schizophrenia brain Jauary 2018
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" as we know, there are ; there are things we knowknown knowns.
We also know there are known unknowns; Tthat is to say we know there are some things we do not know.
But there are also unknown unknowns - the ones we don't know we don't know ".

Donald Rumsfeld, United States Secretary of Defense, briefing, 2002 ...

June 2018 NEW:- 1.
in a letter to the Nature journal meaning - in this case - important news that can't wait for the full article
there is no human adult neurogenesis

previous study agrees

June 2018:-
Influence of placenta

February 2018

stress resilience
Attention goes awry in schizophrenia.

According to a new study, ErbB4 gene coordinates a cascade of brain signals that "bridge" the two regions.
ErbB4 itself encodes a receptor found on the surface of brain cells. The study found that when a protein (neuregulin-1) attaches to the ErbB4 receptor, it triggers a chain reaction that ultimately determines neurotransmitter levels in the prefrontal cortex and hippocampus.
Without ErbB4, neurotransmitter levels go awry. The researchers discovered mice lacking ErbB4 have low levels of a particular neurotransmitter-GABA, or gamma-aminobutyric acid-in their brain. Low GABA levels can lead to impaired top-down attention in the prefrontal cortex, and impairs how the prefrontal cortex can efficiently coordinate with the hippocampus. The researchers concluded that ErbB4 helps link the two brain regions to maintain attention.
networking for Attention

january 2018

untreated scizophrenia leads to hippocampus size reduction


glutamate overactivity

N.B. [ hippocampal failure in neurogenesis would lead to this - reduced neurogenesis means reduced inhibition on Ca3, to glutamate overactivity.

2 b :-dentate neurogenesis

The hippocampus keeps the brain networks ready to respond to living with change in theworld around them, by a steady alerting low wave distribution.
see ready at rest

2c . attention

glutamate overactivity

dentate neurogenesis

roots of NG

origin hippo DG ng

ng diversity origin

? pruning and Immunity problems?

Sekar et al :-

There is one known in the brain of sufferers,

Normally the hippocampus delivers 700 new cells daily: Spalding et al

In those with continuing schizophrenia, neurogenesis is half only of the normal level of hippocampus neurogenesis

Hippocampal failure is the proximate cause of schizophrenia. Before the expression of delusionary thinking and hallucinatory expression, a decline in cognitive behaviour is observed. How is it that the hippocampus reduction in neurogenesis can explain both the early cognitive decline, and the subsequent persint misbeliefs and hallucinations. Sufficient damage to the hippocampus is followed by the loss of memory recall for recent experience. When sufferers lose half their capacity to proliferate new cells they lose thia ability to store new experince, new interests,so that they cannot mature in their lives

They remain stuck with the achievements, level of ability to acquire relationships, direction of interests, that they had acquired before the illness arrive. When the illness arrives late, by that time social skills , work, domestic, and personal achievements, will have been realised.

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms, that have damaged the future abilities of the hippocampus.

Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus,
but the genes and molecular mechanisms accounting for this have been challenging to identify.

Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies.
In mice, C4 mediated synapse elimination during postnatal development.

These results implicate excessive complement activity in the development of schizophrenia.
It may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

the possible connection of immunity response to a cause of pruning, leading to schizophrenia

Howes etc

If immunity plays a part, might it lead to this new treatment ;- go to So, should a trial goes ahead

Well, it might raise questions about capacity of patient subjects to fully understand, to give informed consent.
Side effects of monoclonal anti bodies: Natalizumab

Hippocampal failure is the proximate cause of schizophrenia.

Click these academic references- those supporting and affirming hippocampus failure

< Hippocampus early development will be an important start in thinking how and why things have gone wrong.

[ Schneider describes aprimary delusion ..... = abnormal salience ..... something normally considered insignificant is taken on as significant by sufferer, becomes the basis for a delusional belief.

Beta oscillations play at least two important roles in the processing of incoming task stimuli in healthy subjects, the second of which is disrupted in schizophrenia.
"First, both relevant and irrelevant task stimuli induce a rapid but transient phasic reduction in beta amplitude relative to baseline, probably due to the retuning of local excitatory-inhibitory encoding circuits from the beta to the gamma range."

[ We know that different gamma waves sort out access to which new things are perceived. But how for example how does the amygdala give emotional value priority - how to 'click' on which of the gamma assignments should go into available longterm store for usefully held context enables an intention to proceed correctly ]

"Second, in response to task-relevant stimuli, there is enhancement of a more gradual phasic increase in beta amplitude relative to baseline, postulated to represent a beta signal implicated in integrating information across widely distributed brain regions. Together, these two opposing beta effects (early suppression of local beta in favor of gamma; more gradual increase in long-range beta integrative signal) sum to produce an initial net beta amplitude reduction (beta ERD) followed by a sharp increase (beta ERS).

In schizophrenia, we conclude, the local beta encoding signal, reflected in the early beta desynchronization, is not abnormal. However, in the insula network, the integrative beta signal showed an attenuated response to task-relevant stimuli while conversely actually showed a significantly increased response to irrelevant stimuli.

Taken together with robust evidence for grey matter deficits in the bilateral insula, this suggests that in patients with schizophrenia a faulty salience network fails to signal the salience of task-relevant stimuli, resulting in disruption to the integrative processes required for efficient evaluation of stimuli and appropriate response selection.

Such disruption could lead both to failure to recognize what is relevant, and to attribution of salience to what is irrelevant"
taken from --- E B Liddle

Early hippocampus development

roots of adult ng

perinatal asphyxia and hippocampus damage

Perinatal hippocampus damage

ng diversity

ANATOMY hippocampus

hippocampus stem cells to .....

attention fixes hippocampus

two memories co-operates

stress shifts the memory stream

oscillatory traffic

thalamic spindling: background

Comment on spindling

go to Striatum Studies

Hippocampus is a Hub

a Hub like this

The medial temporal lobes (MTL), and more specifically the hippocampus, are critical for forming mental representations of past experiences-autobiographical memories-and for forming other "nonexperienced" types of mental representations, such as imagined scenarios.[ ED: and futurepossibilities ] . Examining PHC connectivity patterns revealed that the PHC seed was distinctly connected to other MTL structures during the autobiographical task, to posterior parietal regions during the spatial task and to a distributed network of regions for the conceptual task. Examining hippocampal connectivity patterns revealed that the anterior hippocampus was preferentially connected to regions of default mode network during the autobiographical task and to areas implicated in semantic processing for the conceptual task whereas the posterior hippocampus was preferentially connected to medial-posterior regions of the brain during the spatial task. We interpret our findings as evidence that there are MTL-guided networks for forming distinct types of mental representations that align with functional distinctions within the hippocampus.

The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link between the neocortex and the hippocampus. However, neocortical activity is transmitted through the PER and LEC to the hippocampus with a low probability, suggesting the involvement of the inhibitory network. This study explored the role of interneuron mediated inhibition, activated by electrical stimulation in the agranular insular cortex (AiP), in the deep layers of the PER and LEC. Activated synaptic input by AiP stimulation rarely evoked action potentials in the PER-LEC deep layer excitatory principal neurons, most probably because the evoked synaptic response consisted of a small excitatory and large inhibitory conductance. Furthermore, parvalbumin positive (PV) interneurons-a subset of interneurons projecting onto the axo-somatic region of principal neurons-received synaptic input earlier than principal neurons, suggesting recruitment of feedforward inhibition. This synaptic input in PV interneurons evoked varying trains of action potentials, explaining the fast rising, long lasting synaptic inhibition received by deep layer principal neurons. Altogether, the excitatory input from the AiP onto deep layer principal neurons is overruled by strong feedforward inhibition. PV interneurons, with their fast, extensive stimulus-evoked firing, are able to deliver this fast evoked inhibition in principal neurons. This indicates an essential role for PV interneurons in the gating mechanism of the PER-LEC network.

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a carer site


adolescence is a time of brain 'pruning'.
It is also the time when schizophrenia most commonly starts, the florid illness preceded often by a time of cognitive and life coping failure.

What is pruning 'doing'
networking templates

Structural brain modules become more segregated during youth
Targeted strengthening of hub edges simultaneously promotes network efficiency
Enhanced modular segregation mediates improvements in executive function in youth. The human brain is organized into large-scale functional modules that have been shown to evolve in childhood and adolescence.
Evolving modular topology facilitates global network efficiency and is driven by age-related strengthening of hub edges present both within and between modules.
Critically, both modular segregation and network efficiency are associated with enhanced executive performance and mediate the improvement of executive functioning with age.

Together, results delineate a process of structural network maturation that supports executive function in youth.

New August 2017 :-

Human Brains need the structure of a Story

Gazzinga. studying 'splitbrain' patients done for epilepsy suppresion concluded that the left brain does the cognitive and analytic work: the right brain organising the sensory/motor networks. fear arrives

New hippocampus academic research


aimone: ablation ng

adult ng functions

*hippocampus enhances sensory responses.


Bast GABA disinhibition
disrupt prefrontal attention and hippocampal memory function

Important - current academic references

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