Hebbian Cardiac Remodeling in Cardiac Arrhythmia
paneuro@usa.net / September 25, 2021
Muscle Learning in the heart and muscle.
In 1949 Donald Hebb famously proposed in the book, The Organization of Behavior a revolutionary idea: Activation of pre-synaptic neurons leads to strengthening connections between neurons. This idea immediately gave birth to a physiologic model for learning. Any activation of a neuron that stimulates another neuron, especially recurrent activation, could strengthen connections between them, simply put, neurons that fire together wire together. The strengthening of anatomical and physiological connections between neurons is like hikers beating a path in the woods, making it that much easier for future hikers taking the same trail. This anatomical learning model has been a cornerstone of learning theory now for over 70 years.
One useful application in the brain is Kindling. A recurring abnormal electrical discharge which defines an epileptic seizure, will make it that much easier for more seizures to occur, beating a path in the brain. This argues that early control of epilepsy prevents recurrent seizures.
The heart is a quintessentially electrical organ. Like all striated muscle, the heart is a syncytium which means one cell contains many nuclei. The heart, even more than the brain, works as a coordinated unit, utilizing the stereotypic spread of an electrical signal.
Each normal cardiac cycle is the same. The electrical signal spreads from sinus node to atria and crosses into the ventricles via a gateway, the atrio-ventricular (AV) node then through the Bundle of HIS to bundle branches and Purkinje fibers to sequentially excite the ventricles. Heart contractions are brought about by excitation-contraction coupling. As the electrical signal moves through muscle, Calcium is released from the sarcoplasmic reticulum which enables movement of actin on myosin and muscle contraction.
The electrical signal in the atrium in a normal heart reaches the ventricle by only one route, the AV node. That acts as a gate-keeper which continues the journey of the electrical signal governing ventricular contraction. From the atria the electrical signal can go only one way, down into the ventricles. No matter what electrical activity occurs in the atria, which can misfire in a wholly in-coordinated fashion as in atrial fibrillation, the AV node will act as gatekeeper to induce slow coordinated periodic contraction of the ventricles. Under normal circumstances the Sino-Atrial (SA) Node in the right atrium will initiate a rhythmic electrical discharge that leads to the highly stereotyped muscular contraction of the entire 4-chambered heart.
But what may happen if there is an abnormal electrical discharge? For example, the SA node can fail to generate a regular rhythm or to speed up appropriately during exercise as when the heart rate must increase as you bicycle or climb stairs. Scarring, ischemia or other degeneration in the SA node can cause a problem called sick sinus syndrome. As this happens another locale in the myocardium can also of initiate a periodic electrical discharge. With the failure of the SA node rhythm maker, any part of the atrium or ventricular muscle can generate an “escape” electrical discharge automatously. The only thing that stops these other foci of myocardium from issuing their own electrical signal, is the control of the two rhythm making nodes and the heart conduction system. All other foci are literally competing with dominating rhythm makers of the heart.
Should any of these automatous units break free their own electrical discharges will be self- perpetuating in the manner of Hebbian learning, myocytes that fire together, wire together. Now for the first time we have a physiological model of learning that is, alteration of future behavior on the basis of past experience, occurring in another electrically excitable tissue outside the brain, true muscle learning. This results in forming accessory pathways in the heart and likely in other muscle as well.
The implications are great. If learning can occur outside the brain, so might other higher cortical type functions. All of a sudden the brain is not solely responsible for functions generally related to consciousness.
Speaking for the heart itself, the pathological recurrence of electrical discharges does indeed induce structural change. Abnormal pathways are subject to “fire and ice” heat or cryo ablations that are commonly done today to control atrial fibrillation and other arrhythmias. The model of accessory pathways in the heart is the Wolf-Parkinson-White syndrome which is thought to be congenital and genetic. Malignant cardiac arrhythmias frequently occur in genetic and non genetic cardiomyopathies as well. At least some of these conditions may be explained by the existence in development of abnormal electrical discharges that end up dominating normal cardiac rhythm making machinery and creating accessory conduction pathways. This is conjectural and remains to be shown.
The model of creation of abnormal conduction and re-entrant pathways leads to a number of testable hypotheses:
1. Most effective treatment of an abnormal or automatous electrical discharge would be prevention of recurrence.
2. Recurrence of an abnormal electrical discharge will be expected to lead to increased occurrence via positive feedback, alteration of behavior on the basis of previous experience, the very definition of learning.
3. At some point it may be too late to treat.
4. Ablation is better than drugs.
5. Prevention of recurrence is better than ablation.
6. . Pacing may be a valuable early in cases of sinus node (SA node) dysfunction might lead to atrial fibrillation and other arrhythmias.
7.Surgery may more often be recommended as an early treatment for epilepsy
8. Athletic prowess and learning may well occur at the muscular rather than the cerebral level.
In part, this has already been shown to be true. In January 2021 two clinical studies and an editorial did indeed find that early ablation of accessory pathways superior to medication in treatment of atrial fibrillation and disorder of electrical discharges that has been related to accessory pathway formation in keeping with earlier experience.
See:
NEJM January 28, 2021
Contains two clinical trials of early ablation in treatment of paroxysmal atrial fibrillation plus editorial plus Atrial fibrillation review.