# wholeBrain imaging paper

The goal of this work is to provide a broad description of the population activity patterns that occur in developing cerebral cortex.

The main manuscript file is **[wholeBrain_main.md](wholeBrain_main.md)**



## Rationale
The idea is to provide a clear and beautiful representation of the visualized activity patterns within developing brain in vivo.

### Scientific importance
A comprehensive description of the spatiotemporal activity patterns in the immature brain will be crucial to understanding the developmental dynamics that exist between intrinsic and extrinsic factors that regulate circuit development. 

Indeed one of the fundamental goals of the BRAIN Initiative funded by NIH, NSF, and DARPA is provide dynamic maps of the brains electrical activity at an intermediate scale that bridges the local and global assessments garnered through current technologies in animals and humans. [NIH BRAIN working group interim report](http://acd.od.nih.gov/ACD-BRAIN-Working-Group-Report.pdf)

* signature patterns that predict current or future behavior
* construction of self-organizing circuits

### Human health importance
* neurodevelopmental disorders (e.g. autism, schizophrenia, epilepsy)
* activity-dependent structural plasticity. Implications for brain repair.
* development of brain-machine interfaces

### Previous work 

reference                              | FOV info                                                                                                                                                                  | figure snapshot                                       
-------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ------------------------------------------------------  
[Yuste et al.][#Yuste:1992]            | calcium imaging in tangential slices of barrel cortex L4 from P4-5 rats in figure2, and from somatosensory, visual and frontal cortices in general with coronal or tangential slices from P0-7. **500 x 575 µm FOV**. Mean domain size was 96 µm. 50 -120µm range. 'We found no differences in the size, shape, or frequency of domains in different cortical areas.'                               | ![](assets/img/yuste1992-fig2.png)
[Chiu & Weliky][#Chiu:2001]            | linear MEA covering a **3.2 mm strip** across visual cortex Corr activity observed between cortical patches separated by mean distance of 1 mm                            | ![](assets/img/Screen_Shot_2013-09-04_at_2.16.02_PM.png)
[Hanganu et al][#Hanganu:2006]         | single electrodes or 4 shank linear MEAs placed in each hemisphere (0.5-1.0mm spacing, for **1.5-3.0mm total**)                                                           | ![](assets/img/Screen_Shot_2013-09-04_at_2.36.18_PM.png)
[Adelsberger et al][#Adelsberger:2005] | optical fiber implant for freely moving neonatal mice with bulk loading, 400µm diameter FOV imaged in TeA or Ent                                                         | ![](assets/img/Screen_Shot_2013-09-04_at_4.43.51_PM.png)
[Rochefort et al][#Rochefort:2009]     | 100x70µm FOV 2P-MCI in mouse visual cortex at P11                                                                                                                        | ![](assets/img/Screen_Shot_2013-09-04_at_2.47.37_PM.png)
[Colonnese et al.][#Colonnese:2010]    | single pulled electrodes in V1 or linear MEA (16 site silcon probe, 4sites x 4shanks, with 200µm separation, **600µm total**                                            | ![](assets/img/Screen_Shot_2013-09-04_at_1.54.43_PM.png)
[Siegel et al.][#Siegel:2012]          | **219x180 µm FOV** 2P-MCI in visual cortex                                                                                                                               | ![](assets/img/Screen_Shot_2013-09-04_at_2.18.49_PM.png)
[Ackman et al][#Ackman:2012]           | **3.0 x 4.0 mm FOV** WF-MCI in V1, V2, and SC P3-P9 mouse                                                                                                                 | ![](assets/img/Screen_Shot_2013-09-04_at_2.12.16_PM.png)
[Leinekugel et al][#Leinekugel:2002]   | P4-6 rat hippocampus, cortex, 8 tip linear MEA (tungsten wires), 100-300µm vertical tip separation                                                                       | ![](assets/img/Screen_Shot_2013-09-04_at_4.00.40_PM.png)
[Khazipov et al][#Khazipov:2004a]      | P1-6 rat somatosensory cortex, single electrode MUA and PC                                                                                                                | ![](assets/img/Screen_Shot_2013-09-04_at_4.10.07_PM.png)
[Yang et al][#Yang:2009]               | 4x4 linear MEA 200µm spacing, **600µm total**, bilaterally in S1 barrel cortex                                                                                          | ![](assets/img/Screen_Shot_2013-09-04_at_3.54.37_PM.png)
[Yang et al][#Yang:2012a]              | **2.6 x 2.6 mm FOV**, VSD imaging in S1 cortex P0-7 rat. Spont and evoked activity in C2 barrel. 8shank x 4site silicon probe linear MEA (200µm separation, 1.4mm total). Activations were 300-400µm diam and 70% synchronized 1-2 barrel columns wide from P0-7. At P7 there was sig incr in activations synch >6 barrel columns. | ![](assets/img/Screen_Shot_2013-09-04_at_2.26.32_PM.png)
[Golshani et al][#Golshani:2009]       | 2P-MCI in mouse S1 **478 x 186 µm FOV**                                                                                                                                  | ![](assets/img/Screen_Shot_2013-09-04_at_4.13.14_PM.png)
monkey and human                       | EEG performed prenatally [#Vanhatalo:2005][#Tolonen:2007], no fMRI prenatally, (or infant?) but has been done in children for resting state connectivity                  |                                                         

**Conclusion:** The 'meso–macro' scale activity patterns within and between the developing cortical hemispheres have not been reported in any species.


### Future work 
More detailed descriptions of the nature and the functions of these activity patterns can and should be performed in parallel in ongoing and future studies.  
For example:  
 
* What is the intra- vs sub- cortical nature of sensory cortex activity?
* What is the intra- vs sub- cortical nature of ongoing activity in motor- associational-, and other non-primary sensory cortical areas?
* Relationship of imaged patterns to EEG patterns described in other studies?
* Extent to which functional correlations reflect direct synaptic connections?
* Retinal wave drive of other areas?
* Ontogenetic relationships of localized calcium domains?
* Development profile through first postnatal weeks
* Chronic developmental profile in individuals?
* Aberrant activity patterns in developmental disorder and seizure models?



[wholeBrain_main.md]: wholeBrain_main.md

[id2]: https://github.com/ackman678/currOpinRvw/blob/master/currOpin_outline.md

[id3]: https://github.com/ackman678/currOpinRvw/blob/master/README.md 

[id4]: https://gist.github.com/ackman678/6391902

[wholeBrainDX]: https://github.com/ackman678/wholeBrainDX/blob/master/README.md  

<<[references.txt](references.md)
