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A QEEG index of level of functional dependence for people sustaining acquired brain injury: The Seville Independence Index (SINDI)

Jose Leon-Carrion ab; Juan Francisco Martin-Rodriguez ab; Jesus Damas-Lopez b; Juan Manuel Barroso Y. Martin a; Maria Del Rosario Dominguez-Morales b a Human Neuropsychology Laboratory, School of Psychology, Department of Experimental Psychology, University of Seville, Seville, Spain b Center for Brain Injury Rehabilitation (CRECER), Seville, Spain Online Publication Date: 01 January 2008 To cite this Article: Leon-Carrion, Jose, Martin-Rodriguez, Juan Francisco, Damas-Lopez, Jesus, Martin, Juan Manuel Barroso Y. and Dominguez-Morales, Maria Del Rosario (2008) 'A QEEG index of level of functional dependence for people sustaining acquired brain injury: The Seville Independence Index (SINDI)', Brain Injury, 22:1, 61 - 74 To link to this article: DOI: 10.1080/02699050701824143 URL: http://dx.doi.org/10.1080/02699050701824143

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Brain Injury, January 2008; 22(1): 6174

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A QEEG index of level of functional dependence for people sustaining acquired brain injury: The Seville Independence Index (SINDI)

JOSE LEON-CARRION1,2, JUAN FRANCISCO MARTIN-RODRIGUEZ1,2, JESUS DAMAS-LOPEZ2, JUAN MANUEL BARROSO Y. MARTIN1, & MARIA DEL ROSARIO DOMINGUEZ-MORALES2
1

Human Neuropsychology Laboratory, School of Psychology, Department of Experimental Psychology, University of Seville, Seville, Spain and 2Center for Brain Injury Rehabilitation (CRECER), Seville, Spain

(Received 31 August 2007; accepted 23 November 2007)

Abstract Primary objective: To find an easy-to-use, valid and reliable tool for evaluating the level of functional dependence of an individual with brain damage who seeks a diagnosis of his/her functional dependence in daily activities. Methods: Eighty-one patients with acquired brain injury (ABI) in post-acute phase, 40 traumatic brain injury (TBI) and 41 cerebral vascular accident (CVA), were assessed using quantitative electroencephalography (QEEG) and grouped according to the FIM FAM scale. Discriminant analysis was performed on QEEG variables to obtain a discriminant function with the best discriminative capacity between functionality groups. Results: Discriminant analysis showed classification accuracy of 100% in the training set sample and 75% in an external cross-validation sample; 100% sensitivity and 100% specificity were reached. Coherence measures were the most numerous variables in the function. Conclusions: These results point out that the discriminant function may be a useful tool in objective evaluations of patients seeking a diagnosis of their level of dependence and that it could be included in current functionality assessment protocols. Keywords: Traumatic brain injury, stroke, functional independence, QEEG, neuropsychological assessment, forensic assessment

Introduction Neurological damage and acquired brain injury affect a large portion of the population in western countries. An estimated 1.5 million Americans sustain traumatic brain injury (TBI) every year in the US. Of these, 1.1 million are now living with disabilities related to TBI [1]. In the European Union, brain injury accounts for 1 million hospital admissions per year. At discharge, most of these patients show impairments in multiple areas, which affect their ability to carry out daily life activities and cause important legal, professional and personal consequences.

In Europe, new laws are being established by national governments to assist people in accordance with their level of dependency. In Spain, a new law was approved on 15 December 2006 called The Law to Promote Personal Autonomy and to Assist People in a State of Dependence. This law has created a bureaucracy and a medical system that regulate promoting the autonomy of dependent individuals as well as the state-funded care they receive. As a result, medical and social resources are needed to implement this law, which will serve more than 2 000 000 people in Spain alone. More than a third of these individuals are dependent in their daily

Correspondence: Jose Leon-Carrion, PhD, Human Neuropsychology Laboratory, School of Psychology, Department of Experimental Psychology, C/Camilo Jose Cela s/n. University of Seville, Seville-41018. Spain. Tel: 34 95 457 4137. Fax: 34 95 437 4588. E-mail: leoncarrion@us.es ISSN 02699052 print/ISSN 1362301X online 2008 Informa UK Ltd. DOI: 10.1080/02699050701824143

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J. Leon-Carrion et al. EEG (QEEG). Human QEEG measures have been correlated with certain diagnostic categories, both in healthy [8,9] and clinical populations [10]. By meeting certain statistical requirements, these studies have obtained a set of QEEG variables, known as discriminant functions, which can predict the severity of a clinical condition. The advantages of these measurement systems over others include their low cost, speed, lack of cultural influence and minimal human intervention in the analysis of the results. These systems allow predictions to be made on an individuals psychological and functional characteristics based on specific physiological variables. In the field of brain injury, functional independence is normally evaluated using clinical behaviour scales, the most widely used being the FIM FAM [11], the Glasgow Outcome Scale (GOS) [12] and the latters extended version [13]. The first scale was devised by adding FAM items to FIM in order to address functional assessment in the TBI population; the second was designed to evaluate the general state of patients after neurosurgery. These scales, which proved reliable and easy-to-use, were later applied to other areas of evaluation. This caused serious drawbacks to their effectiveness, a common problem being that both scales offered too few items for evaluating higher psychological functions and the possibility of malingering. However, a recent study by van Baalen et al. [14] found the FIM and FAM scales to be highly reliable, sensitive tools for assessing TBI patients. The authors stressed that both scales offered better results during the first phases of post-TBI recovery, as their effectiveness diminished during post-acute phases and rehabilitation (1 year after brain injury). Studies that correlated sensitivity in long-term TBI population (up to 10 year post-injury) reported low contributions from FIM FAM and GOS in functional status assessment [15]. A new tool based on the neurophysiological profile of brain injury patients could help overcome these limitations by establishing a more robust measure for the diagnosis of long-term brain injury population. Studies on QEEG present a consistent and common neurophysiological pattern associated with severity of brain injury, which involves increased slow band amplitudes, decreased fast band amplitudes [16,17] and changes in EEG coherence [18]. The present study pays special attention to the differences in these measures. The aim of the present study is to find the linear combination of QEEG variables, by means of the discriminant analyses, with the best discriminative capacity for functional states. These states include complete dependence (total assistance in various DLA), modified dependence and independence.

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life activities due to neurological disorders, the more prevalent being cerebrovascular disorders and TBIs. Any individual in a state of dependency that asks to be included in the new state-funded system must be clinically evaluated to determine whether they are dependent or not and, if so, at what level. If they are clinically proven to be in a dependent state, then, apart from the state-funded care, they may also receive financial support and other benefits. Under this new legal action, and in order to avoid malingering, an objective evaluation of the functional state of these patients is needed, with new tools that offer high reliability and validity. Nowadays, few objective instruments exist to evaluate independence in people seeking social and legal assistance. Existent tools generally rely on the subjective impressions of caregivers, whose interpretations may distort results and thus provoke false positives. Moreover, exaggerating and malingering symptoms are very common among patients with acquired brain injury, especially when monetary compensation is expected or in litigation, where they make up 1520% of all cases [2]. Individuals with mild brain damage and post-concussional disorders constitute 40% of those seeking compensation [3]. Functionality is considered a multidimensional concept, where the whole cannot be explained by the mere sum of its parts. Instruments that evaluate functionality must be capable of detecting malingering. In current clinical practice, functionality assessment evaluates both the level of independence in basic tasks, such as eating or bathing, as well as in more complex and instrumental tasks, such as getting on a bus. Thus, a full assessment has multiple levels of complexity involving multiple assessors. The need for objective functional assessments would require summarizing this complex concept in an index that informs on the impact of certain medical conditions on the lives of patients. In recent years, advanced technology has been used to locate affected areas of the brain with greater precision. The use of sophisticated imaging software has made it possible to create defined cerebral maps that can be adapted to a patients brain in order to determine which functional areas are affected. In the field of brain injury, this technology is needed in order to make objective evaluations and determine the severity of the condition. When applying neuroimaging techniques to the assessment of brain injury, the electroencephalography (EEG) plays a crucial role, with its relatively low cost, simple application procedure, high testre-test reliability and inherent stability [47]. Moreover, the development of mathematical tools and data visualization has made it possible to quantitatively analyse the human EEG, a technique known as quantitative

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The discriminant analysis helps identify the characteristics that differentiate (discriminate) two or more groups. One will create a function capable of distinguishing between the possible members of each group with highly accurate precision. For classification, the discriminant function must have linearity as one of its characteristics. This feature exists when the function follows the proportionality of magnitudes of the entry and exit variables. When this happens, the scores in this function of the modified dependence group members should fall between those of the complete dependence and independence group members.

multidisciplinary rehabilitation programme which treats neuropsychological, physical and functional sequelae derived from brain injury. Procedure Functional assessment: FIM FAM. The FIM FAM is a multidimensional scale for functional assessments, widely used in evaluating the impact of rehabilitation on the ABI population. The current version of this scale (FIM FAM) stems from a combination of the FIM (Functional Independence Measure) and the FAM (Functional Assessment Measure). It consists of 30 items, 18 from FIM and 12 from FAM. These items are grouped into seven sub-scales: self-care (items 17), sphincter control (89), mobility (type of transfer) (1013), locomotion (1416), communication (1721), psychological adjustment (2225) and cognitive functions (2630). The FIM FAM scales have been widely studied and are considered a valid assessment tool for ABI patients. Statistical studies found a reliability index of 0.860.97 [18,19]. They have also shown reasonable validity, internal consistency and discriminative capacity between brain damaged sub-populations [20]. These characteristics render the FIM FAM scale one of the most popular instruments for evaluating the functional state of neurological patients. Three independent assessors (a physical therapist, a speech therapist and a neuropsychologist) completed the FIM FAM sub-scales. All items were scored from 17 points, where 1 indexes extremely functional dependence and 7 indexes total functional independence. The average interval between functional assessment and QEEG was 1 day (SD 1.32). Averages were calculated for each FIM FAM sub-test, as well as the average of the FAM items, the FIM items and total FIM FAM. Based on

Methods Participants The total sample included 81 patients with acquired brain injury (ABI), 40 of which were traumatic brain injury (TBI) patients and 41 cerebral vascular accidents (CVA). Of these, 48 made it into the training set for the creation of the discriminant function and its subsequent internal validation. The remaining 33 patients participation served to validate the function externally. Patients in the training set sample ranged in age from 1675 (M 40); 27 were TBI patients and 21 CVA; 37 were male and 11 female. All subjects were recruited from the Centre for Brain Injury Rehabilitation (C.RE.CER) in Seville, Spain. Admission criteria were age (over 16) and a clinical background of ABI caused by TBI or AVC, confirmed by neuroimaging tests (CT or MRI). Figure 1 shows sample size and representation of the clinical sub-groups. All of the patients were in chronic or sub-acute phase when examined. The average time period between brain injury and QEEG evaluation was 22 months (range 0.5119 months). They were also participants in a holistic, integral and

Figure 1. Sample sizes and clinical features.

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J. Leon-Carrion et al. QEEG measures. The measures most widely used in QEEG research are spectral patterns and connectivity patterns. The former are based on the analysis of EEG signal frequency spectrum at a specific location; they are independent of time and yield the intensity of the electromagnetic field of that location. The latter are more complex measures that involve spatial-temporal characteristics and include various locations, yielding the strength of the connections between these brain regions. Amplitude measures The most basic amplitude measure is absolute magnitude (amplitude), defined as the average absolute magnitude (expressed in microvolts) of the frequencies that make up a specific band, over a given time period. The relative magnitude is the average relative magnitude (expressed in%) of a specific frequency band (the absolute magnitude divided by total microvolt generated at a particular location by all bands). The amplitude asymmetry is defined as the amplitude difference between two locations in a particular bandwidth. It is calculated as follows: (A B)/(A B), where A and B are different locations [24]. Connectivity measures Connectivity measures (or amplitude independence) are coherence and phase lag. Coherence indexes the degree to which two areas of the cortex are functionally linked. Statistically, this measure is calculated as the likelihood that two random signals will arise from a common generator process and the frequency bands in which this occurs [25]. Coherence is calculated for each frequency band and for each combination of the 19 electrodes. Coherence is calculated as: 2 Gxy f 2 xy f Gxx f Gyy f where Gxy( f ) is the cross-power spectral density and Gxx( f ) and Gyy( f ) are the autopower spectral densities, respectively. Due to the complex analyses involved in this formula, the calculation is made with the cospectrum (r for real) and quadspectrum (q for imaginary). Thus, coherence is obtained using the following formula [26]: 2 xy
2 rxy q2 xy Gxx Gyy

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these averages, three functional groups were created: Complete Dependence (CD; range 12.99), Modified Dependence (MD; range 35.99) and Independence (I; range 67). There were no significant differences between the three functional groups in gender (p 0.448), aetiology of ABITBI or CVA (p 0.111), age (p 0.748) or time period from brain injury to QEEG test (p 0.337).

EEG recordings. EEG recordings were carried out in a softly-lit, sound-proof room, with room temperature set at 23 C. Before each recording, patients were seated in a comfortable armchair or in his/her wheelchair and asked to relax during the recording. Impedance was kept below 10 k . Nineteen scalp locations were taken into account, based on the international 10/20 system [21], using linked ears (A1 and A2) as a reference. The patient was asked (or helped) to close his/her eyes (EC) and remain relaxed and alert while EEG activity was recorded. In order to maintain vigilance, a technician monitored each subject, inspecting the EEG traces on-line and verbally alerting the subject any time behavioural and/or EEG signs of drowsiness appeared. Each recording lasted 3 minutes, with bandwidths of 0.1100 Hz and 256 Hz sampling frequency.

Data selection. Data pre-processing and filtering were carried out offline in Matlab (The Mathworks, MA) using EEGLAB (http:// www.sccn.ucsd.edu/eeglab/index.html) [22] and custom scripts. Low-pass filters were located at 40 Hz and high-pass filters at 0.5 Hz. EEG recordings were visually edited to remove any visible artifact. Continuous artifacts or artifacts present in over 80% of overall time are generally due to the presence of spasticity or any motor artifact in some patients. In most cases, ocular movement in frontal electrodes and muscular tension in temporal derivations caused these artifacts. The authors applied an Independent Component Analysis (ICA), a procedure which has proven reliability in removing signal artifacts [23]. A maximum of two components were selected that isolated the artifacts, which were then removed from the original recording. This process of artifact removal was carried out on a total of 11 recordings (22%) out of 50. Subsequently, fragments free of artifacts in the most representative EEG sections were visually selected, using Neuroguide 2.2.1 software (Applied Neuroscience, Inc., St. Petersburg, FL), for a total of 120 seconds of recordings. Only fragments with over 90% reliability were used for the spectral analysis.

Phase lag is defined as the time it takes one wavelength from a particular location to reach the phase or maximum amplitude of another wavelength originating from a different specific location.

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The contribution of each frequency band to the EEG signal was obtained by means of the Fast Fourier Transformation, FFT. The frequency bands of interest were delta (13.5 Hz), theta (47.5 Hz), alpha (812 Hz) and beta (1225 Hz), including high beta (25.530 Hz). Coherence and phase lag were computed using cross-spectra analysis.

Statistical analyses Descriptive analyses were conducted on both demographic and behavioural variables. A factorial analysis (varimax rotation) was applied to each of the eight measures that make up the FIM FAM scale (all quantitative variables). The highest load factor explained the total variance of 85.52%. Correlation analyses were performed to study the relation between the different measures, with positive results showing Pearson correlation coefficients (r) higher than 0.8. These two results allowed one to select the total FIM FAM measure (average of seven measures) as the dependent variable for the subsequent discriminant analysis. The aim of this experimental design was to obtain a discriminant equation, capable of classifying and predicting the functional state of each patient based on his or her QEEG pattern. The first objective was to differentiate between the extreme groups (independence vs complete dependence). After classifying the two groups, the equation was tested on an intermediate functional group (modified dependence) in order to evaluate the hypothesis on the linearity of functionality. The final step was to classify a new group of patients using this equation.

The procedure for data reduction and creation of the discriminant function is summarized in Figure 2. Power spectral analyses yielded a total of 2755 variables as candidates for the EEG discriminant analysis. Student t-tests were conducted to determine the discriminant capacity of each variable, using the functional group of the patient as grouping factor. Of the 2755 variables, 368 (11 absolute amplitude, 40 relative amplitude, 98 amplitude asymmetry, 184 coherence and 35 phase lag) were significant (taking into consideration the application of the Levene test). No correction for multiple comparisons was applied, given that the objective of this analysis was data reduction, i.e. to distinguish between significant and non-significant variables without making inferences from the analysis. In order to reduce the data, a factorial analysis was applied to each EEG measure (absolute amplitude, relative amplitude, amplitude asymmetry, coherence and phase lag). A Varimax rotation was applied. Variables with the highest load for each factor were identified (three absolute amplitude variables, five relative amplitude, 14 amplitude asymmetry, 18 coherence and 11 phase lag). The result was a total of 51 variables. By using this two-level procedure, the initial set of 2755 variables was reduced by 98.15%. The next step involved performing a discriminant analysis, using the Bayesian criterion in order to adjust for the n difference between groups. A stepwise method was used to obtain information on the individual significance of each variable in the discriminant function. The Wilks Lambda statistic was used to assess each of the 51 variables. In order to demonstrate the linearity of the discriminant equation, this study analysed the correlation between

Figure 2. Procedure used to reduce data and create discriminant function.

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J. Leon-Carrion et al. The QEEG measures represented in the function are absolute amplitude, amplitude asymmetry, coherence and phase lag. The most represented variable was coherence (four variables). Absolute amplitude and absolute asymmetry each contributed with one variable; phase lag contributed with three. All frequency bands were represented. The locations were distributed as follows: one right-hemisphere location, four mid-line locations and four interhemispheric locations. Figure 3 shows the distribution of these variables in the cerebral cortex, according to the 1020 International System. Discriminant analysis: Classification Results showed that the selected QEEG variables allowed distinction between both functional groups, with a canonical correlation of 0.97. Furthermore, centroids of both groups differed significantly (p < 0.001). The coefficients of the function showed that phase lag theta FP1-F8 and phase lag delta F3-Cz had a higher potential for determining a patients group. Patients in the complete dependence group (centroid 3.93) will tend to have negative scores, whereas the independent group (centroid 4.22) will tend to have positive scores. Table III shows the classification accuracy of this logarithm for the 15 patients in the complete dependence group and the 14 patients in the independence group. The precision of the functional analysis was 100%.

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the FIM FAM scores and the corresponding discriminant scores (DS). A one-way ANOVA for independent measures was used to determine the differences between the functional groups discriminant scores, with DS as the dependent variable and functional group as grouping factor (three functional groups: complete dependence, modified dependence and independence). Post-hoc tests were applied to analyse the differences between groups in pairs. Results Functional outcomes The factorial analysis on the 11 variables of the FIM FAM scale (eight measures, FIM items, FAM items and overall FIM FAM) produced a factor that explained the total variance of 85.52%. Furthermore, correlations between these variables reached significance (p < 0.001). The lowest correlation was between the communication and locomotion sub-scales (R 0.56). This data supports the authors hypothesis: a discriminant function for the functional sub-groups of global FIM FAM variables will also correctly discriminate within the other variables of the FIM FAM sub-scales. Table I shows FIM FAM scores within each functional group. Discriminant function: QEEG variable selection Table II shows the variables selected by applying the step-wise method, along with Wilks Lambda and p-values.

Table I. Mean FIM FAM scores within each functional group. Patient classification Independence (n 15) Modified dep. (n 19) Complete dep. (n 14) Sphi.C Sphincter control; CF Cognitive Function. Self-care 1.34 4.47 6.71 Sphi. C 1.8 6.47 7 Trans 1.09 4.21 6.64 Loc 1.17 4.54 6.68 Com 1 3.77 6.59 PA 2.61 5 6.6 CF 2.25 4.34 6.57 FIM 2.15 5.04 6.8 FAM 1.62 4.73 6.7 FIM FAM 2.21 4.77 6.68 Adjustment;

Trans Transfer;

Loc Locomotion;

Com Communication;

PA Psychological

Table II. Variables selected by applying discriminant analysis, Wilks Lambda values and p-value. Variables Type of variable Absolute amplitude Asymmetry Coherence Frequency band Delta Beta Delta Alpha High-Beta Delta Theta Location P4 FP2-F3 T3-Cz F4-O1 Pz-O2 Cz-O2 F3-Cz C3-T4 FP1-F8 Wilks Lambda 0.11 0.16 0.07 0.13 0.05 0.08 0.35 0.28 0.22 Exact F statistics 28.6 24.15 35.30 23.91 37.54 32.87 24.14 21.40 21.56 p 2.55E-09 1.89E-08 3.8E-10 1.38E-08 3.16E-10 6.25E-10 1.18E-06 4.39E-07 1.18E-07

Phase lag

Minimum partial F to enter 3.84; Maximum partial F to remove 2.71.

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Figure 3. International 1020 system location for QEEG variables included in the discriminant function.

Table III. Discriminant analysis classification of Independence and Complete Dependence groups. Classification, % as FIM FAM group N Independence Complete dependence 0 100 (n 15)

Table IV. Summary of the signs of the correlations between FIM FAM and EEG scores. Absolute amplitude Band Delta Theta Alpha Beta High beta Total POS 0 0 1 0 0 1 NEG 1 0 0 2 0 3 Coherence Phase lag

POS NEG POS NEG 56 4 4 1 0 65 0 0 3 37 48 88 5 3 0 1 0 9 0 0 1 1 2 4

Independence 14 100 (n 14) Complete dependence 15 0 Precision of global classification 100%.

Since this procedure tends to over-estimate the precision of the classification, we used the leave-oneout method of classification. This study observed that the global classification accuracy is near 100% (see Table IV). Figure 4 shows the distribution of each functional group and lineal adjustment of the DS obtained with the function. The lineal adjustment is correct and there is distinction between the groups. The clinical validity of the DS was tested by means of the Pearson correlation for each FIM FAM variable. Figure 5 shows the results of this correlation analysis. All correlations reached significance (all ps < 0.001), with a high lineal adjustment ranging from r 0.8 (communication sub-scale) to 0.97 (mobility sub-scale). These results support linearity once again across clinical FIM FAM sub-scales. Cross-validation of the discriminant function In this section, the discriminant function was tested on a new group of patients with an intermediate functional range compared to the other groups. The analysis also tested the linearity hypothesis of the functional state. The modified dependence group was comprised of 19 ABI patients: 6 female and 13 male; 10 TBI, nine CVA; mean age 42.21, SD 18.79). The correlation between DS and FIM FAM scores with these new cases was R 0.81

(p < 0.001; see Figure 6), supporting the hypothesis of linearity between scores. The one-way ANOVA showed that mean DS were different in the three functional groups (F 48.9, p < 0.0001). Post-hoc analysis showed that the Independence group median score was significantly higher than that of the Modified dependence group, which in turn was higher that of the Complete dependence group (all ps < 0.001; see Figure 6). The function was also cross-validated using multiple regression analysis. In this analysis, the dependent variable was the FIM FAM score and the independent variables were the QEEG variables included in the discriminant function. The DS and the predicted values of the multiple regression analysis showed correlations of 0.93 (p < 0.0001; see Figure 7 (left)). Another test that predicts the QEEG of a patients functional state is the correlation between the predicted scores from the multiple regression analysis and the FIM FAM scores. This correlation reached significance with an R 0.85 (p < 0.0001; see Figure 7 (right)). Analysis of the signs of the correlations This analysis was included to determine the direction of the associations between the EEG measures that

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Figure 4. Diagram of distribution and lineal adjustment between DS (x-axis) and total FIM FAM scores (y-axis). The colour code represents the patients FIM FAM scores, red being the lowest score and blue the highest.

showed statistically significant differences between the Independence and Complete dependence groups, using the t-test. A chi-squared analysis was performed with adjusted standardized residual analysis to interpret the signs of the correlations. This procedure was applied only to the measures of absolute amplitude, coherence and phase lag. It was not applied to the measures of relative amplitude and asymmetrical amplitude due to the difficulty of interpreting signs of the correlations for these measures. Table V summarizes the results of the correlations between absolute amplitude, coherence and phase lag and the FIM FAM scores. The correlations of the coherence variable are significantly higher in number than those of absolute amplitude and phase lag (2 142; p < 0.0001). This variable correlates positively throughout delta bands (Adjusted Residuals or AR 10.9) and theta (AR 2.4). Conversely, it correlates negatively throughout beta (AR 5.7) and high-beta (AR 7.2). The last step was to obtain t-scores that corresponded to the 19 locations for the absolute amplitude variable which resulted from the comparative analysis between the complete dependence and independence groups. The selection was done in accordance with the homocedasticity criterion of the Levene test. The 19 scores were interpreted for each frequency band on a cortical topographic map (Figure 8). The EEG scores of complete dependence patients showed greater slow wave activity (delta and theta) and less fast wave activity (alpha and beta). Bands that displayed statistically significant differences were delta, with greater activity in the right hemisphere and posterior regions; alpha, with a generalized decrease; and high-beta, with greater

activity in frontal regions (all ps < 0.01; corrected for multiple comparisons). External validation Once the internal validity of the functions was tested, the next step was to classify new cases to assure external validity. The new sample consisted of 33 ABI patients, 13 TBI and 20 CVA, all over 16 years of age and in post-acute phase. The DS was obtained from each patient. Table VI shows the precision of the classification of this new group of patients, with an overall classification accuracy of 75%. There was a high correspondence between the FIM FAM scale classification and the discriminant function for extreme groups. Patients in the intermediate range reached a classification accuracy of 65%. The remaining 35% of the intermediate cases were classified according the linearity of the function, this is to say those closest to the independence group were classified as such and those nearest the dependence group received this classification. Figure 9 (right) shows the linearity feature of these new patients.

Discussion Principal findings The resulting discriminant function showed a continuum between the three different functional groups. A set of measures was obtained that separate the groups, situating the complete dependence group at the lowest extreme. Patients with modified dependence were situated at the intermediate point and patients with the greatest independence were at the

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Figure 5. Diagram of distribution and lineal adjustment between DS (x-axis) and each FIM FAM sub-scale (y-axis). The colour code represents the patients FIM FAM scores, red being the lowest score and blue the highest.

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Figure 6. Mean DS for the three functional groups: Complete dependence, Modified dependence and Independence. The mean DS for the Modified dependence group falls between the DS of the other two groups. (Overlapped) Diagram of distribution and lineal adjustment between DS (y-axis) and global FIM FAM scores (n 48). The colour code represents the patients FIM FAM scores, red being the lowest score, green being the mid-range and blue the highest.

Figure 7. (Left) Predicted values for the FIM FAM variable for all patients (n 48) based on the multiple regression analysis (y-axis) and the DS (x-axis). (Right) Predicted values for the FIM FAM variable for all patients (n 48) based on the multiple regression analysis (x-axis) and the original FIM FAM scores (y-axis).

Table V. Discriminant analysis classification of Independence and Complete Dependence groups, based on the leave-one-out method. Classification,% as Complete dependence 0 93.3 (n 14)

FIM FAM group Independence Complete dependence

N 14 15

Independence 100 (n 14) 6.7 (n 1)

Overall classification accuracy 96.65%.

highest extreme. Positive correlation and multiple regression analyses supported the linearity hypothesis. The significant positive correlations between the DS and the other measures of the FIM FAM subscales attested to the clinical validity of the function. In addition, EEG frequency-based analysis showed a pattern of the differences in EEGs between dependence and independence patients. The pattern for dependent individuals was characterized by an increase in slow wave amplitude and a decrease in fast wave amplitude. Although the slow wave increase was generalized, there appeared to be a

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Figure 8. Interpolation of 19 t-scores for five frequency bands on a cortical topographic map. (*) indicates significant t-values (p < 0.01) from the comparison between complete dependence and independence patients. Statistically significant differences were only found in delta ( ), alpha () and high-beta ( ) bands.

Table VI. External group classification. FIM FAM groups Complete Modified dependence dependence Independence Total 5 1 0 6 0 11 6 17 0 1 8 9 5 13 18 32

DS groups Complete dependence Modified dependence Independence Total

Overall classification accuracy 75%.

greater presence of these waves in the left hemisphere. The decrease of fast waves was generalized in the group with the highest level of dependence. This finding is in accordance with the literature on brain injury EEGs. A recent study [27] found that TBI patients with a lower response level showed a slower EEG than patients with higher responsiveness. Moreover, a generalized presence of slow waves in the EEG has been identified as a factor in negative prognoses [17,28]. Specific weight of QEEG variables (type, location and band) To create the discriminant function an absolute amplitude variable and an amplitude asymmetry variable were used. No relative amplitude variable was used. The connectivity measures (coherence and phase lag) did, however, take on an important role in

obtaining the function. These measures illustrate the connections between different areas of the cerebral cortex. They also quantify the cortico-cortical coupling, which indicates the level of functional connection between two areas. Analyses on the variables which best distinguished between the two functional states identified those associated with coherence as the most effective. Consequently, this study will now concentrate on the significance of these variables. It is known that areas of the brain are connected to one another at certain levels. When two areas show low coherence, they are functionally disconnected; when they show very high coherence (hypercoherence), they are excessively connected. In both situations, a cerebral connectivity deficit is implied. In the discriminant function, four coherence variables are included in three different frequency bands. These four variables, all of which are long distance connections, involve various cerebral lobes. The discriminant function demonstrates the importance of long distance fibres that connect distant regions of the brain. Since level of dependence/ independence is a global measure, one would not expect one single location in the brain to be responsible for this function. It is more feasible to suggest that there are wide, interconnected brain circuits that account for this complex function. This finding corresponds with the models of a functional brain proposed by Hebb [29], Luria [30] and Fuster [31]. Another interesting result regarding localization is that middle line locations (Fz, Cz, Pz) intervene in both coherence variables. Studies on responses to

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Figure 9. (Left) Scatterplot of distribution and lineal adjustment between DS (y-axis) and global FIM FAM scores (n 80; training sample external sample). The colour code represents the patients FIM FAM scores, red being the lowest score, green being the midrange and blue the highest. The correlation is R 0.826 (p < 0.0001). (Right) Scatterplot and lineal adjustment of the cases of the external sample (n 31). The correlation is R 0.87 (p < 0.0001).

diverse paradigms in these locations, by means of other neurophysiological techniques (see evoked cognitive potentials, e.g. P300 or N400), have shown their importance in processing information, as well as their sensibility to diverse states of pathological consciousness due to traumatic brain injury (TBI) [32]. Measures involving frontal locations are also of particular importance to the function. At least two factors can help explain this. First, the proportion of frontal lobe cortex is comparatively higher than that of the other lobes. Therefore, it is probable that any discriminant analysis will have more locations in this area. Secondly, the frontal lobe is particularly vulnerable to injury, especially in TBI cases, and thus shows a higher number of irregularities in the QEEG pattern. Neurophysiological studies have found that the frontal regions of the brain show greater measures of coherence than the posterior regions [33, 34]. This could be due to the fact that the frontal cortex favours long distance connections, while the posterior cortex participates more in local processes. In delta band coherence measures, a positive correlation was found with the FIM FAM scores, i.e. the higher the coherence in this band, the greater the functionality measure. Beta and high beta frequency bands correlated negatively with the FIM FAM scores, i.e. the lower the coherence in these bands, the lower the functionality. Both results confirm previous findings related to the present EEG pattern. They also support the idea that both slow and fast frequencies bands must be considered

as a set in order to correctly interpret QEEG as a measure of functionality. Sensitivity, specificity and cross-validation of the discriminant function Results show that the discriminant function is capable of clearly discriminating between different functional states of dependence in ABI patients during post-acute phase and rehabilitation. Moreover, the resulting function can classify these patients with a high level of efficacy. It also has an effective predictive capacity, as shown by its highly accurate cross-validation. Results also confirm the linearity of the discriminant function, which, according to its indexes, classifies patients on a dimension where the two extremes represent complete dependence and complete independence and whose mid-range values correspond to patients with intermediate levels of functionality. The obtained discriminant function in this study offered 100% sensibility (i.e. [true positives (15)]/ [false negatives (0)] [true positives (15)] (14/ 15)*100 100%). Specificity also reached 100% (i.e. [true negatives (14)]/[false positives (0)] [true negatives (14)] (14/14)*100 100%). The logarithm had a Positive Predictive Value (PPV) of 100%, meaning that all patients whose FIM FAM scores indicated complete dependency were categorized as such by the logarithm. In this case, the logarithm had a Negative Predictive Value (NPV) of 100%, indicating that no patient was identified as complete dependence when the QEEG is negative

A QEEG index of level of functional dependence for people sustaining ABI

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(the patient is not diagnosed as complete dependence). Cross-validation of the discriminant function was done using the leaving-one-out method of classification, with 95% accuracy. Moreover, all correlations between discriminant scores and FIM FAM variables were significant, as were those between discriminant scores and the predicted scores from the multiple regression analysis. Finally, discriminant indexes were compared to the group of patients with moderate dependence. Results showed, as predicted, that this group was situated between the independence and complete dependence scores. This data shows a lineal relationship between QEEG variables and the functional capacity of patients with acquired brain injury. Validity of QEEG as a tool for evaluating the functional state of a patient with acquired brain injury Finally, the aim of this study was to obtain an index of the functionality of patients in post-acute phase. Contrary to other studies, where functionality is assessed in the acute phase [9, 35], this study focuses on the post-acute phase, considering that brain injury is a dynamic process which entails cerebral restructuring, progress and deterioration. The focus is also on rehabilitation and the potential for recovery of each patient with acquired brain injury. Consequently, the development of a discriminant function was seen, with data on patients from the post-acute phase, as more sensible and stable: sensitive, because it reflects the current functional state of the patient with greater clarity and precision; stable, because non-treated deficits that persist 6 months post-TBI normally are considered possible sequelae. These assumptions are based on the big bump theory of brain injury, which hypothesizes that residual pathology or compensation after brain injury could be detected months and years later using QEEG [10]. Limitations of the discriminant function Certain considerations should be taken into account when using the discriminant function. First of all, it can only be used on patients similar to those used to design the function, that is, TBI or CVA patients in post-acute phase (over 6 months post-injury). Secondly, and no less important, the SINDI is for use as a complement, not as a substitute, to functional assessment.

discriminating between different functional states of dependence in ABI patients during post-acute phase and classifying them with a high level of accuracy. The function offers 100% sensibility and 100% specificity, a PPV of 100%, a NPV of 100% and a cross-validation of 95% accuracy. These results attest to the functions usefulness in providing a QEEG index for the assessment of patients seeking a diagnosis of their dependence state, which in turn could be included in current functionality assessment protocols.

Acknowledgements Presented as an oral communication to the Society of Applied Neuroscience Inaugural Meeting, 1319 September 2006, Swansea, Wales, UK. This study was conducted in the Centre for Brain Injury Rehabilitation C.RE.CER. in collaboration with the University of Seville. Supported by the Ministry of Science and Education as part of the National Plan for Scientific Research, Development and Technological Innovation (20042007) and co-funded by the European Regional Development Fund (ERDF): FIT-300100-2006-77.

References
1. Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE. Traumatic brain injury in the United States: A public health perspective. The Journal of Head Trauma Rehabilitation 1999;14:602616. 2. Mittenberg W, Patton C, Canyock EM, Condit DC. Base rates of malingering and symptom exaggeration. Journal of Clinical and Experimental Neuropsychology 2002;24: 10941102. 3. Larrabee GJ. Detection of malingering using atypical performance patterns on standard neuropsychological tests. Clinical Neuropsychology 2003;17:410425. 4. Lund TR, Sponheim SR, Iacono WG, Clementz BA. Internal consistency reliability of resting EEG power spectra in schizophrenic and normal subjects. Psychophysiology 1995;32:6671. 5. Arruda JE, Weiler MD, Valentino D, Willis WG, Rossi JS, Stern RA, Gold SM, Costa L. A guide for applying principalcomponents analysis and confirmatory factor analysis to quantitative electroencephalogram data. International Journal of Psychophysiology 1996;23:6381. 6. Corsi-Cabrera M, Solis-Ortiz S, Guevara MA. Stability of EEG inter- and intrahemispheric correlation in women. Electroencephalography and Clinical Neurophysiology 1997;102:248255. 7. Hughe JR, John ER. Conventional and quantitative electroencephalography in psychiatry. The Journal of Neuropsychiatry and Clinical Neurosciences 1999;11:190208. 8. John ER, Karmel BZ, Corning WC, Easton P, Brown D, Ahn H, John M, Harmony T, Prichep L, Toro A, Gerson I, Bartlett F, Thatcher F, Kaye H, Valdes P, Schwartz E. Neurometrics. Science 1977;196:13931410.

Concluding remarks The data clearly shows that the discriminant function obtained in this study is a tool capable of

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J. Leon-Carrion et al.
22. Delorme A, Makeig S. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics. Journal of Neuroscience Methods 2004;134:921. 23. Srivastava G, Crottaz-Herbette S, Lau KM, Glover GH, Menon V. ICA-based procedures for removing ballistocardiogram artifacts from EEG data acquired in the MRI scanner. Neuro Image 2005;24:5060. 24. Thornton K. The electrophysiological effects of a brain injury on auditory memory functioning. The QEEG correlates of impaired memory. Archives of Clinical Neuropsychology 2003;18:363378. 25. Lubar JF. Neocortical dynamics: Implications for understanding the role of neurofeedback and related techniques for the enhancement of attention. Applied Psychophysiology and Biofeedback 1997;22:111126. 26. Thatcher RW, Biver C, McAlaster R, Salazar A. Biophysical linkage between MRI and EEG coherence in traumatic brain injury. NeuroImage 1998;8:307326. 27. Leon-Carrion J, Martin-Rodriguez JF, Damas-Lopez J, Barroso y Martin JM, Dominguez-Morales R Brain function in minimally conscious state: A qEEG study. Clinical Neurophysiology. 28. Bricolo A, Turella G. Electroencephalographic patterns of acute traumatic coma: Diagnostic and prognostic value. Journal of Neurosurgical Sciences 1973;17:278285. 29. Hebb DO. The organization of behaviour. New York: Wiley; 1949. pp 6370. 30. Luria AR. Human brain and psychological processes. New York: Harper and Row; 1966. 31. Fuster JM. The cognit: A network model of cortical representation. International Journal of Psychophysiology 2006;60:125132. 32. Neumann N, Kotchoubey B. Assessment of cognitive functions in severely paralysed and severely brain-damaged patients: neuropsychological and electrophysiological methods. Brain Research. Brain Research Protocols 2004;14:2536. 33. Thatcher RW, Krause PJ, Hrybyk M. Cortico-cortical associations and EEG coherence: A twocompartmental model. Electroencephalography and Clinical Neurophysiology 1986;64:123143. 34. Tucker DM, Roth DL, Bair TB. Functional connections among cortical regions: Topography of EEG coherence. Electroencephalography and Clinical Neurophysiology 1986;63:242250. 35. Finnigan SP, Rose SE, Walsh M, Griffin M, Janke AL, McMahon KL, Gillies R, Strudwick MW, Pettigrew CM, Semple J, Brown J, Brown P, Chalk JB. Correlation of quantitative EEG in acute ischemic stroke with 30-day NIHSS score: Comparison with diffusion and perfusion MRI. Stroke 2004;35:899903.

Downloaded By: [Universidad de Sevilla] At: 15:41 8 January 2008

9. Thatcher RW, North D, Biver C. EEG and intelligence: relations between EEG coherence, EEG phase delay and power. Clinical Neurophysiology 2005;116:21292141. 10. Thatcher RW, North DM, Curtin RT, Walker RA, Biver CJ, Gomez JF, Salazar AM. An EEG severity index of traumatic brain injury. The Journal of Neuropsychiatry and Clinical Neurosciences 2001;13:7787. 11. Hall KM, Bushnik T, Lakisic-Kazazic B, Wright J, Cantagallo A. Assessing traumatic brain injury outcome measures for long-term follow-up of community-based individuals. Archives of Physical Medicine and Rehabilitation 2001;82:367374. 12. Jennet B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975;1:480487. 13. Wilson JTL, Pettigrew LEL, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the Extended Glasgow Outcome Scale: guidelines for their use. Journal of Neurotrauma 1998;15:573585. 14. van Baalen B, Odding E, van Woensel MP, Roebroeck ME. Reliability and sensitivity to change of measurement instruments used in a traumatic brain injury population. Clinical Rehabilitation 2006;20:686700. 15. Hall KM, Bushnik T, Lakisic-Kazazic B, Wright J, Cantagallo A. Assessing traumatic brain injury outcome measures for long-term follow-up of community-based individuals. Archives of Physical Medicine and Rehabilitation 2001;82:367374. 16. Ruijs MB, Gabreels FJ, Thijssen HM. The utility of electroencephalography and cerebral computed tomography in children with mild and moderately severe closed head injuries. Neuropediatrics 1994;25:7377. 17. Kotchoubey B, Lang S, Mezger G, Schmalohr D, Schneck M, Semmler A, Bostanov V, Birbaumer N. Information processing in severe disorders of consciousness: Vegetative state and minimally conscious state. Clinical Neurophysiology 2005;116:24412453. 18. Hamilton BB, Laughlin JA, Granger CV, Kayton RM. Interrater agreement of the seven-level Functional Independence Measure (FIM). Archives of Physical Medicine and Rehabilitation 1991;72:. p 790. 19. Linacre JM, Heinemann AW, Wright BD, Granger CV, Hamilton BB. The structure and stability of the Functional Independence Measure. Archives of Physical Medicine and Rehabilitation 1994;75:127132. 20. Doods TA, Matrin DP, Stolov WC, Deyo RA. A validation of the Functional Independence Measurement and its performance among rehabilitation inpatients. Archives of Physical Medicine and Rehabilitation 1993;74:531536. 21. Jasper HH. The ten-twenty electrode system of the International Federation. Electroencephalography and Clinical Neurophysiology 1958;10:371375.