Neurophysiology can free psychiatry from it’s dependence on metaphor.

el Greco

For psychiatry to progress, it can take as it's starting point the most up to date thinking on how the nervous system operates. This necessitates an appreciation of how neurons communicate with each other, how circuits emerge and how CNS tissue is sculpted in the very act of processing information. A short synopsis of some of the main themes in contemporary neurophysiology is presented here. First we shall consider the two main theories of how information is processed in the here-and-now. Then we shall look briefly at spike-timing dependent plasticity, the latest and arguably the most elegant form of plasticity within the brain, which synthesises many strands.

Information Processing

Special gnostic cells

There are two major theoretical accounts of how neural tissue “performs its computations”. The first account postulates the existence of ‘special cells’ at the top of a processing hierarchy. These cells are less ‘concerned’ by the raw ‘building blocks’ of sensory experience – orientation, brightness, colour, pitch etc. Instead, they respond (‘fire’) to whole objects (Gestalts), regardless of perspective, illumination and all the other idiosyncrasies that make up a perceptual scene. The metaphor of the ‘grandmother cell’ captures the idea. “Each time my grandmother comes into consciousness, via any of the sensory channels or in imagination, a ‘special’ cell, somewhere in the brain, is “active”.

The main criticism of the ‘grandmother cell’ hypothesis [aside from its prioritising of perception over thought & movement] is that there are far more potential percepts, than available neurons. Another criticism is that by focusing exclusively on feed-forward pathways, the hypothesis ignores the anatomical 'reality’ of extensive feedback pathways. Nevertheless, in-vivo electrophysiological work in humans undergoing neurosurgical procedures has provided evidence that there are neurons in the medial temporal lobe, which have the characteristics of grandmother cells.

Dynamic Assemblies

The second account prioritizes flexible, dynamic assemblies of neurons over ‘special’ cells. An assembly is defined as a constellation of neurons, which are firing action-potentials within the same narrow time-window (synchronously). Here, processing is a more ‘democratic affair’, and no special cells are required. Feedback and feed-forward connections are equally important, as the network (the assembly) reaches a consensus. Assemblies are transient entities, emerging for a period before ‘dissolving’, perhaps to ‘reappear’ at a later instant. A temporarily ‘dominant assembly' may ‘recruit’ other ‘partners’. Allegiances are flexible, with co-operation at one instant and competition at another. And over longer periods of time, assemblies can become – stronger; by virtue of sheer repetition and the ‘rules’ of long-term-potentiation (LTP), particularly if monoamine systems are co-active – or weaker; if the ‘content’ is fleeting or insignificant. Network oscillations (rhythms) provide a metronome, to ensure that the right cells fire in synchrony. Gamma (30–200 Hz) rhythms ‘bind’ local assemblies, whereas lower frequencies (theta, alpha, and beta) sub-serve long-distance communication between brain areas.

Of course, it is entirely feasible that the CNS makes use of both schemes described above [special cells & dynamic assemblies]. Processing power may reach grand heights when special [gnostic] cells come together as an assembly.

Sculpting CNS tissue

Spike-timing-dependent plasticity (STDP) depends on the conjunction of pre and post-synaptic events, within a narrow time envelope, of the order of tens of milliseconds or so. In the most straightforward version, a synapse is strengthened if a pre-synaptic input occurs immediately prior to a post-synaptic action potential (AP). If on the other hand, the input arrives in the immediate aftermath of a post-synaptic AP, the synapse is weakened. Pre and post-synaptic events beyond the critical time-window (i.e. unpaired ‘events’) leave synaptic strength unchanged. This shows how the precise timing of neuronal firing impacts upon the network. [And this impact is structural, as well as biochemical, Link]. Two aspects of STDP are notable:

1. Conventional neuromodulators appear to ‘tweak’ STDP. Actually ‘tweak’ is an understatement. The presence of a modulator such as dopamine can transform a normal pre-> post strengthening into a depression instead. More succinctly, dopamine can determine the direction of plasticity (+ or -).

2. The critical time window of STDP (tens of milliseconds) is in exactly the same ‘ballpark’ as network oscillations in the gamma band (period ~25ms).

The elegance of STDP is that it begins to reveal how apparently unconnected phenomena [brain-oscillations and neuromodulator systems], are integrated within a fundamental CNS function – how synapses and circuits are sculpted over time.