Riassunto esame Developmental Cognitive Neuroscience, prof. Farroni, libro consigliato Developmental cognitive neuroscience, Johnson

MRI

adulthood. The lack of a later decline may reflect the ongoing lifelong myelination of fibers that adds to the overall volu

me of the brain.

Although different authors have found the rise and fall pattern, not all measures show it (e.g., myelination, white matte

r), measures such as synaptic density are static snapshots of a dynamic process in which both additive and regressive pr

ocesses are continually in progress (not distinct and separate phases) and there are a lot of individual differences within

the normal range (both in structure and function).

[Tramo and his colleagues] reconstructed the cortical areas of two identical twins from MRI scans (genetically identical

individuals), finding differences in their brain structure and functioning.

[Schneider and colleagues] (fMRI) studied the areas of activation following upper or lower visual field stimulation. Whi

le it had classically been assumed that the upper and lower visual field mapped on to the regions above and below the su

lcus, they found a lot of variation, with some typical subjects showing an upper/lower visual field cut that straddles this

structure. a timetable for “normal” postnatal brain development in humans must be interprete

In typical adults, efforts to construct

d with caution.

[Shaw and colleagues] (MRI) → the trajectory of change in cortical thickness (=spessore), and not the thickness itself b

est predicts a measure of intelligence (IQ): more intelligent children went through a larger and clearer pattern of rise and

years than did those with more average intelligence scores → differences in

fall in their cortical thickness between 7-19

the dynamic changes during development are critical for our understanding of individual differences in intelligence and

cognition in adults.

The Development of Cortical Areas: Protomap or Protocortex?

We can consider cortical differentiation in regions as being like the slices of a cake some of which may contain thicker j

am or cream layers. In the adult primate most of the cortical areas can be determined by very detailed differences in the

laminar structure, such as the precise thickness of certain layers. Often, however, the borderlines between areas are indis

tinct and controversial: these anatomically defined areas have particular unique functions (early sensory and motor area

s), but there are many cases of functional regions or borders that do not neatly correspond to known neuroanatomical di

visions.

“The majority of typical adults tend to have similar functions within approximately the same areas of cortex → the divis

ion of the cerebral cortex into structural and functional areas is tightly (strettamente) genetically prespecified”

This assumption is only partially correct.

The two dimensions of cortical structure (laminar and areal) are not entirely independent, since structural areal divisions

are partly specified by detailed differences in laminar structure. While the basic architecture of a network is innate (basi

c circuitry, learning rules, type and number of cells, etc.), the detailed patterns of (dendritic and synaptic) connectivity a

re dependent upon experience. While the network imposes architectural constraints on the representations that emerge w

ithin it, there are no innate representations.

Several aspects of the structure of the cerebral cortex, including the general laminar structure and large-scale regions, do

not require neural activity to be established → much of the fine-scale division into functional areas involves activity-de

pendent processes.

[Pasko Rakic]'s Radial Unit Model

Most cortical neurons in humans are generated outside the cortex itself, in the “proliferative zones”: these cells must mi

grate to take up their locations within the cortex. The laminar organization of the cerebral cortex is determined by the fa

ct that each proliferative unit (in the subventricular zone) gives rise to about one hundred neurons. The progeny from ea

ch proliferative unit all migrate up the same radial glial fiber, (the latest travelling past their older relatives), which act li

ke a climbing rope to ensure that cells produced by one proliferative unit all contribute to one radial column within the c

ortex. a neuron reaches its final location: a cell “knows” what type of ne

Differentiation into particular cell types occurs before

uron it will become (pyramidal, spiny stellate, etc.) before it reaches its adult location within the cortex. Some evidence

suggests that cells do indeed begin to differentiate before they reach their final vertical location (the information require

d for differentiation is present at the cell’s birth in the proliferative zones, it is not dependent upon their distance from th

e proliferative zones, or on the characteristics of the neighborhood in which that cell ends up).

Although in many cases a cell’s identity may be determined before it leaves the proliferative zones, some of the properti

es that distinguish cell types may form later.

[Marin-Padilla] the distinctive apical (=al vertice/apicale) dendrite of pyramidal cells, which often reaches into layer 1, i

s a result of the increasing distance between this layer and other layers resulting from the inside-out pattern of growth. T

he increasing separation between layer 1 and the subplate zone which results from young neurons moving into what will

become layers 2 to 6 means that cells which have their processes attached to layer 1 will become increasingly “stretche

d”; their leading dendrite will become stretched tangential to the surface of the cortex, resulting in the elongated apical

dendrite so typical of cortical pyramidal cells. This long apical dendrite allows the cell to be influenced by large number

s of cells from other (more superficial) layers.

[Blakemore and colleagues]: the termination of projections from the thalamus in layer 4 is governed by molecular mark

ers. Slices of brain tissue are able to survive and grow in a Petri dish for several days under the appropriate conditions. I

ndeed, pieces of thalamus of the appropriate age will actually grow connections to other pieces of brain placed nearby.

When a piece of thalamus (LGN) and a piece of visual cortex were placed close together in the dish, projection fibers fr

om the LGN not only invaded a piece of visual cortex of the appropriate age, but also terminated in the appropriate laye

r 4. Thus, layer 4 appears to contain some molecular stop signal that tells the fibers to stop growing and form connectio

ns at that location.

[Molnar and Blakemore] The visual thalamus had a piece of visual cortex and some other piece of brain placed nearby.

The thalamic fibers turned out to dislike cerebellum, rarely penetrating it, but they did grow into hippocampus (the gro

wth into hippocampus was not spatially confined in the way it had been for visual cortex).

The laminar structure of cortex probably arises from local cellular and molecular interactions, and it's not a result of thal

fibers “know” in

amic and sensory input (the identity and location of neurons are determined before birth and incoming

which layer to stop and make synaptic contacts).

Division of cortex into areas (opposing possibilities):

• The areal differentiation of cortex is due to a protomap (Rakic, 1988): differentiation into cortical regions occu

rs early in the formation of the cortex, is due to intrinsic factors, and the activity of neurons is not required. The

cortex is a mosaic from the start: each cortical area has individually specified features particularly suitable for t

he input it will receive or the functions it will perform.

• The different areas of cortex arise out of an undifferentiated protocortex: differentiation occurs later in the deve

lopment of cortex, and it depends on extrinsic factors like input from other parts of the brain or sensory system

The activity of neurons is required (Killackey, 1990; O’Leary, 2002). The division of cortex into areas in the

s.

adult brain is influenced by information relayed from the thalamus, and from interactions with other areas of c

ortex via inter-regional connectivity.

Literature on the areal differentiation of neocortex

Support to the protomap view:

• The newborns of a strain of “knockout” rodent that genetically lack connections between the thalamus and the

cortex still have normal, well-defined regional gene-expression boundaries within their cortex and some other

characteristics of wild-type mice.

• In vitro studies in which cortical tissue is maintained in culture, and thus isolated from potential extrinsic patter

ning cues, still show patterns of gene expression consistent with the development of the hippocampus.

Support to the protocortex view:

• Regionalization of cortex could emerge from a combination of different gradients of gene expression. [Kingsbu

ry and Finlay] → “hyperdimensional plaid” (vs “mosaic quilt” – protomap view): the patterning that emerges i

n a plaid is the result of small changes in many threads.

While more than one hundred genes may show graded differential expression between two different cortical areas durin

g development, genetic influence over the layered structure of cortex is much more direct: an autonomous and dissociab

le genetic pathway coordinates the development of the deeper layers of cortex from that which contributes to the mid an

d upper layers.

• Primary sensory regions, despite being the best candidates for genetic prespecification, can have their propertie

s significantly changed through experience: sensory input may be vital at least for the maintenance of cortical d

ivisions.

• Evidence for cortical differentiation prior to birth does not allow us to conclude that neuronal activity is not im

portant: spontaneous neural activity within the brain is important for differentiation.

Recent reviews: mid-way views between the protomap and protocortex hypotheses.

Most agree that graded patterns of gene expression create large-scale regions with combinations of properties that may

better suit certain computations. Within these large-scale regions, smaller-scale functional areas arise through the activit

y-dependent mechanisms associated with the protocortex view (one region may receive particular thalamic input project

ions, overlaid with a certain pattern of neurotransmitter expression, and the presence of specific neuromodulators: this c

ombination of circumstances, combined with neural activity, may induce unique features such as particular patterns of s

hort-range or long range connectivity). Differentiation into smaller areas within the larger regions may occur through th

e selective pruning (=cutting) of connections.

[O’Leary and colleagues] “Cooperative concentration” model: some different gradients of gene expression may act as o

pposing forces in shaping cortical regions.

According to Rakic’s protomap hypothesis, regional differentiation occurs largely through the different numbers of cells

generated in different layers in different regions of the cortex: the primary visual cortex (area 17) in primates has a large

r