Explicit Memories are long-term memories that are stored in the following brain structures:

• Hippocampus
• Neocortex
• Amygdala

Implicit Memories are long-term memories that are stored in the following brain structures:

• Basal Ganglia
• Cerebellum

Working Memory and short-term memory are stored in the following brain structure:

• Prefrontal Cortex

1. What Is Memory?

Memory is the faculty of processing, storing, and remembering experiences and knowledge. It is what makes us and what makes our identity.

Memories are processed, stored, and reactivated in specific neurons that interact with each other through synapses which are known as synaptic plasticity.

Memories are made stronger or weaker depending on dynamic interactions between these groups of specialized neurons.

Memory is divided into short-term memory or working memory and long-term memory which includes explicit and implicit memories.

2. What Does It Mean to Have an Explicit Memory?

Explicit memories are conscious memories that recall events that happen to us (episodic memories) or that recall general knowledge of the world (semantic memories).

They are formed and stored in a specific group of neurons found in the hippocampus, neocortex, and amygdala.

2.1. What Does the Hippocampus Do for Memory?

The hippocampus is the structure of the brain where episodic memories are formed and stored. It is situated in the temporal lobe of the brain.

In addition to its role in long-term memory, the hippocampus is also involved in learning, flexible and goal-oriented behavior, navigation, and spatial orientation.

The hippocampus is also one of the two areas of the adult brain where there is still the production of new neurons (hippocampal neurons) due to the presence of neural stem cells.

2.2. What Does the Neocortex Do for Memory?

The neocortex serves as a storage area for temporary memories provided by the hippocampus and that are stored in a form of semantic memories.

It is the largest part of the cerebral cortex and is also involved in sensory perception (perception of outside stimuli), spatial reasoning, language, and the planning, control, and execution of voluntary movement.

2.3. What Does the Amygdala Do for Memory?

The amygdala is an almond-shaped structure of the brain’s temporal lobe involved in the formation and storage of emotional and fear-associated memories.

In addition to its role in memory, the amygdala is also involved in emotional responses (e.g., fear and anxiety) and decision-making in response to external stimuli.

3. What is Implicit Memory?

Implicit memories are unconscious or automatic memories that do not require conscious or voluntary recall to influence our behavior.

Implicit memories are divided into priming memories and procedural memories:

• Priming Memories

A priming memory is an unconscious improvement or change in dealing with a stimulus because of a previous experience with the same or a related stimulus [2].

• Procedural Memories

Procedural memory is associated with performing tasks without being consciously aware of doing them. An example is the capacity of riding a bike even if we did not cycle for a long period.

Implicit memories are formed and stored in a specific group of neurons found in the basal ganglia and cerebellum.

3.1. What Does Basal Ganglia Do for Memory?

Basal ganglia are structures resting deep within the brain and are involved in the storage of procedural memories [3].

Basal ganglia are also involved in many functions of the brain, including cognition, emotion, procedural learning, conditional learning, habit learning, and control of voluntary motor movements.

3.2. What Does the Cerebellum Do for Memory?

The cerebellum is situated at the back of the brain and is involved in procedural memory but also in motor learning and classical conditioning.

In addition, the cerebellum is involved in controlling the body balance, coordination, movement, and motor skills.

4. What Is Working Memory?

Working memory is a temporary storage of a small amount of information ready for immediate mental use [4].

5. What Is Short-Term Memory?

Working memory is a temporary storage of a small amount of information without manipulation of the information stored [5].

Theoretical concepts differentiate between working memory and short-term memory as short-term memory is suggested to refer to the maintenance while working memory involves a combination of maintenance and manipulation of information.

However, correlational studies have not been able to separate between working memory and short-term memory [5].

Working memory and short-term memory are mediated by the prefrontal cortex.

4.1. What Does the Prefrontal Cortex Do for Memory?

The prefrontal cortex is situated at the front part of the frontal lobe and is involved in the storage of a small amount of information.

In addition, the prefrontal cortex is involved in many functions of the brain, including executive processes (differentiating between conflicting thoughts), information processing, attention, judgment, behavioral organization, and certain aspects of language and speech [6].

5. What Are the Types of Memory Loss?

Memory loss is known as amnesia which can be caused by head or emotional trauma, Alzheimer’s disease, brain tumor, alcoholism, seizures, encephalitis, or stroke [7]. There are several types of amnesia:

• Retrograde Amnesia
• Anterograde Amnesia
• Post-Traumatic Amnesia
• Transient Global Amnesia
• Dissociative Amnesia
• Infantile Amnesia

5.1. What Is Retrograde Amnesia?

Retrograde amnesia is the incapacity to recall events or information from the past.

5.2. What Is Anterograde Amnesia?

Anterograde amnesia is the incapacity to recall new events or information following an amnesia incident.

5.3. What Is Post-Traumatic Amnesia?

Post-traumatic amnesia is a state of confusion associated with to incapacity to recall new events or information immediately after a traumatic incident.

5.4. What Is Transient Global Amnesia?

Transient global amnesia is a temporary sudden and total loss of short-term memory.

5.4. What Is Dissociative Amnesia?

Dissociative amnesia is the incapacity to recall personal information following trauma or stress.

5.5. What Is Infantile Amnesia?

Infantile amnesia is the incapacity to recall events or information from childhood.

Conclusion

Memory is a complex process that involves several parts of the brain that process, store, and reactivate conscious and unconscious information from the past and when we need them. Without memories, it is impossible to know who we are, what we are doing, and what we are planning to do.

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• Multiple Sclerosis (MS)
• Neuromyelitis Optica Spectrum Disease (NMOSD)
• Myelin Oligodendrocyte Glycoprotein (MOG)-Antibody Associated Disease
• NMDAR Encephalitis

1- What Is an Autoimmune Disease?

An autoimmune disease is when the body develops an abnormal immune response against certain parts of the body leading to their destruction.

An abnormal autoimmune response is associated with the production of antibodies against compounds (antigens) that belongs to the body, and therefore, that should not be recognized as foreign.

2- What is an Antibody?

Antibodies or immunoglobulins (Ig) are Y-shaped proteins produced by specific types of white blood cells known as lymphocytes B cells in response to pathogens such as bacteria and viruses.

An antibody recognizes and binds a specific antigen on the surface of a bacteria or virus leading to their destruction. It is highly specific and targets a specific antigen, and therefore, cannot target other antigens.

However, when there are abnormalities in the immune response, the antibodies start recognizing antigens on the surface of normal cells which leads to their destruction and the development of autoimmune diseases, including autoimmune diseases of the central nervous system [1].

3- What Causes Autoimmune Diseases?

• Genetic Susceptibility

Although the potential involvement of heredity in autoimmune diseases is unknown, studies of homozygotic twins (identical twins) and heterozygotic twins (non-identical twins) with multiple sclerosis (MS) and myasthenia gravis found an association between genetic factors and autoimmune diseases [2] [3].

• Infections

In multiple sclerosis (MS) and MOG-antibody associated disease, chronic infection with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were suggested as triggers of autoimmune response by mimicking the host (infected individual) normal antigens [4][5].

• Vitamin D Deficiency

Vitamin D is an antioxidant that has also a role as a modulator of immune response by controlling the proliferation (multiplication) of lymphocytes B cells and their production of antibodies.

Although the results are conflicting and require further investigations, studies reported an association between the incidence and susceptibility to multiple sclerosis (MS) and the decrease in the levels of vitamin D [6][7][8][9].

• Gut Flora Unbalance (Dysbiosis)

The gut flora or microbiota is a heterogeneous population of micro-organisms that includes bacteria, fungi, and archaea, and that plays an important role in the digestion and absorbance of food. 

During the process of aging, the function of beneficial microbes, that provide necessary nutrients for the body tissues, is severely affected, while harmful microbes, that contribute to the process, such as chronic inflammation and cancer, flourish.

Studies showed that fecal transplants from patients with multiple sclerosis (MS) into germ-free mice results in a higher incidence or severity of multiple sclerosis in these mice [10][11].

• Tumors

Tumors are characterized by an uncontrolled division of cells due to cancerous mutations in normal cells. When some tumors die, they can release both cancerous and normal antigens that are thought to initiate an autoimmune response [12][13].

4- Autoimmune Diseases of the Central Nervous System

• Multiple Sclerosis

The axons of neurons are covered by a sheath of a fatty acid (lipid), known as myelin, which insulates them and increases the rate of nerve impulses.

In multiple sclerosis (MS), the myelin sheath is damaged through a process called demyelination which disrupts the capacity of the affected neurons to conduct nerve impulses.

It is proposed that multiple sclerosis (MS) is due to a mix between genetics and infections; however, there is no evidence yet to support these hypotheses.

This demyelination of neurons results in the following symptoms:

Effects on the Central Nervous System: Cognitive impairment, anxiety, depression, mood instability, and fatigue.

Effects on the Vision: Inflammation of the optic nerve (Optic neuritis), involuntary eye movement (Nystagmus), perception of two images when looking a single object (diplopia).

Effects on the Musculoskeletal system: Fatigue, spasms, and Ataxia (uncoordinated movements).

Effects on Speech: slurred or slow speech due to a weakness of speech muscles (Dysarthria).

Effects on the Throat: difficulty swallowing (Dysphagia).

Effects on Sensation: Pain, paraesthesia, hypoesthesia.

Effects on the Bowel: Diarrhea or constipation and incontinence.

Effects on the Urinary System: frequent urination or retention of urine.

• Neuromyelitis Optica Spectrum Disease (NMOSD)

NMO is an autoimmune disease affecting the optic nerves, spinal cord, and brainstem. It is associated with autoantibodies targeting an abundant protein in the nervous system known as aquaporin 4 [14].

The causes of NMOSD are unknown and the symptoms are associated with a loss of vision, loss of sensation, weakness, and anomalies in the bladder function.

• Myelin Oligodendrocyte Glycoprotein (MOG)-Antibody Associated Disease

MOG-Antibody Associated Disease is a rare autoimmune disease affecting a protein known as myelin oligodendrocyte glycoprotein (MOG).

MOG is found on the myelin sheaths and produced by a type of neuronal cells called oligodendrocytes. In this disease, autoantibodies are produced against MOG which causes the damage of myelin causing the demyelination of the neurons.

The symptoms of MOG include pain, muscle weakness or paralysis, abnormal sensations, bowel such as Diarrhea or constipation, and anomalies of bladder function.

• NMDAR Encephalitis

NMDAR Encephalitis or anti-receptor encephalitis is an inflammation of the brain that is caused by autoantibodies against a receptor of the neurotransmitter glutamate known as NMDAR [15].

NMDAR is found on neurons where it plays an important role in the control of synaptic plasticity.

NMDAR Encephalitis is mainly caused by ovarian teratoma and by an inflammation of the brain associated with a herpes virus infection.

The symptoms of NMDAR Encephalitis include seizures, depression, mania, visual or hearing hallucinations, acute schizophrenic disorder, and cognitive and movement disorders.

5- How are CNS Autoimmune Diseases Diagnosed?

In addition to the symptoms associated with each CNS autoimmune disease, the patients are tested using magnetic resonance imaging (MRI), electroencephalogram (EEG), computerized tomography (CT) scan, and FDG-positron emission tomography (PET)/CT scan, to detect neuronal lesions [1].

Autoantibody testing is used to detect the presence of autoantibodies against proteins such as NMDAR, MOG, and aquaporin 4 in the serum and cerebrospinal fluid (CSF) using laboratory techniques such as immunohistochemistry, indirect immunofluorescence, western blot, and cell-based assays.

Conclusion

CNS autoimmune diseases are due to the generation of antibodies by lymphocytes B that attack specific proteins that are expressed on neurons and in the brain. Most therapies aim at eliminating the autoantibodies using plasma exchange and immunosuppression [1].

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