1. New Strategies to Improve
Outcomes and Quality of
Life After a Concussion
Dr. Mark D. Allen, PhD and Dr. Alina K. Fong, PhD

2. Short Term Symptoms 0-9 Days
• Lightheadedness
• Headaches
• Cognitive and Memory Dysfunction
• Difficulty Concentrating
• Personality Changes
• Sleep Disturbances
• Emotional Disturbances
• Seizures
Long Term Effects Months to Years
• Personality Change (abrupt, argumentative,
stubborn, opinionated, or suspicious)
• Irritability, Anxiety, and Depression
• Intolerant of Noise, Emotional Excitement,
and Crowds
• Cognitive Decline
• Impaired Memory and Concentration
• Fatigue and Disruption of Sleep Patterns
• 15-20% of those injured develop symptoms
meeting criteria for psychiatric disease
(PTSD, anxiety, panic disorder, and
depression).
Symptoms Alone Are Confusing…
Copyright by Cognitive FX 2017 ©

3. • Current treatment guidelines for mild traumatic brain
injury (mTBI) center on limiting physical and cognitive
activity while limiting exposure to symptom-aggravating
stimuli until it is deemed that the patient has returned to
normal function.
• Pharmacotherapy for psychiatric and neuromuscular
symptoms (Anti-epileptics, anti-depressants, anti-
psychotics, pain medication)
• While this treatment is helping in some aspects is there
an underlying pathology that is not being addressed?
Current Treatment
Copyright by Cognitive FX 2017 ©

4. • Limited reliable, objective assessment of concussion and effective
means of identifying the extent of resulting physiological changes.
• Evaluation and delineation between PCS and independent
psychological conditions.
• Effective treatment for persistent post-concussion symptoms that do
not resolved with current guidelines of rest.
• Pharmacotherapy that can potentially precipitate and aggravate PCS
psychomotor symptomatology.
Current Limitations
Copyright by Cognitive FX 2017 ©

5. • To function, the brain must distribute and
regulate blood flow to different regions for
optimal performance – we call this
Neurovascular Coupling (NVC).
• Feed forward system1
• Anticipates increased metabolic demand
• Direct neuronal control over vessels
• Neural activation tightly controls microvascular
tone
• Neural signaling itself provides its own precise
blood-flow management system throughout
brain2
Neurovascular Coupling (NVC):
The Root Cause
Copyright by Cognitive FX 2017 ©

6. • In the healthy brain NVC is highly reliable
• Metabolic (O2) needs of neurons are
consistently met
• When NVC is compromised, even slightly, brain
function becomes noticeably compromised
• Concussions can alter the efficiency of NVC and
limit cerebral function by changing neuron
metabolism through hyper- or hypo-activation.
• NVC dysfunction caused by trauma alters
distribution and regulation of blood flow that
results in impaired neuronal metabolism.
NVC Dysfunction in PCS
Copyright by Cognitive FX 2017 ©

7. Restoration of NVC
• Standard PCS treatments often facilitate structural
repair, but can be ineffective for reestablishing
coupling.
• For NVC restoration, a unique approach is needed
to promote vascular responsivity and neurogenic
vasoactive signaling.
• Under the current treatment standards the
neurons, vasculature, and microglial cells will
structurally repair but not reestablish coupling.
• For NVC restoration, the brain must be retrained to
optimize and allocate the appropriate blood flow
to different cerebral areas. Copyright by Cognitive FX 2017 ©

8. Concussions Have Fooled
Even the Best of Us…
Q: Most Neuropsychologists giving standardized paper/pencil batteries have
misdiagnosed their patients based solely on the outcome of these tests.
Why?
A: A concussion doesn’t affect whether you get a question right or wrong. In
fact, most mTBIs will do exceptionally well on these tests.
However, a concussion takes a toll on how efficiently the brain is working to
get the right answer.
IN SUMMARY: fMRI is not concerned with right or wrong, but, rather, what it
is COSTING your brain to get the right answer.

9. When solving this
problem
are we measuring
what it costs the brain
to find the answer?
OR
Are we simply measuring
If we can get the
correct answer?

11. Mac Donald et al JAMA
Neurology, 2017
Fool Me Twice – Shame On Me

12. As a first-order measure of NVC, fMRI is poised as ideal
imaging tool for PCS to:
1. Diagnose and quantify severity
2. Guide treatment
3. Assess outcomes
Developing a Clinically Appropriate
form of fMRI to Assess NVC
Copyright by Cognitive FX 2017 ©

13. • However, to actually become THE ideal tool for PCS, fMRI
requires:
• A normative reference atlas
• Biomarkers for PCS with good diagnostic predictive values
(sensitivity/specificity)
• fNCI is a standardized form of task-related BOLD imaging that
meets the above requirements
Functional Neurocognitive
Imaging (fNCI)
Copyright by Cognitive FX 2017 ©

14. fNCI Standardized Test Battery3
• fNCI is a specialized fMRI
testing and norming system
that includes a set of 6
standardized neurocognitive
tests2
• Stimulus materials and timings
refined to elicit maximum
BOLD signal
1. Iterative pilot testing and
protocol refinement
2. Retest stability validation
3. Cross-scanner stability testing

15. Individual patient activation values contextualized within normal curve of age-
matched healthy control sample for 60 functional brain regions
fNCI Normative Reference Atlas3

16. • Five independent patterns of abnormal activation were identified in
an initial sample of 69 concussion patients
• Validation, replication, and differential analyses were performed using
additional samples of 70 and 120 patients, as well as 62 healthy
subjects and 27 non-concussed patients.
• High sensitivity and specificity values were observed for the 5
biomarkers (79-99%)
fNCI Concussion Biomarkers
Copyright by Cognitive FX 2017 ©

17. • Functional Localization
• Assessment of NVC at a cognitive systems level provides targeted
treatment for rehabilitation therapies
• Severity Index Score (SIS)
• Summary score based total biomarker levels present in patient
• SIS used before, during, and after treatment to evaluate treatment
effectiveness, and document recovery stability over time with
follow-up scans
fNCI Metrics for Treatment
Planning and Outcome Assessment
Copyright by Cognitive FX 2017 ©

18. Chances of Having a Biomarker
with a Non-Injured Brain

19. fNCI Conclusions
•fNCI provides reliable measurement of NVC allowing for
identification of concussion pathology
•fNCI guides targeted treatment designed to restore normal
NVC function in chronic PCS
•fNCI derived biomarkers allow assessment of treatment
effectiveness and long-term post-treatment NVC stability
Copyright by Cognitive FX 2017 ©

20. Multi-Disciplinary Team
Treatment Focus
Copyright by Cognitive FX 2017 ©

21. Before EPIC Treatment After EPIC Treatment
Before and After EPIC Treatment
Copyright by Cognitive FX 2017 ©

22. • 90% of patients self-report significant symptom
improvement in the first few days of treatment
• Scan results confirm subjective reports. 50% of
patients show at least 74% improvement and 90% of
patients show at least 50% improvement by the end
of treatment.
Short-Term Results
Copyright by Cognitive FX 2017 ©

23. Retest Comparisons for No-Treatment
Patients and Healthy Controls
• 27/270 PCS patients randomly
selected to compare with 27
patients with no NVC focused
treatment and 13 healthy controls
• Patients with no NVC treatment
show random change in SIS at Scan 2
• Healthy controls remain within
normal limits at both scan times and
show high retest reliability (r = .87)

24. Long Term Results – 9 to 18
Months Post-Treatment
• NVC gains are maintained and
continue to improve with at-
home therapies (n=17)
• Scan 1 – Scan 2 Interval = 5 days
• Scan 2 – Follow-Up Interval =
9-18 Months
Copyright by Cognitive FX 2017 ©

25. What About Gender
Differences?
• Based on recent research there is a higher risk factor for girls being
injured than boys.
• We see this in sports – Treat more girls than boys for sports related
injuries?
• Because we don’t use a blanket cookie cutter approach, gender does
not influence outcomes. Our treatment is based on individual
functionality and restoration of functionality. Each treatment is
unique on a scientific level. Each patient regardless of gender is
treated differently.
Copyright by Cognitive FX 2017 ©

26. • Targeted treatments accelerate recovery.
• Return to daily activity more quickly and with confidence.
• Patients will feel less pressure to hide injury.
• Patients can provide evidence of injury and recovery.
• Patients will feel protected knowing their health and information is more in their control.
• CFX program gives patients of any age the same opportunities for rehab and improvement.
• Patients can get baselines and track their own brain function over the course of their career
and life.
Overall Benefits of fNCI and
EPIC Treatment
Copyright by Cognitive FX 2017 ©

27. Recent Publications
Read Our Past Publications at www.cognitivefxusa.com/technical-reports

28. Questions?

29. 1. Attwell, D., Buchan, A. M., Charpak, S., Lauritzen, M., MacVicar, B. A., & Newman, E. A. (2010). Glial and
neuronal control of brain blood flow. Nature, 468(7321), 232–243.
2. Ellis, M. J., Ryner, L. N., Sobczyk, O., Fierstra, J., Mikulis, D. J., Fisher, J. A., … Mutch, W. A. C. (2016).
Neuroimaging Assessment of Cerebrovascular Reactivity in Concussion: Current Concepts, Methodological
Considerations, and Review of the Literature. Frontiers in Neurology, 7, 61.
3. Allen, M. D., & Fong, A. K. (2008). Clinical application of standardized cognitive assessment using fMRI. I.
Matrix reasoning. Behavioural neurology, 20(3-4), 127-140.
References