Grant Proposal – Peer Reviews Only can pay $15.00

PSY 625 Biological Bases of Behavior

Dr. Nikola Lucas

September 10, 2018

Structural and Neuronal Plasticity

Specific Aims

Neural plasticity has been a topic of interest among neuroscientists for several decades. With the advent of more complex and detailed imaging techniques, such as diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), researchers are able to identify specific brain regions and neural pathways that are affected by traumatic brain injuries. For example, Yuan, Treble-Barna, Sohlberg, Harn, and Wade (2017) utilized DTI to demonstrate the activation of novel neural networks in children who had suffered a traumatic brain injury. The ability of the developing brain and central nervous system (CNS) of young children to circumvent damaged areas or reroute neural networks may lead to more effective rehabilitation programs and lessen the long-term impact of traumatic brain injuries. The severity of the injury however, remains a significant obstacle in the development of these programs, as those who suffer the most severe injuries experience not only the most profound long-term effects, but are less likely to be able to overcome the deficits incurred as a result of the injury (Beauchamp, Catroppa, Godfrey, Morse, Rosenfeld, & Anderson, 2011).

The specific aim of the current proposal is to investigate the manner in which neural networks may reroute as a result of a traumatic brain injury occurring during childhood. This longitudinal study will follow children who have suffered a traumatic brain injury throughout their pre-adolescent years and utilize imaging techniques to map the neural pathways associated with academic performance and behavior. Participants will be provided a number of cognitive intervention programs to determine the effects of these programs on the attributes of interest.

It is hypothesized that children who experience traumatic brain injuries (TBIs) will be at an increased risk for developing behavioral disorders, axons within the brain will mitigate a portion of the damage from the TBI to compensate for recovery of cognitive function through neural plasticity (though, not fully alleviated), and children who suffer a TBI will exhibit poorer performance than control participants in measures of academic success.

Background

Modern behavioral neuroscience, the study of how the brain and its structures affect behavior, was born more than a century ago with the case of Phineas Gage (Bhaskara, 2016). After a railroad accident caused severe damage to Gage’s temporal lobe, his behavior and personality were drastically altered. Since that time, the brain has been examined in relations to plethora behavioral disorders, such as attention deficit disorder. Children who suffer traumatic brain injuries (TBIs) are frequently the participants in research that examines neuronal plasticity due to their underdeveloped brain. Similar to the case of Gage, in which impulse control and self-regulation were negatively affected by the damage to the temporal lobe, Catroppa and Anderson (2009) have identified brain regions that are responsible for deficiencies in a number of developmental domains. One of the most exciting findings in this research was the manner in which the brain compensates for damage to some areas by rerouting axons around damaged areas—a process known as neuronal plasticity. Individuals who have suffered brain injuries that have compromised normal functioning may be able to return to near pre-accident functioning [see also Beauchamp, Catroppa, Godfrey, Morse, Rosenfeld, & Anderson (2011) for a discussion of executive functioning; Froudist-Walsh, López-Barroso, José Torres-Prioris, Croxson, & Berthier (2018) for working memory; and Gerrard-Morris, Taylor, Yeates, Chertkoff Walz, Stancin, Minich, & Wade (2010) and Nadebaum, Anderson, and Catroppa (2007) for cognitive development in children].

The extent to which the brain may recover, however, is limited by the amount of damage and the age at which the injury occurs. Macmillan and Lena (2010) reported that Gage, a middle-aged man, was unable to recover full neurological functioning as a result of the injury he sustained. Prior to the accident, it was reported Gage exhibited behavior congruent with social standards of the day, but, after the accident, exhibited inappropriate behavior (Macmillan & Lena, 2010). In contrast to accidents that occur later in life, such as with Gage, the brains of children who suffer TBIs are more likely to exhibit plasticity, as the brain of a child remains underdeveloped until the beginning of the second decade of life. Young children who suffer TBIs have an improved prognosis for recovery. Krasovsky and colleagues (2017) and Thompson et al. (2009) reported on case studies on an 11-year-old who overcame a brain injury that resulted in a severe motor deficit and a 7-year-old who was left with cognitive deficits, respectively. In both cases, the brain of each child circumvented damaged areas of the brain to resume near-normal functioning after several years. Additionally, treatment programs that utilize a variety of interventions can alleviate symptoms associated with brain injuries.

One of the most significant factors in overcoming a TBI appears to be the home environment. Glenn, Demir-Lira, Gibson, Congdon, and Levine (2018), as well as Giza, Kolb Harris Asarnow, and Prins (2009), found nurturing and stimulating home environments to be rather conducive for overcoming a TBI. Family members engaged the child in a variety of cognitive exercises to assist the brain in creating new neural networks to compensate for the injury. Furthermore, programs have been developed to further assist families and children. Yuan, Treble-Barna, Sohlberg, Harn, and Wade (2017) found the Attention Improvement and Management (AIM) program to be beneficial in improving the structural connectivity of white matter within the brain. Furthermore, other treatment programs focused on specific skills, such as social skills training (Dahlberg et al., 2007), multidimensional physical therapy (Sartor-Glittenberg & Brickner, 2014), and cognitive-process training (Walter, Dickstein, Barnes, & Chard, 2014) have shown some promise in assisting individuals overcome TBIs. Dennis and colleagues (2014), however, reported that determining the efficacy of intervention programs depends on when assessments are conducted. Numerous factors, such as the home environment, the timing of the assessment, and the type of assessment, may compromise the validity of the chose instrument. Therefore, it is imperative that when assessing children who have suffered a TBI that all factors relevant to the child are considered.

Significance

The current proposal will utilize magnetic resonance imaging (MRI) technologies, such functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), to explore the neural networks and pathways present in the brains of children who have experienced a traumatic brain injury and subsequent behavioral disorders (e.g. attention deficit disorder, oppositional defiant disorder, etc.) that may be related to the injury. While the locations and functions of brain structures have been known for some time, the use of imaging technologies will indicate the brain regions being activated (MRI and fMRI) and the pathways within the central nervous system (CNS) upon which action potentials travel (DTI). Furthermore, mapping of these pathways may produce new interventions as the brain structures and alternate neural pathways can then be correlated to design person-specific treatment options that take advantage of neuronal plasticity.

The imaging technologies utilized during the research will allow not only neurologists to map the neural networks activated in the brains of children who have suffered traumatic brain injuries, but will also provide further evidence of neuronal plasticity. By comparing the activation sequences/regions of these neural networks in healthy control group participants and children who have suffered a brain injury (images from initial injury and six-month intervals post-injury), the manner in which neurons engage in self-correction by circumventing damaged areas may become more evident, thus allowing the medical community a deeper understanding of brain function.

Proposed Study

Participants:

The proposed study will utilize 10 normally-functioning children between the ages of four and six years who have not suffered a traumatic brain injury (TBI) during their lifetime. These 10 children will serve as the control group. The experimental group will consist of children who have suffered a mild TBI, were evaluated in a local emergency room, and underwent subsequent magnetic resonance imaging (MRI) scans to determine the extent of the injury. These children will have documented brain injuries, such as a minor hemorrhage or concussion. The goal will be to recruit 5-10 children who have suffered TBIs within the last three months. All advertisements will be posted for a minimum of ten days, with an extension if the goal is unmet during the initial postings. Participants will be recruited through postings in local hospitals, local elementary schools, and newspaper advertisements (including electronic versions of newspapers). Parents will be informed the study is to determine the neural pathways associated with cognitive functioning; the necessity of functional magnetic resonance imaging scans (fMRI), including the likelihood of sedation; and of the necessity of repeated follow-up visits, including fMRI scans, at six, twelve, twenty-four, and sixty months to monitor the developmental trajectory of the neural pathways of interest.

The most significant risk to participants during this study is the possibility of adverse effects from anesthesia during the fMRI. As children are likely to be unable to remain motionless for sufficient time to obtain usable images, the anesthesia will be required. Parents will be informed of the possibility of these effects prior to being provided informed consent forms. The benefits of this study could greatly improve the research field of neuroscience in that it may provide demonstrable evidence of not only the plasticity of the brain, but also the specific pathways that are involved in cognitive development and the specific pathways that are utilized to compensate for damage.

Procedures:

Once a sufficient number of participants are obtained, parents and children will be provided access to online learning programs, such as ABC Mouse, to facilitate cognitive (intellectual development). Additional school-based programs that are available will be at the parents’ discretion, but highly encouraged. Upon entry into the study, all participants will undergo psychological examination to determine their level of cognitive functioning at the beginning of the study. The assessment to be utilized in the proposed study is the Kaufman Assessment Battery for Children, Second Edition (KABC-II). The KABC-II was designed in accordance with the Cattell-Horn-Carroll (CHC) theory of cognitive development (McGill & Spurgin, 2017). Furthermore, the KABC-II measures cognitive functioning in children from a diverse ethnic background—meaning that the hitherto observed trend in intelligence/ standardized testing favors Caucasian children will be mitigated. The use of this assessment should provide results that are more generalizable to a more diverse population of children who have suffered TBIs. All participants will also be assessed for behavioral disorders. [Note: I am still researching this aspect of the study.]

Results from MRI scans from the time of the initial TBI will be obtained from medical providers for the children who have suffered recent TBIs. Children who have not suffered a TBI will be provided fMRI scans at no charge. At intervals of six, twelve, twenty-four, and sixty months, all children will receive fMRI scans at no charge to determine the brain development during the time intervals.

Hypothesis and Analysis:

The analysis of fMRI scans during the initial period will indicate which areas of the brain have been damaged when compared to the control group. It is expected that during subsequent examinations, the brains of children who suffered a TBI will show the activation of alternative pathways for cognitive development. Furthermore, parents will be asked to provide yearly academic (i.e. semester grades) and behavioral (i.e. school disciplinary records) updates on the progress (i.e. semester grades) of their children in the educational environment. Parents will be provided an email address to which these responses can be sent. It is further expected that children who suffered a TBI will have poorer academic and behavioral records than the control participants.

At intervals of six, twelve, twenty-four, and sixty months, participants will be re-evaluated through the KABC-II and fMRI examinations. Given that some participants may be unable to provide every update, only those participants who are unable to complete a minimum of three of the examinations, including the initial examination, will be excluded from the results of the study; however, the results of all examinations may be beneficial to the aims of the study.

The discovery of alternative neural pathways in cognitive development may provide practitioners of many specialties (e.g. neuroscience, child psychology, and education) the evidence to develop more specific interventions or teaching methods to moderate the effects of TBI.

Budget Justification

Funding is requested for a quarter-time graduate research assistant to oversee recruitment and data collection. An additional 10% is requested for the principal investigator to monitor the study, conduct analysis, and publish/present the results of the study. These funds will be distributed during the first month of the study, at the stated examination intervals, and for one month at the end of the study.

Funding is also requested for travel expenses to a national conference for the principal investigator to present the results of the study.

Subjects will be provided with compensation in the amount of $150. This expense provides each participant with $20 at the initial examination and at each subsequent examination (six, twelve, twenty-four, and sixty months). An additional $50 will be provided to each participant for the time required to provide either the requested email updates or postage to submit the updates through the United States Postal System (for those who lack internet access).

Funding is also requested to purchase a Hewlett Packard EliteBook laptop computer (14” screen, 2.7 GHz, 16 GB hard drive) for data collection and analysis. Additional funding is requested for Quality of Life changes during the period of the study and for office supplies,

See Appendix A for detailed budget figures.

References

Beauchamp, M., Catroppa, C., Godfrey, C., Morse, S., Rosenfeld, J. V., & Anderson, V. (2011). Selective changes in executive functioning ten years after severe childhood traumatic brain injury. Developmental Neuropsychology, 36(5), 578-595. doi:10.1080/87565641.2011.555572

Bhaskara P, S. (2016). Footprints of Phineas Gage: Historical beginnings on the origins of brain and behavior and the birth of cerebral localizationism. Archives Of Medicine And Health Sciences, Vol 4, Iss 2, Pp 280-286 (2016), (2), 280. doi:10.4103/2321-4848.196182

Catroppa, C., & Anderson, V. (2009). Neurodevelopmental outcomes of pediatric traumatic brain injury. Future Neurology, 4(6), 811-821. doi:http://dx.doi.org.proxy- library.ashford.edu/10.2217/fnl.09.52

Dahlberg, C. A., Cusick, C. P., Hawley, L. A., Newman, J. K., Morey, C. E., Harrison-Felix, C. L., & Whiteneck, G. G. (2007). Treatment efficacy of social communication skills training after traumatic brain injury: A randomized treatment and deferred treatment controlled trial. Archives Of Physical Medicine And Rehabilitation, 88(12), 1561-1573. doi:10.1016/j.apmr.2007.07.033

Dale, B. A., McIntosh, D. E., Rothlisberg, B. A., Ward, K. E., & Hunt Bradley, M.,(2011). Profile analysis of the Kaufman Assessment Battery for Children, Second Edition,with African American and Caucasian children. Preschool Assessment And Intervention, 48(5), 476-487. doi: 10.1002/pits.20571

Dennis, M., Bigler, E., Spiegler, B., Simic, N., Wilkinson, A., Sinopoli, K., & ... Fletcher, J. (2014). Functional plasticity in childhood brain disorders: When, what, how, and whom to assess. Neuropsychology Review, 24(4), 389. doi:10.1007/s11065-014-9261-x

Froudist-Walsh, S., López-Barroso, D., José Torres-Prioris, M., Croxson, P. L., & Berthier, M. L. (2018). Plasticity in the working memory system: Life span changes and response to injury. Neuroscientist, 24(3), 261. doi:10.1177/1073858417717210

Gerrard-Morris, A., Taylor, H. G., Yeates, K. O., Chertkoff Walz, N., Stancin, T., Minich, N., & Wade, S. L. (2010). Cognitive development after traumatic brain injury in young children. Journal Of The International Neuropsychological Society, 16(1), 157. doi:10.1017/S1355617709991135

Giza, C., Kolb, B., Harris, N., Asarnow, R., & Prins, M. (2009). Hitting a moving target: basic mechanisms of recovery from acquired developmental brain injury. Developmental Neurorehabilitation, 12(5), 255-268. doi:10.3109/17518420903087558

Glenn, D. E., Demir-Lira, Ö. E., Gibson, D. J., Congdon, E. L., & Levine, S. C. (2018). Resilience in mathematics after early brain injury: The roles of parental input and early plasticity. Developmental Cognitive Neuroscience, 30304-313. doi:10.1016/j.dcn.2017.07.005

Krasovsky, T., Landa, J., Bar, O., Jaana, A., Livny, A., Tsarfaty, G., & Silberg, T. (2017). Functional plasticity in the absence of structural change: Apraxia and body scheme disorder 10 years after childhood brain injury. Journal Of Child Neurology, 32(5), 505- 511. doi:10.1177/0883073816688833

Macmillan, M., & Lena, M. L. (2010). Rehabilitating Phineas Gage. Neuropsychological Rehabilitation, 20(5), 641-658. doi:10.1080/09602011003760527

McGill, R. J., & Spurgin, A. R. (2017). Exploratory higher order analysis of the Luria interpretive model on the Kaufman Assessment Battery for Children–Second Edition (KABC-II) school-age battery. Assessment, 24(4), 540-552. doi:10.1177/1073191115614081

Nadebaum, C., Anderson, V., & Catroppa, C. (2007). Executive function outcomes following traumatic brain injury in young children: A five year follow-up. Developmental Neuropsychology, 32(2), 703-728. doi:10.1080/87565640701376086

Sartor-Glittenberg, C., & Brickner, L. (2014). A multidimensional physical therapy program for individuals with cerebellar ataxia secondary to traumatic brain injury: a case series. Physiotherapy Theory & Practice, 30(2), 138-148. doi:10.3109/09593985.2013.819952

Thompson, K., Biddle, K., Robinson-Long, M., Poger, J., Wang, J., Yang, Q., & Eslinger, P. (2009). Cerebral plasticity and recovery of function after childhood prefrontal cortex damage. Developmental Neurorehabilitation, 12(5), 298-312. doi:10.3109/17518420903236262

Walter, K. H., Dickstein, B. D., Barnes, S. M., & Chard, K. M. (2014). Comparing effectiveness of CPT to CPT-C among U.S. veterans in an interdisciplinary residential PTSD/TBI treatment program. Journal Of Traumatic Stress, (4), 438. doi:10.1002/jts.21934

Yuan, W., Treble-Barna, A., Sohlberg, M. M., Harn, B., & Wade, S. L. (2017). Changes in structural connectivity following a cognitive intervention in children with traumatic brain injury: A pilot study. Neurorehabilitation And Neural Repair, 31(2), 190-201. doi:10.1177/1545968316675430

Appendix A: Budget