Where Did My Soul Go?

Exploring the neurocircuitry of loss-of-consciousness seizures.

While the question of a physical basis of consciousness is batted around by armchair philosophers, it is no light or abstract matter for people whose consciousness doesn't work as it should. From coma to narcolepsy, epilepsy and schizophrenia, there are many ways that consciousness can be disturbed for organic reasons (not even to mention pharmacologic and recreational interventions). One type of epilepsy, absence seizure, is a particularly interesting example, characterized by brief (10 seconds) loss of consciousness with no other symptom, typically. The subject just stares into space, or lets the current action such as speaking slow to a crawl. Memory of this time is absent, and the subject is not conscious. Then everything picks up again as though nothing had happened. It sort of resembles a reboot of a machine or computer.

Epilepsy, of which there are dozens of kinds, generally is a syndrome of electrical/chemical over-activity and over-synchrony somewhere in the brain. Our normal state is a chaotic noise from which a surface EEG captures occasional regularities. Consciousness seems to be the occasional and restricted synchrony of coalitions of neurons reaching the various areas which give it content, whether visual, abstract, tactile, etc. Probably also not just any neurons, but coalitions anchored in the cortical and thalamic areas that are most closely associated with loss of consciousness when they are injured. Beyond this, it is not yet possible to say just what consciousness is in physical, anatomical terms.

Yet there is a good deal known about the electrochemical circuits of epilepsy, which is one route to learning more about consciousness in general. Many patients have been helped by careful investigation of where their seizures begin, and intervening by either removing some portion of that brain tissue, or implanting electrodes that give corrective shocks continuously. In the case of absence seizures, which may be a particularly incisive and minimal disruption of consciousness, the driver seems to be a circuit between the cortex and thalamus.

The thalamus sits atop the midbrain and brainstem, and is the gateway to the cortex, relaying sensory information from outside and motor signals back downwards. In the sensory direction, this is an inter-active process. The cortex sends many connections back, at least in part to direct the spotlight of attention to selected inputs. The thalamus also plays central roles in sleep/wakefulness, as it is the source of the slow wave patterns of deep sleep, and damage to it can cause coma.

But sometimes the cortico-thalamic connections get too strong, and evolve into a positive feedback loop of ~ 3Hz waves that characterize the absence seizure. In susceptible persons, (it is a syndrome of children, typically), brief hyperventilation can cause it routinely. This suggests a possible connection with the sleep circuitry, related to the yawning, dizziness, and other effects of hyperventilation.

EEG waves during an absence seizure, which lasts from a few to 20 seconds.

Obviously, the brain circuitry has been difficult to figure out. Not only is the brain in general, and the human brain in particular, hard to experiment on, but the thalamus is especially central and hard to get to. The authors of a recent paper resort to computational modelling, based on the experimental work of others (and their own prior work). The idea is to get as much of the detailed knowledge into a model as possible, and then ask whether the seizures can be reproduced, and if so, what can be done about them.

The answer is that .. yes they can. The model below describes what is known generally about the network involved. It brings in another key anatomical site, the basal ganglia, which sit right next to the thalamus and conduct signals from the cortex to it, substantially increasing the complexity of the network.

Circuitry diagram of brain elements and connections involved in absence seizures, as used in the current paper's model. Glutamate connections are excitatory, while GABA connections are inhibitory.

One theme is that not all connections in the brain are excitatory, as though neuronal connections were simple wires. The red (glutamate neuro-transmitter) arrows represent activating connections, while the blue (GABA) arrows represent inhibitory connections. Just like in organizational management or artificial circuitry, the careful balancing of positive and negative feedback results in optimal control. Here, after constructing a ~40 parameter model containing everything known about the circuitry, the authors find that an unusual and recently-found inhibitory circuit that points from the basal ganglia (GPe, globus pallidus externa) directly back to the cortex might be critical for damping absence seizures.

Dialing up the inhibitory circuit voltage (-Vcp2) from the globus pallidus externa to the cortex, to a modest degree, reliably shuts down the firing rate (Øe) that is characteristic of absence seizures.

A further example of their data, (below), plotting (A, B) the voltage (Vse) from the thalamus (SRN, specific relay nuclei) to the cortex, versus the delay of action (tau in milliseconds) of the inhibitory circuit between the thalamus internal nuclei, TRN (thalamic reticular nucleus) and SRN. Extending the delay, or increasing the excitatory feedback voltage, moves the graph up and right, towards higher-firing states, as show in the lower individual graphs. The absence-seizure type of firing is in graph D, corresponding to the light blue area of graph A.

The absence seizure oscillation (SWD) happens in a sort of sweet spot of voltage applied between the thalamus (SRN) to the cortex. The vertical axis (tau) describes the lag characteristic of the inhibitory circuit between the TRN and SRN areas within the thalamus, which is also influential over the absence seizure oscillation.

While this kind of modelling is no substitute for empirical investigation, it is tremendously useful to advance scientific theorizing and speculation about the systems at hand. Systems about which our knowledge is increasingly complicated to the point that we may not be able to understand them without the help of computerized models that can keep track of a myriad of details and dynamics. In this case, the hypothesis might be, that if treatment is really necessary, an electrode placed into the basal ganglia / globus pallidus externae, to stimulate its inhibitory action with modest constant voltage, may be one way to go about it.

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