(18/07/2022)

In a previous article we talked about our cognitive processes (or higher cortical functions) and their anatomy. Basically, we tried to understand where in our brains the processing of perceptions takes place and where those processes that enable us to experience the world, relate to the external environment, and define some of our abilities take place.

But are we sure that we know as much as possible about the functions of our brain? And what happens if a specific part of it suffers trauma or damage?

The answer, of course, is that we still do not know everything there is to know about our brains; however, we can try to describe what we have learned in History through study, practice and experience, particularly through some truly unique experimental and clinical cases.

Let's imagine that we have in our hands an object, an extremely complex device, a kind of electronic circuit equipped with voltage generators, inductors, capacitors, resistors, but also diodes, field-effect transistors, logic gates, integrated modules and so on; in short, an object consisting of a huge number of sections and components. We may be able to use it, at least a good part of it, but we may not necessarily know the function of all these elements. Somewhat like we often do with our pc or our car's control panel settings.

However, if a component or section suffers damage, it is likely that we will have a loss of some of the functionality of our device, and this will help us to better understand the very usefulness of the elements that have been damaged.

Well, the human brain is sometimes referred to as the most complex object in the entire Universe.

To complete the topic undertaken with the last article, therefore, today we will reason a little more "practically" and see what the cognitive implications of brain damage are; we will do this by reporting some experimental evidence of the role played by the different associative areas of our brain and also cite some interesting real-life clinical cases.

Brain activation in a memory task detected by functional MRI imaging (fMRI) [Sharon S. Simon et al, «Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Trial», Frontiers in Aging Neuroscience, 2018]

• Posterior parietal cortex (PPC)

People with lesions in the right posterior parietal cortex show an inability to perceive, explore, and act in the space contralateral to the site of the damage (although their sensory channels obviously remain unaffected). In fact, the person acts as if they cannot perceive (nor conceive of) the existence of any part of the surrounding space; there is also a lack of perception of the contralateral half of their body ("hemisoma"). People with this condition may, for example, not eat food on the left half of the plate, or not wash the left half of the body. In some cases, a man may shave his beard perfectly, but only on one side.

How a person with "neglect" or "eminegligence" perceives the food on a plate, effectively neglecting half of it

Edoardo Bisiach showed in a famous experiment the existence of "eminegligence" that also involves the memory of extra-personal space, according to a body-centered reference system. It was concluded that PPC is crucial for the awareness of the structure and dimensions of our body - and also of the space around it - and for the related mental representation.

Another fact we know about the right PPC is that it is involved in number cognition (which is part of mathematical cognitive abilities). In short, the PPC would be the seat of the "mental number line" that is, the display of numbers in succession along a line (from left to right). In our brains, therefore, numbers would be said to be somehow "spatially encoded".

The left posterior associative area is also involved in language: this is related to the presence in this area of the angular gyrus, Wernicke's area, and other (perisylvian) areas involved in understanding the read (visually or tactually, i.e., in Braille) or heard word.

Regarding Wernicke's area: a lesion in this area can cause the affected person to "talk gibberish," but with perfect sentence construction, which will then be set in the correct grammatical order.

Cartoon depicting a dialogue between a patient and German scientist Carl Wernicke (1848-1905), who in 1874 discovered the brain area that bears his name. ©Tony De Saulles, 1999

Regarding speech, the correct pronunciation of words is subject to the proper functioning of Broca's area (connected to Wernicke's area by a neural pathway called the arcuate fascicle), which has the function of sending the right message to the motor cortical area that controls the movement of the vocal cords, tongue and lips.

Caricature of English clergyman William A. Spooner (1844 - 1930), from whose name the term "spoonerism" comes: a mispronunciation in which the initials of words are interchanged probably due to a gap in Broca's area.
©Tony De Saulles, 1999

In short, when we talk to someone, we are using several brain areas that coordinate with each other just to control pronunciation and sentence construction; motor areas, then, allow us to make vocal cords, tongue and lips work synergistically, not to mention gestures (which very often allow us to "reinforce" concepts!).

• Inferior parietal cortex (IPC)

This area plays a role in working memory (that which retains information during the implementation of a behavior, for example, when we listen to a sentence or story by combining words into a logical, coherent and complete thought or when, for example, we search for our parked car among others, or even when we choose the best route to a place using the so-called "visuo-spatial notebook"; it seems in particular that the left IPC is the neural substrate of the phonological store for verbal working memory. In contrast, the visuo-spatial notebook for nonverbal working memory would appear to be located in the right IPC. Thus, working memory would arise from coordination between parietal areas (phonological store and visuo-spatial notebook) and prefrontal areas.

• Prefrontal cortex (PFC)

Among humans and nonhuman primates, this is the area that differs most; this suggests its probable responsibility for the higher cortical functions that distinguish us most from these animals. PFC is divided into three regions: dorsal, medial and orbitofrontal (or ventromedial).

Patients with lesions to different sections of the PFC showed what has also been seen through brain imaging experiments performed with normal subjects engaged in different tasks and experiments of lesioning and subsequent recording of the activity of single neurons in monkeys: different areas of the PFC play different roles in higher cortical functions.

For example, the dorsolateral prefrontal cortex (DLPFC) seems to have the main central executive role (a kind of "supervisor system") in working memory. Indeed, it has been seen that animals (including humans) with lesions in this area report severe deficits in working memory: as soon as a "delayed choice task" is proposed by introducing a time delay between the moment when you show the animal in which container (among two or more) food is hidden and the moment when it can select one to feed itself (thus relying on information that it has to store and retain for a few seconds), in the case of a lesion, performance is very poor.

It also seems that the PFC is activated for the performance of complex visual recognition tasks, such as those in which objects are viewed from an unusual perspective: the recruitment of prefrontal areas, in addition to that of posterior associative areas, would allow processes of "mental rotation," in order to be able to recognize the object based on the experience made of it under a "canonical" perspective. Recruitment of prefrontal areas during the performance of "difficult" tasks is also suggested by observations in elderly subjects who maintain good performance in working memory or long-term memory tasks: in such subjects, in fact, bilateral activation of prefrontal areas is observed (an interesting aspect: in young subjects, activation is localized in only one cerebral hemisphere).

PFC also plays a role in the retrieval of declarative memory traces (related to consciously recalled information) formed long ago: in fact, it is activated during the encoding and retrieval of episodic memories (belonging to declarative memory, these are the ones related to our life memories).

In addition, lesions to the prefrontal associative areas cause so-called source amnesia, that is, the inability to remember when and where a new fact was learned.

Damage to the ventromedial sector of the prefrontal cortex, on the other hand, disrupts social behavior: individuals who are also well-adjusted in society become unable to observe social rules and make decisions beneficial to themselves while maintaining normal performance in memory, language, and attention tasks.

A curious case: Phineas Gage

In this regard, the earliest documented case (as well as one of the best known in Neurology) is that of Phineas Gage (1823 - 1860): on September 13, 1848 near the town of Cavendish, Gage, who worked in railroad construction, was inserting an explosive charge into a rock that had to be blown up since it was blocking the passage of the line under construction. Unfortunately, the gunpowder exploded just as Gage was compacting it with an iron bar, which was thrown into the air striking him in the face and piercing the front of his skull. This caused severe trauma affecting the frontal lobes of his brain, particularly injuring the ventral and medial part of the PFC.

Graphic (period) and CGI representation of the area of Phineas Gage's brain affected by the accident

The unbelievable aspect of this event is that Gage survived this incident and was conscious and even able to speak after a few minutes, even returning to leave the house independently 3 weeks after the trauma. However, the event had significant consequences on Gage's personality, who from the sociable, reliable and dedicated person he was became irascible, unsociable, lacking inhibitions, prone to profanity and unable to organize himself in work and life by assessing the risks of his actions. However, this did not prevent him from finding a new job and even performing in front of an audience in shows of a circus nature, as a "man who was hit by a bar that went through his skull and survived." All this makes us realize how the PFC is also involved in defining our personality and emotions, although some (but not all, as we will see in a moment) decision-making processes are located in other areas.

Daguerreotype of Phineas Gage with crushing iron in hand. Note the palpebral ptosis in the left eye.
©originally from the collection of Jack and Beverly Wilgus, now in the Warren Anatomical Museum, Harvard Medical School

The case of Phineas Gage helped to bring remarkable developments in the understanding of certain higher cortical functions and their localization in the brain: also as a result of the reflections following this event, in the mid-20th century, methods (now in total disuse) such as prefrontal lobotomy were used to treat certain types of behavioral disorders (the story of Rosemary Kennedy, sister of John Fitzgerald and Robert, who was lobotomized at the age of 23 because of her mood swings and her free and easy sexual conduct, is sadly known).

Portuguese neuroscientist Antonio Damasio, since 1994, has also pursued the study of this type of patient: using laboratory tests that simulate gambling, he has shown that between a deck of cards whose sequence will give a certain gain and one in which there will be a certain loss, subjects with lesions to the ventromedial areas, which include the orbitofrontal cortex, continue to select the disadvantageous one.

Damasio therefore hypothesized that the inability to make beneficial decisions demonstrated by people with lesions to ventromedial PFCs is caused by damage to an emotional mechanism that stores and signals the value of the consequences of an action. It would thus become apparent that the ventromedial PFC is also implicated in the decision-making mechanisms and mechanisms underlying emotional behavior, as well as in the attribution of the "attractive" quality that some stimuli have for us.

• Medial frontal cortex

This area seems particularly responsible for the flexibility of behavior and its cognitive control. The detection of unfavorable consequences, response errors, conflicting responses and decision-making uncertainties activate certain areas of the medial frontal cortex and evoke neuronal activity in a large part of the posterior medial frontal cortex. The latter also includes the anterior cingulate cortex - and this would correlate with subsequent correction of behavioral performance. The posterior medial frontal cortex would thus appear to be involved in the activity of monitoring behaviors in contexts where we anticipate the presence of a "reward," while the lateral PFC would appear to be involved in implementing corrections to our behavioral strategies.

• H.M.'s memory: medial structures of the temporal lobe

The medial structures of the temporal lobe play a crucial role in declarative memory. The study of the structures involved in this type of memory virtually began in 1953, with the observations of William Scoville and Brenda Milner. That year saw the case of a patient named Henry Molaison, known as H.M. (1926 - 2008), who revolutionized knowledge about the organization of human memory, leading to the emergence of new theories concerning its processes and underlying neural basis.

Due to a severe form of drug-resistant epilepsy, on September 1, 1953, at the age of 27, H.M. underwent surgical ablation of both medial temporal lobes by Dr. Scoville.

The same doctor's description was, “a bilateral resection of the medial temporal lobes was performed, advancing posteriorly for a distance of 8 cm from the midpoint of the temporal lobe border, with the temporal horn composing the lateral margin of the resection”.

H.M. and his cognitive state: unable to store new memories, the patient remembered being 27 years old even when it had been a long time since the operation. In fact, toward the end of his own life he was like "a young man in an old man's body." Below can be seen an illustration of H.M.'s brain compared with that of a healthy person

Following the operation, which reduced the severity of his seizures, H.M. began to suffer from a very severe form of anterograde amnesia: in fact, he had become unable to form new long-term memories related to facts (semantic memory) and events (episodic memory). He also showed limited retrograde amnesia, i.e., loss of memory related to facts or events that occurred before the surgery (which in his case extended backward up to three years). In contrast, the memory of facts and events that occurred several years before the surgery had remained perfectly intact. Despite his condition, H.M. retained the ability to form traces of procedural memory (memory of how things are done and how objects are used, such as tying a shoe or riding a bicycle without "consciously" thinking about it), so he could, for example, learn new motor skills… although he could not remember where or how he learned them.

All of this suggested that implicit (procedural) and explicit (semantic or episodic) memory are presided over by different neural substrates, and that the hippocampus and other structures in the medial temporal lobe are fundamental to the initial formation of a declarative long-term memory trace, to the formation of which information coming from different associative areas contributes. The memory trace constructed from the aforementioned information would then be slowly transferred to the final "storehouse," thus consisting of neocortical associative areas, including precisely the prefrontal areas.

©Tony De Saulles, 1999

In this article and the previous one we have tried to catalog and understand our higher cortical functions and their anatomy, also describing some possible cognitive consequences of brain damage (with some reference to historical, clinical or experimental cases); from here we will be able to go on and talk more specifically about the kind of rehabilitation therapy that intends to counteract these situations, stimulating and rebalancing as much as possible the activity and function of our brain: cognitive rehabilitation.

To summarize: we have summarily defined some cognitive functions, their anatomical substrates, and the consequences of damage to these substrates; in a next article we will mention the type of rehabilitation that intends to respond to these same damages.

Next, we will reflect on the connection between cognitive rehabilitation and "robotic motor therapy" and recall some remedial strategies, i.e., some modes of "exercise" that are currently proposed to patients with cognitive impairments.