Available via license: CC BY-NC 4.0
Content may be subject to copyright.
Uncorrected Author Proof
NeuroRehabilitation xx (20xx) x–xx
DOI:10.3233/NRE-192893
IOS Press
1
Factors affecting cognition and emotion
in patients with traumatic brain injury
1
2
Eun Hee Kwaka,b, Soohyun Wia, MinGi Kima, Soonil Pyoa,c, Yoon-Kyum Shina,c, Kyung Ja Ohb,
Kyunghun Hand, Yong Wook Kimaand Sung-Rae Choa,c,e,∗
3
4
aDepartment and Research Institute of Rehabilitation Medicine, Yonsei University Medical Center, Seoul, Korea5
bDepartment of Psychology, Yonsei University, Seoul, Korea6
cBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea7
dDivision of Sport science, Pusan National University, Busan, Korea8
eRehabilitation Institute of Neuromuscular Disease, Yonsei University College of Medicine, Seoul, Korea
9
Abstract.10
BACKGROUND: Cognitive and emotional disturbances are common serious issues in patients with traumatic brain injury
(TBI). However, predictors associated with neuropsychological functions were not consistent.
11
12
OBJECTIVE: To investigate factors affecting cognition and emotion in patients with TBI, we evaluated executive function,
memory, and emotion based on injury severity and lesion location.
13
14
METHODS: Neuropsychological outcomes of 80 TBI patients were evaluated via Wisconsin Card Sorting Test (WCST),
Color Trail Test (CTT), Controlled Oral WordAssociation Test (COWAT), EverydayMemory Questionnaire (EMQ), Geriatric
Depression Scale (GDS), State-Trait Anxiety Inventory (STAI), and Agitated Behavior Scale (ABS). WCST, CTT, and
COWAT assessed executive function; EMQ assessed everyday memory; and GDS, STAI, and ABS assessed emotion. Patients
were categorized according to lateralization of lesion and existence of frontal lobe injury.
15
16
17
18
19
RESULTS: Patients with longer duration of loss of consciousness (LOC) showed more severe deficits in everyday memory
and agitated behaviors. The frontal lesion group showed poorer performance in executive function and higher agitation than
the non-frontal lesion group. Patients with bilateral frontal lesion showed greater deficits in executive function and were more
depressed than unilateral frontal lesion groups. Especially in those unilateral frontal lesion groups, right side frontal lesion
group was worse on executive function than left side frontal lesion group.
20
21
22
23
24
CONCLUSIONS: Duration of LOC and lesion location are main parameters affecting executive function, everyday memory,
and emotion in neuropsychological outcomes following TBI, suggesting that these parameters need to be considered for
cognitive rehabilitation interventions.
25
26
27
Keywords: Traumatic brain injury, executive function, memory, emotion28
1. Introduction
29
Cognitive and emotional disturbances are com-30
mon serious issues in patients with traumatic brain
31
injury (TBI) (Dikmen et al., 2009; Hammond, Hart,
32
Bushnik, Corrigan, & Sasser, 2004), which exert a
33
∗Address for correspondence: Sung-Rae Cho, Department and
Research Institute of Rehabilitation Medicine, Yonsei Univer-
sity College of Medicine, Rehabilitation Hospital 5th Floor, 50
Yonsei-ro, Seodaemoon-gu, Seoul, South Korea 03722. E-mail:
srcho918@yuhs.ac.
negative impact on their quality of life and rehabilita- 34
tion process (Hesdorffer, Rauch, & Tamminga, 2009; 35
Rogers & Read, 2007). Neuropsychological dysfunc- 36
tion following TBI can be influenced by severity 37
of injury, lesion site, duration after brain injury, 38
intelligence, educational level, age, drug usage, and 39
socioeconomic factors such as family and financial 40
state (Ponsford et al., 2000; Rosenthal, Christensen, 41
& Ross, 1998). 42
Cognitive functions, which are affected by TBI, 43
include attention, memory, information processing 44
ISSN 1053-8135/20/$35.00 © 2020 – IOS Press and the authors. All rights reserved
This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0).
Uncorrected Author Proof
2E.H. Kwak et al. / Factors affecting cognition and emotion in patients
speed, perception, judgment, language, and exec-45
utive function (Carney et al., 1999; Cicerone et46
al., 2000). Emotional and behavioral disturbances
47
can be derived from either direct brain injury or48
secondary psychological responses. The following49
conditions are frequently observed in TBI: agita-
50
tion, impulsivity, restlessness, emotional instability,
51
apathy, unwillingness, depression, anxiety, stress sen-
52
sitivity, and denial (Jorge et al., 2004; Prigatano,
53
1992). It has been known that deficits in executive54
function and memory are easily noticed in TBI due55
to the vulnerability of brain areas such as frontal56
lobe and temporal lobe (Carlozzi, Grech, & Tul-
57
sky, 2013), and these are relatively more difficult to58
treat than other cognitive impairments (Sohlberg &
59
Mateer, 1989).
60
Neuropsychological functions in TBI can be
61
improved, depending on the time after brain injury62
(Ashman et al., 2004; Dikmen, Machamer, Pow-63
ell, & Temkin, 2003; Hammond et al., 2004;
64
Salmond, Menon, Chatfield, Pickard, & Sahakian,65
2006; Senathi-Raja, Ponsford, & Schonberger, 2010;
66
Whelan-Goodinson, Ponsford, Schonberger, & John-67
ston, 2010). In particular, age or educational level
68
before brain injury has been considered to be associ-69
ated with reserved capacity and vulnerability of brain70
against cognitive deficits after TBI, indicating that71
these variables need to be controlled in this study
72
(Scheibel et al., 2009; Sole-Padulles et al., 2009).
73
However, previous studies have shown that some
74
predictors were not consistent in the properties of75
subject groups and study designs, while related vari-
76
ables were not controlled (Ciurli, Formisano, Bivona,
77
Cantagallo, & Angelelli, 2011; Glascher et al., 2009;78
Whelan-Goodinson et al., 2010).79
Emotional issues, shown after brain injury, can80
impair the quality of patient’s life beyond cognitive
81
deficits or physiological disorders. However, the sig-
82
nificance of such issues might have been overlooked83
in previous studies (Binder, Kelly, Villanueva, &
84
Winslow, 2003; Rogers & Read, 2007). Studies on85
predictive variables related to emotional disorders
86
are even more complex (Horner, Selassie, Lineberry,87
Ferguson, & Labbate, 2008; Whelan-Goodinson et88
al., 2010).89
Therefore, the purpose of this study was90
to establish predictors that are associated with91
neuropsychological outcomes by analyzing neurobe-92
havioral assessments and investigating the effects of
93
TBI on executive function, memory, and emotions
94
such as depression, anxiety, and agitation by control-
95
ling the effect of other extraneous variables.
96
2. Methods 97
2.1. Subjects 98
A total of 80 patients (62 males and 18 females) 99
with TBI were recruited (Table 1). Neuropsycho- 100
logical assessment was performed on patients aged 101
between 17 and 63 via Wisconsin Card Sorting Test 102
(WCST), Color Trail Test (CTT), Controlled Oral 103
Word Association Test (COWAT), Everyday Memory 104
Questionnaire (EMQ), Geriatric Depression Scale 105
(GDS), State-Trait Anxiety Inventory (STAI), and 106
Agitated Behavior Scale (ABS). The ranges of period 107
for loss of consciousness (LOC) and time after brain 108
injury were 1–120 days and 3–36 months, respec- 109
tively. Patients were categorized into having left side 110
(n= 19), right side (n= 16), and bilateral (n= 45) 111
lesions. In addition, there were 49 patients with 112
frontal lobe lesion. Of these, 14 patients had only 113
frontal lobe lesion, and 35 patients had lesions on 114
both frontal and non-frontal lobes, while 31 patients 115
had no frontal lesion. Among patients with frontal 116
lesion, 11 patients had lesions on the left side while 117
15 had lesions on the right side, and 23 patients had 118
bilateral lesions. The representative MRI images of 119
each TBI group were shown in Fig. 1. 120
The study was approved by the Ethics Committee, 121
and participants signed informed consent prior to the 122
study. The Institutional Review Board of Severance 123
Table 1
Demographic characteristics of subjects (n= 80)
Variables Values
Age at assessment (years) 36.26 ±13.86
Education (years) 14.24 ±3.15
Period of LOC (days) 16.90 ±21.22
Time after brain injury (months) 11.20 ±10.12
Gender
Male 62 (77.5%)
Female 18 (22.5%)
Site of lesion
LHL 19 (23.8%)
RHL 16 (20.0%)
BDL 45 (56.3%)
FL 14 (17.5%)
F-NFL 35 (43.8%)
NFL 31 (38.7%)
LFL 11 (22.4%)
RFL 15 (30.6%)
BFL 23 (46.9%)
Values are mean ±standard deviation. LOC, loss of
consciousness; LHL, left hemisphere lesion; RHL,
right hemisphere lesion; BDL, bilateral or diffuse
lesion; FL, frontal lobe lesion; F-NFL, frontal-non-
frontal lobe lesion; NFL, non-frontal lobe lesion; LFL,
left frontal lobe lesion; RFL, right frontal lobe lesion;
BFL, bilateral frontal lobe lesion.
Uncorrected Author Proof
E.H. Kwak et al. / Factors affecting cognition and emotion in patients 3
Fig. 1. The representative MRI images of each TBI group. (A) Right frontal injury (B) Left frontal injury (C) Bilateral frontal injury (D)
Non-frontal injury, Right temporal injury. MRI, Magnetic Resonance Imaging; TBI, Traumatic brain injury.
Hospital, Yonsei University Health System approved
124
this procedure as well as the entire study (no. 4-2016-125
0398).126
2.2. Measures127
2.2.1. Wisconsin card sorting test
128
WCST is one of the representative measures of
129
prefrontal executive function, requiring mental flex-
130
ibility and problem solving ability. It was performed
131
by the standardized procedures proposed by Heaton 132
and percentage scores were used for dependent data to 133
control the differences in a number of trials adminis- 134
tered (Heaton RK, 1993). In this study, we analyzed 135
four indices (i.e., percent errors, percent persevera- 136
tive errors, percent conceptual level responses, and 137
number of categories completed) because previous 138
studies reported that these scores are decreased in 139
TBI patients compared to those of healthy control 140
(Haut et al., 1996). 141
Uncorrected Author Proof
4E.H. Kwak et al. / Factors affecting cognition and emotion in patients
2.2.2. Color trail test142
CTT measures visual attention, visual scan-143
ning, and graphomotor skills, while recording the
144
information-processing speed as well as motor-hand145
coordination. Although this test originated from Trail146
Making Test (TMT), it was modified in this study to
147
eliminate the difference arising from cultural diver-148
sity. Reaction time of CTT2 was analyzed as CTT2149
covers alternative patterns of orders, and to evalu-150
ate the system of the frontal lobe (D’Elia, 1996). TBI
151
patients tend to exhibit poor performance in their abil-
152
ity to smoothly change cognitive frames (Kim, 2003).
153
The reaction time was limited to less than 5 minutes,
154
as it has been suggested not to last the task for more
155
than 4 to 5 minutes in order to help lower the influence156
from extreme scores.
157
2.2.3. Controlled oral word association test
158
COWAT is the measurement of word fluency and
159
idea generation as a proper index of divergent think-160
ing by frontal lobe (Milner, 1984). Within one minute,161
participants are required to generate as many words162
as they can that belong to a specific category and
163
begin with a specific letter. The total number of words
164
generated is recorded for two categories and three let-165
ters. Test-retest reliability of COWAT-Korean version166
has been found to be 0.56 to 0.62 in an adult sample167
population (Kang, 2000).
168
2.2.4. Everyday memory questionnaire169
EMQ is direct data on memory defects and ret-170
rospective evaluation of memory failure shown in
171
everyday life in a week, by averaging reports from
172
patients and their families (Sunderland, 1983). This
173
test was translated in Korean and administrated.
174
There were 35 questions in five memory categories175
including language, reading and writing, face and176
place, behaviors, and new learning ability. The total177
score range was 0 to 140.178
2.2.5. Geriatric depression scale
179
GDS is a self-reported, True or False type depres-
180
sion scale (Yesavage et al., 1982). Although GDS
181
was developed for the elderly, it is more useful for
182
brain injury patients with impaired cognition. The test
183
consists of 30 questions, with the total scores rang-
184
ing from 0 to 30. The cut-off point of this test was185
reported as 18 (sensitivity 65.6%, specificity 64.9%)186
in standardized studies in Korea(Jung, 1997).187
2.2.6. State-trait anxiety inventory 188
In this study, STAI state anxiety scale which has 189
been widely used to evaluate anxiety level caused 190
by stress factors such as surgeries, treatments, and 191
examinations was used (Hahn, 2000). The inventory 192
consisted of 20 questions, and total score range was 193
20 to 40. 194
2.2.7. Agitated behavior scale 195
ABS is used to evaluate TBI patients’ behav- 196
iors by measuring them through 14 questions with 197
a four-point scale (1 to 4 point) which includes 198
distraction, impulsivity, noncooperation, aggression, 199
restlessness, repetitive behaviors, and mood swings. 200
The score range was from 14 to 56. This scale that 201
has been suggested to offer a reliable measurement 202
(Cronbach’s ␣=0.84 to 0.92) of behavioral distur- 203
bance in TBI patients (Corrigan, 1989). 204
2.3. Statistical analysis 205
Data were analyzed using the Statistical Package 206
for the Social Sciences (SPSS v.15). Age, education 207
level, duration of LOC and time after brain injury 208
effects on executive function, everyday memory and 209
emotional function were analyzed by Pearson’s cor- 210
relation coefficients. Additionally, age, education 211
level, duration of LOC and time after brain injury 212
effects on brain lesion properties were analyzed by 213
ANOVA. Effects of brain lesion properties on exec- 214
utive function, memory, and emotion were analyzed 215
by MANCOVA and MANOVA. 216
3. Results 217
3.1. Correlations between patient characteristics 218
Detailed information about subjects is listed in 219
Table 1 and correlations patient characteristics (age, 220
education level, duration of LOC and time after 221
injury) and neuropsychological functions were ana- 222
lyzed using Pearson’s correlation coefficients listed 223
in Table 2. Age was negatively correlated with 224
percent conceptual level responses and the num- 225
ber of completed categories of WCST (r=–0.36, 226
p< 0.001; r=–0.43, p< 0.001, respectively), while 227
positively correlated with CTT2, percent error and 228
percent perseverative errors of WCST (r= 0.36, 229
p< 0.001; r= 0.32, p< 0.01; r= 0.26, p< 0.05, respec- 230
tively). Age was also positively correlated with 231
GDS (r= 0.24, p< 0.05). Education level was pos- 232
Uncorrected Author Proof
E.H. Kwak et al. / Factors affecting cognition and emotion in patients 5
Table 2
Factors affecting neuropsychological functions
Age Education Period of LOC Time after brain injury
WCST
% errors 0.32** –0.27* 0.18 –0.13
% perseverative errors 0.26* –0.19 0.08 –0.02
% conceptual level responses –0.36*** 0.28* –0.19 0.10
No. of completed categories –0.43*** 0.27* –0.16 0.06
CTT2 0.36*** –0.23 0.19 –0.11
COWAT –0.21 0.29** –0.14 0.19
EMQ –0.03 –0.14 0.41*** 0.09
GDS 0.24* –0.26* 0.14 0.03
STAI 0.17 –0.10 0.11 0.05
ABS 0.09 –0.34** 0.32** 0.04
*p< 0.05, **p< 0.01, ***p< 0.001. WCST, Wisconsin Card Sorting Test; CTT2, Color Trail Test 2; COWAT,
Controlled Oral Word Association Test; EMQ, Everyday Memory Questionnaire; GDS, Geriatric Depression
Scale; STAI, State-Trait Anxiety Inventory; ABS, Agitated Behavior Scale.
itively correlated with COWAT, percent conceptual
233
level responses and the number of completed cate-234
gories of WCST (r= 0.29, p< 0.01; r= 0.28, p< 0.05;235
r= 0.27, p< 0.05, respectively), while negatively cor-
236
related with percent errors of WCST, ABS and237
GDS (r=–0.27, p< 0.05; r=–0.34, p< 0.01; r=–0.26,238
p< 0.05, respectively). The duration of LOC showed
239
a significantly positive correlation with EMQ and240
ABS (r= 0.41, p< 0.001; r= 0.32, p< 0.01, respec-241
tively). The duration of LOC significantly affected242
everyday memory and agitated behaviors. In case of243
everyday memory, a longer period of LOC showed
244
more severe everyday memory deficits and agitated245
behaviors. However, the duration of LOC did not have246
an effect on percent perseverative errors of WCST,
247
GDS, and STAI when excluding the effects of demo-248
graphic variables.
249
3.2. Comparison of neuropsychological
250
functions by lesion lateralization251
The results of comparison of characteristics of each252
group in regard to lesion lateralization showed no dif-253
ference between groups in the education level, the
254
duration of LOC and time after injury while age
255
was significantly different between groups (F= 3.25,
256
p< 0.05) in Table 3. Bilateral or diffuse damaged257
group were significantly older than the group with
258
unilateral lesion groups.259
To examine any difference in neuropsychological260
functions depending upon the lateralization of brain261
lesion when age was controlled, MANCOVA anal-262
ysis was performed shown in Table 4. Even though263
the types of lateralization of brain lesion had no sig-264
nificant impact on executive function and everyday265
memory in general (Wilks’ Lambda 0.73, F= 1.65,266
p= 0.07), emotional functioning was significantly 267
affected (Wilks’ Lambda 0.80, F= 2.87, p< 0.05). 268
According to the results of MANOVA in Table 5, 269
lateralization of brain lesion showed significant dif- 270
ferences between groups in GDS (F= 8.36, p< 0.001) 271
and STAI (F= 4.70, p< 0.01). In results of post hoc 272
test, TBI groups with unilateral lesion were not dif- 273
ferent in depression and anxiety parameters, while 274
bilateral lesion group was more depressed compared 275
to unilateral lesion group and more anxious than left- 276
sided lesion group. Therefore, bilateral lesion group 277
might be more vulnerable in terms of emotional dys- 278
function than any other lesion group after severe TBI. 279
3.3. Comparison of neuropsychological 280
functions by frontal lobe damage 281
In the results of analysis of properties of sub- 282
groups divided according to the existence of frontal 283
lobe lesion, age (F= 4.70, p< 0.05), education level 284
(F= 3.07, p< 0.05), duration of LOC (F= 8.55, 285
p< 0.001) were different between groups in Table 5. 286
Frontal lobe lesion group was significantly older than 287
the other groups, and non-frontal lesion group was 288
the youngest among three groups. The education 289
level was higher in the non-frontal lesion group com- 290
pared to the two frontal lobe lesion groups while 291
the duration of LOC was significantly longer in 292
the frontal-non-frontal lesion group compared to the 293
other groups. 294
To investigate whether frontal lobe lesion affects 295
neuropsychological functions when controlling the 296
effects of other extraneous variables including age, 297
education level and duration of LOC, MANCOVA 298
was performed shown in Table 6. According to the 299
results, whether the frontal lobe is damaged or not sig- 300
Uncorrected Author Proof
6E.H. Kwak et al. / Factors affecting cognition and emotion in patients
Table 3
Factors associated with lateralization of lesion
LHL RHL BDL F
(n= 19) (n= 16) (n= 45)
Age 29.42 ±6.96 37.56 ±15.51 38.69 ±13.85 3.25*
Education level 15.47 ±2.27 13.81 ±3.73 13.87 ±3.17 1.97
Period of LOC 13.05 ±16.59 10.56 ±12.89 20.78 ±24.55 1.81
Time after brain injury 11.21 ±12.50 10.56±10.07 11.41 ±9.23 0.41
*p< 0.05. LHL, Left Hemisphere Lesion; RHL, Right Hemisphere Lesion; BDL, Bilat-
eral or Diffuse lesion.
Table 4
Multiple analysis of covariances with covariance for neuropsychological functions by lateralization of lesion
Independent variables Dependent variables Wilks’ Lambda(F) univariate F df η2
Lateralization of lesion % errors 0.73(1.65) 1.62 2/75 0.04
% perseverative errors 2.68 2/75 0.07
% conceptual level responses 2.10 2/75 0.05
No. of categories completed 2.06 2/75 0.05
CTT2 0.19 2/75 0.01
COWAT 1.01 2/75 0.03
EMQ 3.21* 2/75 0.08
GDS 0.80(2.87)* 8.36*** 2/75 0.18
STAI 4.70** 2/75 0.11
ABS 1.86 2/75 0.05
*p< 0.05, **p< 0.01, ***p< 0.001 Covariates: Age.
Table 5
Mean comparison of neuropsychological functions by lateralization of lesion
LHL RHL BDL F
(n= 19) (n= 16) (n= 45)
WCST
% errors 32.00 ±14.29 42.87 ±18.91 45.29 ±21.21 1.62
% perseverative errors 17.74 ±7.60 20.56 ±10.47 27.78 ±17.95 2.68
% conceptual level responses 60.47 ±19.05 44.69 ±26.01 41.13 ±27.63 2.10
No. of completed categories 4.58 ±1.71 2.81 ±2.32 2.82 ±2.50 2.06
CTT2 174.84 ±88.74 192.25 ±79.80 206.96 ±90.05 0.19
COWAT 38.68 ±27.64 42.94 ±21.47 33.58 ±20.18 1.01
EMQ 52.79 ±39.37 42.63 ±34.75 67.33 ±39.65 3.21
GDS 7.58 ±5.01 10.69 ±8.96 15.96 ±8.06 8.36***
STAI 39.58 ±9.89 45.69 ±15.02 49.91 ±13.02 4.70**
ABS 6.95 ±8.13 10.38 ±8.59 11.93 ±8.39 1.86
**p< 0.01, ***p< 0.001 Covariates: Age, Sex. LHL, Left Hemisphere Lesion; RHL, Right Hemisphere Lesion;
BDL, Bilateral or Diffuse lesion; WCST, Wisconsin Card Sorting Test; CTT2, Color Trail Test 2; COWAT, Con-
trolled Oral Word Association Test; EMQ, Everyday Memory Questionnaire; GDS, Geriatric Depression Scale;
STAI, State-Trait Anxiety Inventory; ABS, Agitated Behavior Scale.
nificantly affected on the executive functions (Wilks’
301
Lambda 0.69, F= 1.97, p< 0.05) and emotional func-
302
tioning was significantly affected (Wilks’ Lambda
303
0.79, F= 2.99, p< 0.01).304
According to the results of MANOVA, the results305
of WCST showed frontal lobe lesion group signifi-306
cantly performed worse than non-frontal lobe lesion307
group on percent errors (F= 10.89, p< 0.001), per-
308
cent perseverative errors (F= 6.11, p< 0.01), percent309
conceptual level responses (F= 9.23, p< 0.001), and310
number of completed categories (F= 9.53, p< 0.001)
311
as shown in Table 7. Although no significant differ-312
ence in everyday memory was found, patients with 313
frontal lobe lesion showed a significant difference in 314
ABS was observed (F= 8.80, p< 0.001) and more 315
severe agitated behavior compared to non-frontal 316
lobe lesion group shown in Table 8. Furthermore, 317
In results of post hoc, frontal lobe lesion group and 318
frontal-non-frontal lobe lesion group significantly 319
performed worse than non-frontal lobe lesion group 320
on the four indexes of WCST measuring execu- 321
tive function. However, no significant differences 322
in everyday memory were found between patients 323
with or without frontal lobe lesion. Moreover, frontal 324
Uncorrected Author Proof
E.H. Kwak et al. / Factors affecting cognition and emotion in patients 7
Table 6
Factors associated with existence of frontal lobe lesion
FL F-NFL NFL F
(n= 14) (n= 35) (n= 31)
Age 41.71 ±12.44 39.03 ±15.30 30.68 ±10.87 4.70*
Education level 14.71 ±2.79 13.29±3.46 15.10 ±2.69 3.07*
Period of LOC 8.29 ±8.30 27.09 ±27.80 9.29 ±8.00 8.55***
Time after brain injury 5.37 ±4.69 12.42 ±10.41 11.36 ±10.63 2.15
*p< 0.05, ***p< 0.001. FL, frontal lesion; F-NFL, frontal-non-frontal lesion; NFL, non-frontal lesion.
Table 7
Multiple analysis of covariances with covariance for neuropsychological functions depended on existence of frontal lobe lesion
Independent variables Dependent variables Wilks’ Lambda(F) univariate F df η2
With or Without % errors 0.69(1.97*) 10.08*** 2/74 0.23
Frontal lesion % perseverative errors 5.90** 2/74 0.14
% conceptual level responses 9.25*** 2/74 0.20
No. of categories completed 9.73*** 2/74 0.21
CTT2 1.56 2/74 0.04
COWAT 0.96 2/74 0.03
EMQ 1.72 2/74 0.04
GDS 0.79(2.99**) 0.58 2/74 0.02
STAI 0.94 2/74 0.03
ABS 9.03*** 2/74 0.20
*p< 0.05, **p< 0.01, ***p< 0.001 Covariates: Age, Education, period of LOC.
Table 8
Mean comparison of neuropsychological functions depended on existence of frontal lobe lesion
FL F-NFL NFL F
(n= 14) (n= 35) (n=31)
WCST
% errors 53.00 ±19.79 49.97 ±17.96 27.13 ±12.10 10.89***
% perseverative errors 31.86 ±20.65 28.34 ±13.79 15.42 ±9.33 6.11**
% conceptual level responses 32.07 ±26.56 35.49 ±23.88 65.29 ±16.98 9.23***
No. of completed categories 2.00 ±2.32 2.17 ±2.20 5.00 ±1.43 9.53***
CTT2 213.14 ±93.73 227.54 ±77.15 153.65 ±81.04 1.49
COWAT 30.57 ±20.56 32.40 ±21.85 44.23 ±22.39 0.91
EMQ 50.07 ±44.07 74.86 ±34.36 44.97 ±37.38 1.76
GDS 12.07 ±9.47 15.37 ±7.47 10.52 ±8.34 0.57
STAI 44.43 ±13.42 50.26 ±13.26 43.48 ±12.78 0.89
ABS 11.57 ±9.51 14.94 ±8.30 4.84 ±4.11 8.80***
**p< 0.01, ***p< 0.001 Covariates: Age, Education, period of LOC. FL, frontal lesion; F-NFL, frontal-non-frontal
lesion; NFL, non-frontal lesion; WCST, Wisconsin Card Sorting Test; CTT2, Color Trail Test 2; COWAT, Controlled
Oral Word Association Test; EMQ, Everyday Memory Questionnaire; GDS, Geriatric Depression Scale; STAI, State-
Trait Anxiety Inventory; ABS, Agitated Behavior Scale.
lobe lesion group and frontal-non-frontal lobe lesion
325
group showed more severe agitated behavior prob-326
lems than non-frontal lobe lesion group.327
3.4. Comparison of neuropsychological328
functions by lateralization of frontal lobe329
damage330
The comparison between groups with unilateral331
frontal lobe lesion and bilateral frontal lobe lesion
332
showed that there were no differences in age, educa-
333
tion level, duration of LOC, time after injury between
334
the groups in Table 9.
335
To test if the lateralization of frontal lobe damage 336
affects neuropsychological functions, MANCOVA 337
was performed shown in Table 10. The lateralization 338
of the frontal lobe damage significantly influenced 339
executive function and everyday memory in general 340
(Wilks’ Lambda 0.43, F= 2.97, p< 0.001). Addi- 341
tionally, the lateralization of frontal lobe damage 342
significantly affected emotion in general (Wilks’ 343
Lambda 0.72, F= 2.08, p< 0.05). 344
For the executive functions, conceptual level 345
(F= 13.40, p< 0.001), percent error (F= 12.03, 346
p< 0.001), percent perseverative error (F= 10.05, 347
p< 0.001), number of categories completed (F= 8.85, 348
Uncorrected Author Proof
8E.H. Kwak et al. / Factors affecting cognition and emotion in patients
Table 9
Factors associated with lateralization of frontal lobe lesion
LFL RFL BFL F
(n= 11) (n= 15) (n= 23)
Age 38.00 ±13.22 38.73 ±14.70 41.35 ±15.31 0.25
Education level 14.64 ±2.91 14.40 ±3.29 12.78 ±3.41 1.70
Period of LOC 14.27 ±21.11 24.93 ±27.58 23.17 ±25.93 0.63
Time after brain injury 7.81 ±10.20 11.85 ±10.07 10.91 ±10.10 0.54
*p< 0.05, ***p< 0.001. FL, frontal lesion; F-NFL, frontal- non-frontal lesion; NFL, non-frontal lesion.
Table 10
Multiple analysis of covariances for neuropsychological functions by lateralization of frontal lobe lesion
Independent variables Dependent variables Wilks’ Lambda(F) univariate F df η2
Lateralization of frontal % errors 0.43(2.97***) 12.03*** 2/46 0.34
lobe lesion % perseverative errors 10.05*** 2/46 0.30
% conceptual level responses 13.40*** 2/46 0.37
number of categories completed 8.85*** 2/46 0.28
CTT2 3.56* 2/46 0.13
COWAT 4.03* 2/46 0.15
EMQ 4.12* 2/46 0.15
GDS 0.72(2.08*) 4.86** 2/46 0.18
STAI 0.72 2/46 0.03
ABS 0.85 2/46 0.04
*p< 0.05, **p< 0.01, ***p< 0.001.
Table 11
Mean comparison of neuropsychological functions by lateralization of frontal lobe lesion
LFL RFL BFL F
(n= 11) (n= 15) (n= 23)
WCST
% errors 33.45 ±18.37 48.73 ±17.04 60.52 ±11.98 12.03***
% perseverative errors 18.09 ±9.34 23.87 ±10.60 38.30 ±16.51 10.05***
% conceptual level responses 59.00 ±23.88 36.53 ±24.24 21.48 ±13.80 13.40***
No. of completed categories 4.09 ±2.07 2.20 ±2.24 1.13 ±1.60 8.85***
CTT2 199.64 ±90.37 192.93 ±80.75 254.70 ±68.44 3.56
COWAT 34.64 ±27.29 42.33 ±22.39 23.74 ±13.57 4.03
EMQ 57.00 ±42.32 51.60 ±31.27 83.48 ±36.35 4.12
GDS 11.00 ±6.13 11.47 ±8.59 18.00 ±7.42 4.86**
STAI 42.27 ±15.30 45.87 ±11.15 51.00 ±14.00 0.72
ABS 11.00 ±8.94 15.20 ±8.44 14.61 ±8.81 0.85
**p< 0.01, ***p< 0.001. LFL, left frontal lesion; RFL, right frontal lesion; BFL, bilateral frontal lesion;
WCST, Wisconsin Card Sorting Test; CTT2, Color Trail Test 2; COWAT, Controlled Oral Word Association
Test; EMQ, Everyday Memory Questionnaire; GDS, Geriatric Depression Scale; STAI, State-Trait Anxiety
Inventory; ABS, Agitated Behavior Scale.
p< 0.001) of WCST showed significant differences349
between the groups. And there were no significant
350
differences in anxiety and agitation while depres-351
sion (F= 4.86, p< 0.01) was significantly different
352
between groups shown in Table 11. In results of
353
post hoc, bilateral frontal lobe lesion group showed
354
significantly higher percent error, and higher per-
355
cent perseverative error and lower conceptual level of356
WCST compared to the groups with unilateral frontal357
lobe lesion. The number of categories completed was358
not significantly different between right frontal lobe359
lesion and bilateral frontal lobe lesion groups; yet360
these groups were significantly lower than left frontal
361
lobe lesion group. Additionally, the depression of 362
bilateral frontal lobe lesion group was severe than 363
the unilateral frontal lobe lesion group. 364
4. Discussion 365
In this study, we found that the duration of LOC 366
and lesion location are main parameters that affect 367
executive function, memory, and emotion in neu- 368
ropsychological outcomes following TBI. It has 369
been generally accepted that the severity of brain 370
injury induces various degrees of neuropsychologi- 371
Uncorrected Author Proof
E.H. Kwak et al. / Factors affecting cognition and emotion in patients 9
cal impairment after TBI (Fisher, Ledbetter, Cohen,372
Marmor, & Tulsky, 2000; Halldorsson et al., 2008).
373
As patients had longer periods of LOC, their cogni-374
tive and emotional problems were more serious. In375
this study, the duration of LOC was a main parame-376
ter for agitated behavior in severe TBI patients, while
377
no significant associations were noted for anxiety and378
depression. LOC had a strong prognostic value, espe-379
cially for everyday memory and agitated behaviors,380
which is consistent with the results of previous stud-
381
ies: there are many studies showing that mild TBI382
patients exhibit dysfunction in early phase of memory383
formation such as difficulties in encoding strategies,
384
and moderate TBI patients have difficulties in long-385
term memory related to storage; therefore, having
386
severe head injury may induce more serious mem-387
ory impairment (Alexander, Stuss, & Fansabedian,388
2003; Norton, Malloy, & Salloway, 2001). It has been
389
shown that agitation is more common in the acute390
phase when neurological state of brain is unstable,391
and further emotional disturbances due to organic fac-392
tors are more frequently shown in the patients who393
have serious brain injury (Levy et al., 2005). In a394
recent study (Ciurli et al., 2010), severe TBI patients395
frequently showed that various emotional problems,
396
such as apathy and disinhibition, were correlated with
397
severity of brain injury, which was in agreement with398
our results.
399
Although lateralization of brain lesion did not400
affect executive function, everyday memory, agitated401
behaviors, group differences in anxiety and depres-
402
sion were observed in this study. Bilateral lesion403
group was significantly more depressive compared
404
to both left and right lesion groups and showed
405
significantly higher anxiety level than left lesion406
group. Moreover, bilateral lesion group showed lower407
performances on executive function and everyday408
memory with more agitated agitation than the other409
groups. Therefore, bilateral lesion group might be410
more vulnerable to cognition, especially emotional
411
dysfunction, than any other lesion groups after severe412
TBI. Results of previous studies regarding emotional
413
problems in TBI by lateralization of lesion were414
inconsistent and mixed, and emotional characteris-415
tics of bilateral lesion groups were not sufficiently416
analyzed (Gazzaniga, 2002; Grafman et al., 1996;417
Robinson, 1999; Zillmer, 2001).418
Frontal lobe deficit had a significant impact on419
executive function indicated by performances on
420
WCST, showing worse performance on four indices
421
of WCST and exhibiting agitated behaviors more
422
often compared to the group without frontal damage.
423
In contrast, no significant difference in trail making, 424
word fluency, everyday memory, depression, and anx- 425
iety tests was found between frontal and non-frontal 426
lesion groups. Previous study on this subject showed 427
that TBI patients with frontal damage also exhib- 428
ited executive dysfunction (Lindsay Wilson, 1990; 429
Wallesch, Curio, Galazky, Jost, & Synowitz, 2001; 430
Wallesch, Curio, Kutz, et al., 2001). Particularly, a 431
series of investigations have shown that poor per- 432
formance on WCST in patients with frontal lesion 433
compared to patients with non-frontal lesion (Stuss 434
& Levine, 2002; Stuss et al., 2000; Wallesch, Curio, 435
Galazky, et al., 2001). On the other hand, there were 436
studies suggesting that frontal lobe lesion in TBI was 437
significantly associated with emotional restlessness, 438
agitation, and impulsive behaviors (Ciurli et al., 2011; 439
Lequerica et al., 2007). 440
Bilateral frontal lesion group scored significantly 441
worse than unilateral frontal lesion groups on WCST. 442
Compared to unilateral frontal group, they lacked the 443
ability to respond against external feedback and the 444
insight on accurate conceptual classification, while 445
having severe preservation due to internal rigidity. On 446
the other hand, left side frontal lesion group showed 447
a significantly better performance in percent error, 448
percent conceptual level responses, and completed 449
categories compared to right side frontal and bilat- 450
eral frontal lesion groups. Performance of right side 451
frontal lesion group was somewhat intermediate in 452
general. Bilateral frontal lesion group was also more 453
depressive than unilateral frontal lesion group. How- 454
ever, lateralization of frontal lesion had no significant 455
impact on visual tracking, word fluency, everyday 456
memory, anxiety, and agitation. It has been suggested 457
that the brain activity of left hemisphere increases 458
after TBI (Scheibel et al., 2009), and if it is explained 459
as a compensation mechanism of brain dysfunction, 460
left frontal lesion patients may have relatively better 461
performances on executive function tasks compared 462
to right frontal lesion patients. However, there were a 463
few and inconsistent previous studies exist on depres- 464
sion after TBI (Jorge et al., 2004; Kim, 1991; Lee, 465
1990; Robinson & Szetela, 1981). 466
Nonetheless, using the duration of LOC and lesion 467
location, this study may provide meaningful informa- 468
tion for not only setting the framework for predicting 469
cognitive and emotional dysfunctions and functional 470
recovery after severe TBI, but also for identifying 471
the patients who are exposed to high risk of suf- 472
fering from serious neuropsychological impairments. 473
Using these parameters in clinical setting could help 474
determine the direction of intervention. 475
Uncorrected Author Proof
10 E.H. Kwak et al. / Factors affecting cognition and emotion in patients
5. Conclusions476
Duration of LOC and lesion location are main477
parameters affecting executive function, every-478
day memory, and emotion in neuropsychological
479
outcomes following TBI, suggesting that these480
parameters need to be considered for cognitive reha-481
bilitation interventions.482
Conflict of interest
483
None to report.
484
References
485
Alexander, M. P., Stuss, D. T., & Fansabedian, N. (2003). Califor-486
nia Verbal Learning Test: performance by patients with focal487
frontal and non-frontal lesions. Brain, 126(Pt 6), 1493-1503.
488
Ashman, T. A., Spielman, L. A., Hibbard, M. R., Silver, J. M.,
489
Chandna, T., & Gordon, W. A. (2004). Psychiatric challenges490
in the first 6 years after traumatic brain injury: cross-sequential491
analyses of Axis I disorders. Arch Phys Med Rehabil, 85(4492
Suppl 2), S36-S42.493
Binder, L. M., Kelly, M. P., Villanueva, M. R., & Winslow, M. M.
494
(2003). Motivation and neuropsychological test performance495
following mild head injury. J Clin Exp Neuropsychol, 25(3),
496
420-430. doi:10.1076/jcen.25.3.420.13806497
Carlozzi, N. E., Grech, J., & Tulsky, D. S. (2013). Mem-498
ory functioning in individuals with traumatic brain injury:499
an examination of the Wechsler Memory Scale-Fourth Edi-
500
tion (WMS-IV). J Clin Exp Neuropsychol, 35(9), 906-914.501
doi:10.1080/13803395.2013.833178502
Carney, N., Chesnut, R. M., Maynard, H., Mann, N. C., Patterson,503
P., & Helfand, M. (1999). Effect of cognitive rehabilitation on504
outcomes for persons with traumatic brain injury: A systematic505
review. J Head Trauma Rehabil, 14(3), 277-307.506
Cicerone, K. D., Dahlberg, C., Kalmar, K., Langenbahn, D.
507
M., Malec, J. F., Bergquist, T. F., & Morse, P. A. (2000).508
Evidence-based cognitive rehabilitation: recommendations for
509
clinical practice. Arch Phys Med Rehabil, 81(12), 1596-1615.510
doi:10.1053/apmr.2000.19240
511
Ciurli, P., Bivona, U., Barba, C., Onder, G., Silvestro, D., Azic-512
nuda, E., & Formisano, R. (2010). Metacognitive unawareness513
correlates with executivefunction impairment after severe trau-514
matic brain injury. J Int Neuropsychol Soc, 16(2), 360-368.515
doi:10.1017/S135561770999141X516
Ciurli, P., Formisano, R., Bivona, U., Cantagallo, A., & Angelelli,517
P. (2011). Neuropsychiatric disorders in persons with518
severe traumatic brain injury: prevalence, phenomenology,519
and relationship with demographic, clinical, and func-520
tional features. J Head Trauma Rehabil, 26(2), 116-126.521
doi:10.1097/HTR.0b013e3181dedd0e
522
Corrigan, J. D. (1989). Development of a scale for assessment523
of agitation following traumatic brain injury. J Clin Exp Neu-
524
ropsychol, 11(2), 261-277. doi:10.1080/01688638908400888525
D’Elia, L. F., Satz, P., Uchiyama, C. L., & White, T. (1996). Color 526
Trails Test. Professional manual. Odessa, FL: Psychological 527
Assessment Resources. 528
Dikmen, S. S., Corrigan, J. D., Levin, H. S., Machamer, J., Stiers, 529
W., & Weisskopf, M. G. (2009). Cognitive outcome following 530
traumatic brain injury.J Head Trauma Rehabil, 24(6), 430-438. 531
doi:10.1097/HTR.0b013e3181c133e9 532
Dikmen, S. S., Machamer, J. E., Powell, J. M., & Temkin, N. R. 533
(2003). Outcome 3 to 5 years after moderate to severe traumatic 534
brain injury. Arch Phys Med Rehabil, 84(10), 1449-1457. 535
Fisher, D. C., Ledbetter, M. F., Cohen, N. J., Marmor, D., & Tul- 536
sky, D. S. (2000). WAIS-III and WMS-III profiles of mildly 537
to severely brain-injured patients. Appl Neuropsychol, 7(3), 538
126-132. doi:10.1207/S15324826AN0703 2 539
Gazzaniga, M. S., Ivry, R. B., & Mangun, G. R. (2002). Cogni- 540
tive Neuroscience: the biology of the mind. New York: W. W. 541
Norton & Co. 542
Glascher, J., Tranel, D., Paul, L. K., Rudrauf, D., Rorden, C., 543
Hornaday, A., & Adolphs, R. (2009). Lesion mapping of cog- 544
nitive abilities linked to intelligence. Neuron, 61(5), 681-691. 545
doi:10.1016/j.neuron.2009.01.026 546
Grafman, J., Schwab, K., Warden, D., Pridgen, A., Brown, H. 547
R., & Salazar, A. M. (1996). Frontal lobe injuries, violence, 548
and aggression: a report of the Vietnam Head Injury Study. 549
Neurology, 46(5), 1231-1238. 550
Hahn, D. W.,LEE, C. H., Chon, K. G., & Spielberger, C. D. (2000). 551
Korean versionState-Trait Anxiety Inventory for Adults. Seoul: 552
Hakjisa. 553
Halldorsson, J. G., Flekkoy, K. M., Arnkelsson, G. B., Tomasson, 554
K., Gudmundsson, K. R., & Arnarson, E. O. (2008). The prog- 555
nostic value of injury severity, location of event, and age at 556
injury in pediatric traumatic head injuries. Neuropsychiatr Dis 557
Treat, 4(2), 405-412. 558
Hammond, F. M., Hart, T., Bushnik, T., Corrigan, J. D., & Sasser, 559
H. (2004). Change and predictors of change in communica- 560
tion, cognition, and social function between 1 and 5 years after 561
traumatic brain injury.J Head Trauma Rehabil, 19(4), 314-328. 562
Haut, M. W., Cahill, J., Cutlip, W. D., Stevenson, J. M., Makela, 563
E. H., & Bloomfield, S. M. (1996). On the nature of Wisconsin 564
Card Sorting Test performance in schizophrenia. Psychiatry 565
Res, 65(1), 15-22. 566
Heaton, R. K., C. G., Talley, J. L., Kay G.G., Curtiss G. (1993). 567
Wisconsin Card Sorting Test manual: Revised and expanded.568
Odessa, FL: Psychological Assessment Resources. 569
Hesdorffer, D. C., Rauch, S. L., & Tamminga, C. A. (2009). Long- 570
term psychiatric outcomes following traumatic brain injury: a 571
review of the literature. J Head Trauma Rehabil, 24(6), 452- 572
459. doi:10.1097/HTR.0b013e3181c133fd 573
Horner, M. D., Selassie, A. W., Lineberry, L., Ferguson, 574
P. L., & Labbate, L. A. (2008). Predictors of psycho- 575
logical symptoms 1 year after traumatic brain injury: a 576
population-based, epidemiological study. J Head Trauma 577
Rehabil, 23(2), 74-83. doi:10.1097/01.HTR.0000314526. 578
01006.c8 579
Jorge, R. E., Robinson, R. G., Moser, D., Tateno, A., Crespo- 580
Facorro, B., & Arndt, S. (2004). Major depression following 581
traumatic brain injury. Arch Gen Psychiatry, 61(1), 42-50. 582
doi:10.1001/archpsyc.61.1.42 583
Jung, I. K., Kwak, D. I., Shin, D. K., Lee, H. S., & Kim, J. Y. 584
(1997). A reliability and validity study of geriatric depression 585
scale. Journal of Korean Neuropsychiatric Association, 36(1), 586
103-112. 587
Uncorrected Author Proof
E.H. Kwak et al. / Factors affecting cognition and emotion in patients 11
Kang, Y., Jin, J., Na, D., Lee, J., & Park, J. (2000). A normative
588
study of the Korean version of Controlled Oral Word Associ-589
ation Test (COWAT) in the elderly.590
Kim, J. S., Chon, S.K., & Hwang, I.S. (1991). Relationship
591
between psychiatric symptoms and lesion site of brain in592
patients with hesd trauma. Journal of Korean Neuropsychiatric593
Association, 30(6), 996-1003.594
Kim, M. K., Hyun, M. H., & Han, S. I. (2003). The Performance
595
of Trail Making B Test of the Organic Patients and Alcoholics.
596
The Korean Journal of Clinical Psychology, 22(2), 463-473.
597
Lee, J. Y., Yum, T. H., & Jang, H. I. (1990). Cognitive and emo-
598
tional Disturbances in patients with frontal and temporal lobe599
damages. Journal of the Korean Neuropsychiatric Association,600
29(5), 1059-1074.601
Lequerica, A. H., Rapport, L. J., Loeher, K., Axelrod, B.602
N., Vangel, S. J., Jr., & Hanks, R. A. (2007). Agitation
603
in acquired brain injury: impact on acute rehabilita-604
tion therapies. J Head Trauma Rehabil, 22(3), 177-183.
605
doi:10.1097/01.HTR.0000271118.96780.bc
606
Levy, M., Berson, A., Cook, T., Bollegala, N., Seto, E., Tursanski,607
S., & Bhalerao, S. (2005). Treatment of agitation following608
traumatic brain injury: a review of the literature. NeuroReha-609
bilitation, 20(4), 279-306.610
Lindsay Wilson, J. T. (1990). The relationship between neu-611
ropsychological function and brain damage detected by612
neuroimaging after closed head injury. Brain Injury, 4(4), 349-
613
363.614
Milner, B., & Petrides, M. (1984). Behavioural effects of frontal-615
lobe lesions in man. Trends in Neurosciences, 7(11), 403-407.616
Norton, L. E., Malloy, P. F., & Salloway, S. (2001). The impact of
617
behavioral symptoms on activities of daily living in patients618
with dementia. Am J Geriatr Psychiatry, 9(1), 41-48.619
Ponsford, J., Willmott, C., Rothwell, A., Cameron, P., Kelly, A. M.,620
Nelms, R., & Ng, K. (2000). Factors influencing outcome fol-621
lowing mild traumatic brain injury in adults. J Int Neuropsychol622
Soc, 6(5), 568-579.623
Prigatano, G. P. (1992). Personality disturbances associated with
624
traumatic brain injury. J Consult Clin Psychol, 60(3), 360-368.
625
Robinson, R. G., Murata, Y., & Shimoda, K. (1999). Dimensions of
626
social impairment and their effect on depression and recovery627
following stroke. International Psychogeriatrics, 11(4), 375-
628
384.629
Robinson, R. G., & Szetela, B. (1981). Mood change follow-630
ing left hemispheric brain injury. Ann Neurol, 9(5), 447-453.631
doi:10.1002/ana.410090506632
Rogers, J. M., & Read, C. A. (2007). Psychiatric comorbidity fol-633
lowing traumatic brain injury.Brain Inj, 21(13-14), 1321-1333.634
doi:10.1080/02699050701765700635
Rosenthal, M., Christensen, B. K., & Ross, T. P. (1998). Depres-636
sion following traumatic brain injury. Arch Phys Med Rehabil,637
79(1), 90-103.638
Salmond, C. H., Menon, D. K., Chatfield, D. A., Pickard,
639
J. D., & Sahakian, B. J. (2006). Changes over time640
in cognitive and structural profiles of head injury
641
survivors. Neuropsychologia, 44(10), 1995-1998.642
doi:10.1016/j.neuropsychologia.2006.03.013643
Scheibel, R. S., Newsome, M. R., Troyanskaya, M., Steinberg, 644
J. L., Goldstein, F. C., Mao, H., & Levin, H. S. (2009). 645
Effects of severity of traumatic brain injury and brain reserve 646
on cognitive-control related brain activation. J Neurotrauma, 647
26(9), 1447-1461. doi:10.1089/neu.2008.0736 648
Senathi-Raja, D., Ponsford, J., & Schonberger, M. (2010). 649
The association of age and time postinjury with 650
long-term emotional outcome following traumatic 651
brain injury. J Head Trauma Rehabil, 25(5), 330-338. 652
doi:10.1097/HTR.0b013e3181ccc893 653
Sohlberg, M. M., & Mateer, C. A. (1989). Training use 654
of compensatory memory books: a three stage behav- 655
ioral approach. J Clin Exp Neuropsychol, 11(6), 871-891. 656
doi:10.1080/01688638908400941 657
Sole-Padulles, C., Bartres-Faz, D., Junque, C., Vendrell, P., 658
Rami, L., Clemente, I. C., & Molinuevo, J. L. (2009). 659
Brain structure and function related to cognitive reserve 660
variables in normal aging, mild cognitive impairment and 661
Alzheimer’s disease. Neurobiol Aging, 30(7), 1114-1124. 662
doi:10.1016/j.neurobiolaging.2007.10.008 663
Stuss, D. T., & Levine, B. (2002). Adult clinical neuropsychology: 664
lessons from studies of the frontal lobes. Annu Rev Psychol, 665
53, 401-433. doi:10.1146/annurev.psych.53.100901.135220 666
Stuss, D. T., Levine, B., Alexander, M. P., Hong, J., Palumbo, 667
C., Hamer, L., & Izukawa, D. (2000). Wisconsin Card Sorting 668
Test performance in patients with focal frontal and posterior 669
brain damage: effects of lesion location and test structure on 670
separable cognitive processes. Neuropsychologia, 38(4), 388- 671
402. 672
Sunderland, A., Harris, J.E. & Baddeley, A.D. (1983). Do labo- 673
ratory tests predict everyday memory : a neuropsychological 674
study. Jornal of verbal learning &verbal behavior, 22(3), 675
341-357. 676
Wallesch, C. W., Curio, N., Galazky, I., Jost, S., & Syn- 677
owitz, H. (2001). The neuropsychology of blunt head 678
injury in the early postacute stage: effects of focal lesions 679
and diffuse axonal injury. J Neurotrauma, 18(1), 11-20. 680
doi:10.1089/089771501750055730 681
Wallesch, C. W., Curio, N., Kutz, S., Jost, S., Bartels, C., & Syn- 682
owitz, H. (2001). Outcome after mild-to-moderate blunt head 683
injury: effects of focal lesions and diffuse axonal injury. Brain 684
Inj, 15(5), 401-412. doi:10.1080/02699050010005959 685
Whelan-Goodinson, R., Ponsford, J. L., Schonberger, M., & John- 686
ston, L. (2010). Predictors of psychiatric disorders following 687
traumatic brain injury.J Head Trauma Rehabil, 25(5), 320-329. 688
doi:10.1097/HTR.0b013e3181c8f8e7 689
Yesavage, J. A., Brink, T. L., Rose, T. L., Lum, O., Huang, V., 690
Adey, M., & Leirer, V. O. (1982). Development and validation 691
of a geriatric depression screening scale: a preliminary report. 692
J Psychiatr Res, 17(1), 37-49. 693
Zillmer, E., & Spiers, M. (2001). Principles of Neuropsychology. 694
Belmont: Wadsworth, 321-355. 695
