Aphasia: Definition, clinical contexts, neurobiological profiles and clinical treatments

Starting from the general concept of Aphasia, the present work focuses on the clinical, neurobiological, and functional aspects of the morbid condition, suggesting a multidimensional treatment between physiotherapy, psychotherapy, and rehabilitation exercises for lost skills. Review Article Aphasia: Defi nition, clinical contexts, neurobiological profi les and clinical treatments


Contents of the manuscript
The loss of the ability to understand, produce and reproduce a language, due to injuries to the areas of the brain responsible for its processing, is the defi nition of the neurological condition called "aphasia" (from the Greek ἀφασία, mutism). Therefore, speech disorders caused by primary sensory defi cits, intellectual defi cits, psychiatric disorders, or weakness of the musculoskeletal system are not included in aphasias [1][2][3].
In general, therefore, aphasia is caused by lesions of the areas of the brain primarily responsible for language processing (Broca area and Wernicke area) or other areas of connection with different brain centers variously involved in the function.
These areas are generally located in the left hemisphere for right-handed subjects (in the rare cases in which they are located in the right hemisphere it is called "cross aphasia").
In left-handed people, in 60% of cases they are in the right hemisphere, while in the remaining 40% in the left hemisphere or both [3,4].
Some studies suggest that there is a lower incidence of aphasia in women because they may have more bilaterality of language function, although women have a higher incidence of Wernicke's aphasia than men [4]. Common age can be considered an important factor in recovery: some studies suggest that recovery from stroke aphasia has failed in patients over seventy years of age compared to younger patients; however, at any age, various degrees of recovery can occur even in remote times from brain injury. [5,6].
However, remaining on the etiological profi le, it is important to underline that any brain disorder is capable of causing aphasia, as long as it affects the dominant hemisphere and the structures responsible for language processing. In this case we will speak of acquired aphasia. Among the most frequent causes, which can generate a temporary or permanent aphasic status, we fi nd: [1,4,[7][8][9].  as happens in anxious states [10] and depressants [11], in posttraumatic stress events [12] caused by serious psychological trauma [13], in panic attacks [14], in sleep disturbances on a psychosomatic basis [15], in obsessive disorders-compulsive [16] and psychopathological personality disorders in general.
Aphasia is also one of the causes that increases suicidal risk [17], especially concerning the subjective value of language for the patient.
The clinical alterations of cognitive functions related to language that fall within the term of aphasia include can concern both the understanding and the production, both the repetition and the structuring itself of the language, based on the brain areas affected by structural and functional damage.
The aphasic phenomenon can manifest itself in various ways.
Therefore, the ability to recognize a word or to choose the right word may be lacking. A word can be replaced with another of a different meaning but from the same family, or a wrong word with a sound similar to the right one or a completely different word and without any apparent link with the correct one can be used; furthermore, the disturbance can involve only speech, the ability to repeat a sentence, the structuring of a meaningful speech, or even the ability to write. In clinical observation, in particular, it has been observed on many individuals affected by this pathology that the forgetting of words follows a very precise order, without exception: the fi rst words to be forgotten are proper names, then common names, follow the adjectives and fi nally verbs and prepositions [4].
Modern neuropsychology bases the study of aphasia on the system of components of the language elaborated by psycholinguistics, identifying "specifi c defi cits" about three levels of elaboration [18,19].

Phonological level:
Evaluates the production of the fundamental units of words (phonemes). In verbal production, phonetic and phonemic level disturbances are therefore observed. The former is studied using instruments that detect the movements of the individual articulatory organs and the VOT (Voice Onset Time, or the interval of time between the opening of the phonoarticulatory duct and the beginning of the vibration of the vocal cords), and mainly consist of distorted sounds, variations that do not exist in the patient's language and increased pronunciation times (visible more for consonants than for vowels); the latter are disturbances in the conversion of the sounds of words (which maintain a correct representation in the patient's mind) into forms appropriate for the articulation and manifest themselves with phonemic paraphasias, i.e. replacement, omission, repetition or addition of phonemes within the words, which in serious cases become unrecognizable, giving rise to neologisms and neologistic jargon (if not even a word is understood) or phonemic jargon (in case a few words are still understood).

Lexical-semantic level:
Concerns knowledge related to the meaning of words, thus implying semantic memory. In verbal production there are naming and anomaly defi cits. The fi rst is the inability to produce the correct name of an object or situation upon request; the second concerns the inability to spontaneously produce a word during the speech, furthermore lacking any implicit knowledge about the word, such as the initial, the number of syllables, the position of the accent.

Syntactic-grammatical level:
Studies the rules for the formation of sentences, and the rules for the selection of words and sounds that have a grammatical function (free grammatical morphemes and grammatical morphemes linked to the root). Among the syndromes concerning verbal production at this level, there are agrammatism and paragrammatism: in the fi rst one there are mainly omissions of function words and substitution of bound morphemes and is generally associated with Broca's aphasia, therefore with a language not fl uent, with the simplifi cation of syntactic structures, reduction of the length of sentences and diffi culty in producing the correct order of words in the sentence; Paragrammatism has been studied much less than agrammatism, and some authors even question its specifi city, since it would be characterized by the substitution of bound morphemes (a feature that has recently been associated with agrammatism). In extreme synthesis however we could say that in the agrammatics there are errors for omission, while in the nosing errors and additions for substitution.
The traditional classifi cation of aphasias has generated several problems and disputes. It is not always possible to position a subject in one of the traditional categories; moreover, patients classifi ed in the same group can differ, even a lot, in the quality of the mistakes made. Finally, in several cases, the patient's pathology evolves and this no longer allows us to classify him in the same initial syndrome. For simplicity we can summarize them in the following forms: "Fluent aphasias" and "Not fl uent aphasias". Fluent aphasics have a relatively productive speech, in fact they manage to generate twenty words per minute with sentences composed of 5-6 elements; they also have relatively normal prosody and intonation of the phrase. They generally don't seem to realize their defi cits. Their language is characterized by the contemporary presence of appropriate words and words without connection; the sentences, often long, do not follow the rules of syntax and are made inaccurate by the frequent use of periphrases; however, Not fl uent aphasics are characterized by a scarce spontaneous verbal production, they can produce only isolated words or very short sentences composed of two / three elements, reducing the expression in some cases to a stereotype or a verbal formula; they also have a strongly slowed down and abnormal prosody and intonation of the phrase. They use very simple syntactic structures: they use a few verbs, sometimes not even conjugated, and they use a telegraphic style, that is, they do not use particles as articles, prepositions, and pronouns. Often, noticing the diffi culties in communication, patients become discouraged and give up speech or compensate for needs with non-verbal language. Not fl uent aphasias are caused by frontal lesions of the left hemisphere [3].
There are several possible aphasia that can be found: however, understanding is less damaged than production.
The patient with Broca's aphasia has the awareness of his situation and it is not uncommon for him to burst into tears easily feeling frustrated and depressed. In general, after a few weeks, aphasia can regress but in some cases this language can remain agrammatic or it remains a spoken with a foreign accent as it violates some phonetic laws typical of the original language (in fact, the possible similarity with some languages is completely random). This phenomenon is called accent syndrome foreigner [20], it is a rare event (just over twenty cases in the world) and has been known since 1919. In a third of these cases, the problem resolves within a year; in others, however, it remains for life.
3) "Wernicke's aphasia" (or "receptive aphasia"). It is caused by a cortical lesion of the Wernicke area, the associative auditory cortex, and the inferior parietal lobule. Wernicke's aphasia poses problems both in understanding language and in production. The ability to process a speech fl uently is maintained; the speech is paraphrastic and rich in circumlocutions with neologisms. The patient does not realize that his language is incomprehensible and can appear choleric and paranoid. The only understanding preserved is when he is ordered movements that use axial musculature (getting up, closing his eyes, turning around) but he doesn't understand the question "what's your name?".

4)
"Transcortical aphasia". It is a particular type of aphasia characterized by a relative saving of repetition. It is divided into three subgroups: a) The sensory type, in which all the skills of understanding, processing, and production of language are severely compromised, except for repetition. The lesions of this aphasic form are located in the areas adjacent to the Wernicke area; b) The motor type, in which the competence in the production of language is severely compromised, but with a relatively conserved understanding and elaboration. The lesion is located in the frontal cortex.
c) The mixed type, particularly severe non-fl owing form. Patients present completely incomprehensible language, while the only remaining skills are those of repetition and automatic language (songs, prayers, etc.).

5)
"Conduction aphasia". It is a fl uent aphasia characterized by a serious defi cit in repetition, that is, in producing a stimulus on imitation, and by numerous phonemic paraphasias. It was hypothesized by Wernicke and described for the fi rst time by Lichtheim in 1885. The lesion that causes this type of aphasia is at the level of the left parietal lobe (angular gyrus) and of the arched fi le.

6)
"Anomic aphasia". It is a particular type of fl uent aphasia where patients have diffi culty fi nding the exact terms to express themselves with, yet they manage to pronounce those same words on imitation. Understanding and skills for written language are generally less compromised.

7)
"Primary non-fl uent progressive aphasia" [21]. About dementias, atypical degenerative forms have been described since the nineteenth century, characterized by a non-amnesic focal onset but interesting in language, visual and visuospatial analysis, and face recognition. Pick (1892) and Serieux (1893) fi rst described cases of subjects with progressive speech disorder associated with brain atrophy at the level of the frontal and temporal regions of the left hemisphere. In 1982, Marek-Marsel Mesulam described a series of six patients with a progressive reduction of verbal expressive abilities, coining the term "slowly progressive aphasia". Snowden, in 1989, spoke of "semantic dementia", then redefi ned in 2011 as "progressive non-fl uent aphasia". Primary progressive It has been found that multilingualism affects the structure, and essentially, the cytoarchitecture of the brain. Learning more languages re-structures the brain and some researchers argue that it increases the brain's capacity for plasticity. Most of these differences in brain structures in multilinguals may be genetic at the core. Consensus is still confused; it may be a mixture of both experiential (language acquisition during life) and genetic (predisposition to brain plasticity) conditions. In the normal human brain, associated linguistic processing areas are less rigid than previously thought. For example, greater familiarity with a language has been found to lead to reductions in brain activation in the left dorsolateral frontal cortex (Brodmann's areas , 9,10,46). Bilingualism implies the use of two languages by an individual or a community.
Neuroimaging studies of gender bilingualism focus on the comparison between areas activated when using the fi rst language (L1) and second language (L2). Studies of language production using functional neuroimaging methods, investigate the brain representation of bilingual language activities. These methods (e.g. PET and fMRI) subjects distinguished mainly on the basis of age of acquisition L2 and not on the level of competence in L2. With the use of PET in the study of endstudent, cerebral blood fl ow (rCBF) regional distribution was found to be comparable between L1 and L2. Word repetition engages overlapping neural structures across both languages; that, differences in neural activation are observed only in the left putamen when individuals repeat words in their second language. The putamen, therefore, plays a fundamental role, because the process of articulation places a greater demand on the brain's resources when a second language learned in old age is being produced.
Investigating an aphasic patient is not easy, as the disorder presents a variety of different symptoms on various neurocognitive levels of speech. After a brain injury, the defi cits, which are not always evident, can however be highlighted using specifi c tests. Often, even when it is thought that the initial aphasia has regressed (the patient has returned to speak normally), it is still possible to fi nd serious disorders evident only in the most complex tests. For a correct examination, it is important (fi rst of all) to ensure the patient's collaboration and to exclude all those disorders that can alter the language but that come from a global disorganization of brain functioning (as in the case of dementia or mental confusion) or it comes from the sensory systems (blindness, deafness), the motor systems (dysarthria, dysphonia, respiratory problems) and serious and chronic psychiatric disorders. In patients with Alzheimer's disease, aphasic symptoms are one of the fi rst symptoms to appear, along with memory impairment [9,26].
It should also be remembered that aphasia can also occur concurrently with other neuropsychological disorders, related to language (stuttering), writing (agraphy), reading (dyslexia and alexia, understood as the loss of the cognitive abilities needed to read a text), calculus (acalculia); therefore, the evaluation of the different levels must be done in a structured way, in reference to the expression (spontaneous language, repetition of words and phrases of increasing length, production of automatic series, naming of images, shapes and objects, description of a complex image, repetition of a story) that to understanding (indicating objects and images, executing simple orders, executing complex orders), passing through reading (identifi cation of letters, syllables, words, reading aloud, understanding language written, execution of written orders, correspondence of words written with images, of sentences written with actions), writing (spontaneous, copied, dictated) and elaborate tests (defi nition of words, idioms and proverbs construction of a sentence with two or three words given to the patient, critique of absurd stories, interpretation of a text heard or read). The most used and useful language assessment tests to follow the functional recovery of the patient are CADL (Communicative Abilities in Daily Life), Token Test, MAE (Multilingual Aphasia Examination), BDAE (Boston Diagnostic Aphasia Examination) and AAT (Aachener Aphasie Test).
The best diagnosis, therefore, cannot be separated from an anamnestic evaluation that takes into account the medical condition and the use of a battery of specifi c tests, such as the Aphasic defi cit analysis (BADA), which allows more easily to arrive at a functional diagnosis and approach with correct rehabilitation (speech therapy treatment), also taking into account cognitive-behavioral or strategic psychotherapeutic profi les [27], in case of need.