The code provided is a computational model simulating the effects of transcranial alternating current stimulation (tACS) on essential tremor. Essential tremor is a common neurological condition characterized by involuntary and rhythmic shaking, which predominantly affects the hands but can impact other parts of the body. The underlying cause is not fully understood, but it is believed to be a result of abnormal oscillatory activities in certain brain regions. ### Biological Basis of the Model **1. Cellular Components:** - **Inferior Olivary Neurons (ION):** The model includes these neurons, which are known for their role in generating synchronous oscillations. They are thought to play a crucial part in rhythmic motor control and are implicated in tremor generation. - **Purkinje Cells (PC):** Located in the cerebellum, Purkinje cells are fundamental in modulating motor activities and coordination. Their output is inhibitory and they integrate a significant amount of synaptic input, which is crucial for controlling the timing and precision of motor commands. - **Deep Cerebellar Nuclei (DCN):** As a major cerebellar output, these nuclei receive inhibitory input from Purkinje cells and excitatory inputs from other sources. They play a central role in the timing and patterning of motor signals. - **Thalamocortical Neurons (TC):** Part of the thalamus, these neurons relay motor signals between the cerebellum and motor cortex. They are crucial for motor information processing and coordination. - **Motor Cortex (MC):** While not detailed, the motor cortex is implied to receive thalamic output and participate in motor execution. **2. Synaptic Connectivity:** - The model includes synaptic interactions such as ION to PC, PC to DCN, DCN to ION (feedback loop), and DCN to TC, reflecting cerebellar and thalamocortical pathways involved in motor control. These pathways are critical in maintaining and modulating rhythmic motor activities. **3. Oscillatory Activity:** - Tremor is modeled using oscillatory inputs, such as those from sinusoidal clamps (`SinClamp`) applied to mimic tACS. This reflects the hypothesis that altering brain oscillations can modulate symptoms of essential tremor. - The ION neurons are specifically stimulated to initiate oscillations, which serve as tremor triggers, modeling the genesis of tremor-like rhythmic activity. **4. Stimulation Parameters:** - The model simulates non-phase-locked tACS, which means the external oscillatory stimulation does not align perfectly with the natural neuronal oscillations. This reflects experimental approaches where tACS is used to disrupt abnormal oscillatory circuits involved in essential tremor. **5. Recording and Analysis:** - Action potentials (APs) are recorded for different neuron types, allowing for the analysis of neural activity patterns and the effects of interventions. In summary, this model attempts to replicate the neural circuits and oscillatory dynamics involved in essential tremor, exploring the therapeutic potential of tACS by targeting these neural oscillations. This reflects current scientific efforts to understand and mitigate tremor through neuromodulation techniques by leveraging neural plasticity and oscillatory control mechanisms.