Considering the approximately 4000 enzyme systems, 1000 mediators and more than 250 nutrients known to be important to human health, the complexity of optimal cell function and inter-regulatory mechanisms should become apparent. Paracrine signals are transferred between cells. Autocrine signals are used to monitor the intracellular environment and endocrine signals are transmitted through the body. Regardless of the type of signaling, the signal transduction, similar to an electronic circuitry process, comprises of amplification, distribution and feedback.
Defective feedback, or a communication breakdown, has become increasingly apparent as one characteristic of many chronic, neurodegenerative diseases and cognitive dysfunctions.
Interruption of the homeostasis of an organism from a signal and response point of view implies the tipping of delicate chemical balances. Countless influences act on chemical balances from outside and within the body, such as acute and chronic stress, diet, exercise, lifestyle, etc. Functional Medicine concerns itself with the unbalanced, seeking answers in what has shifted in the flow of biochemical information, physical structure, emotion and energy, within the interconnected functionality of the body.
Starting with an overview of memory and amnesia, their basic systems as well respective mechanisms involved, the article follows to introduce the concept of systemic inflammation (gut irritation, gluten sensitivity, leaky gut) as a trigger in system communication failure and consequent neurodegenerative disease.
Since the dysfunction of cellular insensitivity to insulin signaling is an exemplary model for visualising the interconnections of complex disease (and is strongly connected to food intake & stress) as per signal breakdown and its consequences, the ‘metabolic syndrome’ is briefly outlined and discussed.
After summarising the principles of neuropsychological assessment, the ‘Functional Medicine Essence’ is recapped, illustrating the benefit and absolute necessity of the inclusion of various disease and infection markers within any cognitive profile or diagnostic assessment. Critical thinking will hopefully avoid systematic logic errors and possible misinterpretations of actual predictors or types of patient information when seen as part of an interrelated web of functional optimisation.
Memory and amnesia: Grandpa and the chicken or the egg?
Broadly speaking, memory commonly tends to be assimilated with an old photograph of grandpa smiling or the one-eyed teddybear stored up in the attic. Amnesia, on the other hand, is mostly perceived as a ‘condition’, a resultant state of impaired cognition and retrieval, past or future, on account of an accident, trauma, etc. Amnesia appears to be a separate entity, if somewhat connected to memory; and memory’s sole responsibility seems to be remembering grandpa – vastly underestimating both.
Amnesia can’t happen without memory, and memory serves to record all of life’s protocols in order to maintain and establish function. Holistically speaking, behaviour coupled with cognition is based and formed by experience and the processing of such. This initiates learning, leading to memory formation and consequent adaptation or action. A thought results from a pattern of stimulation of many parts of the nervous system simultaneously. Specific areas of the stimulated cortex determine discrete characteristics of the thought, such as specific localization of sensations of the surface of the body and objects in the field of vision, the feeling of textures, visual recognition and other individual characteristics entering overall awareness of a particular instant (Guyton&Hall, 2006). Hence not only the photograph of grandpa might slip out mind in memory loss, but our awareness of a particular instant and the interpretation of such might be impaired.
Memory could therefore be seen as the active process in the formation, storage and consolidation of experience as well as consequential actions, whereas amnesia is the passive degeneration or destruction of already consolidated experience, namely long-term memories.
Memory loss alike amnesia carries the same consequence: an inability to retrieve relevant information or to initiate awareness and respond appropriately; where amnesia presupposes the formation of memory while leaving its activity, if not effectively functional, in tact. There are a lot of marbles to lose.
A short recap on memory, amnesia and regions/ structures/ systems implicated on damage
‘As amnesia demonstrates a basic functional independence of memory from other cognitive capacities, memory can be compromised in apparent isolation of such’ (Banich&Compton, 2011, p.267). Depending on the brain region damaged, multiple deficits may arise. Long term amnesia results from extensive damage to the medial temporal lobe involving sub-cortical and cortical structures like the hippocampus, dentate gyrus, subiculum, amygdala, parahippocampal, entorhinal, peripheral cortices, the midline diencephalic region and dorsomedial nucleus of the thalamus as well as the mamillary bodies of the hypothalamus. (Banich&Compton , 2011). Amnesia therefore affects a wide range of memory material in accordance with the implicated areas. Whereas anterograde amnesia refers to a deficit of learning new information after impairment, retrograde amnesia leads to memory impairment prior to the event that caused amnesia. As long as the damage does not extend into neocortical brain regions, individuals maintain intellectual and basic perceptual, motor, linguistic competencies from before onset (Banich, Compton, 2011).
Depending on the type of memory affected, various functions are implicated coupled with specific areas. The Hippocampus enables short-term online holding of information while it is being processed. The short, online holding is what is termed the ‘working memory’, which ‘includes mainly short-term memory that is used during the course of intellectual reasoning but is terminated as each stage of the problem is solved’ (Guyton&Hall, 2006, p.723). Animal model experiments have shown that the hippocampal system possesses anatomical connections and neural mechanisms that allow the association of disparate pieces of information together in memory, such as objects presented in the environment, spatial relations among them, events in which they play roles and their temporal relation as well as affective and behavioural response they elicit (Banich&Compton, 2011).
The hippocampus therefore allows not only the online holding, short-term memory, but also the processing of conjunctions or co-occurrences of inputs, turning the info into intermediate long term memories lasting for days to weeks, or long term memories, ‘which, once stored, can be recalled up to years or even a lifetime later’ (Guyton&Hall, 2006, p.723).
Various theories attempting to capture the essence of memory processing and the responsible memory type have been stipulated, ranging from the declarative, explicit memory system, which is the ‘conscious’ recollection of prior experiences and facts, to the procedural, implicit memory system allowing prior experiences to affect behaviour without consciously retrieving the memory or even being aware of it. According to this model, the hippocampal system would be deemed declarative & explicit, leading us to the the implicit, procedural processor: the basal ganglia, which has a pattern of deficits opposite to hippocampal damage-affecting learning associations between stimuli and response, either motor, skill-learning or expected outcome based (Banich&Compton, 2011). Perhaps it is more useful to remember that no memory system, type or structure works entirely independently nor is it free of the need of a stimulus. The amygdala (part of the limbic system), for example, represents an interface between memory and emotion, mediating learning and expression of emotional responses to stimuli whose emotional significance is not automatic but has been learned via association (mainly fear) (Banich&Compton, 2011).
The amygdala is critical for learning stimulus-reward association, which intrinsically motivates everything we do, being human…
So where do memories go?
Memories are in part stored by the same brain regions (neocortical) that were originally involved in processing info for a given experience, e.g. domain specific damage such as to the fusiform gyrus will lead to a visual processing impairment. Memories are encoded by the hippocampus and prefrontal cortex, maintained overtime by setting memory traces (changing the chemical milieu surrounding the cell), stored (by changing the cell structurally) in the corresponding cortical region and strengthened as well as be made accessible (Banich&Compton, 2011). The brain can retain info in more than one manner, so it can be best used to optimally suit a particular situation or instance. The retrieval of such depends on the nature of information needed.
Semantic as well as episodic memory is predominantly stored in the anterior temporal regions. Consolidated memories, for example, will not be affected by damage to the hippocampus, whereas unconsolidated ones will be. Prefrontal regions may play a role in mediated strategic aspects of memory, focusing on organising or inhibiting irrelevant information. The hippocampus is responsible for the retrieval of an event and the prefrontal cortex records it. Retrieval in the hippocampus relies on ‘dual process models’, engaging different neural systems by familiarity (peripheral cortex & connections with dorsal medial nucleus) as compared to recollection (hippocampus & related diencephalic structures). Retrieval in the prefrontal cortex involves the organising and monitoring of verbal tasks (left posterior prefrontal cortex), the left prefrontal region produces items that are retrieved (recall).The right prefrontal regions monitor whether or not info is stored in memory (recognition) and the left parietal cortex plays a role in memory retrieval regardless of the nature and content (Banich&Compton, 2011).
It is important to know at this point, that the working memory is not implicated by hippocampal damage even though the working memory and long term memory work somewhat parallel. On account of the multiple working-memory capacities, deficits are always tied to a very specific processing domain, leaving other processes intact (Banich&Compton, 2011).
The prefrontal cortex can be seen as the ‘central executive’, being activated for maintaining, updating, comparing and inhibiting while choosing selectively according to importance. The amygdala interfaces memory and emotion. Whereas the motor cortex records, the basal ganglia enable the procedural processing (striatum: putamen & globus pallidus & caudate nucleus). The hippocampus mainly serves long-term memory and the inferior temporal cortex fulfills the short-term/ working memory requirements. Hence one system supports the learning of implicit & semantic memory whereas the other encodes and stores specific instances of events by combining specific pieces of info. Both work symbiotically, transferring and transforming info as expected by stimulus input (Banich&Compton, 2011).
Leaking Brain or Leaky Gut? Part 2 – Communication…
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4. Guyton, A.C., Hall, J.E. (2006). Textbook of Medical Physiology. Philadelphia: Elsevier Saunders