Case Report
Efficacy of Acupuncture Treatment to Improve Cognitive Function in a Brain Injury Patient: A Case Study
Ann Guernon1,2*, Brett Blabas2,3, Gouri Chaudhuri1 and Theresa L-B Pape2,4
1Marianjoy Rehabilitation Hospital/Northwestern Medicine, Wheaton, USA
2Edward Hines Jr. VA Hospital, USA
3Chicago Association for Research and Education in Science (CARES), USA
4Department of Physical Medicine &Rehabilitation, Feinberg School of Medicine, Northwestern University, USA
*Corresponding author: Ann Guernon, Research Department, Marianjoy Rehabilitation Hospital, 26W171 Roosevelt Road, Wheaton, IL 60187, USA
Published: 08 Aug, 2017
Cite this article as: Guernon A, Blabas B, Chaudhuri G,
Pape TL-B. Efficacy of Acupuncture
Treatment to Improve Cognitive
Function in a Brain Injury Patient: A
Case Study. Ann Clin Case Rep. 2017;
2: 1413.
Abstract
This case study explored the relationship between acupuncture and cognitive therapy with cognition and neural function following TBI. Outcome measures were the Rivermead Behavioral Memory Test (RBMT), Wisconsin Card Sorting Test (WCST) and fMRI. Results revealed improvements on the RBMT and WCST from baseline to endpoint that were maintained at follow-up. fMRI showed small clusters of activation at baseline with more widespread activation at end point. Activation decreased at follow-up but remained stronger than baseline. Acupuncture with cognitive therapy may have improved cognition in this case. Future research should address acupuncture plus cognitive therapy using larger samples and randomized control design.
Keywords: Acupuncture; Brain injury; Functional neuroimaging; Cognition; fMRI
Introduction
Acupuncture has been part of Chinese health care for thousands of years and was introduced
in the U.S. in 1972. Acupuncture is practiced for relief or prevention of pain and various health
conditions [1]. According to the 2002 National Health Interview Survey of complementary and
alternative medicine 8.2 million U.S. adults were using acupuncture at the time and 2.1 million U.S.
adults used acupuncture in the previous year [2].
Acupuncture, as a medical intervention, is based on the premise that there are patterns of energy
flow (Qi; pronounced “Chee”) through the body and these Qi are essential for health. Disruptions
of this flow are believed to be responsible for disease. Acupuncture theoretically corrects imbalances
of energy flow [3,4].
Acupuncture has become more widely used in recent years and is becoming a more common
complement to traditional therapies [5]. However, there is limited evidence acupuncture is effective
for treating cognitive disorders following neurological injury. In a meta-analysis of four clinical
trials (n = 368) the overall estimate regarding neurological functioning suggested the odds of
improvement in global neurological deficit was higher in the acupuncture group compared with
the control group (odds ratio = 6.55) [6]. A more recent meta-analysis targeting acupuncture as a treatment for cognitive impairment following stroke included 21 trials and 1,421 patients. The
conclusions were that acupuncture may have a positive effect on cognitive function [7]. Additionally,
a single study of 20 adults incurring Traumatic Brain Injuries (TBI) two to three years prior to study
enrollment, functioning at a Rancho level V (Confused, Inappropriate, Non-Agitated-Maximal
Assistance) or better and randomized to acupuncture or control was published. While the study was
not designed to address the question of cognitive gains directly related to acupuncture, the evidence
of improved cognitive test performancefor the acupuncture group suggests a possible relationship
between cognitive gain and acupuncture [8]. The available literature shows promise for acupuncture as a treatment for cognitive disorders, however, more evidence is needed to determine the benefit of
acupuncture for cognitive impairments specifically related to Traumatic Brain Injury (TBI). Given
mechanistic, epidemiologic and cognitive sequelae differences between stroke and TBI, evidence of
effect of acupuncture on cognition after TBI is warranted [9].
The purpose of this case study was to explore the potential relationship between acupuncture in
conjunction with cognitive therapy and changes in cognition for a person experiencing persisting cognitive impairments due to a TBI. The secondary purpose was
to explore the possible relationship between acupuncture with
cognitive therapy and changes in activation volume in the bilateral
temporal areas, anterior cingulate cortex and/or the right pre-frontal
dorsolateral area as shown by functional neuroimaging measures.
Case Description
Research participant
The participant was a 39 year old, Caucasian, English speaking
male who sustained a TBI at the age of 28. Cause of injury was a highspeed
motor vehicle accident where he was a restrained front seat
passenger. At time of injury, the participant had a Glasgow Coma
Scale score of 3 indicating severe TBI. CT scan of the brain revealed
right cerebral edema with hemorrhage extending into the third and
fourth ventricles. At time of study participation, 11 years post-injury,
this high school educated, unmarried gentleman was unemployed
receiving disability benefits. He was at a Rancho Los Amigos
Cognitive Level VII characterized by the ability to perform daily
activities, slower than normal rates of carry-over for new learning and
impaired judgement. No rehabilitation services were being provided
at study enrollment nor during study participation. There was no preinjury
history of learning disabilities or mental health disorders.
Study design
This research participant received weekly acupuncture sessions
lasting 30 minutes followed by one hour of cognitive therapy over
eight weeks. Treatment effects were measured via performance on
cognitive tests and functional magnetic resonance imaging (fMRI).
These measures were completed at baseline, at end of the Eight-Week
Treatment (Endpoint), and two times during an eight-week washout
phase (at four weeks – mid-point follow-up and eight weeks –
final follow-up). At final follow-up study participation was complete
(Figure 1).
The acupuncture, cognitive therapy and cognitive testing were
conducted at an acute rehabilitation hospital in the Midwest region of
the U.S. Neuroimaging was conducted at an imaging facility affiliated
with a large, urban acute care hospital and university. Informed
consent was obtained from the participant prior to engaging in study
procedures. Institutional Review Board approvals were obtained at
both participation sites prior to subject recruitment.
Acupuncture procedures
Each acupuncture session involved manual acupuncture at eight
points. Acupuncture sessions were conducted by a licensed and
certified physician/acupuncturist in an outpatient medical clinic.
Seisin #5 acupuncture needles were used. The depth of penetration
in the skin/subcutaneous locations was 1 to 2 mm. Table 1 provides
location and description of these points. The eight points were Gall
Bladder 39 (GB-39), Heart 7(H7), Spleen 6 (SP6), Master of Heart
(MH6 or PC6), Stomach 36 (ST36), Large Intestine 4 (Li4), Triple
Heaters 8 (TH8) and Spiritual (GV20). All points have theorized
relationships to the brain and cognitive functions such as orientation,
impulsivity, short term memory, attention, executive function,
categorization and agitation in addition to other physical, mental and
emotional symptoms (e.g., headaches, quality of life).
Cognitive treatment description
A standardized cognitive therapy program was provided by a
licensed speech-language pathologist. Each individualized session
addressed six cognitive domains: orientation, short term memory,
shifting attention, directed attention, categorization, and executive
functioning.
Repeated measures assessment battery
A cognitive testing battery was administered at four time points.
The tests were selected to measure orientation, memory, attention,
executive function and quality of life. All tests were administered
by a licensed speech-language pathologist with experience in
administration of standardized tests. For repeated tests, alternate
forms were used when available. the tests included were as follows:
• Galveston Orientation Amnesia Test (GOAT), which
examines orientation to time, place and person and is a valid
and reliable measure of post traumatic amnesia [10,11].
• Rivermead Behavioral Memory Test-3 (RBMT-3), which
was developed as an ecologically valid assessment of everyday memory
skills in persons with brain injury [12]. This version of the RBMT
has been shown to be a reliable and valid measure of memory skills
[12]. RBMT-3 is comprised of 14 sub-tests that assess the domains
of verbal memory, visual memory, spatial memory, prospective
memory, orientation and new learning. Raw scores range from 4 -
51 points and are converted to a scaled score of 1-19 with a mean
of 10 (SD = 3) [12]. The General Memory Index (GMI) is an overall
score obtained by converting the summed subtest scaled scores to a
standardized score with a mean of 100 (SD = 15).
• Wisconsin Card Sorting Test (WCST), which examines
executive function through requirements of planning, organization,
use of environmental feedback to shift cognitive sets and regulating
impulsive responses [13].
Participants are provided with a stack of cards and asked to match
the cards while the test administrator tells the patient if their matches
were correct or incorrect. The participant must determine the sorting
rules based on the administrator’s responses which shift throughout
the test. Scores are generated with regard to number of categories
achieved, number of trials completed, number of errors and number
of perseverative errors [14].
• Satisfaction with Life Scale (SWLS) is a five item self-rated
questionnaire on a Likert scale and measures global life satisfaction
[15].
Functional neuroimaging methods
Functional images were acquired on a Siemens 3T Tim Trio
scanner with a 12-channel head coil. The Counting Stroop task was
acquired using the following parameters: repetition time = 2200 ms,
echo time = 20 ms, flip angle = 80,159 slices, field of view = 896 x 812,
and acquisition voxel size = 1.7 mm x 1.7 mm x 3 mm. Scan duration
was approximately six minutes. A T1-weighted anatomical image was
also acquired for registration purposes using a 3D magnetizationprepared
rapid gradient-echo sequence (repetition time = 2300 ms;
echo time = 2.97 ms; inversion time = 900 ms; flip angle = 9; 176
slices; 1 mm x1 mm x 1 mm voxel resolution; field of view = 256 mm).
The participant was instructed to remain as still as possible during
scans.
The Counting Stroop task examines task directed attention and
provides insight into cognitive effects experienced as a result of
attention fatigue [16]. The task is also a measure of cognitive control.
The Counting Stroop is a block design with a total of nine blocks;
four are interference blocks and five are neutral blocks. Neutral-word
control trials contained single semantic category common animals
(e.g. ‘dog’ written three times), while interference trials contained
number words that were incongruent with the correct responses
(e.g., ‘two’ written four times). A total of 16 items were in each block.
Each item was presented for a maximum of two seconds or until the
participant responded. The inter-stimulus interval was two seconds.
During this task, the participant was instructed to respond by pushing
a button (one to four) to indicate the number of words on the screen
for each item, regardless of word meaning.
Neuroimaging data was preprocessed within Statistical
Parametric Mapping (SPM8) toolbox. Data were realigned to the
first functional image, coregistered, normalized to MNI space and
spatially smoothed (full width at half maximum = 8 mm x 8 mm
x 8 mm). The first five images were discarded to allow for gradient
stabilization. The T1 MPRAGE volume was processed using voxelbased
morphometry. A general linear model was created using a first level design. Motion was regressed out of the data using the framewise
displacement (FD <1.0 mm) as a cut-off [17]. T-maps were generated
to look at Interference-Neutral, Neutral-Interference and Interference
+ Neutral conjunction contrasts. Small volume correction was
applied to the activation data at p <.05 uncorrected using a mask that
contained 26 regions of interest and setting the voxel extent to five.
Of the 26 ROIs, 23 were extracted from the Harvard-Oxford atlas
from Functional MRI Software Library (FSL) [18-20]
Figure 1
Figure 2
Figure 3
Figure 3
Rivermead behavioral memory test results. Scores for immediate
and delayed novel task and delayed picture recognition.
Figure 4
Figure 4
Wisconsin Card Sorting Test Results. Scores for novel task
immediate and delayed and delayed picture recognition.
Figure 5
Results
Cognitive testing
There were no meaningful changes in orientation. GOAT scores
remained stable from baseline (14/16) to final follow-up (16/16)
indicating the patient maintained emergence from Post-Traumatic
Amnesia throughout study participation.
Results from the RBMT-3 are illustrated in Figures 2 and 3.
Figure 2 illustrates the improved GMI test performance between
baseline (GMI = 67) and endpoint (GMI = 88) with maintenance of
this improvement through the follow-up (GMI = 87). Examination
of specific subtest scores of the RBMT-3 revealed improvements
of at least 1 standard deviation (SD = 3) on the subtests of Picture-
Recognition Delayed, Novel Task Immediate and Novel Task Delayed (Figure 3).
WCST results are provided in Figure 4. WCST standard scores
at baseline were in the range of mild-moderate impairment (number
of errors = 74, % perseverative errors = 77 and non-perseverative
errors = 74) and mild impairment (perseverative responses = 81,
perseverative errors = 77), which improved at endpoint to mild
impairment (number of errors = 82) or average performance
(perseverative responses = 93, percent perseverative responses = 96,
perseverative errors = 92). This improvement was maintained at the
final follow-up. Number of correct trials improved from 72 at baseline
to 85 at endpoint, which declined to 80 at final follow-up.
Scores on the SWLS did not show meaningful changes. Baseline
score of 12 remained stable at the mid-point and final follow-up with
scores of 13 and 12 respectively. There was a considerable decline to 5
at the endpoint, however, the participant had received some troubling
news just prior to completing the SWLS. Scores in the range of 10-14
are classified as dissatisfied with life [21].
Functional neuroimaging
When comparing all interference blocks with all neutral blocks,
activation at baseline was seen in the left inferior and medial temporal
lobes and the right medial temporal lobe (Figure 5). At endpoint
(Figure 5) activation was seen in the right motor cortex, left inferior
and medial temporal lobes, right superior temporal lobe and the left
hippocampus for the same contrast. At final follow-up, (Figure 5)
activation was seen in the same areas as endpoint except for the right
superior temporal lobe and left hippocampus. Additional activation
was seen in the anterior cingulate cortex, left motor cortex, right
superior parietal lobule, right inferior temporal lobe and left superior
temporal lobe.
When looking at the interference and neutral blocks combined,
activation in the bilateral motor cortices, bilateral superior parietal
lobules and anterior cingulate cortex was seen at all three time points.
The right DLPFC was activated in both conditions at baseline and
end-point, but not at final follow-up. Similarly, the left hippocampus
was activated in both conditions at baseline and endpoint, but not at
final follow-up (Table 2).
Table 1
Table 2
Discussion
The purpose of this case study was to explore the potential of
acupuncture provided with cognitive therapy as a treatment to
improve cognition for a person experiencing persistent cognitive
impairments 11 years after TBI. Changes were measured according
to cognitive test performance, behavioral performance, reported life
satisfaction and changes in volume of activation with fMRI. Results
show improvements in WCST scores, RBMT-3 scores and increased
activation on neuroimaging measures in brain regions with key roles
in learning and memory.
The WCST and RBMT-3 results indicate improved visual
memory, new learning, attention and executive function temporally
aligned with the provision of the treatment. Improvements were
reported in memory and problem solving based on immediate and
delayed performance for the novel RBMT task. This task requires the
participant to recreate a design using different sized puzzle pieces.
These gains between baseline and endpoint, and maintained at final
follow-up, indicate improved ability to learn new information both
immediately following presentation and with a delay. Reduction of
trials administered on the WCST between baseline and final follow-up
serve as additional evidence of improved learning, possibly supported
by increased attention and executive function skills. These gains in
memory, problem solving and learning are consistent with evidence
from a meta-analyses of acupuncture to treat cognitive impairment
following stroke [7].
Functional neuroimaging results showed increased activation
in the frontal and temporal lobes. These areas are principal brain
areas for learning and memory and are consistent with our
aforementioned findings of improved cognitive test performance
and behavioral performance. Imaging findings are also consistent
with our hypothesis for increased activation immediately following
acupuncture and cognitive therapy and after final follow-up. These
results are also consistent with previous findings reported by Wang21
who provided acupuncture at LI4 (as well as Liv3) to participants with
Alzheimer’s Disease or Mild Cognitive Impairment. They reported
changes in activation of the frontal and temporal lobes following
acupuncture [22].
Our findings of activation changes are consistent with the
literature related to brain regions showing activation during the
Counting Stroop task [16]. However, our findings of changes between
neutral and interference blocks are dissimilar with results for healthy
people [23] where activation in regions known to comprise the
cognitive/attention network (anterior cingulate cortex, right DLPFC
and superior parietal lobules) [24] was seen during both interference
and neutral blocks at baseline and endpoint.Our findings at final
follow-up, however, indicate continued activation between the
anterior cingulate cortex and the superior parietal lobules but absence
of right DLPFC activation. This could indicate improved connection
between these regions that are structurally connected through the
cingulum white matter fibers and are part of an attention/cognition
network. A potentially improved connection between the anterior
cingulate cortex and the superior parietal lobules is indicated further
by WCST improvement in accuracy of responses and reduction in
perseverative responses, which could be attributed to improved
attention and executive function skills.
Functional activation findings for this case are also inconsistent
with activation findings for healthy persons who show increased
activity in the anterior cingulate cortex during Interference blocks
(compared to neutral blocks) [23]. While our participant manifested
activity in the anterior cingulate cortex at all three time points for the
Interference and Neutral blocks separately, the increased activation in
the anterior cingulate cortex during Interference and Neutral blocks
was only seen at final follow-up. This dissimilarity is also true for
the right superior parietal lobule. This finding suggests the anterior
cingulate cortex for this patient does not function efficiently when
presented with multiple tasks and given the established role of the
anterior cingulate cortex in allocating attentional resources this likely
contributes to persisting cognitive impairments.
A final noteworthy result is the detected changes in hippocampal
and temporal lobe activation. Bilateral medial and left inferior
temporal lobe activation was identified at baseline and endpoint; with
additional activation at endpoint within the right superior temporal
lobe and left hippocampus. At final follow-up, activation was identified
in the anterior cingulate cortex, right inferior and left superior
temporal lobe. There was no hippocampal activation at baseline
or final follow-up, but the left hippocampal activation at endpoint
is consistent with improved RBMT memory scores at endpoint.
While the activation in the hippocampus was not maintained the
behavioral improvements in RBMT memory scores were maintained
at final follow-up. Changes in fMRI activation and evidence of
cognitive improvement with clinical cognitive testing indicate
possible molecular changes that may be attributed to acupuncture.
Literature from animal models showing a positive change in cognitive
impairment after acupuncture point to the modulation of signaling
pathways such as cholinergic and dopaminergic transmissions [25].
These cholinergic and dopaminergic pathways are well documented
as pathways necessary for cognitive function [26].
Improvements in cognitive function in a patient 11 years after
injury are very promising results, but this case study’s generalizability
to the larger TBI patient population is limited. An additional
limitation is the patient’s use of prescribed medications was not
recorded. Repeated administration of the cognitive tests may have
resulted in practice effects, but this was minimized by using alternate
forms of the RBMT.
Conclusion
For our participant, the reported findings collectively suggest
acupuncture combined with cognitive therapy may have improved his
cognitive test performance and behavioral performance. Furthermore,
the effects of acupuncture combined with cognitive therapy may result
in improved performance extending beyond the period of treatment.
Improvements on the RBMT-3, WCST and increased activation in
key brain regions indicate a possible relationship between improved
memory, attention, executive function and neuroplasticity. Given
the consistency of our findings with findings in the literature, the
likelihood of a relationship between provision of acupuncture and
cognitive therapy with improved cognition is further supported.
Future research should focus on using acupuncture with cognitive
therapy in a larger sample size and a randomized control design.
Addition of functional neuroimaging techniques measuring diffusion
tension imaging or resting state functional connectivity may also
be helpful to better understand the effect acupuncture is having on
neuroplasticity.
Sources of Support: This work was supported by a charitable
donation from the Marianjoy Russel C. Page Charitable Trust.
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