Neuroscience and the Neuronal Correlates of Consciousness

Neuroscience and the Brain

Even the most enthusiastic neuroscientist will concede that the human brain is not much to look at: a 1.5kg cauliflower of grey, spongy matter. But despite their modest outward appearance, our brains are the most complex objects known to man, and still represent the greatest problem in biology: how the timed firing of electrical signals from neurons, along with glial cells and neurotransmitters, can give rise to something as remarkably abstract as our own consciousness.

With recent advances in the field of neuroscience, the way we think about the way we think is changing, and the quest for the physical basis of consciousness promises to be a voyage of discovery as fascinating as the quest for the structure of DNA in the early 1950s. But what exactly are the problems facing neuroscientists, and how are these being solved today?

Defining Consciousness and Awareness

Perhaps the first issue is in defining consciousness itself. As human beings, we experience the world. When light of a certain wavelength hits the cone photoreceptors of our retina, we experience the sensation of seeing “red”, for instance, and we have feelings that correspond to this experience.

We are also probably not the only animals who experience the world in this way. Experimenting (humanely) with chimpanzees and dolphins has demonstrated that they are capable of complex, abstract tasks such as recognising themselves in mirrors (Gallup, 1970) and planning future actions (BBC), activities which should be impossible without some form of consciousness, or inner mental life.

Even the humble fruitfly has demonstrated that it is capable of complex behaviours involving choice (Heisenberg and Wolf, 1984). As such, Descarte’s idea of there being a “threshold of consciousness” over which only humanity has stepped has begun to sound as outdated as the concept of a geocentric universe.

Are Computers Conscious?

However, a neat sliding scale of consciousness also has its faults. Everyone has experienced what happens when a computer finds a fault in its hardware: you will likely receive a cryptic error message, or simply the “blue screen of death” as the damaged system struggles to function. But the idea that computers sense this line of code as analogous to pain, or that they experience the world on any level at all, can be discarded fairly quickly.

That is not to say that this suggestion does not have its proponents. Some scientists, like David Chalmers of the University of Arizona, postulate that all systems capable of processing information, even digital systems, are conscious in some sense, if only on a rudimentary level. Chalmers does concede, however, that it would probably not feel like much “to be a thermostat” (Koch & Krick).

Were this theory correct, it would suggest that our spinal columns, for instance, along with many parts of our brain and even the 100 million or so neurons found in the intestinal wall, could themselves be conscious. After all, they, too, process enormous amounts of information every second. If they are, of course, they are certainly not telling us about it!

Studying the Brain

One problem for scientists is that in-depth study of the brain is necessarily an invasive and life-threatening procedure. Much has been learnt from studies involving electrodes measuring the brain’s electrical field from outside the skull, but this is as problematic as trying to learn about the structure of the ocean by studying its waves.

As such, a vast majority of recent developments in the science of our own minds comes from what happens when they go wrong. Patients suffering massive epileptic seizures must undergo complicated surgery to have electrodes placed inside their brain in order to locate the troublesome tissue causing their seizures. This gives scientists a unique opportunity to study the way the brain works, and in particular how its workings give rise to consciousness.

The Clinton Neuron

One remarkable discovery has involved a specific neuron found in a seizure patient that fires whenever the subject sees a picture of former US president Bill Clinton. The patient was shown photographs of other white-haired men, other former presidents and hundreds of random control pictures, none of which elicited a response. Every time Mr. Clinton entered the subject’s field of view, the electrical readings from this single neuron spiked.

The implications of this are enormous, since it places the firing of neurons right at the start of the chain of mechanisms that create consciousness. When this neuron and the possibly hundreds of other “backup” duplicates fire, they somehow start a series of events that results in the patient recognising a face. But the question remains: how does this binary system of neurons either firing or remaining dormant create the almost infinite intricacies of our minds?

How Do Bacteria Make People Sick?: Bacterial Pathnogenicity, Virulence Factors and Infectious Disease

In order to cause disease, potentially harmful bacteria must first enter the body, usually through breaks in the skin, penetrating the mucous membrane or colonizing the gastrointestinal (GI) tract. This is considered infection, when bacteria breech the first line defenses of the body.

Bacterial disease starts with infection, but infection does not always result in disease. Many bacteria are beneficial. And even when pathogens infect the body, the immune system may be able to eliminate the infection before symptoms of disease occur.

Bacterial Pathogenicity and Virulence

To cause disease, bacteria must be present in sufficient numbers. But what is it about bacteria that make an infected person ill? Disease is not merely caused by the presence of microbes.

Pathogenicity (path-o-jen-ISS-ity) refers to a microbe’s ability to cause disease, and some microbes are more pathogenic—better able to cause disease—than others. The degree of a microbe’s pathogenicity is considered its “virulence.” For example, highly virulent bacteria frequently cause disease, whereas less virulent bacteria may only cause disease when present in large numbers or within hosts that have weakened immune systems.

Many pathogenic, or disease-causing bacteria have special weaponry, traits that enable them to infect and damage host tissue. These disease-causing traits are called “virulence factors”. The following sections describe different types of virulence factors.

Adhesion Factors, Glycocalyces and Biofilms

Once bacteria get into the body, they must be able to stick to the host’s cells in order to increase in number. Bacteria that are able to stick to host cells have special structures or chemicals, collectively called adhesion factors. These adhesins are found on bacterial cell extensions, such as fimbriae and flagella, and also on glycocalyces, a sticky layer surrounding some bacterial cells that enable bacteria to stick to surfaces and to each other in biofilms. For example, the inside of the mouth and teeth are covered with a sticky bacterial biofilm, particularly in the morning, before brushing, because bacteria have been multiplying in the mouth throughout the night.

Bacterial Extracellular Enzymes

Some pathogenic bacteria are able to produce and secrete enzymes that compromise cell structure of the host and enable the bacteria to work their way further into the body.

Bacterial Toxins

Bacteria may also produce toxins that cause damage to host cells either directly, by destroying tissue, or indirectly, by triggering an intense or prolonged host immune response. Bacterial toxins fall into two general categories based on their position relative to the cell that produces them; exotoxins, which are secreted by bacteria, and endotoxins, such as lipid-A, which are part of the Gram-negative bacterial cell.

Evading Host Immune System

The human immune system has special white blood cells called phagocytes, which search out, engulf and digest invading pathogens. The sooner a pathogen can be eliminated from the body, the less damage it will have the opportunity to cause. However, bacteria have developed means of evading phagocytes.

The bacterial capsule, a type of glycocalyx, can help a bacterium hide from the immune system. This coating is often made of chemicals that are found in the human body, and that don’t trigger an immune response.

Other bacteria produce chemicals that prevent them from being digested once engulfed by a phagocytic white blood cell, allowing the bacteria to live and reproduce inside the host cells designed to eliminate them. Other antiphagocytic chemicals can prevent bacteria from being engulfed by white blood cell, or can even destroy white blood cells.

Antibiotic Susceptibility Tests – Types and Ways: Antibiotic Evaluation, Antimicrobial Effectiveness In Vitro In Vivo

Proper antibiotic susceptibility testing of microbial pathogens isolated from patients is critical. The use of an ineffective antibiotic could lead to a patient’s death

Today, if someone gets a bacterial infectious disease the first thought is “what antibiotic will help or work?” The doctor and the patient both desire the best and most effective antibiotic. This is what makes testing and analysis of antibiotics very interesting.

In the 1950’s and 60’s there were sufficient antibiotics on the medical scene to require a closer look at standardized testing of antibiotics. A better way was sought to accurately and precisely forecast which antibiotic would work and which would not.

Drs. Kirby, Bauer, and Sherris established a defined scientific approach to antibiotic testing (KBS technique) . This greatly improved the accuracy and results of testing. There are several important ways to determine antibiotic susceptibility.

Solid, Liquid and Animal Tests of Antibiotics

  • When chemicals and antibiotics were first tested they were added to nutrient agar petri dishes (circular glass, or plastic, with larger top glass cover overlapping a bottom reservoir) with bacteria streaked over the surface. The next day a zone of inhibition was looked for as shown in figures below (click to enlarge these figures).
  • Bacteria can also be tested in test tubes with nutrient broth. Sequential dilutions of the chemical or antibiotic are done first, followed by addition of a measured bacterial inoculum to each tube. After overnight incubation the tubes are analyzed: clear tubes indicate inhibition and cloudy tubes indicate bacteria not inhibited by that concentration or titer of antibiotic. In this way scientists can correlate later how much antibiotic yields what zone size on agar.
  • The zone sizes produced on plates by dropped antibiotic disks are plotted versus the amount in the disk. Simply, this is a regression analysis graph. It is possible to establish MIC (minimum inhibitory concentration) values in broth, blood or serum in this way. Typically, the more resistant a microbe is the smaller the zone. The more susceptible, the bigger the zone.
  • Finally, if an antibiotic looks promising, it can be tested in mice or rabbits for toxicity (harmful) and effectiveness.

Measurement of the amount of antibiotic injected, or ingested, is the dose. The antibiotic titer is the MIC = minimum inhibitory concentration ( an actual value attainable in blood or serum). MIC is measured in micrograms or units. MIC can be evaluated in blood and tissue fluids . The higher the MIC the more resistant the bacterium is to that antibiotic.

Standardized Antibiotic Testing

Antibiotic testing should always be done with a pure culture of the organism.

The KBS technique eliminates the variables that affect the zone size and could cause false positives or false negatives.

The agar used is Mueller-Hinton. The depth and pH of the agar,inoculum size and incubation temperature are standardized. The click-on photos below show several things:

  • different antibiotics have characteristic zone sizes for MIC
  • the same antibiotic at different concentrations will give different zone diameters
  • resistant bacteria cause zone size decreases. No zone = complete resistance
  • regression analyses enable microbiologists to determine MIC vs disk zones
  • populations of the same species vary from susceptible (S) to intermediate (I) to resistant R)

Recently, the valuable E-test (see photo) allows determination of MIC of a microbe with one disk that forms an antibiotic gradient. This permits rapid, clear medical evaluations of antibiotic effectiveness.