sate-space trajectory. Figure 9?represents a state of the system as a point in a space representing all possible stated that the system can potentially assume?

Figures 10 to 12 show the dynamics possible by such a network model

Figure 13 shows how by strengthening connection you can embed information in the network model. One neuronal ensemble can represent a banana (the ensemble activated) another (non activated) can represent an apple and so on.?Thus, the process of strengthening connections embed (Learning) information (memories) in the network.

Once a memory is embedded into the model it creates an ‘attractor’ because the system is attracted to that representative state of the system, attraction is presented by a deformation of the space of the system with attractors as Bayesians and propellors a peaks, Figure 14

One can see that similar states are close to each other and different states are far away from each other. In total entire sets of information memories and experiences are embedded in a configurational map of state -space of the brain Figure 15

Experience is naturally embedded in the brain by internal representations of past memories. The internal representations are updated from interactions with the events in the environment. The internal representations act as predictions made by past experiences and updated by changing current events see figure 16

Evidence shapes our prior beliefs into posterior beliefs based on evidence Figure 17

The predictive brain also called the Baysan Brain acts to predict signal from reality by correcting errors. This translates to the level of brain tissue by predicting neuronal firing patterns ascending neuronal networks at the tisuue level Figure 18 and the anatomical circuits Figure 19

The Bayesian brain continually predicts and represents the world experience to minimalize the differences (Delta) called FREE ENERGY this is done using both mechanism one operating in the environment to minimize the differences between what is represented and what actually happens in the real world the other mechanism is adapting the internal representations to what is actually occurring using updates of memories and adjustments to internal representations See Figures 20 to 22

Figure 23 schematizes what OPTIMIZATION and DEOPTIMIZATIONS are. The whole brain dynamics that optimizes internal representations and minimizes free energy has an emergence property that is mood elevating and antidepressant on the opposite end, the increase of Free energy and the deoptimization of internal representations compared to environmental occurrences has the emergence property of Depressed mood.

Now we can appreciate the connection between plasticity and mood since the environment is highly changing and fluctuating (Figure 24) an effective brain that is highly plastic can effectively adapt and reduce free energy (delta) thus maintaining good mood and avoiding depression once the brain is not plastic enough such as in Dementia the free energy increases deoptimization dynamics tale hold and depression manifests.

Oscillations can happen between optimization and deoptimization dynamics resulting in bipolar disorders.

As recently discovered it seems that the dynamics of a beadsman brain is governed by the Salient network manipulating the Central Executive Network and the Default Mode Network to this end see Figure 26?