====== 🧠 Brain Network Disease ======

> Brain network diseases are neurological or psychiatric conditions arising from dysfunction in the brain's structural or functional connectivity, rather than from localized damage alone.

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^ 🧩 Concept                     ^ 💡 Explanation                                                                 |
| **Brain Networks**            | Interconnected brain regions that work together to perform cognitive or motor tasks |
| **Structural Connectivity**   | Physical white matter tracts (mapped via DTI/tractography)                         |
| **Functional Connectivity**   | Temporally correlated activity between brain areas (fMRI, EEG, MEG)               |
| **Disconnectivity**           | Loss or dysfunction of network communication                                       |
| **Diaschisis**                | Remote functional impairment caused by a focal lesion                             |

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=== 🔗 Examples of Brain Network Diseases ===

^ Disease                           ^ Affected Network(s)                       ^ Manifestation                                 |
| **Alzheimer’s Disease**          | Default Mode Network (DMN)                | Memory loss, disorientation                   |
| **Epilepsy**                     | Thalamocortical and other circuits        | Seizures due to network hyperexcitability     |
| **Parkinson’s Disease**          | Basal ganglia-thalamocortical loops       | Tremor, rigidity, cognitive slowing           |
| **Schizophrenia**                | Salience, frontoparietal, DMN             | Hallucinations, delusions, cognitive deficits |
| **Autism Spectrum Disorder**     | Social brain network                      | Atypical social interaction and communication |
| **Stroke (with diaschisis)**     | Variable depending on location            | Deficits extend beyond lesion site            |
| **Functional Neurological Disorder** | Limbic-attention-motor network         | Non-lesional motor or sensory symptoms        |

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=== 🧪 Tools for Studying Brain Networks ===

  * 🧲 **fMRI** – Functional connectivity via BOLD signal (task or resting state)
  * 🔬 **DTI (Diffusion Tensor Imaging)** – Structural mapping of white matter
  * ⚡ **EEG / MEG** – Temporal resolution of network activity
  * 🧠 **Graph Theory** – Models brain as nodes and edges (connectomics)
  * 🧬 **Connectome** – Global map of brain connectivity

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🎯 **Clinical Relevance:**  
Understanding brain network dysfunction helps:
  * Guide **non-lesional epilepsy surgery**
  * Explain **cognitive and behavioral syndromes** beyond structural lesions
  * Design **neuromodulation therapies** (DBS, TMS) targeting entire circuits
  * Understand recovery via **neural plasticity and compensation**
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[[Idiopathic generalized epilepsy]] (IGE) is a [[brain network disease]], but the location of this [[network]] and its [[relevance]] for [[treatment]] remain unclear. 
Ji et al. combine the locations of brain abnormalities in IGE (131 coordinates from 21 studies) with the human [[connectome]] to identify an IGE network. 
They validated this network by showing alignment with structural brain abnormalities previously identified in IGE and brain areas activated by generalized epileptiform discharges in simultaneous electroencephalogram-[[functional magnetic resonance imaging]]. The [[topography]] of the IGE network aligns with brain networks involved in motor control and loss of [[consciousness]] consistent with generalized seizure [[semiology]]. To investigate therapeutic relevance, they analyzed data from 21 patients with IGE treated with [[deep brain stimulation]] (DBS) for generalized seizures. [[Seizure]] frequency reduced a median 90% after DBS and stimulation sites intersect an IGE network peak in the centromedian nucleus of the [[thalamus]]. Together, this study helps unify prior findings in IGE and identify a brain network target that can be tested in [[clinical trial]]s of [[brain stimulation]] to control [[generalized seizure]]s
((Ji GJ, Fox MD, Morton-Dutton M, Wang Y, Sun J, Hu P, Chen X, Jiang Y, Zhu C, Tian Y, Zhang Z, Akkad H, Nordberg J, Joutsa J, Torres Diaz CV, Groppa S, Gonzalez-Escamilla G, Toledo M, Dalic LJ, Archer JS, Selway R, Stavropoulos I, Valentin A, Yang J, Isbaine F, Gross RE, Park S, Gregg NM, Cukiert A, Middlebrooks EH, Dosenbach NUF, Turner J, Warren AEL, Chua MMJ, Cohen AL, Larivière S, Neudorfer C, Horn A, Sarkis RA, Bubrick EJ, Fisher RS, Rolston JD, Wang K, Schaper FLWVJ. A [[generalized epilepsy network]] derived from brain abnormalities and [[deep brain stimulation]]. Nat Commun. 2025 Mar 24;16(1):2783. doi: 10.1038/s41467-025-57392-7. PMID: 40128186.)).