Archives of Rehabilitation Research and Clinical Translation (2020) 2, 100031

Archives of Rehabilitation Research and Clinical Translation

Archives of Rehabilitation Research and Clinical Translation 2020;2:100031

Available online at www.sciencedirect.com

Original research

Effects of Chronic Brain Injury on Quality

of Life: A Study in Patients With Left- or
Right-Sided Lesion
Madhushree Chakrabarty, PhD a,
Eliza M. Pflieger, Dr. rer. medic b, Eileen Cardillo, DPhil c,
Anjan Chatterjee, MD d

a
Center for Cognitive Neuroscience and Department of Neurology, University of Pennsylvania,
Philadelphia, Pennsylvania
b
Novarea RPK Aachen, Aachen, Germany
c
Center for Cognitive Neuroscience and Department of Neurology, University of Pennsylvania,
Philadelphia, Pennsylvania
d
Center for Cognitive Neuroscience and Department of Neurology, University of Pennsylvania,
Philadelphia, Pennsylvania

KEYWORDS Abstract Objectives: To test the hypothesis that quality of life (QOL) is made up of different
Quality of Life; components, and each of these has different anatomic and demographic contributors.
Chronic brain injury; Design: Questionnaire-based study.
Rehabilitation Setting: Center for Cognitive Neuroscience, University of Pennsylvania.
Participants: People with chronic brain injury (NZ52) volunteered for the study. After
excluding patients with severe communication deficits, bilateral lesions, and incomplete data,
42 patients with focal lesions were included in the final study: 22 patients with left hemisphere
injury (LHI) (9 women and 13 men; mean age
SD, 60.6
11.2y [range: 36-83]; mean chronicity

SD, 11.5
4.2y) and 20 patients with right hemisphere injury [RHI] (16 women and 4 men;
mean age
SD [62.7
12.8y] [range: 31-79]; mean chronicity
SD 10.1
4.3y).
Interventions: Not applicable.
Main Outcome Measures: We administered the RAND36-Item Health Survey (RAND-Version-
1.0), Stroke Impact Scale (version 3.0), Positive Affect and Negative Affect Scale, and Distress
Thermometer to measure QOL in LHI and RHI patients. Exploratory factor analysis with prin-
cipal component method reduced these measures to 5 factors, roughly categorized asd(1)
physical functioning; (2) general health; (3) emotional health; (4) social functioning; and (5)

List of abbreviations: ANOVA, analysis of variance; FA, factor analysis; KMO, Kaiser-Meyer Olkin; LHI, left hemisphere injury; PANAS,
Positive Affect and Negative Affect Scale; QOL, quality of life; RHI, right hemisphere injury; SIS, Stroke Impact Scale; ToM, theory of mind.
Disclosures: A.C. served as a cognitive consultant for Genentec in the PRISMS stroke trial. M.C. is supported by USIEF FulbrighteNehru
Postdoctoral Award (no. 2172/FNPDR/2016). The other authors have nothing to disclose.
Cite this article as: Arch Rehabil Res Clin Transl. 2020;2:100031.

https://doi.org/10.1016/j.arrct.2019.100031
2590-1095/ª 2019 The Authors. Published by Elsevier Inc. on behalf of the American Congress of Rehabilitation Medicine. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2 M. Chakrabarty et al.

cognitive functioning. Exploratory analyses attempted to relate these factor scores to demo-
graphic variables, neuroanatomical data, and neuropsychological measures.
Results: Physical functioning was the biggest contributor to reduced QOL, explaining 32.5%, of
the variance. Older age, less education, and larger lesion size predicted poorer physical func-
tioning (P<.001). Age also affected emotional health. (PZ.019). Younger patients reported
poorer emotional health than older patients. LHI patients reported less satisfaction with their
cognitive functioning (PZ.009) and RHI patients with their physical functioning (PZ.06).
Exploratory neuroanatomical analyses hinted at brain areas that may be associated with the
perception of disability in each QOL component.
Conclusions: QOL is composed of 5 components. Clinical and demographic factors appear to
differentially affect these aspects of patients’ perceived QOL, providing hypotheses for further
testing and suggesting potential relations for therapeutic interventions to consider.
ª 2019 The Authors. Published by Elsevier Inc. on behalf of the American Congress of Rehabil-
itation Medicine. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

Advances in medicine have allowed us to extend the length considered patients either undergoing treatment or patients
of life of people with neurologic illnesses. Health care who had just completed a treatment plan or in whom re-
professionals think beyond morbidity and mortality to covery was not complete.12,15,18 Consequently, their reports
include well-being as an end target of their treatment. on QOL were relatively unstable and likely to change with
Consequently, well-year is now recognized as a unit of time and the acquisition of compensatory strategies. Only
health status.1 Greater importance is being attached to rare studies13 addressed the long-term effects of stroke.
patients’ subjective assessments of well-being and their Dhamoon et al13 found a significant effect of lesion laterality
satisfaction with treatment, as distinct from objective on QOL. However, in this study13 the patient, family member,
clinical measures of their health status. Quality of life or health care provider rated the patient’s QOL. Conse-
(QOL) is important for evaluating efficacy and cost utility of quently, the study did not exclusively reflect the subjective
different treatment plans or interventions. experience or QOL perception of the patients themselves.
Recently, the mortality rates of patients with brain injury The present study is motivated to understand the
(eg, stroke,2 traumatic brain injury,3 brain tumor4) have neuroanatomic underpinnings of threats to QOL experi-
decreased. However, their health status is far from satis- enced by patients with focal brain injuries. At the coarsest
factory.5 According to Lai et al,5 only 25% of stroke patients level, we test the hypothesis that laterality of damage
return to the level of everyday participation and physical contributes differentially to QOL. However, for the reasons
functioning comparable to community-matched persons who listed above, this hypothesis might be inadequately
have not had a stroke. Survivors of traumatic brain injury6 formulated if QOL cannot be reduced to a single construct.
and brain tumors7 also have significant functional and psy- We also consider the possibility that laterality itself may be
chosocial impairments, limiting them in everyday activity too coarse to assess brain-QOL relations. Consequently, our
and participation. Identifying the different factors that study is a preliminary investigation to test the hypothesis
affect QOL for patients with brain injury is necessary to guide that QOL is made up of different components, each of
focused rehabilitation strategies. which is associated with different locations of brain injury.
Laterality of lesion may be one such factor. Functional We also considered how demographic variables and neuro-
lateralization in human brain8 means that patients with left psychological impairments might affect QOL.
hemisphere lesions have different deficits than patients To test these hypotheses: (1) we selected patients with
with right hemisphere lesions. However, few studies have chronic focal lesions broadly, because of stroke, tumor
investigated the effect of laterality on the QOL of patients resection, hemorrhage, or aneurysmal rupture; (2) we
with brain injury and their results are not consistent.9 Some assessed QOL in this group by administering a battery of
reports support the idea that the right hemisphere is not as relevant measures of QOL, 2 specific to QOL and 2 per-
crucial as the left hemisphere for maintaining a good taining to mood; and (3) we used exploratory factor analysis
QOL.10-13 Others assert that lesions in the right hemisphere with principal component method to distinguish different
cause significant reductions in QOL.14,15 Several studies also aspects of QOL and investigate the effects of lesion location
report no differences based on the side of the lesion.16-19 on these components.
The inconsistent results of studies regarding the role of
laterality in determining QOL may stem from differences in
the tools used to measure QOL. Notably, the same group of Methods
patients performed differently on different scales of QOL.19
Previous studies have also focused on particular etiologies Participants
rather than on the laterality of lesion, per se, making it un-
clear whether their results are tied to the particular etiology Patients (NZ52) enrolled in the Center for Cognitive
or reflect anatomy. In addition, most of these studies Neuroscience Focal Lesion Database at the University of
Quality of life in chronic brain injury 3

Pennsylvania participated in the study. Database eligibility instructions for each questionnaire before presenting it to
requirements include a diagnosis of a focal brain injury the participants to complete.
verifiable by magnetic resonance imaging or computed to-
mography scan, and absence of any other neurologic dis- Statistical analyses
order or injury, learning disorder, or psychiatric condition.
Additional requirements of this study included absence of A factor analysis (FA) using principal component method with
moderate or severe aphasia that would make understanding a varimax (orthogonal) rotation was conducted on data ob-
the survey instruments difficult. All database volunteers tained from 42 patients. We obtained 21 measures per pa-
meeting these criteria and active during the study recruit- tient: PANAS (2), Distress Thermometer (1), RAND subscales
ment period (May 2013-August 2014) were invited to (8), RAND health change (1), SIS subscales (8), and SIS stroke
participate. All participants signed an informed consent recovery (1). Because the sample size is smaller than typi-
approved by the Institutional Review Board of the Univer- cally obtained for FA, we calculated a recommended mea-
sity of Pennsylvania and were compensated financially for sure in designs where the ratio of cases to variables is less
their time. After excluding patients with severe communi- than 1:5dthe Kaiser-Meyer Olkin (KMO) measure of sampling
cation deficits (nZ1), bilateral lesions (nZ3), and incom- adequacy.30 Examination of the KMO value indicated that the
plete data (nZ6), 42 focal lesion patients with unilateral sample was factorable despite the small size (KMOZ.7).
injury were included in the analyses: 22 patients with left Homogeneity of variance was confirmed by Bartlett’s test (c2
hemisphere injury (LHI) (9 women and 13 men; mean age
[210]Z511.6, P<.001). Communalities were above .5 for all
SD, 60.6
11.2y [range: 36-83]; mean education
SD, items in the initial analysis. The diagonals of the anti-image
14.9
2.7y; mean lesion size
SD, 34.3
44.9 cc; mean correlation matrix were over .5 for all items except the
chronicity
SD, 11.5
4.2y) and 20 patients with right positive and negative affects scores of the PANAS (PA_PANAS
hemisphere injury (RHI) (16 women and 4 men; mean age
and NA_PANAS). We repeated the analysis after dropping
SD, 62.7
12.8y [range: 31-89]; mean education
SD, PA_PANAS and NA_PANAS due to their low sampling ade-
13.5
2.3y; mean lesion size
SD, 45.0
53.2 cc; mean quacy. KMO of the new model was .7 and Bartlett’s test was
chronicity
SD, 10.1
4.3y). A total of 64% of the brain- significant (c2 [171]Z452.9, P< .001). One item (SIS-Hand-
injured patients considered in this study had experienced a icap) did not load above .5 on any component and was
stroke. The other patients had focal injuries resulting from dropped from the analysis. The final FA was conducted on 18
tumor resections, hemorrhages, and ruptured aneurysms. items. The KMO of the final model was .703 and Bartlett’s test
There were no significant differences in age, education, of sphericity was significant (c2 [153]Z423.7, P<.001), again
lesion size, and chronicity across LHI and RHI groups. The confirming that the data were factorable.30 Communalities
demographic and neurologic details of individual patients were above .5 for all items in the final analysis.
are presented in table 1. Also included in table 1 are scores To anticipate the results, 5 factors were identified. A
from 4 neuropsychological tests collected as part of their mixed-design analysis of variance (ANOVA) with group (LHI,
database participation and reflective of their overall high RHI) as a between-participant variable and the 5 QOL
level of cognitive function: Western Aphasia Battery,20 components as within-participants variables was conducted
American National Adult Reading Test,21 Philadelphia Brief to test for an interaction between group and QOL compo-
Assessment of Cognition,22 and Mini-Mental State Exami- nents. This analysis was followed by independent sample t
nation.23 All patients had their lesions mapped onto a tests to determine if LHI and RHI groups differed across the
standard brain template by a board-certified neurologist 5 QOL components. A discriminant analysis was performed
with the exception of 2 patients for whom films were not to test how accurately patients’ perceived QOL in the 5
available. Data from these 2 patients were not included in domains could discriminate the LHI and RHI groups.
the regression or exploratory lesion analyses. Stepwise regression was conducted to test if de-
mographic (age, education) and neurologic factors (lesion
QOL test materials size, chronicity) predicted the QOL components. Last,
exploratory lesion analyses were conducted to consider
We administered the RAND36-Item Health Survey (RAND- whether injury to specific brain areas are associated with
version-1.0),24 perhaps the most widely used general lower scores on any of the QOL components. To better
assessment of health-related quality of life,25 and the understand the observed patterns and the potential effect
Stroke Impact Scale (SIS-version 3.0),26 the most widely of other participant differences, we also considered the
used disease-specific health-related quality of life tool for effect of neuropsychological test performance and sex in
stroke patients. We also included 2 standard depression post hoc analyses. Statistical analyses were done in SPSS
scalesdPositive Affect and Negative Affect Scale (PANAS)27 Statisticsa and lesion analyses were done in MRIcron.b
and Distress Thermometer.28 Depression and hopelessness
have been associated with a poorer present QOL,29 moti- Results
vating our inclusion of the depression measures.
The final FA was done on 18 items. We extracted 5 com-
Procedure ponents with eigenvalues above 1. The 5 components
explained 32.5%, 16.3%, 9.8%, 7.4%, and 6.2% of the vari-
Participants completed all 4 printed questionnaires in a ance, respectively. The cumulative percentage of variance
single session either at the Hospital of the University of explained by the 5 components was 72.2%. The rotated
Pennsylvania or their homes. A researcher explained the component matrix with the communalities of the items is
Table 1 Demographic, neurologic, and neuropsychological details of LHI and RHI patients

4
ID Sex Age Edu (y) Lesion Location Lesion Cause Chronicity AQ AMN/ART PBAC- PBAC- PBAC- PBAC- PBAC- MMSE
Side Size (CC) (y) (Revised, Memory Visuospatial Language (12) Executive Behavior (30)
2/10) (27) (18) (26) (24)
85 F 65 15 Left Ins 13.1 Stroke 16.9 98.8 122.0 18 18 11 19.5 24 29
107 M 72 16 Left FP 33.2 Stroke 16.2 N/A 103.0 N/A N/A N/A N/A N/A N/A
141 F 54 16 Left Ins 21.6 Stroke 14.0 98.8 113.0 N/A N/A N/A N/A N/A N/A
215 M 64 14 Left F 17.4 Stroke 14.5 94.4 106.0 18 17 11 18.5 24 29
236 M 68 19 Left FP 156.0 Stroke 20.7 90.8 100.0 17.5 17 8.5 9.5 24 29
244 M 60 15 Left TþCerþ 47.2 Stroke 13.9 98.4 109.0 N/A N/A 12 18.5 24 27
Pons
318 F 63 12 Left BG 20.7 Stroke 13.4 99 112.0 21.5 18 12 19 24 29
342 F 60 12 Left OþTþCs 42.1 Stroke 13.0 93.4 N/A N/A N/A N/A N/A N/A N/A
343 M 58 14 Left TþCer 20.1 Stroke 12.8 N/A N/A N/A N/A N/A N/A N/A N/A
363 M 76 16 Left F 16.8 Stroke 11.7 91.4 104.6 14 18 9 15.5 24 25
384 M 73 12 Left F 11.3 Hemorrhage 12.3 93.1 102.4 14 13 10 19.5 24 22
428 M 58 12 Left ACCþ 3.6 Stroke 12.2 95.5 109.4 15.5 12 10.5 17.5 24 30
FþCC
493 M 70 14 Left F 22.4 Aneurysmþ 10.3 92.1 104.0 10 18 10.5 15.5 24 24.5
hemorrhage
529 F 68 12 Left F 9.0 Stroke þ 10.4 94.9 95.0 13 13 8 17.5 23 26
aneurysm
534 F 63 16 Left F N/A Aneurysm 10.1 N/A 120.0 N/A N/A N/A N/A N/A N/A
541 M 49 19 Left F 18.8 Tumour 10.4 N/A 122.0 21.5 18 11 22 24 25
resection
565 M 56 12 Left F 14.5 Aneurysmþ 10.6 N/A 121.0 N/A N/A N/A N/A N/A N/A
hemorrhage
642 M 79 12 Left P 8.0 Stroke 11.4 96.8 N/A 16 18 11 19 24 25
755 F 50 16 Left Cer N/A Stroke 3.9 N/A 120.0 20 18 12 21.5 24 30
775 M 45 20 Left F 27.3 Aneurysm 6.1 99.2 110.4 13 16 11 20.5 24 29
792 F 31 14 Left F 167.3 Tumor 2.2 99.6 106.2 14.5 14 10 17 24 27
resection
795 F 52 20 Left F 15.2 Tumor 6.6 96.0 124.8 21.5 18 12 20 24 30
resection
83 M 72 12 Right FTP 8.0 Stroke 16.6 99.8 114.0 17 16 12 23.5 24 29
87 F 74 15 Right F 10.5 Stroke 16.7 99.1 113.0 23.5 17 10 20 24 28
112 F 50 16 Right OþTh 4.7 Stroke 16.6 100 119.0 22 18 12 23 24 29
264 F 63 12 Right F 45.3 Hemorrhage 14.5 N/A 116.0 N/A N/A N/A N/A N/A N/A

M. Chakrabarty et al.
444 F 82 12 Right TP 15.5 Stroke 11.5 95.5 99.0 15 13 11.5 21.5 24 25
474 F 53 11 Right P 22.2 Stroke 10.8 95.1 89.0 21 12 12 17.5 24 28
552 F 64 13 Right F 4.1 Aneurysm 13.7 99.4 106.0 18.5 18 12 22 24 30
569 F 75 12 Right FTþBG 37.4 Stroke 8.6 99.8 104.0 23 17 11 23 24 30
577 F 83 11 Right Cer 4.2 Stroke 15.3 85.3 88.96 8.5 13 8 13 23 26
592 F 46 12 Right FP 130.6 Stroke 11.8 97.8 110.0 19 14 12 19 22 29
(continued on next page)
 Quality of life in chronic brain injury 5

given in table 2. Based on inspection of the contributing

Abbreviations: ACC, anterior cingulate cortex; AMNART, American National Adult Reading Test; BG, basal ganglia; Cau, caudate; CC, cingulate cortex; Cer, cerebellum; Cs, centrum
semiovale; Edu, education; F, frontal (location); I, insula; MMSE, Mini-Mental State Examination; O, occipital; P, parietal; PBAC, Philadelphia Brief Assessment of Cognition; T, temporal;
MMSE

individual items, we named the 5 factors: (1) physical

(30)

N/A
N/A

N/A

N/A
27

28
30

27

30

30
functioning; (2) general health; (3) emotional health; (4)
social functioning; and (5) cognitive functioning. Four items
Behavior

had cross-loadings >0.4 on other components, but they had

PBAC-

primary loadings >0.6. The factors emotional health and

(24)

N/A
N/A

N/A

N/A
24

24
24

24

24

24
cognitive functioning had <3 item loadings but we retained
them as separate factors because (1) emotional health and
Executive

cognitive functioning are theoretically different concepts,

PBAC-

15.5

21.5

20.5 and (2) both RAND and SIS scales had fewer items measuring
(26)

N/A
N/A

N/A

N/A
22

21

20
these 2 constructs.
A mixed ANOVA was conducted to assess the effect of
Language (12)

laterality of lesion (LHI [nZ22] vs RHI [nZ20]) on the 5

factors. There was no significant main effect of group
(F1,40Z0.96, PZ.333) or factor scores (F4,160Z.006, PZ1).
PBAC-

11.5
N/A
N/A

N/A

N/A
However, there was a significant factor scores  group
9
10

12
12

10 interaction (F4,160Z2.54, PZ.042; observed powerZ.7).

Visuospatial

Thus, the factor scores differed significantly in the LHI and

the RHI groups (fig 1). An independent sample t test
PBAC-

revealed that cognitive functioning was perceived as more

(18)

N/A
N/A

N/A

N/A

impaired by the LHI group (mean
SD, .37
1.1) than the

10

18
18

18

18

14

RHI group (mean
SDZ .40
.63) [t(33.44)Z2.78, PZ.009,

Memory

Cohen’s dZ0.86]. RHI patients reported lower perceived

PBAC-

physical functioning than LHI patients, a difference that

10.5

15.5

16.5
(27)

N/A
N/A

N/A

N/A
21
22

26

approached significance [t(40)Z 1.934, PZ.06, Cohen’s

d Z0.59]. The results are summarized in table 3. To further
AMN/ART
(Revised,

explore the locus of the perceived difference in cognitive

95.4
2/10)

126.0
126.2
110.0

106.0

125.4

114.7

functioning between LHI and RHI patients, we conducted a

N/A

N/A

N/A

post hoc comparison of the groups on 4 neuropsychological

measures (Mini-Mental State Examination, American Na-
96.8
99.2

96.2

98.4
99.1
N/A

N/A

N/A

N/A

tional Adult Reading Test, Western Aphasia Battery, Phila-

100
AQ

delphia Brief Assessment of the Cognition). No significant

differences were observed (table 4).
Chronicity

In the discriminant analysis, the overall chi-square test

was significant (Wilks lZ.738, c2Z11.38, dfZ5, canonical
7.3

8.0
6.5
5.6
4.7

6.0

5.5
7.9

4.6
10.0
(y)

correlationZ.51, PZ.04). Cognitive functioning (rZ.82)

and physical functioning (rZ .6) were highly correlated
with the discriminant function. Reclassification of cases
aneurysm
resection

resection

resection
Strokeþ

based on the new canonical variable was successful. A total

Stroke

Stroke
Stroke
Stroke

Stroke

Stroke
Tumor

Tumor

Tumor
Cause

of 73.8% of the cases were correctly reclassified into their

original categories. RHI and LHI groups were reclassified
with 80% (16/20) and 68.2% (15/22) accuracy, respectively
Size (CC)

(table 5).
Lesion

7.7
27.8
64.6
33.6
30.1

46.5

32.2

22.8
170.1

182.1

Given the uneven distribution of sex in the sample, we

ran a post hoc analysis to consider its potential effect
on the results. A mixed ANOVA examining the effect
brainstem
FTPþBGþ

CerþPons

FPþBGþ
Location

CauþIns

of sex (men [nZ17] vs women [nZ25]) on the principal

Th, thalamus; WAB, Western Aphasia Battery.

component scores did not yield any significant differ-

Cau

Tþ
Cer
PO
TP

ences. There was no significant main effect of sex

P

(F1,40Z.68, PZ.416), no significant main effect of prin-

Lesion

cipal component scores (F4,160Z.06, PZ.994), and no

Right

Right
Right
Right
Right

Right

Right

Right
Right

Right
Side

significant sex  principal component scores interaction

(F4,160Z1.51, PZ.201).
Edu (y)

An exploratory stepwise regression analysis was con-

ducted to predict the 5 factors. Education (bZ .567,
Table 1 (continued )

12

13
18
18
14

12

17

16
12

12

tZ4.68, P<.001), lesion size (bZ .452, tZ 3.59,

PZ.001), and age (bZ .307, tZ 2.47, PZ.019) pre-
Age

52

52
72
77
54

36

71

62
60

56

dicted perceived physical functioning (F3,39Z11.32,

P<.001, R2Z.485,Cohen’s f2Z.94), indicating lesser edu-
Sex

M
F

F
F

cation, larger lesion size, and older age were associated

593

612
640
657
665

694

716

738
785

797

with worse perceived physical functioning after injury. Age

ID

(bZ.369, tZ2.45, PZ.019) also predicted perceived

6 M. Chakrabarty et al.

Table 2 Rotated component matrix with communalities of the items

Items 1. Physical 2. General 3. Emotional 4. Social 5. Cognitive Communalities
Functioning Health Health Functioning Functioning
SIS strength 0.92 0.9
RAND PF 0.863 0.834
SIS mobility 0.802 0.82
SIS ADLþIADL 0.767 0.827
SIS hand function 0.635 0.465 0.722
SIS stroke recovery 0.575 0.424 0.716
Distress 0.716 0.733
RAND general health 0.706 0.681
RAND health change 0.675 0.544
RAND energy fatigue 0.638 0.421 0.73
SIS emotion 0.763 0.634
RAND EWB 0.625 0.522
RAND pain 0.701 0.791
RAND RLPF 0.681 0.7
RAND RLEP 0.66 0.42 0.781
RAND SF 0.474 0.639 0.642
SIS COMM 0.809 0.727
SIS memory 0.705 0.659
Abbreviations: ADL, activities of daily living; COMM, communication EWB, emotional well-being; IADL, instrumental activities of daily
living; PF, physical functioning; RLPF, role limits physical functioning; RLEP, role limits emotional problems; SF, social functioning.

emotional health (F1,39Z6.00, PZ.019, R2Z.136, Cohen’s Discussion

f2Z.16), indicating that younger patients reported worse
perceived emotional health. However, none of these fac- Our study was motivated to understand the neuroanatomic
tors predicted perceived general health, social functioning, and demographic variables that impair QOL in people with
or cognitive functioning. Chronicity did not predict any of focal brain injury. We conducted a FA to identify compo-
the 5 principal components. nents of QOL experienced by people with chronic focal le-
To identify the brain areas associated with each of sions. Our study was motivated by the hypothesis that QOL
these factors, we conducted exploratory lesion subtrac- is not a unitary construct and that people’s QOL varies
tion analyses. First, factor scores were rank ordered along different dimensions. A 5-factor model explained
from the smallest to the highest. Then, for each factor, 72.2% of variance in QOL. Physical functioning was the most
we subtracted lesions of patients within the upper important QOL component that explained the most vari-
quartile (ie, top 25% on that factor) from the lesions of ance, followed by general health, emotional health, social
patients within the lower quartile (ie, bottom 25% who functioning, and cognitive functioning.
scored low on that factor). In this way, we plotted the We did not observe any effect of sex on the QOL
brain areas that corresponded to the perception of components. In contrasts to Dra ca,31 who reported that
dissatisfaction in each of these QOL factors. The lesion frequency of stroke in RH was significantly higher in men,
coverage map and subtraction plots for all 5 factors are we had few (4/20) male patients in the RHI group and a
shown in fig 2A-F. limited number of female patients in the LHI group (9/22).

Fig 1 Mean and standard deviations of the 5 QOL factors in patients with RHI and LHI *P<.05.
Quality of life in chronic brain injury 7

Table 3 Result of independent sample t test of the 5 PCA components

Components Group n Mean
SD t df P Value
1-Physical functioning RHI 20 0.3
1.02 -1.934 40 .06
LHI 22 0.28
0.92
2-General health RHI 20 0.05
1.01 0.304 40 .763
LHI 22 0.05
1.01
3-Emotional health RHI 20 0.11
0.98 0.681 40 .5
LHI 22 0.1
1.03
4-Social functioning RHI 20 0.09
1.03 0.543 40 .59
LHI 22 0.08
0.99
5-Cognitive functioning RHI 20 0.41
0.63 2.781 33.438 .009
LHI 22 0.37
1.14

Larger sample size may be more sensitive for detecting and physical functioning, but the result clearly suggests that
potential differences in how men and women experience sociodemographic factors influence physical QOLdwhich in
QOL after brain injury. If evident, determining neurologic, turn may affect prognosis and rehabilitation. People with
sociologic, or demographic factors that might underly sex higher education may have access to better medical care or
differences in QOL would be an important area for future be more likely to follow-up, thereby improving the odds of a
research. better QOL. Adequate counseling sessions for patients with
Although cognitive functioning explained the least vari- lower education levels and subsidized follow-up treatment
ance, it distinguished the left and right hemisphere injured may help improve their physical functioningdthe most
patients. We assessed the effect of laterality on each factor important component of QOL and, consequently, the one
of QOL and ran exploratory analyses to identify the pre- having a major effect on the QOL of caregivers as well.33
dictors and brain-behavior correlates of these factors. Here Reports in the literature are inconsistent regarding the
we discuss these findings and their implications. role of age and education in the health related QOL of
brain-injured patients. Although some studies find age5,34,35
and education36,37 crucial, others do not.19,38-40 The effect
Physical functioning of these factors may apply to specific QOL components, as
found in our study. Global scores of QOL may be insensitive
In our sample, QOL was affected most by patients’ to the specificity of the effect.
perceived level of physical disability. We also found that Our exploratory lesion analyses indicated that lesions
age, education, and lesion size were predictors of involving predominantly right motor cortex were associated
perceived physical functioning. with low perceived physical functioning. This observation is
Consistent with Jun et al,32 patients with higher educa- counterintuitive as the left hemisphere controls the domi-
tion reported better perceived physical functioning. Without nant right hand and most of our patients were right-handed.
an objective measure of physical functioning, we cannot be However, the kinds of motor-intentional deficits associated
certain of the relation between sociodemographic variables with right frontal damage might account for this

Table 4 Comparison of standard neuropsychological tests in LHI and RHI patients

Cognitive Scales Patient Group n Mean
SD t Value df P Value
WAB-AQ RHI 15 97.43
3.74 1.373 29 .18
LHI 16 95.76
3.01
AMNART RHI 17 109.57
11.73 -0.354 34 .725
LHI 19 110.78
8.69
PBAC-memory RHI 15 18.6
4.86 1.33 28 .194
LHI 15 16.53
3.56
PBAC-visuospatial RHI 15 15.6
2.69 -0.886 28 .383
LHI 15 16.4
2.23
PBAC-language RHI 15 11
1.3 0.892 29 .38
LHI 16 10.59
1.24
PBAC-executive RHI 15 20.2
2.93 1.932 29 .063
LHI 16 18.16
2.96
PBAC-behavior RHI 15 23.8
0.56 -0.892 29 .38
LHI 16 23.94
0.25
MMSE RHI 15 28.4
1.59 1.496 29 .145
LHI 16 27.28
2.45
Abbreviations: AMNART, American National Adult Reading Test; AQ, aphasia quotient; MMSE, Mini-Mental State Examination; PBAC,
Philadelphia Brief Assessment of Cognition; WAB, Western Aphasia Battery.
8 M. Chakrabarty et al.

their emotional well-being and vocational rehabilitation for

Table 5 Result of discriminant analysis
successful return to work51 and to alleviate their anxiety over
Standardized Canonical Discriminant Function Value financial insecurities. Most areas implicated in our explor-
Coefficients atory anatomic analysisdleft middle orbitofrontal cortex,
Function 1 left frontal areas, right frontal areas, bilateral insula, right
Physical functioning .636 caudate, right putamen, right thalamus, bilateral temporal
General health .109 cortex, right parietal cortexdare associated with the neural
Emotional health .242 bases of emotion processing.52
Social functioning .194
Cognitive functioning .824 Social functioning
Functions at Group Centroids
RHI .609 Age, education, lesion size, side, and chronicity did not pre-
LHI .554 dict social functioning. However, the subtraction plot
included areas implicated in theory of mind (ToM) (right
angular gyrus, right medial frontal areas, left temporal
observation.41 Apart from lesions in the motor cortices, le- pole),53 areas important for action observation (left inferior
sions in the bilateral-occipital lobe and the right superior frontal gyrus, right inferior parietal lobule),53,54 and subcor-
temporal area were also associated with lower subjective tical areas involved in social cognition (right cingulum and left
ratings of physical functioning. One possibility is that lesions caudate).55,56 ToM refers to the ability to understand and
in these areas lead to difficulty in vision, exploration of interpret another person’s beliefs, emotions, and intentions.
objects, and processing of space-related information, all of ToM requires both cognitive and emotional perspective taking
which might restrict physical mobility and the activities of and is necessary for social functioning.57 Similarly, under-
daily life.42 standing the intentions of others while observing their actions
is a fundamental aspect of social behavior.58
General health
Cognitive functioning
Age, education, lesion size, and chronicity did not predict
levels of general health. Lesion side (left, right) also did not Age, education, lesion size, and chronicity did not predict
have any effect on this component. The exploratory sub- the level of perceived cognitive functioning. However,
traction plot suggests that many right hemisphere areas are patients with LHI reported significantly lower perceived
important to general healthdsuperior parietal, middle cognitive functioning than patients with RHI. This sub-
occipital, precentral, angular gyrus, thalamus, caudate, jective report was obtained despite LHI patients not
putamen, and insuladas well as the bilateral anterior exhibiting significant differences from RHI patients on
cingulate. We could speculate how damage to these areas standard neuropsychological measures of language,
affects self-care and general health. For example, the right memory, visuospatial abilities, or executive function. One
superior parietal-occipital region is usually associated with reason for this discrepancy between subjective and
neglect. Lesions in the thalamus are reported to disturb the objective reports could be that although patients of both
total sensory motor relay, attenuate the body’s arousal groups were able to answer with comparable accuracy,
system, disrupt emotion processing, and cause mood dis- LHI patients may have had to exert greater cognitive
orders. Acute poststroke depression is often associated effort. The lack of self-awareness generally associated
with thalamic lesion.43 Thalamic lesion can also cause pain with right hemisphere lesions is another possible expla-
or Dejerine-Roussy syndrome.44 Lesions in the caudate45 nation for this difference. Lunven et al19 observed that
and anterior cingulum46 may cause emotional distur- right-brain-injury patients, but not left-brain-injury pa-
bances. Lesions in the insula can affect awareness.47 Future tients, underestimated their difficulties when their scores
prospective studies could target the occurrence of these were compared to scores provided by caregivers. Our
neurobehavioral symptoms with subjective reports of the subtraction analysis reveals that lesions primarily
quality of general health that patients with injuries in these affecting language and memory areas of the brain (eg,
areas experience. bilateral angular gyrus and left inferior frontal cortex
[pars triangularis], middle frontal, middle temporal gyrus,
Emotional health insula, putamen, caudate) were associated with subjec-
tive assessments of lower cognitive functioning. Although
Only age significantly predicted emotional health in the limited by reverse inference, this pattern is more consis-
present study. Older patients reported better emotional tent with a cognitive effort than an awareness-related
health than younger patients. This finding is consistent with interpretation of the laterality effect. Patients’ percep-
previous studies observing greater emotional well-being with tion of their abilities and disabilities appear more fine-
age.48 Others report that older adults move out of a negative grained than our rigorously designed clinical tests.
emotional state faster than younger adults and are less likely
to experience negative affect consistently.49 Younger people Study limitations
may be burdened by liabilities like dependents to care for
and these stresses may contribute to their low emotional This study was conducted on a relatively small sample
health.50 Younger patients may need counseling to boost consisting of 42 patients, making our behavioral findings
Quality of life in chronic brain injury 9

Fig 2 (A-F) The colored scale represents the number of lesions for each pixel. (A) Lesion coverage map; (B-F) subtraction plots
(left side represents the right hemisphere and right side represents the left hemisphere).
10 M. Chakrabarty et al.

preliminary and limiting our power to conduct detailed Suppliers

brain-behavior analyses. We consider the results of our
lesion analyses to be hypothesis generating. Future studies a. IBM SPSS Statistics version 25.0; IBM Corp.
are needed to verify these brain-behavior correlations. b. MRIcron software; NeuroDebian.
Although our sample size was smaller than typical of prin-
cipal component analyses, the Kaiser-Meyer-Olkin measure
of sampling adequacy and Bartlett’s test of sphericity Corresponding author
confirmed that the data set can be used for FA. We found a
large effect size (Cohen’s dZ.86) for the difference in
Madhushree Chakrabarty, PhD, 126, Jodhpur Park, Kolkata
perception of cognitive functioning across the LHI and RHI
68, West Bengal, India. E-mail address: madhushree1976@
groups. The effect size of the regression analysis for QOL
gmail.com.
component 1 (physical functioning) was also large (Cohen’s
f2Z.94)..The regression analysis for QOL component 3
(emotional health) had a small but nontrivial effect size
Acknowledgments
(Cohen’s f2Z.16). Thus, the effect size measures reassure
that the study reports significant and relevant information
on patients with brain injury despite having a low We are grateful to Ayanendranath Basu, PhD (statistician),
sample size. Indian Statistical Institute, Kolkata, for his valuable
The varied etiologies of the patient population are both suggestions, and Jon Yu, BS, for his assistance with data
a strength and weakness of the design. Postinjury reorga- collection.
nization may differ between stroke and tumor patients, and
different risk profiles and medications may contribute
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