Aphasia

In aphasia (sometimes called dysphasia),^[a] a person may be unable to comprehend or unable to formulate language because of damage to specific brain regions.^[2] The major causes are stroke and head trauma; prevalence is hard to determine, but aphasia due to stroke is estimated to be 0.1–0.4% in the Global North.^[3] Aphasia can also be the result of brain tumors, epilepsy, autoimmune neurological diseases,^[4] brain infections,^[5] or neurodegenerative diseases (such as dementias).^[6][7]

To be diagnosed with aphasia, a person's language must be significantly impaired in one (or more) of the four aspects of communication. Alternatively, in the case of progressive aphasia, it must have significantly declined over a short period of time. The four aspects of communication are spoken language production and comprehension and written language production and comprehension; impairments in any of these aspects can impact on functional communication.

The difficulties of people with aphasia can range from occasional trouble finding words, to losing the ability to speak, read, or write; intelligence, however, is unaffected.^[7] Expressive language and receptive language can both be affected as well. Aphasia also affects visual language such as sign language.^[2] In contrast, the use of formulaic expressions in everyday communication is often preserved.^[8] For example, while a person with aphasia, particularly expressive aphasia (Broca's aphasia), may not be able to ask a loved one when their birthday is, they may still be able to sing "Happy Birthday". One prevalent deficit in all aphasias is anomia, which is a difficulty in finding the correct word.^[9]: 72

With aphasia, one or more modes of communication in the brain have been damaged and are therefore functioning incorrectly. Aphasia is not caused by damage to the brain resulting in motor or sensory deficits, thus producing abnormal speech — that is, aphasia is not related to the mechanics of speech, but rather the individual's language cognition. However, it is possible for a person to have both problems, e.g. in the case of a hemorrhage damaging a large area of the brain. An individual's language abilities incorporate the socially shared set of rules, as well as the thought processes that go behind communication (as it affects both verbal and nonverbal language). Aphasia is not a result of other peripheral motor or sensory difficulty, such as paralysis affecting the speech muscles, or a general hearing impairment.^{[citation needed]}

Neurodevelopmental forms of auditory processing disorder are differentiable from aphasia in that aphasia is by definition caused by acquired brain injury, but acquired epileptic aphasia has been viewed as a form of APD.

People with aphasia may experience any of the following behaviors due to an acquired brain injury, although some of these symptoms may be due to related or concomitant problems, such as dysarthria or apraxia, and not primarily due to aphasia. Aphasia symptoms can vary based on the location of damage in the brain. Signs and symptoms may or may not be present in individuals with aphasia and may vary in severity and level of disruption to communication.^[10] Often those with aphasia may have a difficulty with naming objects, so they might use words such as thing or point at the objects. When asked to name a pencil they may say it is a "thing used to write".^[11]

Given the previously stated signs and symptoms, the following behaviors are often seen in people with aphasia as a result of attempted compensation for incurred speech and language deficits:

• Self-repairs: Further disruptions in fluent speech as a result of mis-attempts to repair erred speech production.^[12]
• Struggle in non-fluent aphasias: A severe increase in expelled effort to speak after a life where talking and communicating was an ability that came so easily can cause visible frustration.
• Preserved and automatic language: A behavior in which some language or language sequences that were used frequently prior to onset are still produced with more ease than other language post onset.

• Subcortical aphasia's characteristics and symptoms depend upon the site and size of subcortical lesion. Possible sites of lesions include the thalamus, internal capsule, and basal ganglia.

While aphasia has traditionally been described in terms of language deficits, there is increasing evidence that many people with aphasia commonly experience co-occurring non-linguistic cognitive deficits in areas such as attention, memory, executive functions and learning.^[13][14][15] By some accounts, cognitive deficits, such as attention and working memory constitute the underlying cause of language impairment in people with aphasia.^[16] Others suggest that cognitive deficits often co-occur, but are comparable to cognitive deficits in stroke patients without aphasia and reflect general brain dysfunction following injury.^[17] Whilst it has been shown that cognitive neural networks support language reorganisation after stroke,^[18] The degree to which deficits in attention and other cognitive domains underlie language deficits in aphasia is still unclear.^[19]

In particular, people with aphasia often demonstrate short-term and working memory deficits.^[15] These deficits can occur in both the verbal domain^[20][21] as well as the visuospatial domain.^[22] Furthermore, these deficits are often associated with performance on language specific tasks such as naming, lexical processing, and sentence comprehension, and discourse production.^{[23][15][24][25]} Other studies have found that most, but not all people with aphasia demonstrate performance deficits on tasks of attention, and their performance on these tasks correlate with language performance and cognitive ability in other domains.^[15] Even patients with mild aphasia, who score near the ceiling on tests of language often demonstrate slower response times and interference effects in non-verbal attention abilities.^[26]

In addition to deficits in short-term memory, working memory, and attention, people with aphasia can also demonstrate deficits in executive function.^[27] For instance, people with aphasia may demonstrate deficits in initiation, planning, self-monitoring, and cognitive flexibility.^[28] Other studies have found that people with aphasia demonstrate reduced speed and efficiency during completion of executive function assessments.^[29]

Regardless of their role in the underlying nature of aphasia, cognitive deficits have a clear role in the study and rehabilitation of aphasia. For instance, the severity of cognitive deficits in people with aphasia has been associated with lower quality of life, even more so than the severity of language deficits.^[30] Furthermore, cognitive deficits may influence the learning process of rehabilitation^[31][32] and language treatment outcomes in aphasia.^[33][34] Non-linguistic cognitive deficits have also been the target of interventions directed at improving language ability, though outcomes are not definitive.^[35] While some studies have demonstrated language improvement secondary to cognitively-focused treatment,^[36] others have found little evidence that the treatment of cognitive deficits in people with aphasia has an influence on language outcomes.^[37]

One important caveat in the measurement and treatment of cognitive deficits in people with aphasia is the degree to which assessments of cognition rely on language abilities for successful performance.^[38] Most studies have attempted to circumvent this challenge by utilizing non-verbal cognitive assessments to evaluate cognitive ability in people with aphasia. However, the degree to which these tasks are truly "non-verbal" and not mediated by language is unclear.^[19] For instance, Wall et al.^[23] found that language and non-linguistic performance was related, except when non-linguistic performance was measured by "real life" cognitive tasks.

Aphasia is most often caused by stroke, where about a quarter of patients who experience an acute stroke develop aphasia.^[39] However, any disease or damage to the parts of the brain that control language can cause aphasia. Some of these can include brain tumors, traumatic brain injury, epilepsy and progressive neurological disorders.^[40] In rare cases, aphasia may also result from herpesviral encephalitis.^[41] The herpes simplex virus affects the frontal and temporal lobes, subcortical structures, and the hippocampal tissue, which can trigger aphasia.^[42] In acute disorders, such as head injury or stroke, aphasia usually develops quickly. When caused by brain tumor, infection, or dementia, it develops more slowly.^[7][43]

Substantial damage to tissue anywhere within the region shown in blue (on the figure in the infobox above) can potentially result in aphasia.^[1] Aphasia can also sometimes be caused by damage to subcortical structures deep within the left hemisphere, including the thalamus, the internal and external capsules, and the caudate nucleus of the basal ganglia.^[44][45] The area and extent of brain damage or atrophy will determine the type of aphasia and its symptoms.^[7][43] A very small number of people can experience aphasia after damage to the right hemisphere only. It has been suggested that these individuals may have had an unusual brain organization prior to their illness or injury, with perhaps greater overall reliance on the right hemisphere for language skills than in the general population.^[46][47]

Primary progressive aphasia (PPA), while its name can be misleading, is actually a form of dementia that has some symptoms closely related to several forms of aphasia. It is characterized by a gradual loss in language functioning while other cognitive domains are mostly preserved, such as memory and personality. PPA usually initiates with sudden word-finding difficulties in an individual and progresses to a reduced ability to formulate grammatically correct sentences (syntax) and impaired comprehension. The etiology of PPA is not due to a stroke, traumatic brain injury (TBI), or infectious disease; it is still uncertain what initiates the onset of PPA in those affected by it.^[48]

Epilepsy can also include transient aphasia as a prodromal or episodic symptom.^[49] However, the repeated seizure activity within language regions may also lead to chronic, and progressive aphasia. Aphasia is also listed as a rare side-effect of the fentanyl patch, an opioid used to control chronic pain.^[50]

Magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) are the most common neuroimaging tools used in identifying aphasia and studying the extent of damage in the loss of language abilities. This is done by doing MRI scans and locating the extent of lesions or damage within brain tissue, particularly within areas of the left frontal and temporal regions- where a lot of language related areas lie. In fMRI studies a language related task is often completed and then the BOLD image is analyzed. If there are lower than normal BOLD responses that indicate a lessening of blood flow to the affected area and can show quantitatively that the cognitive task is not being completed.

There are limitations to the use of fMRI in aphasic patients particularly. Because a high percentage of aphasic patients develop it because of stroke there can be infarct present which is the total loss of blood flow. This can be due to the thinning of blood vessels or the complete blockage of it. This is important in fMRI as it relies on the BOLD response (the oxygen levels of the blood vessels), and this can create a false hyporesponse upon fMRI study.^[51] Due to the limitations of fMRI such as a lower spatial resolution, it can show that some areas of the brain are not active during a task when they in reality are. Additionally, with stroke being the cause of many cases of aphasia the extent of damage to brain tissue can be difficult to quantify therefore the effects of stroke brain damage on the functionality of the patient can vary.

Neural substrates of aphasia subtypes

MRI is often used to predict or confirm the subtype of aphasia present. Researchers compared three subtypes of aphasia — nonfluent-variant primary progressive aphasia (nfPPA), logopenic-variant primary progressive aphasia (lvPPA), and semantic-variant primary progressive aphasia (svPPA), with primary progressive aphasia (PPA) and Alzheimer's disease. This was done by analyzing the MRIs of patients with each of the subsets of PPA.^[52] Images which compare subtypes of aphasia as well as for finding the extent of lesions are generated by overlapping images of different participant's brains (if applicable) and isolating areas of lesions or damage using third-party software such as MRIcron. MRI has also been used to study the relationship between the type of aphasia developed and the age of the person with aphasia. It was found that patients with fluent aphasia are on average older than people with non-fluent aphasia. It was also found that among patients with lesions confined to the anterior portion of the brain an unexpected portion of them presented with fluent aphasia and were remarkably older than those with non-fluent aphasia. This effect was not found when the posterior portion of the brain was studied.^[53]

Associated conditions

In a study on the features associated with different disease trajectories in Alzheimer's disease (AD)-related primary progressive aphasia (PPA), it was found that metabolic patterns via PET SPM analysis can help predict progression of total loss of speech and functional autonomy in AD and PPA patients. This was done by comparing an MRI or CT image of the brain and presence of a radioactive biomarker with normal levels in patients without Alzheimer's Disease.^[54] Apraxia is another disorder often correlated with aphasia. This is due to a subset of apraxia which affects speech. Specifically, this subset affects the movement of muscles associated with speech production, apraxia and aphasia are often correlated due to the proximity of neural substrates associated with each of the disorders.^[55] Researchers concluded that there were 2 areas of lesion overlap between patients with apraxia and aphasia, the anterior temporal lobe and the left inferior parietal lobe.^[56]

Treatment and neuroimaging

Evidence for positive treatment outcomes can also be quantified using neuroimaging tools. The use of fMRI and an automatic classifier can help predict language recovery outcomes in stroke patients with 86% accuracy when coupled with age and language test scores. The stimuli tested were sentences both correct and incorrect and the subject had to press a button whenever the sentence was incorrect. The fMRI data collected focused on responses in regions of interest identified by healthy subjects.^[57]  Recovery from aphasia can also be quantified using diffusion tensor imaging. The accurate fasciculus (AF) connects the right and left superior temporal lobe, premotor regions/posterior inferior frontal gyrus. and the primary motor cortex. In a study which enrolled patients in a speech therapy program, an increase in AF fibers and volume was found in patients after 6-weeks in the program which correlated with long-term improvement in those patients.^[58] The results of the experiment are pictured in Figure 2. This implies that DTI can be used to quantify the improvement in patients after speech and language treatment programs are applied.

Aphasia is best thought of as a collection of different disorders, rather than a single problem. Each individual with aphasia will present with their own particular combination of language strengths and weaknesses. Consequently, it is a major challenge just to document the various difficulties that can occur in different people, let alone decide how they might best be treated. Most classifications of the aphasias tend to divide the various symptoms into broad classes. A common approach is to distinguish between the fluent aphasias (where speech remains fluent, but content may be lacking, and the person may have difficulties understanding others), and the nonfluent aphasias (where speech is very halting and effortful, and may consist of just one or two words at a time).^[59]

However, no such broad-based grouping has proven fully adequate, or reliable. There is wide variation among people even within the same broad grouping, and aphasias can be highly selective. For instance, people with naming deficits (anomic aphasia) might show an inability only for naming buildings, or people, or colors.^[60] Unfortunately, assessments that characterize aphasia in these groupings have persisted. This is not helpful to people living with aphasia, and provides inaccurate descriptions of an individual pattern of difficulties.

There are typical difficulties with speech and language that come with normal aging as well. As we age, language can become more difficult to process, resulting in a slowing of verbal comprehension, reading abilities and more likely word finding difficulties. With each of these, though, unlike some aphasias, functionality within daily life remains intact.^[9]: 7

• Individuals with receptive aphasia (Wernicke's aphasia), also referred to as fluent aphasia, may speak in long sentences that have no meaning, add unnecessary words, and even create new "words" (neologisms). For example, someone with receptive aphasia may say, "delicious taco", meaning "The dog needs to go out so I will take him for a walk". They have poor auditory and reading comprehension, and fluent, but nonsensical, oral and written expression. Individuals with receptive aphasia usually have great difficulty understanding the speech of both themselves and others and are, therefore, often unaware of their mistakes. Receptive language deficits usually arise from lesions in the posterior portion of the left hemisphere at or near Wernicke's area.^{[9][63]: 71} It is often the result of trauma to the temporal region of the brain, specifically damage to Wernicke's area.^[64] Trauma can be the result from an array of problems, however it is most commonly seen as a result of stroke^[65]
• Individuals with expressive aphasia (Broca's aphasia) frequently speak short, meaningful phrases that are produced with great effort. It is thus characterized as a nonfluent aphasia. Affected people often omit small words such as "is", "and", and "the". For example, a person with expressive aphasia may say, "walk dog", which could mean "I will take the dog for a walk", "you take the dog for a walk" or even "the dog walked out of the yard." Individuals with expressive aphasia are able to understand the speech of others to varying degrees. Because of this, they are often aware of their difficulties and can become easily frustrated by their speaking problems.^[66] While Broca's aphasia may appear to be solely an issue with language production, evidence suggests that it may be rooted in an inability to process syntactical information.^[67] Individuals with expressive aphasia may have a speech automatism (also called recurring or recurrent utterance). These speech automatisms can be repeated lexical speech automatisms; e.g., modalisations ('I can't ..., I can't ...'), expletives/swearwords, numbers ('one two, one two') or non-lexical utterances made up of repeated, legal, but meaningless, consonant-vowel syllables (e.g.., /tan tan/, /bi bi/). In severe cases, the individual may be able to utter only the same speech automatism each time they attempt speech.^[68]
• Individuals with anomic aphasia have difficulty with naming. People with this aphasia may have difficulties naming certain words, linked by their grammatical type (e.g., difficulty naming verbs and not nouns) or by their semantic category (e.g., difficulty naming words relating to photography, but nothing else) or a more general naming difficulty. People tend to produce grammatic, yet empty, speech. Auditory comprehension tends to be preserved.^[69] Anomic aphasia is the aphasial presentation of tumors in the language zone; it is the aphasial presentation of Alzheimer's disease.^[70] Anomic aphasia is the mildest form of aphasia, indicating a likely possibility for better recovery.^{[69][additional citation(s) needed]}
• Individuals with transcortical sensory aphasia, in principle the most general and potentially among the most complex forms of aphasia, may have similar deficits as in receptive aphasia, but their repetition ability may remain intact.
• Global aphasia is considered a severe impairment in many language aspects since it impacts expressive and receptive language, reading, and writing.^[71] Despite these many deficits, there is evidence that has shown individuals benefited from speech language therapy.^[72] Even though individuals with global aphasia will not become competent speakers, listeners, writers, or readers, goals can be created to improve the individual's quality of life.^[66] Individuals with global aphasia usually respond well to treatment that includes personally relevant information, which is also important to consider for therapy.^[66]
• Individuals with conduction aphasia have deficits in the connections between the speech-comprehension and speech-production areas. This might be caused by damage to the arcuate fasciculus, the structure that transmits information between Wernicke's area and Broca's area. Similar symptoms, however, can be present after damage to the insula or to the auditory cortex. Auditory comprehension is near normal, and oral expression is fluent with occasional paraphasic errors. Paraphasic errors include phonemic/literal or semantic/verbal. Repetition ability is poor. Conduction and transcortical aphasias are caused by damage to the white matter tracts. These aphasias spare the cortex of the language centers, but instead create a disconnectio