The brain operates through intricate electrical signals, forming the basis of all thought, emotion, and movement. Cortical excitability refers to how readily these brain cells, known as neurons, can be activated to transmit these signals. This fundamental property of neurons is central to communication within the nervous system, influencing processes like learning, memory, and behavior. Understanding this electrical responsiveness helps illuminate how the brain functions and how its deviations can lead to various neurological conditions.
The Brain’s Electrical Balance
The brain’s ability to process information and control bodily functions relies on a delicate electrical equilibrium between excitation and inhibition. Neurons communicate through electrical currents called action potentials, which can either promote signal transmission (excitatory) or reduce the likelihood of it (inhibitory). While excitatory neurons encourage other neurons to fire, inhibitory neurons regulate this activity, preventing uncontrolled electrical surges.
This intricate balance is maintained by various chemical messengers known as neurotransmitters. Glutamate, for instance, is the most common excitatory neurotransmitter, increasing the chance of a postsynaptic cell generating an action potential. Conversely, gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain, decreasing the likelihood of an action potential propagating. The precise interplay of these and other neurotransmitters, acting on specific receptors and ion channels, determines a neuron’s excitability.
The brain works to maintain a stable ratio between excitatory and inhibitory activity, a concept known as the global excitatory/inhibitory (E/I) balance. This homeostatic mechanism ensures that neural circuits can process incoming information accurately while remaining stable. This dynamic regulation of E/I balance is fundamental for healthy brain function throughout life.
Measuring Brain Activity
Scientists and clinicians employ non-invasive techniques to assess and understand cortical excitability in humans. Electroencephalography (EEG) is one such method, measuring the brain’s electrical activity from electrodes placed on the scalp. EEG can provide insights into the intrinsic excitability of neural circuits by analyzing patterns in brainwave signals.
Another widely used technique is Transcranial Magnetic Stimulation (TMS), which directly probes cortical excitability. TMS involves applying short magnetic pulses to the skull, inducing an electric field that depolarizes neurons in specific brain regions. When applied over the motor cortex, this stimulation can evoke muscle twitches, known as Motor-Evoked Potentials (MEPs), which are recorded using electromyography (EMG).
The intensity of TMS needed to reliably produce MEPs, known as the motor threshold, serves as a direct measure of motor cortex excitability. By combining TMS with EEG, researchers can also record TMS-evoked potentials (TEPs) from the scalp, offering a way to study excitability and connectivity in areas beyond the motor cortex with high spatio-temporal resolution. These non-invasive tools allow for detailed investigation of brain function without requiring surgery.
When Excitability Goes Awry
Alterations in cortical excitability are associated with various neurological and psychiatric conditions, highlighting the importance of the brain’s delicate electrical balance. In epilepsy, for instance, there is an excessive and synchronized firing of neurons, leading to recurrent seizures. The epileptic brain exhibits distinct abnormalities in cortical excitability. During a seizure, the normal excitatory-inhibitory balance breaks down, resulting in a sudden, uncontrolled burst of electrical activity.
Major depressive disorder (MDD) is also linked to altered cortical excitability, often involving a perturbation of the normal balance between excitatory and inhibitory neurotransmitter systems. Studies using TMS have shown impaired modulation of cortical excitability in depressed patients. This suggests that an imbalance in neuronal responsiveness contributes to the symptoms experienced by individuals with depression.
Cortical excitability is also significantly impacted by traumatic brain injury (TBI) and stroke. Following a stroke, an imbalance in interhemispheric interaction often occurs, characterized by decreased excitability in the lesioned motor cortex and increased excitability in the non-lesioned hemisphere. Similarly, TBI can lead to motor deficits and changes in cortical excitability, with the contralesional cortex often exhibiting periods of hyperexcitability following injury. These disruptions in the brain’s electrical properties contribute to the wide range of neurological impairments seen in patients recovering from such injuries.
Targeting Excitability for Treatment
Understanding cortical excitability has paved the way for therapeutic approaches aimed at restoring brain function by modulating neuronal activity. Non-invasive brain stimulation techniques like repetitive Transcranial Magnetic Stimulation (rTMS) are used to adjust cortical excitability in targeted brain regions. rTMS involves delivering magnetic pulses to the cerebral cortex, and depending on the frequency, it can either increase or decrease excitability.
rTMS has gained attention for its potential to treat conditions like treatment-resistant depression. Another non-invasive method is Transcranial Direct Current Stimulation (tDCS), which applies a low-level constant direct current to the scalp through electrodes. Anodal tDCS generally enhances cortical excitability by depolarizing neuronal membranes, while cathodal stimulation tends to reduce it. tDCS is a promising and more affordable option for modulating cortical excitability.
Beyond external stimulation, certain medications also work by directly altering neuronal excitability. Anti-epileptic drugs (AEDs), for example, are designed to re-establish the balance between neuronal excitation and inhibition that is disrupted in epilepsy. Many AEDs work by blocking channels that cause repetitive firing, enhancing inhibitory signals, or reducing excitatory ones. These pharmacological interventions highlight the diverse strategies used to normalize cortical excitability for therapeutic benefit.