Nancy E. Schoenberger, Ph.D., Consultant, Center for Research in Complementary and Alternative Medicine, Kessler Medical Rehabilitation Research and Education Corporation, West Orange, NJ.
Samuel C. Shiflett, Ph.D., Director, Center for Research in Complementary and Alternative Medicine,
Kessler Medical Rehabilitation Research and Education Corporation, West Orange, NJ.
Len Ochs, Ph.D., President, Flexyx, LLC, Walnut Creek, CA.
Note: These were the authors’ primary affiliations at the time this
project was conducted. Dr. Shiflett is
now at the Center for Health and Healing, Beth Israel Medical Center, New York,
NY.
Participants: Twelve people aged 21 to 53 who had experienced mild to moderately severe closed head injury at least 12 months previously, and who reported substantial cognitive difficulties following injury, which interfered with their functioning.
Conclusion: Based on these results, FNS appears to be a
promising new therapy for TBI and merits more extensive evaluation.
Key
Words: brain injuries, biofeedback, neurotherapy, alternative medicine
The
authors gratefully acknowledge the invaluable feedback provided by the men and
women who participated in this study.
Their collaboration was essential to the success of the project.
This
research was supported by NIH grant U24 HD32994 from the National Center for
Complementary and Alternative Medicine (NCCAM) and the National Center for
Medical Rehabilitation Research (NCMRR).
Introduction
Traumatic
brain injuries (TBI) affect as many as 500,000 Americans each year, producing
sensory, cognitive, physical, affective and behavioral symptoms. In many cases problems are chronic and
interfere with physical, occupational, and social functioning. Rehabilitation programs provide a variety of
services, but once the acute stage has passed, it is often assumed that
restoration of brain function is not possible, so therapies focus on
compensatory strategies to address symptoms and functional problems.1 Despite gains made during rehabilitation,
many people with traumatic brain injury continue to experience symptoms that
produce chronic impairments in occupational and interpersonal functioning. This study investigated an innovative
therapy, Flexyx Neurotherapy System, which attempts to treat chronic sequalae
of TBI in order to ameliorate symptoms and improve functional outcomes and
quality of life in people with TBI.
Flexyx
Neurotherapy System (FNS) is a form of biofeedback that was developed by the
fourth author. The rationale for its
use was derived from a number of fields of study. First, it is known that cognitive problems, such as those
observed in Attention Deficit Disorder and following TBI, are often associated
with a particular electroencephalogram (EEG) pattern in which there is too much
activity in lower frequencies of the EEG (i.e. 4-8 Hz) and/or reduced activity
in higher frequencies (i.e. 12-18 Hz).2-3 Second, it has been found that reversal of this EEG pattern using
conventional EEG biofeedback is sometimes associated with improvement in
cognitive symptoms and problematic behaviors.4-6 Third, studies have revealed that rhythmic
auditory and photic stimulation can alter EEG patterns in predictable ways.7-8 Based on these observations, FNS was
designed to combine conventional EEG
biofeedback and photic stimulation in an effort to alter EEG patterns
associated with cognitive dysfunction and ultimately to improve functioning.
The
FNS equipment used in this study provides feedback in the form of subthreshhold
photic stimulation. Clients wear
glasses that have light emitting diodes (LEDs) embedded in the lenses. EEG activity is measured using standard
equipment and a single electrode, which is moved to different places on the
head during treatment. The EEG records
the amount (amplitude) of electrical activity across a range of frequencies
(1-30 Hz). During FNS, a client’s
momentary dominant, or peak, EEG frequency is measured and used to reset the
frequency at which the LEDs pulse, which in turn influences the EEG. The intensity of the feedback is set at
subthreshhold levels, and cannot be seen by the person wearing the
glasses. Low levels of stimulation are
used because many people who have experienced a head injury or other trauma to
the central nervous system cannot tolerate exposure even to dim flashing light.
Although
FNS was developed based on principles that also underlie conventional EEG
biofeedback, the two treatments are somewhat different, particularly with regard
to role of active learning and the portions of the EEG targeted for
change. During conventional EEG
biofeedback, clients learn to suppress EEG activity in certain frequency bands
and/or to increase the amplitude in other bands. Auditory or visual cues provide clients with feedback that they
have achieved the desired EEG pattern.
Generally, the goal is to increase activity in the range of 12-18 Hz,
and reduce activity in the range of 4-8 Hz.
In contrast, during FNS treatment, clients do not attempt conscious
control of EEG activity. The feedback
system produces changes in EEG patterns without clients’ effort. People with chronic symptoms following TBI
often have greater EEG amplitudes in the lower frequency (1 – 8 Hz) range. The goal of FNS is to achieve a balance of
activity across the EEG spectrum, not to exert any specific effect on higher
frequency activity.
The
beneficial effects of conventional EEG biofeedback have been supported by
empirical research. There is modest
evidence that conventional biofeedback produces improvements in disorders of
the central nervous system, including attention deficit disorder (ADD).4,6,9-11
Preliminary
work has been done using conventional EEG biofeedback with people who have
experienced a brain injury.12
An early study using alpha training with 250 people with brain injury
indicated improvement in many cases.13 Results of a case study of a
woman who was treated with 31 sessions of neurofeedback four years following a
mild brain injury indicated improvement on neuropsychological measures and a
checklist of symptoms typically reported following TBI.14 Changes in quantitative EEG (QEEG) variables
were also observed.
One
drawback with conventional EEG biofeedback as it is currently practiced is that
a large number of sessions may be required to produce the desired effects.
Studies of ADD use upwards of 40 treatment sessions that are each 45 minutes in
length.9-10 One study has
been attempted using EEG biofeedback for headache and cognitive dysfunction
following traumatic brain injury.15
While the technique was apparently helpful for some people, only 3 of 13
participants enrolled in the study completed all 30 treatment sessions, the
others discontinuing treatment after fewer than 15 sessions. In contrast, clinical reports indicate that
FNS produces changes in EEG activity and associated improvement in symptoms in
many fewer sessions than conventional EEG biofeedback, but these claims require
documentation in controlled studies.
While
the present study represents preliminary work on a specific treatment system
using EEG recording in relation to photic feedback, this paradigm is not
unique. Other investigators have used
fixed frequency photic stimulation, consisting of visible light flashes, as an
adjunct to conventional EEG biofeedback in the treatment of 32 children with
attention deficit disorder.16
Following 15 sessions of treatment during which stimulation was
gradually withdrawn, participants in the treatment group demonstrated decreased
impulsivity and improved attention, while the wait-list control group showed no
change. Another group of researchers
has developed a system of EEG-driven photic stimulation, which is different
from the Flexyx Neurotherapy System that is evaluated in this study in terms of
(1) system hardware, (2) feedback intensity, and (3) relationship between EEG
activity and feedback. This EEG-driven
photic stimulation has been used in the treatment of depressive disorders, but
no information is available regarding efficacy beyond a single case report.17
FNS
has been used clinically to treat disturbances of the central nervous system,
including TBI, autism, and ADD. Initial
indications of the efficacy of FNS have come from clinical records, but until
recently there was no experimental research.
In one clinical case series, a sample of 20 outpatients with mild to
moderately severe closed head injury were treated with FNS.18 These patients had a range of symptoms and
were, on average, 3 years post-trauma.
They were given an average of sixteen 20-minute treatment sessions, with
the number of treatments determined by the number and severity of remaining
symptoms. Nineteen of 20 patients
reported better sleep, less depression, irritability, and explosiveness, better
concentration, more energy, and better ability to understand written and verbal
information. For patients with head
injury, Ochs reported that improvement in affect was generally seen after an
average of six sessions of FNS.19
More subtle neuropsychological skill recovery (including attention,
concentration, ability to judge social cues, and academic performance) was
observed after an average of 16 sessions.18
Clinical
observations regarding the effectiveness of treatment require validation in
experimental research. This study was
designed as a preliminary evaluation of the efficacy of Flexyx Neurotherapy
System for people who have experienced a traumatic brain injury. It differs from Ochs’ clinical case series18
by comparing people who receive immediate treatment to those in a wait-list
control group, using standardized treatment procedures and outcome measures,
and applying statistical tests to evaluate efficacy. Based on previous research on EEG biofeedback and photic
stimulation and on clinical observations of the use of FNS for people with
brain injuries, it was hypothesized that (1) participants in the immediate
treatment group would demonstrate greater improvement on measures of cognitive
and emotional functioning compared to those in the wait-list control group, and
(2) these improvements would be maintained over time.
This
study received IRB approval before recruitment of participants began. Potential participants were recruited from
clients who sought treatment at the office of the third author and by informing
area neurologists and rehabilitation specialists about the project. Prior to beginning study procedures, all
participants signed an informed consent document. A structured interview and symptom checklist were administered in
order to determine whether potential participants qualified for this
study. People were excluded from the
study if they had a penetrating head injury, pre-injury substance abuse or
dependence, pre-injury diagnosis of psychotic illness, or pre- or post-injury
seizure. Women who were pregnant or
trying to become pregnant were also excluded.
Participants were 2 men and 10 women, aged 21 to 53
who had experienced mild to moderately severe closed head injury at least 12
months previously, as determined by referring professionals and medical
history. Corroborating documentation
from medical records was obtained for 9 participants. One additional participant was referred for treatment by a
neurologist. Time since injury ranged
from 36 months to 21 years. Eleven
participants were injured in motor vehicle accidents and one fell from a second
story balcony. Duration of loss of
consciousness ranged from less than one minute to 27 days. Five participants reported post-traumatic
amnesia. The injuries of most
participants were classified as mild, although there were three people with
moderately severe injuries. During the
structured interview and on the symptom checklist, all participants reported
substantial cognitive difficulties following injury, which interfered with
their functioning.
Measures
were selected to assess a range of symptoms frequently experienced following
TBI including depression, fatigue, emotional distress and cognitive
dysfunction. Specifically,
neuropsychological measures evaluated memory, attention, information
processing, verbal fluency, and integrated functions.
Individualized Symptom Rating Scale. Participants
were asked to list the 5 primary symptoms for which they were seeking treatment
and to rate the severity of each symptom over the past week using an 11 point
Likert scale. An average score was
obtained, with a range from 0-10.
Beck Depression Inventory (BDI). The BDI is a
21-item self-report scale used to assess symptoms of depression. The total score has a range from 0-63. The scale has good reliability and validity
as assessed in a number of studies.20
Multidimensional Fatigue Inventory (MFI). The MFI is a
20-item self-report measure designed to measure fatigue and covers 5
dimensions: general fatigue, physical fatigue, mental fatigue, reduced
motivation, and reduced activity. The
severity of each item is rated on a 5-point scale, and scores on each subscale
range from 4-20. The scale has adequate
internal consistency, and construct validity has been confirmed using several
different samples.21
Symptom Checklist-90-Revised (SCL-90-R). The SCL-90-R
is a 90-item self-report inventory on which respondents rate symptom severity
using 5-point scales. Nine primary
dimensions are covered, including somatization, interpersonal sensitivity, and
anxiety. The primary measure used in
this study was the Positive Symptom Distress Index (PSDI), which reflects the
intensity of symptoms that are endorsed.
Internal consistency was quite good, Cronbach’s alpha > .75 for all
scales in two studies, and validity has been supported in a number of studies.22
Auditory Verbal Learning Test (AVLT). Rey’s AVLT
assesses memory using two lists of 15 nouns.
Participants were read the first list 5 times and recall was tested
after each trial. Recall was then
tested once for a second, distractor list.
Then, immediate and 30-minute recall were assessed for the first
list. Scores range from 0-15 words for
each trial. In order to minimize
practice effects, alternate forms using different word lists were employed for
each assessment. Equivalency to the Rey
AVLT has been demonstrated for the alternate forms.23 People with head injuries tend to have
poorer than normative scores on all trials.24
Paced Auditory Serial Addition Test
(PASAT). The PASAT assesses information processing and sustained attention
using a serial addition task.
Participants listened to an audiotape that presented a list of single
digit numbers and were instructed to add the numbers in pairs, the first and
second, second and third, etc. and to give their answers aloud.25 There are four trials, with scores ranging
from 0-49, in which the digits are presented at successively faster rates of
speed. Many people with head injuries
perform below control-group averages on this test.24
Rey-Osterrieth Complex Figure. This
complex-figure task evaluates perceptual organization and visual memory in
people with head injuries.24
Participants were given up to 5 minutes to copy the figure and then were
asked to reproduce the figure after a 20-minute delay. Recall scores were used to assess visual
memory in this study, and explicit scoring criteria were used to increase
reliability.26 Points are
given for accurate recall of specific elements of the figure, and the total
score has a range from 0-36. Each
drawing was scored by two raters who were unaware of participants’ group
assignment and date of assessment, and the average score was entered in data
analyses. Inter-rater reliability was
.96.
Trail Making Test. Part B of
this test, which is included in the Halstead-Reitan battery, requires subjects
to connect randomly placed numbers and letters in alternating order using
pencil lines.24 The task
involves sustained attention, motor speed, and visuomotor tracking. The evaluator corrects errors as they occur
and time to completion is used as the score. Part A was administered first in
order to standardize administration, but scores were not analyzed.
Controlled Oral Word Association. Verbal
fluency was assessed using this measure, which is commonly known as the
F-A-S. Participants are asked to name
as many words as they can with each of these initial letters; they are allowed
60 seconds for each letter. Using
proper names or giving the same word with a different ending are not allowed. The score is the sum of all admissible
words. This test has proven a sensitive
gauge of brain injury.24
Digit Span Backwards. During this task, increasingly long lists of numbers
are read aloud, and participants must repeat each list in the reverse
order. One point is given for each correct
list. Raw scores range from 0-14. This subscale of the Wechsler Adult
Intelligence Scale-Revised (WAIS-R) was used because it is sensitive to the
effects of brain injury.24 The Digit Span Forward task was
administered first in order to standardize administration, but scores were not
analyzed.
Digit Symbol. During this
symbol substitution task, participants draw symbols in rows next to single
digit numbers based on a key that pairs a unique symbol to each number. The task involves sustained attention,
response speed, and visuomotor coordination.
One point is given for each correct symbol, and raw scores range from
0-93. This subscale of the WAIS-R is
also sensitive to the effects of brain injury.24
Following
individual pretreatment assessments, participants were randomly assigned to one
of two conditions: (1) immediate treatment or (2) wait-list control group,
which received treatment following a 6-8 week waiting period. The experimental design is depicted in
Figure 1.
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Insert Figure 1 about here
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For
purposes of statistical analysis, the experimental design is divided into two
parts. Part 1 is a classic
between-groups design with repeated assessment (before-after) including a
treatment group and a no-treatment control group. Part 2 is a within-groups longitudinal design, since both groups
have received the treatment by Time 3.
Two sets of complementary statistical analyses were conducted in order to
examine the overall pattern of findings.
Between-group analyses took advantage of the rigorous research design
using a randomized control condition, but with a small sample size, statistical
power was limited. Repeated measures
(within-group) analyses examined changes over time with the groups
combined. This provided more
statistical power by allowing participants to serve as their own controls
thereby reducing error variance.
However, these analyses do not make use of a comparison group or control
for practice effects. Since the
within-groups analyses were conducted within the context of the Part 1
between-groups design, they can be interpreted as supporting or confirming
results obtained there. At each
assessment, participants were administered the same battery of self-report
measures and neuropsychological tests.
Treatments
were administered using the J&J Enterprises I-400 EEG biofeedback system
(Poulsbo, WA). The I-400 was connected
to a Synetic Systems light generator PC board driving LED embedded glasses
(Seattle, WA), which were also linked to a 486 DX2-66 PC running proprietary
software developed by the fourth author (Flexyx, Walnut Creek, CA).
Participants
received 25 sessions of treatment administered over a 5-8 week period. Treatment
sessions were conducted by the third author at her outpatient office. During FNS treatment, participants sat
comfortably with their eyes closed, wearing the LED embedded glasses, and
engaged in no specific activity. Each
patient’s dominant EEG frequency, between 1 and 30 Hz, was extracted every 0.5
seconds and used to reset the frequency of the LEDs, which pulsed
simultaneously in front of the left and right eyes. Feedback was administered in periods of 18 seconds duration. The strobe frequency was offset from the
dominant EEG frequency in the range of +5 Hz to +20 Hz. The magnitude of the offset changed every 18
seconds, and the maximum strobe frequency was set at 30 Hz. All stimulation was minimized in brightness
to lowest available level, and participants were unable to detect the LED
output even when their eyes were open.
The
first session was an introductory session during which a single electrode was
placed at the FPZ site (the middle of the forehead between the eyes). EEG recording began with 1 minute of no
stimulation, followed by up to 4 minutes of stimulation, and a final minute
without stimulation. The subsequent few
sessions were mapping sessions during which 18 seconds of stimulation were administered
with monopolar EEG recording at each of 21 sites. This yields approximately 6 minutes of stimulation. If a movement artifact was detected, the
time at that site was repeated in order to obtain accurate data. Average amplitude and variability of the EEG
were recorded in both delta and alpha frequency bands at each site and used to
create a sort sequence from lowest amplitude and variability to highest.
During
remaining sessions, FNS treatment was administered following the delta activity
sort sequence. Each site was treated in
the following way. The reference
electrode was applied to the left earlobe, the skin was prepared, and impedance
was reduced to 3K Ohm. Then, the active
lead was applied to sites successively, as specified in the delta activity sort
sequence, and feedback was administered at each site. Although we attempted to standardize the amount of stimulation
provided during treatment sessions, the exact duration of feedback during each
session was based on participants’ reactions.
Some participants were quite sensitive to the feedback, and the duration
was reduced in these cases.
Participants’ reactions changed over the course of treatment, and
duration of feedback was modified accordingly.
Therefore, the duration of stimulation received during an individual
session ranged from 5 seconds to 20 minutes.
Four participants received feedback for an average of less than 5
minutes per session. For other
participants, feedback averaged between 10 and 15 minutes per session.
Analyses
of covariance (ANCOVAs) were conducted to compare groups after only the
immediate treatment group had received FNS treatment (see Time 2 in Figure 1),
while controlling for baseline differences.
Group means and standard deviations are found in Table 1. Because this was the first controlled
evaluation of FNS, we did not want possible effects of treatment to go
unnoticed. Therefore, alpha was set at
.05 and was not adjusted for multiple tests.
For the self-report measures, four ANCOVAs were conducted initially. The treatment group was significantly
improved compared to the control group on the individualized rating scale (F=12.38,
p<.01), and the Beck Depression Inventory (F=10.01, p<.02). Between-group differences were not
significant for the total score on the Multidimensional Fatigue Inventory (p<.09),
or the Positive Symptom Distress Index of the SCL-90 (p<.19). However, the MFI was designed with 5
independent subscales, which we analyzed separately to determine if there were
between-group differences only for some of them. The treatment group was significantly improved compared to the
control group on the General Fatigue (F=8.04, p<.02), and
Mental Fatigue (F=9.10, p<.02) subscales. No significant differences were noted for
Physical Fatigue (p<.13), Reduced Activity (p<.64), or
Reduced Motivation (p<.20).
--------------------------------------------
Insert Table 1 about here
--------------------------------------------
Similar
ANCOVAs were conducted for the neuropsychological measures. The treatment group was significantly
improved compared to the control group on Digit Span Backwards (F=5.37, p<.05),
the interference trial (F=5.54, p<.05), and the delayed recall
trial (F=7.47, p<.03) of the AVLT, and the most difficult
trial of the PASAT (F=8.08, p<.02). In addition, the results approached significance for Digit Symbol
(F=3.64, p<.09) and the first immediate recall trial of the AVLT (F=4.52, p<.07).
Repeated
measures analyses of variance were used to examine changes over time. Data were used from three assessments:
pre-treatment (just prior to treatment), post-treatment (just following
treatment), and follow-up (the next subsequent assessment). The two groups (immediate treatment and
delayed treatment control) were combined for these analyses, because all
participants had received treatment before the third assessment. Means and standard deviations are found in
Table 2.
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Insert Table 2 about here
--------------------------------------------
ANOVAs
showed significant improvement over time for each self-report measure except
the reduced activity and reduced motivation subscales of the Fatigue Inventory,
which were less problematic for participants.
Even prior to treatment, they remained motivated to participate in
activities, despite their fatigue.
Among the fatigue subscales, participants reported the greatest
improvement in their mental fatigue.
Most neuropsychological measures showed significant improvement over
time.
If
the repeated measures ANOVA was statistically significant for a measure
(p<.05), then the within-subjects contrasts were examined to determine when
changes occurred. Of particular
interest were the hypotheses that improvement would occur following treatment
and be maintained at follow-up assessment.
Significant improvement was observed following treatment for almost all
self-report measures, including the Fatigue Inventory total score and the
Positive Symptom Distress Index, for which the differences between the immediate
treatment and delayed treatment groups failed to reach significance. Results for the Fatigue Inventory subscales
confirmed the results of the between-groups analyses. For the neuropsychological measures, there was significant change
from pre-treatment to post-treatment for Digit Span Backwards (p<.01),
Digit Symbol (p<.05), and the first (p<.05), third (p<.01), and
fourth (p<.001) trials of the PASAT.
Overall, these findings support and extend the results of the
between-groups analyses. Treatment
gains were maintained from post-treatment to follow-up, and in some cases
further improvement was observed.
Participants reported even less emotional distress at follow-up on the
Positive Distress Symptom Index (p<.05). Performance improved on a number of neuropsychological measures,
and many scores were significantly
better at follow-up than pre-treatment (see means in Table 2). Thus, participants did not experience a reversal
of symptoms following the end of treatment, and continued improvement was observed
for some measures.
Table
3 presents a summary of outcomes and selected participant characteristics. Four of the participants had been through
extensive rehabilitation programs, three of them as inpatients. Prior to treatment, all 12 participants
reported difficulty with their ability to work or complete academic
courses. Following treatment, 7 of them
were able to work professionally or engage in full academic work. Two other participants reported improvement
in some areas following FNS treatment.
Three people did not respond to the treatment. Three participants had very low amplitude resting EEGs, including
two of the three who did not report much improvement. Clinical experience suggests that people with severely low amplitude
EEG require a different treatment protocol than was used in this study.
With treatment, 2 of 8 participants who had been taking medications were able to reduce the dosage for these prescriptions and 3 were able to eliminate them entirely. Three had no change and 4 were not taking medication. For 15 years, one person had required large doses of pain medications as well as weekly walk-in clinic or emergency room visits to manage post-traumatic migraine headaches. After 9 treatments, the headaches were gone, pain medications were greatly reduced and mild headaches, which were responsive to over-the-counter medication, subsequently recurred less than once a month. One person with post-traumatic fibromyalgia substantially reduced medication by the end of treatment. After eighteen months, she still required only low doses of medication and was working full-time.
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Insert Table 3 about here
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FNS
is generally safe, however, the most common side effect experienced during
treatment was a temporary intensification of symptoms that had previously been
problematic. Many of the participants
experienced again symptoms that had occurred at the time of the TBI. Symptoms included pressure in the head or
headache (3 people), dizziness (4 people), nausea (1 person), tingling
sensation (1 person) or physical pain associated with broken bones or other
injuries occurring at the time of the accident (2 people). Such reactions usually occurred within the
first 6 or 7 sessions and typically resolved within a few days. Adverse reactions may also be caused by
over-treatment. At each session, participants
were asked about their reactions to treatment in order to determine the length
of the next treatment session. Fatigue
(3 people) and restlessness (1 person) were the most common indications of
over-treatment and session length was reduced accordingly. Following treatment, one person reported
unexplained hair loss.
The
overall pattern of results from this preliminary investigation strongly
suggests that Flexyx Neurotherapy System (FNS) may be an efficacious treatment
for people who have experienced a traumatic brain injury. Compared to a wait-list control group, FNS
treatment produced significant improvement in depression and a range of other
symptoms reported by participants as most problematic. Treatment also produced significant
improvement on some measures of cognitive functioning, specifically those
involving working memory, immediate memory of new material, and retention of
information. Results for other measures
also indicated improvement, but failed to reach statistical significance. Longitudinal analyses of all participants
receiving treatment supported and extended these findings. With the added statistical power afforded by
repeated-measures analyses, significant improvement was observed for additional
self-report and cognitive measures.
Follow-up assessments showed clearly that improvements were maintained
following the end of treatment.
Although there were not any substantial delayed effects of treatment,
some small continued improvements were noted.
The
lack of significant findings for some measures suggests several
possibilities. First, if the effect
size is smaller for these measures, this sample may have been too small to
detect the effect of treatment. This
possibility is supported by the observation that a greater number of measures
achieved statistically significant results when analyses with more statistical
power (e.g. repeated-measures analyses) were used. Second, some of the neuropsycholgical tests used may not have
been sensitive enough to detect changes experienced by study participants. Specifically, measures often fail to capture
the complexity of a real-world environment that places multiple simultaneous
demands on cognitive processing. Third,
FNS treatment may be more effective for treating some symptoms than others. Fourth, practice effects on some
neuropsychological measures may have been strong enough to obscure improvement
produced by treatment. Fifth,
variability in location and severity of damage to the brain may have obscured
improvement as measured by average group scores, because changes were
experienced by only some of the participants.
Efforts
were made to reduce practice effects that result from multiple exposure to the
same content. Alternate word lists were
used for the AVLT. Sequences in digit
span backwards and digit symbol cannot be memorized. However, practice effects still occur from increased familiarity
with the process of each test. People
develop better strategies for handling these tasks, particularly the
participants in this study who generally had a high level of functioning prior
to their injuries. Therefore,
improvement in scores on neuropsychological measures may be due to repeated
exposure to tests rather than effects of treatment. This is a difficult issue that impacts any research in which
multiple assessments are required. In
this study, the results of the within-groups analyses must be considered in the
context of the between-groups design, which controls for practice effects by
including a wait-list control group.
Because
this study was among the first experimental examinations of the effects of FNS,
we did not want to overlook any potential benefits of treatment. Therefore, given the small sample size,
alpha level was not adjusted for multiple statistical comparisons. Nonetheless, the number of findings that
reached statistical significance was greater that would be expected by chance.
The
research design used in this study does not eliminate the possibility that
participants improved simply because they believed that action was being taken
to help them, rather than as a result of the specific treatment
administered. This phenomenon of
positive response to an intervention regardless of its content has been termed
the Hawthorne effect, and was first described in studies with non-injured
people performing repetitive low-skill tasks.
The Hawthorne effect is almost certainly a minor explanatory factor in
this study, however, because simple attention is unlikely to have a substantial
long term effect on individuals who have experienced brain injuries and who
have reached a stable performance plateau after receiving prior medical
treatment and rehabilitation. Many of
these participants experienced improvement with FNS after other interventions
had failed to benefit them.
Nonetheless, a placebo control group or a control group involving irrelevant
attention will eventually be needed to completely eliminate attention as an
explanatory cause of improvement, and should be included in future research on
FNS.
It
is important to note that clinical observations made by participants and
therapist during the course of the study indicated that meaningful change
occurred in many areas. Several
participants were able to return to work or academic study following
treatment. Generally, reports indicated
improvements in quality of life, some of which were profound. However, there were three people (25%) for
whom improvement was minimal. Clinical
efforts are already underway to identify those people who may require a
different FNS treatment protocol, or for whom FNS may not be appropriate.
Taken
as a whole, the findings of this study are strong enough to identify FNS as a
promising new treatment for traumatic brain injury, which merits further
evaluation. The mechanism of action is
unclear, but other research suggests that normalizing EEG activity is associated
with benefits in cognitive and behavioral functioning.3,12 Subsequent studies should use a larger
sample and a more comprehensive assessment battery that includes quantitative
EEG as an objective measure of change in addition to cognitive and functional
measures. A more homogeneous group of
people with regard to severity of injury, time since injury, and presenting
problems would also be beneficial.
Recently developed improvements in FNS technology will also enable the
use of a double-blind procedure with a placebo control group, which will
increase the quality of subsequent research.
Such research will provide a clearer picture of the benefits of FNS in
the treatment of traumatic brain injury and help determine which symptoms are
most responsive to FNS and what circumstances optimize treatment outcome.
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adults. In: Deelman BG, Saan RJ, van
Zomeren AH, editors. Traumatic brain
injury: clinical, social and rehabilitation aspects. Amsterdam: Swets &
Zeitlinger. P. 121-143.
2. Lubar JF. Discourse on the development of EEG diagnostics and
biofeedback for attention-deficit/hyperactivity disorders. Biofeedback
Self Regul.
1991;16:201-225.
3. Thatcher RW, Walker RA, Gerson I, Geisler F. EEG discriminant
analyses of mild head trauma. Electroencephalogr.
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Table 1
|
|
Immediate Treatment Group |
Delayed Treatment Control Group |
|
||||
|
|
Time 1 |
Time 2 |
Time 1 |
Time 2 |
|
||
|
Measure |
Mean (SD) |
Mean (SD) |
Mean (SD) |
Mean (SD) |
F |
||
|
Symptom average |
8.47 (1.31) |
3.80 (2.38) |
8.49 (0.91) |
7.62 (0.96) |
12.38** |
||
|
Beck Depression |
22.50 (9.89) |
7.00 (5.25) |
16.67 (9.81) |
16.17 (12.19) |
10.01* |
||
|
Fatigue Inventory Total |
74.83 (20.43) |
48.50 (20.89) |
61.50 (18.85) |
61.33 (20.58) |
3.68† |
||
|
General Fatigue |
17.17 (4.02) |
9.83 (4.83) |
14.83 (4.17) |
14.00 (4.56) |
8.04* |
||
|
Physical Fatigue |
16.00 (6.23) |
10.00 (3.52) |
10.50 (4.51) |
10.83 (5.34) |
2.88 |
||
|
Reduced Activity |
14.33 (5.57) |
11.33 (5.35) |
10.67 (4.68) |
10.83 (4.96) |
0.24 |
||
|
Reduced Motivation |
10.17 (4.75) |
7.00 (2.83) |
10.00 (3.90) |
10.00 (4.86) |
1.99 |
||
|
Mental Fatigue |
17.17 (3.31) |
10.33 (6.31) |
15.50 (3.83) |
15.67 (3.50) |
9.10* |
||
|
PSDI |
2.42 (0.58) |
1.65 (0.24) |
1.96 (0.29) |
1.82 (0.40) |
2.04 |
||
|
AVLT trial 1 |
6.83 (2.64) |
8.17 (1.94) |
5.17 (1.72) |
5.33 (1.63) |
4.52† |
||
|
AVLT trial 2 |
10.17 (3.19) |
10.50 (2.26) |
8.33 (1.75) |
8.17 (2.32) |
1.54 |
||
|
AVLT trial 3 |
11.50 (1.38) |
12.00 (2.10) |
10.67 (1.21) |
10.33 (2.07) |
1.40 |
||
|
AVLT trial 4 |
11.50 (2.74) |
13.17 (0.98) |
12.00 (1.41) |
11.33 (2.16) |
3.04 |
||
|
AVLT trial 5 |
12.17 (2.40) |
13.50 (1.22) |
11.67 (1.21) |
11.67 (1.97) |
3.26 |
||
|
AVLT list B |
5.83 (2.23) |
7.17 (1.72) |
4.83 (2.48) |
5.33 (0.52) |
5.54* |
||
|
AVLT immediate recall |
11.00 (1.79) |
11.00 (1.67) |
8.50 (1.87) |
10.00 (2.45) |
1.29 |
||
|
AVLT delayed recall |
10.33 (2.94) |
12.00 (1.79) |
9.00 (1.26) |
9.00 (1.67) |
7.47* |
||
Measure
|
Immediate Treatment Group |
Delayed Treatment
Control Group
|
|
||||
|
|
Time 1
|
Time 2 |
Time 1 |
Time 2
|
|
||
|
|
Mean (SD)
|
Mean (SD) |
Mean (SD) |
Mean (SD) |
F |
||
|
PASAT trial 1 |
25.00 (6.54) |
36.17 (11.09) |
27.17 (5.56) |
33.50 (8.69) |
0.45 |
||
|
PASAT trial 2 |
26.67 (6.09) |
32.83 (8.04) |
23.50 (6.44) |
29.00 (6.03) |
0.94 |
||
|
PASSAT trial 3 |
21.83 (6.49) |
28.67 (6.12) |
17.67 (6.71) |
25.17 (10.30) |
0.01 |
||
|
PASAT trial 4 |
15.83 (4.40) |
24.50 (7.64) |
17.33 (3.56) |
18.17 (8.86) |
8.08* |
||
|
Trails B (in seconds) |
78.17 (15.69) |
70.83 (32.71) |
79.00 (16.73) |
71.00 (31.83) |
0.01 |
||
|
Rey figure recall |
13.79 (3.53) |
17.75 (4.13) |
16.50 (4.80) |
18.75 (5.20) |
1.45 |
||
|
F-A-S total |
37.67 (15.19) |
44.33 (13.09) |
29.83 (8.77) |
32.83 (8.08) |
2.95 |
||
|
Digit Span Backward |
6.00 (0.89) |
8.17 (2.14) |
5.83 (1.72) |
5.67 (1.37) |
5.37* |
||
|
Digit Symbol |
50.00 (6.96) |
61.67 (13.02) |
54.67 (14.04) |
53.50 (12.28) |
3.64† |
||
Note:
PSDI = Positive Symptom Distress Index from the Symptom Checklist 90 – Revised;
AVLT = Auditory Verbal Learning Test; PASAT = Paced Auditory Serial Addition
Test
†p<.10; * p<.05; **p<.01
|
|
Pre-treatment
|
Post-treatment |
3-Month Follow-Up |
|
|
Measure |
Mean (SD) |
Mean (SD) |
Mean (SD) |
F
|
|
Symptom Average |
a8.04 (1.18) |
b3.65 (2.04) |
b3.67 (1.86) |
34.42*** |
|
Beck Depression |
a19.33 (11.09) |
b7.92 (6.91) |
b7.83 (6.74) |
18.29*** |
|
Fatigue Inventory Total |
a68.08 (20.78) |
b50.08 (19.01) |
b47.33 (20.03) |
8.43** |
|
General Fatigue |
a15.58 (4.42) |
b11.17 (4.76) |
b10.45 (5.05) |
6.50** |
|
Physical Fatigue |
a13.42 (6.16) |
a9.83 (3.33) |
a9.27 (4.89) |
4.02* |
|
Reduced Activity |
12.58 (5.35) |
10.08 (4.80) |
8.00 (4.20) |
3.48† |
|
Reduced Motivation |
10.08 (4.58) |
8.00 (3.64) |
7.73 (4.43) |
2.72 |
|
Mental Fatigue |
a16.42 (3.34) |
b11.00 (4.94) |
b10.73 (4.36) |
14.68*** |
|
PSDI |
a2.12 (0.57) |
b1.53 (0.38) |
c1.37 (0.35) |
18.83*** |
|
AVLT trial 1 |
a6.08 (2.23) |
b7.08 (1.93) |
7.33 (2.06) |
3.19† |
|
AVLT trial 2 |
9.17 (2.86) |
10.25 (2.05) |
10.50 (3.00) |
1.66 |
|
AVLT trial 3 |
a10.92 (1.78) |
ab11.83 (1.90) |
b12.58 (2.19) |
4.32* |
|
AVLT trial 4 |
a11.42 (2.35) |
ab12.50 (1.31) |
b13.42 (1.88) |
3.93* |
|
AVLT trial 5 |
11.92 (2.11) |
12.33 (2.50) |
13.17 (1.85) |
1.68 |
|
AVLT list B |
5.58 (1.56) |
6.50 (2.20) |
6.83 (1.70) |
2.97† |
|
AVLT immediate recall |
10.50 (2.11) |
10.17 (1.90) |
12.25 (2.80) |
3.26† |
|
AVLT delayed recall |
9.67 (2.39) |
11.08 (2.54) |
12.00 (2.86) |
3.42† |
|
PASAT trial 1 |
a29.25 (8.57) |
b36.42 (8.99) |
b40.42 (6.01) |
13.97*** |
|
PASAT trial 2 |
a27.83 (5.91) |
a31.67 (9.13) |
b37.08 (8.76) |
12.06*** |
|
|
Pre-treatment
|
Post-treatment |
3-Month Follow-Up |
|
|
Measure |
Mean (SD) |
Mean (SD) |
Mean (SD) |
F
|
|
PASAT trial 3 |
a23.50 (8.39) |
b29.00 (8.02) |
c32.75 (9.07) |
18.48*** |
|
PASAT trial 4 |
a17.00 (6.78) |
b23.75 (8.36) |
b27.00 (8.95) |
13.75*** |
|
Trails B (in seconds) |
a74.58 (24.22) |
ab67.17 (26.68) |
b59.92 (20.67) |
3.77* |
|
Rey figure recall |
a16.27 (4.97) |
ab17.50 (6.39) |
b19.02 (6.92) |
3.43* |
|
F-A-S total |
a35.25 (11.87) |
ab38.83 (11.68) |
b40.50 (11.37) |
3.45* |
|
Digit Span Backward |
a5.83 (1.11) |
b7.33 (2.19) |
b7.75 (2.34) |
5.80** |
|
Digit Symbol |
a51.75 (9.69) |
b59.00 (11.29) |
b61.16 (11.62) |
6.93** |
Note: PSDI = Positive Symptom Distress Index from the
Symptom Checklist 90 – Revised; AVLT = Auditory Verbal Learning Test; PASAT =
Paced Auditory Serial Addition Test
†p<.10; *p<.05; **p<.01; ***p<.001
a Means with different subscripts differ significantly
from each other (p<.05).
|
ID |
Time Since Injury (yrs.) |
Severity of Injury |
Very Low Amplitude EEG |
Change in Medication |
Functional Outcome |
|
1 |
9.5 |
Mild |
No
|
Eliminated |
From working part-time with great effort to working full-time. Adult child with M.D. reported return to pre-injury functioning. |
|
2 |
7.5 |
Moderate |
No |
Eliminated |
Able to complete post-graduate courses with less effort. |
|
3 |
5.5 |
Moderate |
Yes |
Not Taking |
Little change. Did report improvement in spatial orientation, and was therefore able to travel by subway and car without getting lost. |
|
4 |
3.0 |
Mild |
Yes |
Not Taking |
From working in low-skill job to seeking position in pre-injury field of employment. |
|
5 |
15.0 |
Mild |
No |
Decreased |
From no
employment to working full-time.
|
|
6 |
9.0 |
Mild |
No |
Not Taking |
From no employment to working full-time with good reviews of job performance. Better social relationships due to decreased irritability. |
|
7 |
21.0 |
Moderate |
No |
Eliminated |
Able to complete tasks of daily living and to participate in other activities due to reductions in pain and fatigue. |
|
8 |
7.0 |
Mild |
No |
Decreased |
Taking required courses in preparation for return to work in professional field. |
|
9 |
3.5 |
Mild |
No |
No Change |
Little change. |
|
10 |
3.0 |
Mild |
Yes |
No Change |
Temporary improvement that did not persist. |
|
11 |
5.5 |
Mild |
No |
No Change |
Reduced anxiety / panic attacks. Little cognitive change. |
|
12 |
3.0 |
Mild |
No |
Not Taking |
From taking few college courses and getting low grades to making the Dean’s list (3.5 grade point average with full course load). Better social relationships due to decreased irritability. |