Science Blockbuster Special Issue: No Neuron Is an Island" 4 reviews reveal the importance of brain connectivity

To coordinate the body's myriad functions, behaviors, and thoughts, a large number of neurons need to act
in concert.
Innovative neuroscience techniques allow researchers to specifically stimulate selected groups of neurons in animals and noninvasively measure how they activate other parts of
the brain.
Advances in brain imaging techniques have revealed anatomical projection and functional connection patterns, allowing us to see their activation
in real time.

By better understanding the complexity of normal brain connections, we can learn more about what goes wrong
when they are disrupted.
Connection patterns in various organisms are beginning to reveal evolutionary steps
from the simplest networks of neurons to multilayered, multinucleated mammalian brains.
Without a well-running connection, the brain is nothing more than a bunch of neurons, so "not a single neuron is an island.
"

Recently, the journal Science launched a special issue, using 4 reviews to describe brain connectivity
.
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01 Use Atlas data to map the connections and architecture of the brain

A detailed understanding of the neural connections between brain regions is key
to advancing our understanding of normal brain function and the changes that occur with aging and disease.
The researchers used a range of experimental techniques to map connections at different scales in rodent models, but the results are often difficult to compare and integrate
.
The 3D reference map of the brain provides new opportunities
to accumulate, integrate, and reinterpret research findings across studies.

Here, the authors review methods for integrating data describing neural connections and other patterns in rodent brain atlases and discuss how map-based workflows facilitate whole-brain analysis
of neural network organization related to other aspects of neural architecture.

Figure 1.
Workflows
for data integration and Atlas-based analytics.

Atlas played a key role
in this effort.
They provide standardized representations of anatomical locations and are embedded in software tools for integration and analysis
.
The Atlas framework allows direct comparison
with data from large-scale mapping work.
The new paradigm for brain connectivity and brain structure research is often to bring research data into the same reference space, share data, and prepare data
for systematic reanalysis and reinterpretation of our understanding of the brain.
As these new methods are introduced into neuroscience, literature mining can be complemented
by powerful mining of the data behind the explanations contained in publications.

02Addressing brain circuit function and dysfunction through computational modeling and optogenetic fMRI

Can we build a model of brain function to understand the whole brain circuit mechanism of neurological diseases and use it to predict the outcome of therapeutic interventions? How is the pathology of neurological disorders related to brain circuits and brain function?

In this review, the authors discuss the methods used so far and the future directions
that can be explored to answer these questions.
By combining optogenetic functional magnetic resonance imaging (fMRI, Figure 2) with computational modeling (Figure 3), cell type specificity, large-scale brain circuit function, and dysfunction begin to be quantified parameterized
.
The authors envision that these developments will pave the way
for future therapeutic developments in systems engineering methods that directly restore brain function.

Figure 2.
Optogenetic functional magnetic resonance imaging spans scales
.

Figure 3.
Computational modeling of NMR data reveals whole-brain functional interaction dynamics
.

These recent advances in cell type-specific neuromodulation, whole-brain functional imaging, and computational modeling are beginning to pave the way
for a major turning point in neuroscience.
The goal of the authors of this paper is to establish new methods that mimic brain function that can replicate and predict behaviors
of interest.
This will change the way many neurological disorders, including Parkinson's disease, are treated
.

03Scale matters: nested human connectomes

A comprehensive description of how neurons and entire brain regions are connected to each other is essential
for understanding brain function and dysfunction mechanically.
On the basis of diffusion magnetic resonance imaging and fiber beam imaging, neuroimaging has developed a way
to approach the connection of the human brain.
At the same time, polarization, fluorescence, and electron microscopy became available, which pushed spatial resolution and sensitivity to the axon and even synaptic level
.
New approaches must be employed to inform and constrain whole-brain fiber bundle imaging
through region, high-resolution ligation data, and local fiber geometry.

Machine learning and simulation can provide predictions
in the absence of experimental data.
Future interoperable Atlases require new concepts, including high-resolution templates and directionality, to represent variants of fiber beam imaging solutions and estimate
their accuracy.

Figure 4.
Human brain fiber structure
.

As an interesting concept, the authors see the connectome not only as a multiscale system, where each scale has different characteristics, but also as a system
with repeating properties.
However, to reveal the principle of connectivity within the experimentally accessible scale—in other words, to describe the "nesting" of the human brain, a critical re-examination of the approach, including fiber bundle angiography
, is required.
Future fiber beam imaging can be progressively moved from lower resolution to higher resolution, while understanding the regional characteristics of the next higher resolution and the basic geometry of the fiber
.

04Properties that connect the brain

Brain connectivity is more than just the transmission
of signals between brain regions.
Behavior and cognition emerge
through cortical regional interactions.
This requires integration
between local and remote regions coordinated by a densely connected network.
Brain connections determine the functional organization
of the brain.
Imaging of connections in living brains provides an opportunity
to identify the drivers behind cognitive neurobiology.
Differences in connectivity between species and between humans further deepen the understanding
of brain evolution and different cognitive traits.
Brain pathology amplifies this variability through disconnection, which leads to the breakdown of cognitive function
.
The prediction of long-term symptoms is now preferentially based on brain disconnection
.
This paradigm shift will reshape our brain map and challenge current brain models
.
Figure 4.
Breakdown of brain function by disconnection
.

summary

Going forward, we need to consolidate these new concepts by developing specialized software, which gives us additional resources to strengthen our observations
.
These developments will include, for example, tools that can represent high-dimensional data in the same latent space, as cross-scale, cross-species, and cross-imaging modalities while considering individual-level neural variability to capture factor interactions
.
To do this, researchers should build professional networks, integrate ideas, and share data
openly.

Together, these efforts will advance brain connectivity research to integrate across imaging modalities, develop new frameworks and advance our understanding of
brain development and evolution.
This joint effort will advance our current cutting-edge research and pioneer advanced neuroimaging methods, personalized anatomical models, and clinical implications
.