Human cognition depends upon slow-firing neurons

Good mental health and clear thinking depend upon our ability to store and manipulate thoughts on a sort of "mental sketch pad."

In a new study, Yale School of Medicine researchers describe the molecular basis of this ability -- the hallmark of human cognition -- and describe how a breakdown of the system contributes to diseases such as schizophrenia and Alzheimer's disease.

Prof Amy Arnsten

"Insults to these highly evolved cortical circuits impair the ability to create and maintain our mental representations of the world, which is the basis of higher cognition," said Amy Arnsten, professor of neurobiology and senior author of the paper published in the Feb. 20 issue of the journal Neuron.

High-order thinking depends upon our ability to generate mental representations in our brains without any sensory stimulation from the environment.

These cognitive abilities arise from highly evolved circuits in the prefrontal cortex.

Mathematical models by former Yale neurobiologist Xiao-Jing Wang, now of New York University, predicted that in order to maintain these visual representations the prefrontal cortex must rely on a family of receptors that allow for slow, steady firing of neurons.

The Yale scientists show that NMDA-NR2B receptors involved in glutamate signaling regulate this neuronal firing.

These receptors, studied at Yale for more than a decade, are responsible for activity of highly evolved brain circuits found especially in primates.

Earlier studies have shown these types of NMDA receptors are often altered in patients with schizophrenia.

The Neuron study suggests that those suffering from the disease may be unable to hold onto a stable view of the world.

Also, these receptors seem to be altered in Alzheimer's patients, which may contribute to the cognitive deficits of dementia.

The lab of Dr. John Krystal, chair of the department of psychiatry at Yale, has found that the anesthetic ketamine, abused as a street drug, blocks NMDA receptors and can mimic some of the symptoms of schizophrenia.

The current study in Neuron shows that ketamine may reduce the firing of the same higher-order neural circuits that are decimated in schizophrenia.

"Identifying the receptor needed for higher cognition may help us to understand why certain genetic insults lead to cognitive impairment and will help us to develop strategies for treating these debilitating disorders," Arnsten said.

The above story is reprinted from materials provided by Yale University.

Dementia and the Late Onset of Dyslexia

Searching for Utopia

This post examines the differences between  Semantic dementia (SD), a progressive neurodegenerative disorder characterized by loss of semantic memory in both the verbal and non-verbal domains AND Semantic Aphasia (AD), a progressive neurodegenerative disorder or aphasia, characterised by the loss of recognition of the meaning of words and phrases.

The NIH paper this is taken from is very 'technical' in its form and is primarily for cognitive scientists to review and discuss but, with some effort on our part, we can see through the jargon to determine that current research is able to distinguish between the onset of Dementia and its effect on our cognitive abilities.


Below is an extract from the paper:

"This NIH study examined the impact of semantic impairment on a variety of “pre-semantic tasks” – lexical decision, object decision, colour decision, reading aloud, spelling to dictation, past tense generation and delayed picture copying – in semantic dementia (SD) and semantic aphasia (SA).

Previous research indicates that all of these tasks are affected in a highly predictable way by the semantic degradation in Semantic Dementia (see Patterson et al., 2006).

SD patients have difficulty with transformations that are atypical and make “regularisation errors” in which irregular items are produced as if they were domain-typical.

In contrast, we found that comprehension impairment in Semantic Aphasia did not result in this pattern.

1. In all seven “pre-semantic” tasks that we examined, the SA patients were less sensitive to typicality than the SD patients (producing significant group by regularity interactions), even though the two groups were matched for performance on semantic tests. 
2. In several tasks, the aphasic group were also less sensitive to item frequency and/or showed a smaller frequency by typicality interaction than the patients with SD. 
3. In production tasks, the SA patients made fewer regularisation errors and many more implausible responses than the SD group – for example, unrelated, semantic and perseverative errors.

The predicted effects of semantic impairment on pre-semantic tasks have been demonstrated most frequently in patients with SD.

In contrast, patients who show a breakdown in this association – i.e., preserved reading of irregular words despite pronounced semantic memory problems – are typically individuals with AD and stroke aphasia (Gerhand, 2001; Lambon Ralph et al., 1995).

These cases are viewed as highly significant by some researchers because they suggest that semantic memory impairment and regularisation errors on “pre-semantic” tasks are dissociable.

However, our findings indicate that strong typicality effects in “pre-semantic” tasks follow degradation of ATL semantic representations and not poor executive control of semantic cognition.

As the semantic deficit in SA and to some extent AD is likely to be related to poor executive control, individuals with these conditions do not disconfirm the hypothesis that semantic representations play an important role in “pre-semantic” cognition.

Read the full paper here at NIH website