Universidade de Aveiro
Ano 2018/2019
Departamento de Educação e Psicologia
CÁTIA DANIELA PINTO
MARTINS
VERBAL MEMORY IN PATIENTS WITH DIFFUSE
AXONAL INJURY
MEMÓRIA VERBAL EM DOENTES COM LESÃO
AXONAL DIFUSA
Dissertação apresentada à Universidade de Aveiro para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Psicologia da Saúde e Reabilitação Neuropsicológica, realizada sob a orientação científica do Doutor José Ignacio Guinaldo Martin, Professor do Departamento de Educação e Psicologia da Universidade de Aveiro
Dedico este trabalho aos meus pais pelo apoio incondicional desde o primeiro instante.
o júri
presidente Profª. Doutora Anabela Maria Sousa Pereira
Professora Associada C/ Agregação do Departamento de Educação e Psicologia, Universidade de Aveiro
Profª. Doutora Maria Madalena Jesus Cunha Nunes
Professora Adjunta da Escola Superior de Saúde, Instituto Politécnico de Viseu
Prof. Doutor José Ignacio Guinaldo Martin
agradecimentos Ao Professor José Martin que me orientou ao longo deste percurso. Obrigada por todos os ensinamentos.
Ao Professor Doutor Carlos Fernandes Silva por ser um docente admirável, pelo entusiasmo e paixão no ensino, pela forma como transmite os seus conhecimentos de neuropsicologia.
À Universidade de Aveiro por permitir o desenvolvimento da presente investigação.
Ao CMRRC-RP por autorizar a realização deste trabalho com os seus doentes, e por me ensinarem e transmitirem o rigor e a ética com que trabalham na área da investigação.
À Dra. Ana Gabriel Marques, Neuropsicóloga do CMRRC-RP, pela ajuda prestada ao longo de grande parte do processo de realização deste trabalho. Aos meus pais e aos meus irmãos a quem devo tudo, a quem devo as conquistas que já fiz até aqui e as que continuo e continuarei a fazer, porque sem eles nada seria possível.
Aos meus avós e a toda a minha família, por me fazerem sentir capaz de realizar qualquer coisa.
Ao Cristiano por me acompanhar e apoiar em todos os momentos e por me relembrar que consigo ultrapassar as dificuldades, mesmo quando estas parecem impossíveis de superar.
À Paula, à Joana, ao Sérgio, à Anabela e à Diana Rita pelo apoio incondicional, por toda a paciência e por toda a amizade.
Por fim, à Dora por todas as partilhas e por todos os desabafos. Obrigada por teres estado comigo lado a lado nos desafios que foram surgindo ao longo do tempo.
palavras-chave Lesão axonal difusa (LAD), memória verbal, traumatismo crânio-encefálico (TCE), Teste de Aprendizagem Audio-Verbal de Rey, Memória Lógica I e II - Escala de Memória de Wechsler-III
resumo A lesão axonal difusa (LAD) é uma lesão microscópica provocada por uma aceleração rotacional da cabeça, resultado de um traumatismo crânio-encefálico (TCE) e está associada a níveis elevados de morbilidade e mortalidade. Investigadores têm estudado a origem dos défices de memória verbal nesta população. A presente investigação objetiva analisar a relação entre as diferentes medidas de desempenho de memória verbal (memória imediata, memória diferida, evolução da aprendizagem e percentagem de retenção) de doentes com LAD. Para tal foram recolhidos 14 doentes adultos com LAD do CMRRC-RP, os quais realizaram uma das seguintes provas: Memória Lógica I e II (ML) da Escala de Memória de Wechsler-III (WMS-III) ou o teste de Aprendizagem Audio-Verbal de Rey (RAVLT). Foram realizados coeficientes de correlação de Pearson e de Ponto-Bisserial e os resultados mostraram correlações significativas entre o sexo e a variável memória
imediata (rpb=-.63, p=.008), bem como correlações entre as variáveis memória
imediata e a evolução da aprendizagem (r=.73, p=.003), memória imediata e a
memória diferida (r=.91, p=.000), memória imediata e a percentagem de
retenção (r=.81, p=.003), memória diferida e a evolução da aprendizagem
(r=.88, p=.000), memória diferida e a percentagem de retenção (r=.95, p=.000)
e por fim, evolução da aprendizagem e a percentagem de retenção (r=.78,
p=.005). Ao contrário do esperado, os resultados não mostraram correlações significativas entre estas variáveis e as variáveis clínicas pontuação da GCS e tempo de coma. De uma forma geral, foi possível inferir que as quatros variáveis dependentes correlacionam-se entre si, o que significa que o desempenho dos doentes com LAD numa destas variáveis influenciará o seu desempenho nas restantes. Isto acontece uma vez que as fases do processo de memória estão relacionadas. Se fases mais primárias do processo de memória falharem, as posteriores não irão obter sucesso, refletindo-se em fracos desempenhos de memória verbal.
keywords Diffuse axonal injury (DAI), verbal memory, traumatic brain injury (TBI), Rey Auditory Verbal Learning Test, Logical Memory I and II- Wechsler Memory Scale III
abstract Diffuse axonal injury (DAI) is a microscopic injury caused by a rotational acceleration of the head, the result of a traumatic brain injury (TBI), and is associated with high levels of morbidity and mortality. Researchers have studied the origin of verbal memory deficits in this population. This study aims at analyzing the relation between the different measures of verbal memory performance (immediate memory, deferred memory, learning progress, and percentage of retention) of patients with DAI. To this end, 14 adult patients with CMRRC-RP DAIs were collected, who willingly performed one of the following tests: Logic Memory I and II (ML) of the Wechsler Memory Scale -III (WMS-III), or the Auditory Verbal Learning Test (AVLT). Pearson's and Ponto-Bisserial's correlation coefficients were performed, and the results showed significant
correlations between sex and the immediate memory variable (rpb=-.63, p=.008)
in addition to the correlations between the variables immediate memory and the evolution of learning (r=.73, p=.003), immediate memory and deferred memory (r=.91, p=.000), immediate memory and the percentage of retention (r=.81, p=.003), deferred memory and the evolution of learning (r=.88, p=.000), deferred memory and the percentage of retention (r=.95, p=.000), and finally evolution of learning and the percentage of retention (r=.78, p=.005). Contrary to expectations, the results showed no significant correlations between these variables and the clinical variables; GCS score and coma time. In general, it was possible to infer that the four dependent variables correlate with each other, which means that the performance of patients with DAI in one of these variables will influence their performance in the others, because the stages of the memory process are correlated. If primary phases of the memory process fail, subsequent ones will not be successful, resulting in poor verbal memory performance.
Table of Contents
Introduction ... 1
Diffuse axonal injury ... 1
Verbal memory ... 1
Systematic literature review ... 2
Methodology ... 4 Participants ... 4 Instruments ... 5 Procedures ... 6 Results ... 6 Discussion ... 8 References ... 13
Index of Appendixes
Appendix A. Systematic Literature Review ……….………..……..20 Appendix B. Sociodemographic and clinical characterization of participants……..……45 Appendix C. Results of Pearson's Correlation Coefficients and Point-Bisserial Coefficients………...46 Appendix D. Sociodemographic Questionnaire ………...48 Appendix E. Informed Consent ………49
1 Introduction
Diffuse axonal injury
Diffuse Axonal Injury (DAI) is one of the most important types of brain injury, which occurs as a result of a traumatic brain injury (TBI), through brain acceleration, especially rotational acceleration (Adams et al., 1989; Gennarelli, Thibault, & Graham, 1998). DAI can be defined as the occurrence of a diffuse lesion in axons in the cerebral hemispheres, corpus callosum, brainstem, and sometimes in the cerebellum (Adams et al., 1989). In general, it is clinically defined by a coma with a duration of 6 hours or more, excluding the cases of cerebral edema or ischemic brain damage (Vieira et al., 2016). DAI is associated with a continuous spectrum of increasing severity related to the increase in the number of affected axons (Gennarelli et al., 1998).
This lesion is cognised as having serious consequences for individuals and is associated with significant morbidity and mortality. It is the most common cause of post-traumatic coma, disability, and persistent neurovegetative states (Vieira et al., 2016). It may cause cognitive, physical, and behavioural changes that compromise of social reintegration, return to productivity, and quality of life of patients and relatives (Adams et al., 1989; Gennarelli, 1996, 1997; Gennarelli et al., 1982; Vieira et al., 2016).
Verbal memory
Verbal memory is extremely important in the process of learning new information (Lah et al., 2017). Its impairment is one of the cognitive deficits that may result from the occurrence of DAI (Levine et al., 2002; Timmerman & Brouwer, 1999; Wallesch et al., 2001; Wright, Schmitter-Edgecombe, & Woo, 2010).
In order to remember, it is necessary that three aspects of the memory process are carried out successfully: encoding, consolidation, and retrieval (Gleitman, 1999). The acquisition of new information is followed by the encoding that refers to the way the information is placed in the memory, as if it were a record of the knowledge that comes from the sense organs (Baddeley & Kopelman, 2004; Gleitman, 1999). The consolidation proceeds the encoding and corresponds to the maintenance of the information over time, which is consolidated and preserved in a more or less permanent way (Baddeley & Kopelman, 2004; Gleitman, 1999). The last aspect is the retrieval, wherein the individual
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recalls (consciously) information stored along with many others. Retrieval can be achieved by two methods; recall or recognition (Baddeley & Kopelman, 2004; Gleitman, 1999).
Having knowledge of this process and its damage after brain injury, several researchers have been conducting numerous studies, both in adults and children who have already suffered brain injury, in an endeavor to understand the specific nature of verbal memory difficulties. It is questioned whether the verbal memory impairment reflects a problem in the encoding phase, consolidation phase or retrieval phase. One of the studies revealed that verbal memory difficulties were the result of the deficits in the encoding phase (e.g., DeLuca, Schultheis, Madigan, Christodoulou, & Averill, 2000). On the other hand, other researchers concluded that verbal memory damage was owing to consolidation deficits (e.g., Vanderploeg, Crowell, & Curtiss, 2003). More recent studies have shown significant results regarding the existence of deficits in the retrieval phase (e.g., Freitas & Aguiar, 2012). It is important to mention that the existence of a deficit in one of these phases may not clearly and evidently reflect the deficit in that phase, and the deficits in the consolidation phase may arise and reflect a deficit in the encoding, retrieval, or a combination of the two phases (Vanderploeg, Crowell, & Curtiss, 2003). In fact, memory faults may originate at any stage of this process, either because the information has not been encoded, or because it has not been properly classified in memory, or for other reasons that lead to consequential failures in retrieval (Gleitman, 1999).
Thus, there are discrepancies in the investigators' conclusions regarding the origin of the deficits, making it imperative to continue the investigation of verbal memory in patients with brain injuries. Advances in the investigation of deficits in patients with DAI may lead to relevant conclusions in their compression, inferences that may become crucial for the establishment of neuropsychological rehabilitation programs, and thus contribute to a more favorable evolution of verbal mnesic capacity (Voss et al., 2006).
Systematic literature review
A systematic literature review was conducted using the following method: we consulted the Pubmed site (Medline service), which serves as a scientific database. An advanced research of the main theme "diffuse axonal injury" crossed with "psychology" resulted in 33 scientific articles, while research of the same theme crossed with "neuropsychology" resulted in 6 scientific articles (The research was conducted on the
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December 2018). Articles related to literature reviews (3), case studies (4), articles whose investigation had not been completed (1) and articles that were repeated in both studies (3) were excluded. Articles that were not written in English were also excluded (3). In total, 25 articles were included.
Appendix A contains a table that presents information from the review performed as the objective of the study, the sample used, the instruments, the study method, the main results, and the conclusions.
This review concluded that the patients with DAI have deficits in several cognitive functions, such as executive functions (planning, cognitive flexibility, and attention), memory (work, visual, and verbal), slowness in information processing, deficits in the recognition of facial emotions as well as deficits in inhibiting imitation, and greater behavioral deregulation (Bottari, Gosselin, Guillemette, Lamoureux, & Ptito, 2011; Felmingham, Baguley, & Green, 2004; HIROTA et al., 2016; Lauer et al., 2017; Li et al., 2012; Sanchez-Carrion et al., 2008; Schroeter et al., 2007; Yassin et al., 2017). Some studies noted improvements in cognitive functions over time in patients with DAI, such as working memory and visual memory, while other studies did not verify the same (Sanchez-Carrion et al., 2008; Zaninotto et al., 2017). Finally, some researchers are satisfied with the use of Magnetic Resonance Imaging (MRI) in the detection of DAI and the deficits caused by it, however others report the need for new and more accurate methods, such as the use of Diffusion Tensor Images (DTI) and SPECT (eZIS) (Esbjörnsson et al., 2013; Okamoto, Hashimoto, Aoki, & Ohashi, 2007; Sugiyama et al., 2007; Wozniaka et al., 2007).
Thus, these inferences are of great importance both for clinical practice and the investigation. The studies carried out contributed to the characterization of DAI in several domains (neuropsychological, neurological, neuroanatomic), a task hampered by its diffuse character. Therefore, these findings are useful for the delineation of a rehabilitation process of patients, understanding of the prognosis, and the evaluation of issues related to their social reintegration (insurance, disability pensions, professional / school situation). Moreover, the studies carried out pointed out the need for the use of new neuroimaging methods that will be advantageous in performing the diagnosis and analysis of DAI, since they may be essential in the discovery of a pattern of deficits and new information that conventional resonances cannot provide. Obtaining this information can be useful in carrying out a clinical
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intervention and discovering its possible effectiveness. Conducting research that adopts new neuroimaging methods has become a future challenge for DAI investigators.
The objectives of this study are to investigate the association of sociodemographic variables with measures of verbal memory as well as to explore the relation between Glasgow Coma Scale scores and coma times with verbal memory performance through statistical analysis and a case study. is the study also intends to analyze the relation between the different measures of verbal memory performance (immediate memory, deferred memory, evolution of learning, andpercentage of retention) of patients with DAI.
Methodology Participants
The participants were hospitalized at the Centro de Medicina de Reabilitação da Região Centro - Rovisco Pais (CMRRC-RP), an institution that aims at providing differentiated rehabilitation care to the patients with various central neurological pathologies (CMRRC-RP, 2018). The group consisted of 14 participants aged between 19 and 61 years (M= 33.36, SD=13.077), of both genders (4 females and 10 males; 28.6% and 71.4% respectively), with a mean of 10.21 years of education (SD=2.992), where 50% participants had an education below 9 years.
Regarding clinical characteristics, the most frequent type of TBI among the participants was the Closed TBI (n=4, 28.6%). It was not possible to obtain this information for 50% participants. The most common cause of the injury was road traffic accidents (n=11, 78.6%), and the mean coma time was 22.11 days (SD=15.374), taking into account that this information is not known for 35.7% participants. The mean of the initial Glasgow Coma Scale (GCS) (at the time of admission to the emergency service) was 8.15 (SD = 3.738). According to the GCS classification, 9 participants suffered from severe TBI (64.3%), 2 participants suffered from moderate TBI (14.3%), and 2 participants suffered from mild TBI (14.3%). It was not possible to know the GCS score of 1 participant (7.1%). The mean time of evolution was 232.21 days (SD=254.616) (Table 1, Appendix B). There is an above-average standard deviation, since the evolution time of case 8 is extremely high in relation to the others.
Patients with TBI and DAI (diagnosed by neuroimaging) with previously performed memory evaluation participated in this study. Patients with impairments that could condition
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the performance of the tests, such as impaired understanding, expression aphasia, dysarthria, and significant hearing problems, previous history of neurological (e.g. stroke, aneurysm, acute or progressive neurological diseases), neuropsychological and psychiatric disorders as along with patients with a history of alcoholism or drug addiction were not included in the study.
Instruments
In order to evaluate the participants' verbal memory, two tests were selected: Logic Memory I and II of the Wechsler Memory Scale -III (Wechsler, 2008) and the Auditory Verbal Learning Test (AVLT) (Cavaco et al., 2015; Rey, 1958). It is imperative to clarify that the choice of the scale to be applied to the participant was made in accordance with the institution's protocol.
Wechsler Memory Scale-III (WMS-III) has good construct validity to assess mnesic performance in adults who suffered from TBI (Carlozzi, Grech, & Tulsky, 2013). The Logical Memory I and II subscale (ML; WMS-III) showed predictive validity of memory deficits in a sample that included patients with TBI of 72.5% (Wright et al., 2009), and has therefore been used in studies assessing this cognitive ability (e.g., Ladowsky-Brooks, 2016). This subscale permits the evaluation of immediate and deferred verbal memory and is composed of two parts (I and II), which contain two distinct histories, A and B. This subscale also consists of a third part, called Recognition.
Auditory Verbal Learning Test (AVLT) permits the evaluation of immediate and delayed verbal memory and is also a test that has been used in other studies (e.g. Walker et al., 2010) as well as clinical practice, since it has a good sensitivity to cognitive dysfunction (Cavaco et al., 2015). This test encompasses immediate evocation trials, deferred evocation trials, and deferred recognition trials.
Glasgow Coma Scale (GCS) is a tool utilized to standardize the examination of the state of consciousness of coma patients and has been used as part of the evaluation of patients with TBI. It evaluates the eye opening and the best motor and verbal response. This scale permits to classify the severity of the TBI; a score from 13 to 15 indicates a mild TBI, a score from 9 to 12 indicates a moderate TBI, and a score below 8 indicates a severe TBI (Teasdale & Jennett, 1974).
In this study, four common scores were used for the two memory scales that function as dependent variables, which include immediate memory score (total score of Logic
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Memory I recall and total learning of AVLT), the score of the evolution of learning (evolution of learning of Logical Memory and learning throughout trials of AVLT), the deferred memory score (total recall score of Logic Memory II and deferred recall score of AVLT), and the percentage of retention score (retention percentage of Logical Memory and long-term retention percentage of RAVLT). A mean of 10 and a standard deviation of 3 were used to evaluate the scalar scores of the participants' mnesic performances. Performances with 1 to 1.5 standard deviations below the mean indicate mild cognitive impairment (Cavaco et al., 2015).
It should be noted that the tasks involving immediate recall provide information regarding the process of acquisition and learning as well as consolidation and especially encoding. On the other hand, the task scores that involve recall and recognition transmit information regarding retrieval capacity as well as consolidation (Cavaco et al., 2015; Vanderploeg, Crowell, & Curtiss, 2001).
Procedures
Participants' data were collected in two ways: through the consultation of clinical files of patients who had previously been hospitalised in this institution (retrospective method), giving a total of 13 patients; and through neuropsychological assessment within the clinical practice (only one participant was recruited through this methodology). In order to meet the criteria to carry out the memory assessment, the formal or informal caregivers of the patients were contacted when it was impossible for the participant to be able to give his or her permission to participate.
The Statistical Package for Social Sciences (IBM-SPSS), version 24.0 (IBM Corp., 2016) was used to perform the statistical analyses. The value adopted to consider significant differences was p =.05. Pearson's correlation coefficient (r) was used to explore the association between the interval variables and the Point-Biserial correlation coefficient (rpb)
for studying the relationship between nominal and interval variables.
This study was authorised by the Ethics Committee for Health (CES) of CMRRC-RP.
Results
Table 2 (Appendix C) shows the correlations of the Pearson (r) and Point-Biserial (rpb) coefficients between the sociodemographic and clinical variables. Table 3 (Appendix
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C) shows the correlations of the Pearson (r) and Ponto-Bisserial (rpb) coefficients between
the dependent variables (immediate memory, deferred memory, evolution of learning, and percentage of retention) and the sociodemographic and clinical variables.
After knowing the correlations between the sociodemographic variables (Table 2, Appendix C), it was possible to verify a significant positive correlation between age and civil status (rpb=.89, p=.000).
From the correlations between the clinical variables, it was not possible to verify any significant correlations (Table 2, Appendix C).
Correlations were also made between the sociodemographic variables and the clinical variables (Table 2, Appendix C). From this analysis, it was possible to verify a significant positive correlation between age and type of TBI of the participants (rpb=.77, p=.004).
Thereafter, correlations were tested between the four dependent variables (immediate memory, deferred memory, evolution of learning, and percentage of retention) and the sociodemographic variables (Table 3, Appendix C). It was possible to conclude that there is a significant negative correlation between gender and the dependent variable immediate memory (rpb=-.63, p=.008). So, higher scores for the immediate memory variable are
associated with male gender.
A correlation was also made between the dependent variables (Table 3, Appendix C). These analyses suggest that there is a significant positive correlation between the dependent variable immediate memory and the evolution of learning variable r=.73, p=.003, which indicates that higher scores for the immediate memory variable are associated with higher scores for the evolution of learning variable. The same occurs between the immediate memory and the deferred memory (r=.91, p=.000) together with the percentage of retention variable (r=.81, p=.003). Moreover, the evolution of learning variable is associated with a positive and significant correlation with the variables deferred memory (r=.88, p=.000) and percentage of retention (r=.78, p=.005). Higher scores for the evolution of learning variable are associated with higher scores for the other variables. There is also a significant positive correlation between the deferred memory variable and the other dependent variables: immediate memory (r and p values as mentioned above), evolution of learning (r and p values as mentioned above), and percentage of retention (r=.95, p=.000). Thus, higher scores for the deferred memory variable are associated with higher scores for the others. The same happens with the percentage of retention variable, which is also positively correlated with
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the three dependent variables (r and p values mentioned). In general, it is possible to verify that the four dependent variables correlate with each other. This indicates that the higher/lower the score of one of them, the higher/lower the scores of the others.
There were no significant correlations between the dependent variables (immediate memory, deferred memory, evolution of learning, and percentage of retention) and the clinical variables (Table 3, Appendix C). The severity of the high lesion measured by GCS (low scores) and high coma times (over 8 days) are usually associated with bad prognosis, and there are persistent memory deficits over time (Santos, 2002; Silva et al., 2018; Vakil, 2005; Wilson et al., 2017). It seems that severe lesions or high coma times may explain the weak mnesic performance of patients. In case 5, the opposite happens, wherein a lower severity of the lesion led to better verbal memory performances.
On the other hand, there are cases such as 1 and 11, wherein high severity of injury or high coma times are not associated with weak verbal memory performance. Thus, in these cases, these variables are not associated and do not justify the patients' performance as shown by the absence of a correlation. Case 4 shows good performance in two of the four verbal memory variables, despite being a patient who suffered from severe TBI and was in coma for a long period of time. On the other hand, mild lesions are not associated with good performance, such as case 6 that presents a mild TBI. Despite this, the patient evidences high coma times that justify his bad performance. The presence of one or both variables ends up interfering with the patients' performance, but not consistently in this study. According to a research that focused on the study of measures of injury severity in patients with TBI and DAI (Katz & Alexander, 1994), it is important to assess both the severity of the injury and the coma time. Nevertheless, the severity of the lesion measured by GCS seems to have a greater influence on the determination of cognitive performance, contrary to what is evidenced in case 6. One study verified that all patients with severe TBI at the end of eight days after the injury presented neuropsychological sequelae, whereas these only existed in 44% of the patients with the same coma time but with less severe TBI (assessed after the same time) (Jurado as cited in Santos, 2002).
Discussion
The correlation of the Point-Bisserial coefficient showed that males score the highest in the immediate memory variable, contrary to what was expected. Women perform better
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in verbal memory tests than men, mainly in deferred memory tasks (Martins et al., 2012). This incongruity may be owing to the fact that only 4 female participants are part of this sample. Moreover, age was expected to show a correlation with dependent variables as age differentiates individuals in their performance in both tests (Cavaco et al., 2015; Martins et al., 2012; Wechsler, 2008). There was no correlation between age and dependent variables, possibly owing to the fact that ages of the patients only ranged from 19 to 61 years, being mostly young adults (only 4 of the 14 patients were over 40 years old).
In this study, no correlation was found between dependent and clinical variables, which was not expected (Brooks, 1974, 1975). As already mentioned, the GCS score and coma time are indicators of the severity of the injury of patients with TBI (Santos, 2002), which appear related to the mnesic performance. Lower GCS scores and higher coma times indicate greater severity of the lesion and are associated with poorer prognosis, poorer lesion evolution, and persistent memory impairment in these patients (Santos, 2002; Silva et al., 2018; Vakil, 2005; Wilson et al., 2017). As such, it was expected that these clinical variables could be shown to be correlated with the verbal memory performance of patients with DAI. This was not the case may be due to the influence of other variables on verbal memory performance, such as post-traumatic amnesia time (PTA). This is also an indicative variable of severity (PTA of less than 4 weeks indicates favorable evolution of the lesion) (Katz & Alexander, 1994; Santos, 2002) and can therefore determine or influence the performance of patients with DAI in verbal memory tests. As such, it may be responsible for the inconsistencies found (Levin, 1990).
From the analysis between the four dependent variables, it was possible to determine correlations between them. The immediate memory showed a significant correlation with the evolution of learning, which is expected since this variable is concerned with the patients' performance throughout the immediate evocations, which translate into the performance of the patient's immediate memory. In addition, immediate memory tasks convey information regarding acquisition and learning as mentioned above (Cavaco et al., 2015). Therefore, good performance over immediate memory tasks can indicate successful learning (Gleitman, 1999). It should be noted that the calculation performed to obtain the learning progress takes into account the score obtained by the patient in the tests of immediate memory.
Immediate memory has correlated significantly with deferred memory. For effective retrieval, successful encoding and consolidation are required (Baddeley & Kopelman, 2004;
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Gleitman, 1999). Deficiencies in encoding and consolidation can be reflected in weak immediate memory performance (Vanderploeg, Crowell, & Curtiss, 2001). As a consequence, these deficits lead to impairments in the ability to retrieve information, which can translate into poor deferred memory performance (Freitas & Aguiar, 2012; Gleitman, 1999; Griffiths et al., 2005; Vanderploeg et al., 2003). The way encoding is performed (the memorization strategy used by the individual) may also interfere with this performance (Gleitman, 1999). Investigations inferred that encoding and, to a lesser extent, consolidation represent most of the variance in the deferred recall (Freitas & Aguiar, 2012; Griffiths et al., 2005; Wright et al., 2010). That said, immediate memory was expected to be correlated with deferred memory as the memory phases underlying the tasks are related.
The significant correlation between the dependent variables, immediate memory and percentage of retention, was expected, given that errors in one of the memory processes (e.g. encoding), which can be translated into poor performance in immediate memory tasks, can cause retention difficulties, interfering with the consolidation of the information (Baddeley & Kopelman, 2004; Gleitman, 1999; Lah et al., 2017; Vanderploeg et al., 2003). Again, the relationship between the phases of the memory process may explain the association of variables. It is important to mention that the calculation that is performed to obtain the amount of information retained by the patient during the test takes into account the performance achieved in the tasks of immediate memory.
The same significant correlation was found between the evolution of learning variable and the deferred memory. The evolution of learning is basically concerned about the patient's performance throughout the recapitulation of the various trials of the test, where the learning of the test information takes place. Therefore, if an individual learns the new information properly, the probability of recall will increase, since he or she was able to encode and consolidate it. That said, there is also a higher probability that the information will be stored in another type of memory, long-term memory (Baddeley & Kopelman, 2004; Baddeley, Eysenck, & Anderson, 2009; Gleitman, 1999). Thus, it was expected that the two dependent variables will be correlated.
The evolution of learning and the percentage of retention are significantly correlated. When the learning of external information is successfully performed (encoded and consolidated), the patient is expected to retain this information and recall it, as described in the previous paragraph. Therefore, if the patient succeeds in learning tasks, he or she will
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also achieve good performance in retaining information. Previous studies have indicated the possibility that impairments in the necessary encoding phase during the learning may lead to deficits in the consolidation of information, thus preventing the individual from being able to retain it (Lah et al., 2017; Vanderploeg et al., 2003).
Finally, the deferred memory variable was correlated with the percentage of retention. This happens since if an individual is able to retain (consolidation of the information), he will be able to recall later. Once again, the ability to recall later seems to be associated with the capacity to retain information that was once presented (Baddeley & Kopelman, 2004; Baddeley et al., 2009; Gleitman, 1999). It must be mentioned that the calculation of the percentage of information retained by patients requires the score obtained by them in deferred memory tasks.
In conclusion, the dependent variables that express the verbal memory performances of patients with DAI were shown to be related. Deficits in immediate memory tasks can impair patient performance in tasks necessitating learning, retention, and retrieval. This is due to the fact that primary phases of the memory process, such as encoding and storage, are linked to subsequent phases of memory, such as retrieval (Gleitman, 1999). These stages underlie the tasks of verbal memory and in order for the performances to be successful, it is necessary that the phases of the memory process are properly carried out. These conclusions warn of the erroneous attribution of the origin of verbal memory deficits, since the deficit may be in the first phase of the memory process, the encoding, but may be reflected not only in immediate memory difficulties but also in deferred memory difficulties.
Like most investigations, the present study has limitations. In this study, patients from only one institution were selected, resulting in a reduced number of the sample and not being geographically representative. This reduction is also owing to the exclusion of patients who did not comply with the inclusion criteria defined at the beginning of the study. Another limitation is related to the (mostly) retrospective character of this study, which led to the limitation of the collection of interesting variables to be added to the research, such as the time of post-traumatic amnesia, the presence and type of cerebral hemorrhage, the degree of DAI, and the location of the lesion.
In the future, it would be crucial to collect other data, such as the clinical variables mentioned above and data on the existence or otherwise of the treatment during time of patient evolution. It would also be interesting to carry out a study using other verbal memory
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instruments that include measures of interference (proactive inhibition) such as the California Verbal Learning Test (CVLT) and more accurately evaluate encoding, consolidation, and retrieval as the Item Specific Deficit Approach (ISDA) since researcr finds several methodological flaws in the use of tests that do not accurately measure these processes (Vanderploeg et al., 2001; Vanderploeg et al., 2003).
13 References
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19 Appendixes
20
21
Titulo Objetivo Amostra Instrumentos Método Principais resultados Conclusões Diffuse axonal injury due to traumatic brain injury alters inhibition of imitative response tendencies (Schroeter et al., 2007) Investigar o desempenho de pacientes com TCE em duas tarefas que envolvem diferentes processos funcionais e redes estruturais suportados pelos lobos frontais. 10 pacientes com LAD devido a TCE e 10 pacientes do GC TAP; BADS; Paradigma modificado do teste de Stroop; WMS-R; CVLT; Inventário neuropsiquiátri co. Dois paradigmas foram aplicados: a tarefa de palavras coloridas do teste de Stroop e uma tarefa na qual os sujeitos tinham que inibir tendências de resposta imitativa (3 condições: linha de base, congruente e incongruente ). -Os processos executivos examinados com a tarefa de Stroop permanecera m inalterados; - Uma vez inalterados, pacientes com LAD inibiram as respostas imitativas com mais sucesso do que o GC. -Os défices estavam fortemente correlaciona dos tanto com o compriment o da amnésia pós-traumática como com os distúrbios comportame ntais. -Prejuízos na tarefa de inibição da imitação podem indicar alterações na rede neural fronto-mediana anterior, mesmo após anos da lesão cerebral traumática. Deficits in predictive smooth pursuit after mild traumatic brain injury (Suh, Kolster, Sarkar, McCandlis s, & Ghajar, 2006) Investigar se pacientes com TCE leve apresentam défices na previsão do SPEM 21 pacientes com TCE leve e 26 indivíduos do GC HISC; Eye-traking (Eyelink II); WAIS; CVLT-II. Utilizado o paradigma sinusoidal periódico (apresentaçã o de estímulos em ecrã: o estímulo movia-se numa trajetória circular no sentido horário de 7,0◦ de raio a uma taxa de 0,4 Hz). - Pacientes com TCE demonstrara m diminuição da previsão do alvo, um maior erro da PO e uma maior VPO, o que se correlacionou com diminuição da PV; - Em todos os indivíduos a PMA, o erro de PO e a VPO correlacionar am-se com os scores relacionados - Pacientes com TCE apresentam alteração na previsão do SPEM e na VPO, prejuízos que se correlaciona m com défices cognitivos.
22 à atenção e à FE; -Os défices observados não decorrem de um prejuízo oculomotor geral ou de um QI reduzido. Characteris ing effects of impact velocity on brain and Behaviour in a model of diffuse traumatic axonal injury (Yan, Johnstone, Alwis, Morganti-Kossmann, & Rajan, 2013) Visão abrangente da interação entre a VI e a GL em roedores num modelo de WDIA Ratos Sprague-Dawley machos adultos (11 ratos para a condição 5,4 m/s de VI; 9 ratos para a condição 5,85 m/s de VI ; 14 ratos para a condição 6,15 m/s VI; 6 ratos do GC) Teste rotarod; Testes de balanceamento e caminhada; Elétrodos (medição fisiológica e de deflexões)
Aos ratos foi provocada uma LAD utilizando o modelo WDIA. Para isto, modificou-se o modelo para produzir 3 velocidades de impacto distintas: 5,4, 5,85 e 6,15 m/s, mantendo o peso e a altura da queda constantes. - Variações graduais da VI produziram graus progressivos da GL medidos a nível comportamen tal, eletrofisiológ ico e anatómico; - Houve reduções no desempenho sensório-motor e na depressão cortical, que dependem da VI; -A lesão axonal apenas foi visível na maior VP. -O modelo WDIA é capaz de produzir uma lesão axonal de forma repetitiva e, como tal, esta descoberta será útil no estudo da biomecânica , da fisiopatologi a e de um potencial tratamento da LAD. A longitudina l fMRI study of working memory in severe TBI patients with diffuse axonal injury (Sanchez-Carrion et al., 2008) Investigar mudanças ao longo do tempo na ativação do cérebro durante uma tarefa de MT num grupo de pacientes com TCE grave e difuso. 12 pacientes com TCE grave e difuso (todos provocado s por acidentes com veículos automotor es) e 10 participant es do GC GOAT; Subescala de dígitos e sequência de números e de letras (WAIS); Tarefa n-back. Todos foram submetidos a duas avaliações da MT num intervalo de 6 meses. Realizaram MR (duas) enquanto faziam uma tarefa visual de n-back (3 condições: 0, 2 e 3). - Observou-se alterações significativas na ativação cerebral ao longo do tempo nos pacientes com TCE, mas não no GC; - Na primeira MR verificou-se uma baixa ativação do GFS direito no grupo TCE, no - Evidenciou-se uma normalizaçã o progressiva do padrão de ativação da MT após LAD em pacientes com TCE grave, coincidindo com uma melhora no desempenho nesta função.
23 entanto, as diferenças entre o grupo com TCE e o GC diminuíram significativa mente após 6 meses (segunda ressonância); - Maior aumento da ativação no CF superior direito no grupo com TCE do que no GC (levando à normalização do padrão de ativação cerebral). Frontal Hypoactiva tion on Functional Magnetic Resonance Imaging in Working Memory after Severe Diffuse Traumatic Brain Injury (Sánchez-Carrión et al., 2008) Investigar défices de MT em pacientes com LAD e determinar a contribuição das disfunções da ativação cerebral para estes défices. 18 pacientes com TCE grave e LAD e 14 participant es do GC GOAT; Subtestes memória de dígitos e sequência de letras e números (WAIS-III); Tarefa n-back. Todos os participantes sujeitos a uma fMRI para se avaliar a ativação cerebral durante as tarefas n-back (3 condições: 0, 2 e 3). - O grupo de pacientes com TCE mostrou um prejuízo significativo na MT nas condições 2-back e 3-back; - Grupo de pacientes com TCE mostraram menor ativação cerebral nas RFP bilaterais do que o GC; -Diminuição da ativação cerebral no grupo de pacientes com TCE mais observada principalmen te no CF superior e médio direito; - Os pacientes com TCE grave e com LAD evidenciara m um padrão de hipoativação cerebral nas regiões frontais média e superior direita durante tarefas de MT e apresentam um prejuízo no seu desempenho .
24 - O GC apresentou correlação negativa entre desempenho e ativação no CPF, enquanto que os pacientes com TCE apresentaram correlação positiva no CP direito para uma carga baixa de MT, e no PH esquerdo para uma carga alta de MT. Effects of Diffuse Axonal Injury on Speed of Informatio n Processing Following Severe Traumatic Brain Injury (Felmingha m et al., 2004) Investigar se a LPI em TCE está relacionado com a LAD. 20 indivíduos com TCE (10 com LAD e 10 com LM) e 10 participant es do GC SDMT; TMT A e B; Tarefa de tempo de reação simples e escolha; SNST. Participantes realizaram as seguintes atividades: SDMT, TMT A e B, Tarefa de tempo de reação simples e escolha e SNST. - Grupo com LAD apresentou menor VBPI do que o grupo LM; -O grupo LM apresentou VBPI inferior, comparativa mente ao GC; - O grupo com LAD apresentou a maior recuperação ao longo do tempo; - Relativament e à flexibilidade cognitiva, o grupo de pacientes com LAD apresenta prejuízos significativos em comparação ao GC; - No que toca à atenção - O grupo de pacientes com LAD foi mais lento nas tarefas de processamen to de informação do que os grupos de LM e GC.
25 seletiva, em tarefas de tempo de reação complexas, o grupo com LAD apresentara tempos de reação significativa mente mais lentos comparativa mente GC (isto não se verifica para o grupo misto). Augmented neural activity during executive control processing following diffuse axonal injury (Turner & Levine, 2008) Investigar o processame nto do controlo executivo da MT em pacientes com LAD. 8 pacientes com LAD e 12 participant es do GC SILS. Realização da Tarefa Alphaspan (tarefa que envolve o processamen to do controlo executivo da MT) enquanto se realizava uma fMRI. - O desempenho dos pacientes com TCE e do GC foi equivalente na tarefa; - No entanto, observou-se um padrão de um maior recrutamento das regiões inter e intra-hemisféricas do CPF e do CP nos pacientes com LAD; - Maiores ativações cerebrais foram verificadas no CPF dorsolateral esquerdo (GF médio), no CPF-ventro-lateral direito (GF inferior), nos CP posteriores bilaterais e na junção TO esquerda no mesmo grupo. - Um recrutament o funcional aumentado pode funcionar como um marcador neural da eficiência ou de uma capacidade limitada que podem determinar o resultado funcional do paciente após um TCE com LAD.
26 The problem of axonal injury in the brains of veterans with histories of blast exposure (Ryu et al., 2014) Investigar a caracterizaç ão neuropatoló gica da lesão criada por exposição à explosão Comparara m cérebros de 4 grupos: - veteranos com história prévia de exposição à explosão - GC saudáveis - GC com overdose de opiáceos ou com encefalopa tia anóxico-isquémica - GC com TCE devido a quedas e colisão de veículos Sonda fracionária de área aérea; Software Stereo Investigator (MicrobrightF ield). Os cérebros foram preparados antes da sua análise. Existiam diversas substâncias que funcionaram como marcadores: PPA como marcador de axónios anormais; GFAP como marcador de astrócitos; anticorpo de molécula 1 de ligação de cálcio ionizado como marcador de microglial; epítopos de neurofilame ntos fosforilados mistos como marcadores axonais génicos. -Verificaram-se anomalias axonais da PPA(+) em vários locais cerebrais, principalmen te na SBF dorsal média, no grupo com história prévia de exposição à explosão; -No grupo com TCE devido a colisão de veículos foram encontradas anomalias axonais de microglia IBA1(+) reativa; - O grupo com overdose de opiáceos mostraram anormalidade s axonais de PPA(+) (intensidade das lesões inferior às apresentadas no grupo com história prévia de explosão). - É possível concluir que casos com história de exposição à explosão são caracterizad os por axonopatia PPA(+) que pode estar relacionada com a ocorrência dessa exposição à explosão. Traumatic axonal injury in the mouse is accompanie d by a dynamic inflammato ry response, astroglial reactivity and complex Investigar a LAT e respostas inflamatória s dinâmicas, reatividade astroglial e alterações comportame ntais complexas. 20 camundon gos com lesão por percussão central de fluidos e 9 camundon gos com lesão simulada (não foi provocada nenhuma lesão). Teste MCSF; Diversos equipamentos de gravação vídeo, contagem da pontuação da frequência, duração e latência e de velocidade e distância percorrida. Foi provocada uma lesão por percussão central de fluidos em 16 ratos (redução da amostra devido a morte). Foram analisadas 14 secções coronais dos -Verificou-se uma lesão axonal bilateral generalizada e um aumento da permeabilida de da barreira hematoencef álica; - Observou-se uma reatividade das células gliais em - O modelo que foi aplicado em camundongo s parece ser adequado para o estudo de mecanismos da lesão. - A LAT resultou em respostas bilaterais astrogliais e neuroinflam
27 behavioral changes (Ekmark-Lewén et al., 2013) ratos (método morfológico ). Todos os animais foram submetidos ao teste MCSF individualm ente no dia 2 pós-lesão (ensaio 1) e no dia 9 (ensaio 2) (medida padrões comportame ntais). regiões corticais; -Após três dias da lesão, verificou-se um pico de reatividade em espaços importantes da substância branca; -Comparativa mente ao grupo de ratos com lesão simulada, os ratos com lesão axonal mostraram um aumento do número de microglia ativada, da infiltração de neutrófilos e de células T, um dia após LAT, na matéria branca subcortical; - Os padrões comportamen tais (atividade geral e comportamen to exploratório) diferiram entre os ratos com LAT e o GC com lesão simulada. atórias, bem como em alterações comportame ntais complexas.
28 Independen ce in managing one’s finances after traumatic brain Injury (Bottari et al., 2011) Investigar se a tarefa orçamentári a do IADLP discrimina indivíduos com TCE de controlos saudáveis e identificar a natureza das dificuldades observadas. 27 adultos com TCE moderado ou grave e 27 participant es do GC. Todos foram classificad os relativame nte à sua responsabi lidade financeira: Nenhuma responsabi lidade pela gestão financeira, responsabi lidade parcial e responsabi lidade total. Tarefa orçamentária do IADLP; A gravação e a transcrição de vídeos foram realizadas para avaliar onde ocorre a quebra do desempenho da tarefa. Numa única sessão, os participantes foram sujeitos a uma tarefa orçamentária . No final, os participantes relatavam a frequência e qual a responsabili dade que tinham em tarefas idênticas à realizada. - Os participantes com TCE (maioritariam ente com lesões frontais ou LAD) são mais propensos a ter dificuldades em todas as operações relacionadas à tarefa do que o GC. - O planeamento é a operação mais afetada nos participantes com TCE. - Estes défices têm impacto nas habilidades financeiras, principalmen te para os participantes com TCE que reportam total responsabilid ade pelas suas finanças. - Há diferenças no desempenho da tarefa orçamentária do IADLP entre indivíduos com TCE e o GC. - O planeamento é a operação que mostrou dificuldades mais significativa s. Cognitive impact of traumatic axonal injury (TAI) and return to work (Esbjörnsso n et al., 2013) Investigar a função cognitiva após TCE e suspeita de LAT aos 6 e 12 meses após lesão e associação com o estatuto de trabalho aos 12 meses. 16 pacientes com menos de 65 anos de idade. BNIS; Reakta III; FTT da Bateria de Teste Neuropsicológ ico de Halstead-Reitan; Subescala de Código e subescala Memória de Dígitos (WAIS-III); GCS; Philips Intera versão 1.5. Foram realizadas MR convenciona is aos pacientes 2 semanas após a lesão, seguidas de uma triagem cognitiva. Os participantes foram avaliados em três momentos diferentes: na fase - Após 6 meses verificou-se uma recuperação das funções cognitivas dos pacientes. -No entanto, aos 12 meses verificou-se um declínio cognitivo na maioria dos pacientes. -Após 12 meses ainda se verificava - A triagem cognitiva pode identificar o impacto a longo prazo da LAT identificada através da MR convenciona l.
29 aguda, aos 6 meses e aos 12 meses. disfunção cognitiva. - Pacientes que não retomaram ao seu trabalho apresentaram -se cognitivamen te mais debilitados do que os pacientes que conseguiram regressar ao trabalho (4 pacientes). Acute and Chronic Changes in Diffusivity Measures after Sports Concussion (Henry et al., 2011) Investigar os efeitos da concussão desportiva na substância branca usando três medidas diferentes de DTI: FA, MD e AD. 16 atletas que sofreram de concussão desportiva e 8 atletas que não sofreram concussão desportiva (GC). PCSS; Siemens Trio 3-T (sistema de MR). Os aletas foram sujeitos a vários momentos de scanning: Os atletas que sofreram de concussão realizaram scanning 5 dias após a lesão e aos 6 meses após o primeiro scanning. Os atletas que não sofreram de concussão realizaram scanning aos 18 meses após o primeiro. -Nos dois momentos de avaliação, os atletas que sofreram de concussão apresentaram efeitos significativos da mesma em regiões dorsais e no corpo caloso em imagens da FA. -Imagens de DA mostraram efeitos no trato corticoespinh al direito (atletas com concussão apresentaram valores elevados comparativa mente com os outros atletas nos dois momentos de avaliação/sca nning). -Os valores da DM são menores em atletas que sofreram de - As concussões desportivas provocam mudanças na difusividade do corpo caloso e do trato corticoespin hal que não são detetadas quando se utiliza técnicas de neuroimage m convenciona l.
30 concussão, sendo que se verificaram diferenças significativas entre os atletas que sofreram de concussão e os restantes atletas no trato corticoespinh al e no corpo caloso em ambos os momentos. Accelerated long‐term forgetting is not epilepsy specific: Evidence from childhood traumatic brain injury (Lah et al., 2017) Investigar se crianças com TCE apresentam défices na memória de novas informações verbais após um longo prazo (7 dias). Investigar também uma possível associação entre lesões no lobo temporal, no lobo frontal e/ou LAD, todas comuns no pós-TCE, e a aceleração do esqueciment o a longo prazo. 28 crianças com TCE divididas em dois grupos: grupo leve-moderado (15 crianças) e grupo grave (13 crianças). 62 crianças saudáveis (GC). Subescalas Vocabulário e Raciocínio Matricial (WASI); Subteste memória de dígitos (WISC-IV); Subteste memória da história (WRAML-2); Versão adaptada do CVLTC. Primeiramen te, foi realizada uma entrevista semi-estruturada aos pais das crianças via telefone. Os participantes foram sujeitos a duas sessões de avaliação: a primeira foi realiza numa sala do hospital e a segunda foi realizada via telefone (telefonema de acompanha mento de 7 dias) na qual se solicitou a recordação das palavras. -Crianças com TCE grave obtiveram pontuações significativa mente mais baixas em comparação ao GC na recordação da informação verbal após um prazo padrão de 30 minutos; -Crianças com TCE apresentaram aceleração do esquecimento a longo prazo; -A manutenção de um TCE grave e de um dano subcortical difuso estava relacionada com a aceleração do esquecimento a longo prazo. - Em 6 das 8 crianças a aceleração do esquecimento - Este estudo mostra que é possível encontrar aceleração do esqueciment o a longo prazo em crianças com TCE, que não estava a ser diagnosticad a e tratada nesta população de pacientes. -Mostrou também que a aceleração do esqueciment o a longo prazo é um fenómeno que está relacionado a convulsões do lóbulo temporal.
31 a longo prazo era indetetável pelos testes padronizados . Neural correlates of visual memory in patients with diffuse axonal injury (Lauer et al., 2017) Investigar se pacientes com TCE e com diminuição do volume da substância cinzenta e branca no CF e no CP, bem como nos lobos medial temporal e occipital, teriam um mau desempenho nos testes de memória visual analisados. 39 pacientes com LAD (TCE de leve a grave) e 53 participant es saudáveis (GC). CANTAB; scanner Siemens Trio de 3 T para a realização de MR. Realizaram três tarefas da CANTAB: tarefa memória de reconhecime nto de padrões, tarefa memória de reconhecime nto espacial, tarefa aprendizage m de associações emparelhada s - Os pacientes com TCE mostraram um desempenho significativa mente inferior comparativa mente ao GC em todas as tarefas avaliadas. - Este desempenho foi associado a reduções generalizadas no volume de substância cinzenta e branca de várias estruturas corticais e subcorticais, bem como ao aumento do espaço do líquido cefalorraquid iano. - Este estudo mostrou que a memória visual comprometi da em pacientes com TCE está relacionada a um padrão distribuído da perda de volume em regiões mediadoras da memória e do processamen to atencional. Statistical machine learning to identify traumatic brain injury (TBI) from structural disconnecti ons of white matter networks (Mitra et al., 2016) Apresentar uma abordagem denominada de Statistical machine learning para classificar os participante s com TCE, baseada em padrões alterados de conectivida de estrutural. 179 pacientes com TCE e 146 controlos Foi utilizado um scanner 3 T Siemens TimTrio para a realização das MR. A abordagem do estudo foi realizada em duas fases: Inicialmente , a análise da conectividad e da rede para seleção dos recursos e, posteriorme nte, a extração de característic as discriminati vas usando - Observou-se conectividad e alterada em várias vias intra e inter-hemisféricas de substância branca associadas à LAD. -Este estudo permitiu mostrar o potencial deste tipo de abordagens (Statistical machine learning ) aplicadas a conectividad es estruturais para identificar pacientes com LAD.