====== Neuromodulation Strategies ======

=== 1. Invasive Electrical Stimulation ===

^ Technique ^ Main Applications ^ Remarks ^
| **DBS (Deep Brain Stimulation)** | Parkinson’s disease, essential tremor, dystonia, OCD, epilepsy | Continuous or intermittent stimulation of deep brain nuclei. Adjustable and reversible. Well-established with evolving indications. |
| **Phase‑locked Bilateral DBS (PL‑DBS)** | Bilateral postural tremor, essential tremor, advanced Parkinson's disease | Innovative technique that delivers stimulation synchronized ("phase-locked") to the oscillatory pattern of tremor on both sides. Aims to enhance efficacy while minimizing side effects. Requires real-time sensing and closed-loop stimulation systems. |
| **SCS (Spinal Cord Stimulation)** | Neuropathic pain, failed back surgery syndrome, ischemic limb pain | Dorsal column stimulation. Newer systems include adaptive "closed-loop" control. |
| **VNS (Vagus Nerve Stimulation)** | Drug-resistant epilepsy, treatment-resistant depression | Intermittent stimulation of the left vagus nerve. Explored for Alzheimer’s and autoimmune modulation. |

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=== 2. Non-Invasive Electrical Stimulation ===

^ Technique ^ Main Applications ^ Remarks ^
| **tDCS (Transcranial Direct Current Stimulation)** | Stroke rehabilitation, chronic pain, depression | Low-voltage direct current stimulation. Modest effects, but safe and portable. |
| **TMS (Transcranial Magnetic Stimulation)** | Major depressive disorder, OCD, migraine | FDA-approved. Includes theta-burst protocols and deep TMS variations. |
| **tACS (Transcranial Alternating Current Stimulation)** | Experimental: cognition, epilepsy, sleep modulation | Modulates brain oscillations; remains largely investigational. |

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=== 3. Emerging and Experimental Techniques ===

^ Technique ^ Status ^ Potential Uses ^
| **Optogenetics** | Preclinical / Animal studies | Cell-type specific activation/inhibition using light-sensitive proteins. Potential in epilepsy and circuit mapping. |
| **Low-Intensity Focused Ultrasound (LIFU)** | Early clinical trials | Non-invasive and highly focal neuromodulation. Investigated for thalamic and subcortical targets. |
| **Closed-loop Neuromodulation** | In development | Adaptive systems that monitor neural activity and adjust stimulation in real time. Especially promising for Parkinson’s, epilepsy, and pain. |

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=== 4. Chemical and Biological Neuromodulation ===

^ Approach ^ Examples ^ Remarks ^
| **Targeted pharmacological modulation** | GABA agonists, serotonin modulators, dopamine precursors | Traditional neurochemical modulation remains foundational. |
| **Gene and viral therapy** | Modified ion channels, optogenetic viral vectors | Experimental; enables durable, localized modulation. |
| **Gut-brain axis interventions** | Probiotics, prebiotics, fecal microbiota transplant | Emerging field linking gut microbiota to CNS function and neuromodulation. |

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=== 5. Future Trends ===

  * **Brain-Computer Interfaces (BCI)**: Control of external devices through neural activity (e.g., prosthetics, communication aids).
  * **Multimodal Stimulation**: Integration of neuromodulation with cognitive-behavioral, physical, or pharmacological therapy.
  * **AI-driven personalization**: Use of machine learning to optimize stimulation parameters based on patient-specific biomarkers.