Research Papers On Traumatic Brain Injury

After what seemed to be mild car accident five years ago, “John” began suffering from a host of symptoms—headaches, fatigue, irritability, difficulty concentrating. At the time of the accident—John was rear-ended by the driver behind him—he was diagnosed with concussion and mild whiplash. But he and his wife had been struggling with the aftermath ever since.

Brain scans showed no visible damage, and during the next few years John saw several doctors and specialists who gave him a haphazard regimen of drugs and recommendations, but no solutions. Apathy, depression, anger, and mood shifts strained his marriage and family life to the breaking point. “It was just an awful situation,” he says. Finally his wife got him an appointment with Beth Adams, a neurotrauma rehabilitation specialist and case manager at Spaulding Hospital North Shore. Adams diagnosed post-concussion syndrome and connected the couple with doctors including Charlton professor of physical medicine and rehabilitation Ross Zafonte at Spaulding Rehabilitation Hospital in Boston.

Seeing the team of specialists there “has completely changed my life around,” John says. He has been on a more systematic regimen of medications for his symptoms, and is receiving cognitive behavioral therapy to learn to manage the mood swings and fatigue.

John is one of more than five million people in the United States living with the long-term effects of a traumatic brain injury (TBI) caused by the sudden force of a fall, hit, or blast. Some injuries leave patients alive but unconscious or severely impaired. Others are seemingly mild, yet cause subtle but persistent changes in mood, memory, and cognitive abilities. An estimated 1.4 million Americans sustain a traumatic brain injury every year, and millions more suffer sports or recreation-related concussions. (Most of the latter recover quickly, but some experience symptoms for months or years.) Among U.S. soldiers who have sustained injuries in Iraq and Afghanistan, one estimate puts the rate of TBI at nearly 20 percent.

We tend to think of a traumatic injury as a simple, physical process, like a cut or bruise. But Zafonte, chair of the department of physical medicine and rehabilitation at Harvard Medical School (HMS), says it is more accurate to think of TBI as a disease, because its effects extend well beyond the physical injury and can unfold over long periods of time. Unlike the damage resulting from a stroke, which is often localized to one part of the brain, traumatic injuries often affect many areas of the brain in sometimes unpredictable ways.

TBI has attracted new interest recently, in large part reflecting growing awareness of the problems of soldiers and of such high-profile victims as Arizona Congresswoman Gabrielle Giffords and athletes who have died or developed brain disease after multiple hits to the head. Zafonte says the field was largely quiet when he arrived at HMS several years ago, but he now expects Harvard to become a leading center for work on TBI in the next few years. Today, researchers at Spaulding and other Harvard-affiliated hospitals are gathering data about patients and investigating therapies and interventions that could improve recovery from acute injuries or related long-term effects. Using imaging, animal studies, and experiments on cultured cells, they hope to help dispel the mysteries surrounding brain injury.

The Spectrum of Consciousness

Improvements in medical care have saved the lives of people with some of the most severe brain injuries. But there are consequences of success: the healthcare system now faces the long and complicated challenge of rehabilitating these patients. “Not only are all these people surviving,” says Zafonte, “but they’re surviving severely disabled.”

Joseph Giacino, director of rehabilitation neuropsychology at Spaulding and associate professor of physical medicine and rehabilitation, sees some of the most severely injured patients, those who have often been dismissed as hopeless. He was recruited to the hospital a year and a half ago to lead a program of treatment and research on disorders of consciousness—seeing patients with TBI and other conditions whose injuries have impaired their consciousness in some way.

Consciousness is not simply an on/off state, but a spectrum: at one end are patients trapped in comas in which their movement, awareness, and even respiratory systems are entirely switched off. Those who are awake but show no evidence of awareness are considered to be in a vegetative state. They often transition to what is called a minimally conscious state: awake and sometimes aware of their surroundings, but unable to respond consistently to any but the simplest questions.

This is the state that grips Anthony Adamo now. In a conference room at Spaulding, Giacino sits with physiatrist and instructor in physical medicine and rehabilitation Ronald Hirschberg and several residents and nurses to discuss Adamo’s case and assess his progress. A man in his fifties who owned a construction business and has a wife and two children, Adamo suffered a fall on the job that caused a severe brain injury. Now, three months later, he sits in a wheelchair, moves fitfully with only half of his body, and is wearing a helmet to protect his skull, which still has an opening after a brain surgery. As occurs in many patients, the events after his injury damaged his brain as much as the initial trauma. Bleeding and swelling made it necessary for surgeons to remove brain tissue. Before meeting with him, Giacino and Hirschberg reviewed MRI images of his brain that showed in stark relief a gap on one side.

Now, Giacino stands next to Adamo and attempts to communicate with him. He asks Adamo if he knows where he is, and asks him to touch his nose. The patient seems confused and mumbles answers that trail off. Giacino holds Adamo’s hand, which has been moving distractedly.

“Who’s your favorite football team?” Giacino asks. “The….”

There’s no reply. Giacino persists. “New England….”

“Patriots,” Adamo responds softly.

“Who’s their quarterback? Tom…..”


For Adamo’s doctors and nurses, progress comes in these small victories. Severely impaired though he is, Adamo has improved dramatically. But he still doesn’t consistently answer yes and no questions correctly, and when Giacino gives him a plastic cup and asks him how it’s used, he doesn’t respond. Tasks like recognizing an object’s use require multiple brain areas working together and clear thinking—but at this point in his recovery, Adamo seems too distracted. When he can accomplish at least one of these two tasks, he’ll be classified in a higher state of consciousness, called the post-traumatic confusional state, in which higher functions remain impaired but basic activities of daily living reemerge.

Though this classification system is helpful, injuries like Adamo’s are very hard to categorize and track. Patients seem to get better and then lapse. Whether abilities like language are damaged by an injury or simply hampered by confusion, distraction, or incapacity to attend to questions is difficult to know.

After the examination, Giacino and Hirschberg discuss Adamo’s progress, medications, and possible therapeutic strategies. Hirschberg says it is not yet clear how far he will ultimately progress, but that he has the potential to make a meaningful—if not complete—recovery. Giacino says that while many patients in this situation have been dismissed as unsalvageable, “we now have long-term data that patients get better”—vital evidence in making the case to treat them.

Giacino has been a leader in efforts to establish standards of care for patients with disorders of consciousness. In addition to treating them, he is gathering a wealth of information about their condition and progress and has helped create a consortium of 10 centers in the United States and Europe that has amassed a large data set and will begin releasing its initial findings this year. “We have no gold standard for measuring consciousness and very little evidence concerning treatment effectiveness,” he says; part of his goal is to bring more rigorous definitions and standards to this slippery concept, to better track which interventions work.

He is also involved in studies to look for drugs that could speed recovery. Currently, he says, “There is not a single proven treatment for promoting recovery from brain injury.” Instead, physicians manage medical symptoms and rely on rehabilitation to help restore cognitive and motor functions.

Giacino has also been involved in brain-imaging studies which have, in the past few years, revealed surprising activity in patients who appear to be unconscious, suggesting that even in the case of devastating brain injury, there may be a residual capacity for the brain to function, which might be aided by therapies. He is now working to use functional MRI imaging as a window into the minds of unresponsive patients. Perhaps looking into the brain will help clinicians make better decisions about how to help them.

Comprehending Concussion

Concussions, the most common brain injuries, occur when a rapid rotational acceleration to the head—such as a hit or fall—causes a temporary loss of brain function. It doesn’t cause detectable structural damage, but its symptoms can range from headaches to loss of consciousness to seizures. New research has raised puzzling questions about these incidents.

Concussions related to sports are common among children and teenagers, and probably more widespread than records indicate. Studies have found that one-third of athletes don’t recognize their symptoms as concussion (most concussions don’t involve a loss of consciousness) and many athletes ignore or avoid reporting any symptoms they may have (see “Hits, Heads, Helmets,” January-February 2010). Nevertheless, awareness has grown: “There’s much more understanding of the severity of the injury,” says neurosurgeon and associate professor of surgery Mark Proctor, who leads the Brain Injury Center at Children’s Hospital.

Yet “concussion” is still frequently used to mean a mildly traumatic brain injury, and barely a decade ago, says pediatrician William Meehan, director of the Sports Concussion Clinic at Children’s Hospital, the idea that concussion could cause more than temporary problems was controversial. “People thought you just got better,” he explains—and because most concussions do resolve quickly, people who complained of long-term symptoms were sometimes dismissed as malingerers.

But studies of athletes who have experienced concussions show a measurable drop in cognitive function after a single incident. Most subjects recover, but as they sustain additional injuries, the declines become more pronounced, and even permanent. Meehan and colleagues decided to explore the issue in animal studies (“Mice don’t malinger,” he says). By developing a system for inducing a concussion in anesthetized mice, the scientists have been able to study the injury’s effects in much more detail than could be done in humans. The research affirms what has been seen in athletes: even when concussions don’t cause visible structural damage to the brain or individual brain cells, they can still impair performance on memory tests.

The model has also facilitated study of the effects of multiple concussions—a common experience for athletes. The investigators find that repeat injuries cause cumulative impairments, particularly if there’s little recovery time between episodes.

One puzzling aspect of concussions is why they affect people differently. Roughly 98 percent of those who suffer such an injury are symptom-free within a month. Meehan says the question is, “Is there a way to predict who will fall into that 2 percent?” Researchers seek to determine if certain people are susceptible to severe or long-term effects of concussion because of a genetic predisposition or some other factor. Using genetically altered mice, the team is testing the effect of one possible genetic connection, a variation in the gene apolipoprotein E that has been linked to a worse outcome after brain injuries. It’s not yet clear whether the same gene has a role in concussion.

Meehan hopes that these models will help answer other questions, such as whether concussion’s effect on the still-developing brains of children and adolescents differs from its impact on the brains of adults. Another concern is a rare event called second impact syndrome, which occurs when an athlete returns to play too soon after a concussion and suffers another, leading to severe and life-threatening swelling of the brain. Not surprisingly, Meehan and Proctor advocate for better awareness of the dangers of concussion, better medical attention for athletes who suffer injuries, and stricter rules about return to play and contact in school sports. They also collaborate with the Center for the Study of Traumatic Encephalopathy at Boston University, which is studying whether multiple concussions can cause chronic traumatic encephalopathy (CTE), a devastating degenerative brain disease that can cause dementia and depression.

“TBI on a Chip”

Although TBI begins with a physical trauma, it quickly leads to a series of chemical and structural changes in the brain—some immediate, others unfolding slowly over time. For Kevin “Kit” Parker, Tarr Family professor of bioengineering and applied physics in the School of Engineering and Applied Sciences, this interface between physics and chemistry represents a potential therapeutic opportunity. Parker’s research usually focuses on the heart (see “Life Sciences, Applied,” January-February 2009), but he and other researchers in his lab have begun to take on the question of TBI at a cellular level. Their interest is personal: nine lab members are military veterans (including Parker, a major in the U.S. Army), so they have seen how improvised explosive devices can devastate the lives of soldiers who survive such attacks.

During a blast, a quick pressure wave rips through the air; the question is what happens when that wave meets brain tissue. Parker says many people assumed that blast-induced TBI damages the brain by ripping small holes in brain cells, causing them to die. He had a different theory: that the mechanical forces of a blast might trigger a chemical shake-up within the cells, initiated by proteins called integrins at the cell surface. (He had previously studied these proteins in other types of cells.)

Parker first outlined this hypothesis in a 2006 conversation with Borna Dabiri ’07, now a graduate student in SEAS. During the next few years, Parker’s team at the Disease Biophysics Group at SEAS and the Wyss Institute for Biologically Inspired Engineering developed a way to study blast-like forces affecting individual cells. This past July they published papers in the Proceedings of the National Academy of Sciences and PLoS One showing that their original hunch was correct.

Integrins help anchor cells’ inner “skeletons” to the outer tissue in which they are embedded, but they also activate chemical changes inside cells. The studies provide evidence that integrins may translate mechanical blast forces into cellular damage in both neurons and blood-vessel tissues. The team placed rat neurons on a plastic surface and then subjected them to brief, abrupt stretching forces, using a highly controllable, piston-like device developed by graduate student Matthew Hemphill and staff engineer Josué Goss, a U.S. Marine with two combat tours in Iraq who used his knowledge of explosives to mimic the forces passing through the brain in a blast. As a result, Parker’s team found it possible to induce TBI-like injuries in cells without physically ripping them.

To study integrins in more detail, they also attached tiny magnetic beads to neurons coated with a protein that binds specifically to integrins. They found that applying an electromagnetic force to beads attached to the axons—the long tails—of neurons could injure them, and that forces stressing one bead propagated through the cell’s skeleton down another axon, causing that distant axon to break or be injured. Parker says the propagation of forces through neurons explains why physical damage in human brains may appear far from the original injury site.

The researchers used a similar technique to study mechanical forces in the cells that line blood vessels, creating artificial vessels from sheets of smooth-muscle cells. High-speed pulses of stretching, they found, caused the blood vessels to contract and the sheets to fold, inducing chemical changes in the cells. That result suggests that integrins mediate another medical phenomenon that occurs in brain injuries but is particularly common to blast victims: cerebral vasospasm, a dangerous narrowing of the brain’s blood vessels that can emerge days to weeks after the initial injury. Treating damaged neurons and blood-vessel cells with a drug that inhibits a protein activated by integrins lessened the effect of the injury. Parker hopes that by isolating a chemical process involved in the pathology of TBI, the team will find a drug that can be given to soldiers before or immediately after an injury to lessen its damage to the brain.

These cell studies are the first step in what Parker calls a “TBI on a chip,” a highly simplified model to screen for drugs to treat brain injury. He wants “to build a one-cubic-millimeter piece of brain” that he could then grow in dozens of tiny wells in microfluidic chips suitable for high-throughput screening of possible drugs. Parker’s team is now at work on growing different types of cells together, which would mimic the multiple cell types found in the brain. The chips would be subjected to forces that simulate a blast, and then screened for chemicals that prevent damage. Developing this kind of tool, he hopes, could entice pharmaceutical companies to direct resources into a search for TBI drugs.

“The Most Complicated Disease”

Zafonte calls TBI “the most complicated disease in the most complicated organ known to man.” This complexity explains why the disease has so vexed scientists and clinicians, and why so many clinical trials for treatments to improve recovery have failed. Traumatic brain injury remains a puzzle on many levels, from the events unfolding in brain cells to the complex and varied way those events play out in a human life.

Efforts to solve those puzzles vary as well, from Parker’s pared-down, engineering approach to the collection of data about real patients at Spaulding and other Harvard-affiliated hospitals. Zafonte leads a program on TBI and Neurotrauma for the Center for Integration of Medical Innovation and Technology (CIMIT), a nonprofit consortium in Boston that funds new techniques for monitoring and treating brain injury. Its research aims to understand the biological processes underlying mild and severe brain injuries, why individuals respond differently, and whether clinicians can better detect and monitor injuries through novel imaging techniques or even chemical changes in the blood.

Today, treating TBI patients is still a matter of trial and error, so Zafonte’s goal is a more scientific set of treatments. With all these efforts, he says, he hopes to offer his patients proven ways to help the brain heal: “It’s the way our colleagues went in cardiac therapies, in HIV, in all these other areas where there have been huge successes.”

Top-Cited Articles in Traumatic Brain Injury

Bhanu Sharma1,* and David Wyndham Lawrence2

1Toronto Rehabilitation Institute, University of Toronto, Toronto, ON, Canada

2Department of Family and Community Medicine, St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada

Edited by: Aron K. Barbey, University of Illinois at Urbana-Champaign, USA

Reviewed by: Arun Bokde, Trinity College Dublin, Ireland; Rachael Danielle Rubin, University of Illinois at Urbana-Champaign, USA

*Correspondence: Bhanu Sharma, Toronto Rehabilitation Institute, University of Toronto, 550 University Avenue, Toronto, ON M5G 2A2, Canada e-mail: ac.otnorotu.liam@amrahs.unahb

This article was submitted to the journal Frontiers in Human Neuroscience.

Author information ►Article notes ►Copyright and License information ►

Received 2014 Jul 8; Accepted 2014 Oct 12.

Copyright © 2014 Sharma and Lawrence.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

This article has been cited by other articles in PMC.


A review of the top-cited articles in a scientific discipline can identify areas of research that are well established and those in need of further development, and may, as a result, inform and direct future research efforts. Our objective was to identify and characterize the top-cited articles in traumatic brain injury (TBI). We used publically available software to identify the 50 TBI articles with the most lifetime citations, and the 50 TBI articles with the highest annual citation rates. A total of 73 articles were included in this review, with 27 of the 50 papers with the highest annual citation rates common to the cohort of 50 articles with the most lifetime citations. All papers were categorized by their primary topic or focus, namely: predictor of outcome, pathology/natural history, treatment, guidelines and consensus statements, epidemiology, assessment measures, or experimental model of TBI. The mean year of publication of the articles with the most lifetime citations and highest annual citation rates was 1990 ± 14.9 years and 2003 ± 6.7 years, respectively. The 50 articles with the most lifetime citations typically studied predictors of outcome (34.0%, 17/50) and were specific to severe TBI (38.0%, 19/50). In contrast, the most common subject of papers with the highest annual citation rates was treatment of brain injury (22.0%, 11/50), and these papers most frequently investigated mild TBI (36.0%, 18/50). These findings suggest an intensified focus on mild TBI, which is perhaps a response to the dedicated attention these injuries are currently receiving in the context of sports and war, and because of their increasing incidence in developing nations. Our findings also indicate increased focus on treatment of TBI, possibly due to the limited efficacy of current interventions for brain injury. This review provides a cross-sectional summary of some of the most influential articles in TBI, and a bibliometric examination of the current status of TBI research.

Keywords: traumatic brain injury, head injury, concussion, bibliometric, citation


In an effort to improve clinical outcomes following traumatic brain injury (TBI), leading scientific institutions have pioneered an international, multidisciplinary research initiative (The Lancet, 2012). In particular, the Canadian Institutes of Health Research, the National Institutes of Health, and the European Commission – leading research agencies within their respective jurisdictions – have recently collaborated to fund and advance TBI research through the International Initiative for Traumatic Brain Injury Research (European Commission, 2012; The Lancet, 2012; The Lancet Neurology, 2013; Tosetti et al., 2013). This unprecedented effort at TBI-specific international collaboration and resource pooling is a testament to the global burden of this injury (The Lancet Neurology, 2013), and it is perhaps a response to calls for increased funding for brain injury research and greater networking between institutions studying TBI (Zitnay et al., 2008). The pressing need to advance TBI research is most evident when considering predictions that TBI will become the third leading cause of death and disability worldwide by the year 2020 (World Heath Organization, 2002; The Lancet, 2012).

Commitments to advance our understanding of TBI and the management strategies available to treat this injury will be effectuated by an increase in research activity (The Lancet, 2012). It is important, therefore, to examine current TBI literature and identify the areas of research that are well established and those in need of further development, as this may inform researchers and granting agencies where to focus future research efforts. Reviewing the literature with this aim is especially important considering that consensus statements report that our understanding of TBI has progressed further in some areas than in others (Zitnay et al., 2008).

One way to objectively identify a well-developed area of the literature is to measure the number of citations it has accumulated (Patsopoulos et al., 2005; Ponce and Lozano, 2010). Publications that are highly cited are well recognized, widely read and referenced, regularly discussed, and likely to be considered important within their respective subfields (Lipsman et al., 2014). Moreover, the number of times a publication is cited serves as a proxy for its influence within a discipline (Garfield, 1986; Lipsman et al., 2014). An analysis of the top-cited articles in a given field, therefore, provides clinicians and researchers with a cross-sectional summary of some of the most important work on a topic (Yang and Pan, 2006; Ibrahim et al., 2012; Lipsman and Lozano, 2012; Lipsman et al., 2014). Bibliometric citation analyses can also reveal the breadth (Lipsman et al., 2014) and existing patterns or themes within a literature (Rubin, 2004), while evaluating annual citation rates may indicate how the science is trending (Lipsman and Lozano, 2012).

The primary objective of our review was to identify and characterize TBI publications that have (1) the greatest number of lifetime citations and (2) the highest annual citation rates. We categorized and analyzed top-cited articles according to characteristics such as their primary focus, sample, design, and country of correspondence. Other groups have conducted similar analyses within different areas of research (Yang and Pan, 2006; Lefaivre et al., 2010; Ponce and Lozano, 2010; Shadgan et al., 2010; Ibrahim et al., 2012; Lipsman and Lozano, 2012; Lipsman et al., 2014). Collectively, the publications reviewed here highlight some of the most influential articles in TBI, and also the studies that may be shaping the direction in which this growing field is heading.


We used the publically available software Harzing’s Publish or Perish v.4.6.3 (Harzing, 2007) to conduct our citation analysis. This software computes various citation metrics after collecting raw citation data through Google Scholar. It should be noted that other groups have conducted bibliometric citation analyses using Harzing’s Publish or Perish (Lipsman and Lozano, 2012; Lipsman et al., 2014). Citation metrics are accurate to May 1, 2014.

Our search included a comprehensive set of terms. In particular, we searched for articles that contained the term “head trauma,” “head injury,” “head injuries,” “head injured,” “brain trauma,” “brain injury,” “brain injuries,” “brain injured,” “traumatic brain injury,” “traumatic brain injuries,” “TBI,” “concussion,” or “concussions” in the study title. We manually reviewed the full list of the top-cited TBI articles generated by Harzing’s Publish or Perish (Harzing, 2007) in consecutive order until a total of 50 articles that met our inclusion and exclusion criteria (outlined below) were identified. We also sorted the data in Harzing’s Publish or Perish (Harzing, 2007) by “citations/year” to identify the 50 TBI articles, meeting our inclusion and exclusion criteria, with the highest annual citation rates. There were no restrictions on date of publication.

To be included in our final sample, it was necessary for TBI to be the primary focus of the article (e.g., the article could not be about acquired brain injuries in general), the full article to be electronically accessible, and for the article to be peer reviewed. We included primary publications, consensus statements/guidelines, commentaries, and review articles. An article was excluded if it was not peer reviewed, and/or if it was a report or book chapter (Figure ​1).

Figure 1

Flow diagram representing the study selection process. (A) Lifetime citation cohort. (B) Annual citation rate cohort.

A grounded theory methodology (Strauss and Corbin, 1990) was used to code each article, with respect to overall focus/topic. After independently coding the same set of 40 articles (at which point data saturation was achieved), the authors met to reach a consensus on the categorization strategy and ensure that similar codes were being grouped together consistently. After coding articles from both citation cohorts (i.e., the 50 most-cited articles in TBI and the 50 articles with the highest annual citation rates), differences in coding were reconciled by debate until consensus was reached. Both cohorts of articles were analyzed similarly. Only descriptive statistics were performed.


The publications that comprise the two citation cohorts are listed in Tables ​1 and ​2. On average, the 50 most-cited articles in TBI accumulated a lifetime total of 834.8 ± 248. 8 citations (range: 574–1645). The average annual citation rate of these papers was 48.0 ± 43.4 citations per year, with a range between 8.1 and 192.7. In contrast, the annual citation rate of the 50 TBI papers that have accumulated the most citations per year since publication was 65.5 ± 35.4 citations per year (range: 39.1–192.7). The absolute number of citations this latter cohort of papers accumulated since publication ranged from 169 to 1645, with an average of 654.7 ± 350.6 lifetime citations. Over half (27/50, 54.0%) of the publications with the highest annual citation rates were common to the 50 TBI papers with the most lifetime citations.

Table 1

TBI publications with the most lifetime citations (n = 50).

Table 2

TBI publications with the highest annual citation rates (n = 50).

Most papers with the greatest number of lifetime citations were published over a 30-year span starting in the mid-1970s (mean year of publication: 1990 ± 14.9 years). Conversely, the majority of TBI-specific papers with the highest annual citation rates were published within the last 15 years (mean year of publication: 2003 ± 6.7 years) (Figure ​2). Both citation cohorts are further characterized in Table ​3.

Figure 2

Publication year of each of the articles that comprise the two citation cohorts.

Table 3

Characterization of the two citation cohorts.

All papers were classified into one of seven general categories. Table ​4 provides the distribution of papers from both citation cohorts into these seven categories (and sub-categories where appropriate). A more detailed discussion of category-specific findings follows.

Table 4

Categorical dissection of publications in both citation cohorts.

Predictor of outcome

Of the 50 most frequently cited articles in TBI, 17 (17/50, 34.0%) primarily studied predictors of outcome. Most predictor studies involved human subjects (14/17, 82.4%), with a subset focusing exclusively on athletes (1/14, 7.1%) and war veterans (1/14, 7.1%). Nearly half of all predictor articles (8/17, 47.1%) studied severe TBI, while five centered on mild TBI (5/17, 29.4%); the remainder (4/17, 23.5%) were composed of a heterogeneous sample with respect to injury severity. None of the top-cited studies investigating predictors of outcome were randomized control trials, although many were prospectively conducted (15/17, 88.2%).

Comparatively, of the 50 articles with the highest annual citation rates, only eight (8/50, 16.0%) investigated predictors of outcome. Of these eight studies, half (4/8, 50.0%) were common to the 50 top-cited articles in TBI. Most predictor studies in the citation rate cohort were prospectively conducted (4/8, 50.0%), and half of all predictor studies (4/8, 50.0%) focused on a specialty population (i.e., athletes or war veterans). However, in comparison to the cohort of papers with the most lifetime citations, a greater percentage of predictor studies with the highest annual citation rates were specific to mild TBI (3/8, 37.5%).

Pathology/natural history

The 50 top-cited articles in TBI included 10 studies (10/50, 20.0%) primarily focused on characterizing pathological outcome following brain injury. Nine of the pathology papers (9/10, 90.0%) were primary research articles; the other was a review article (1/10, 10.0%). The majority of pathology articles were of a prospective design (8/10, 80.0%) and involved human subjects (6/10, 60%). Severe TBI was studied in four articles (4/10, 40.0%), mild TBI in three papers (3/10, 30.0%), and two studies (2/10, 20.0%) had a mixed sample with respect to TBI severity. Information on TBI severity was not available for one study (1/10, 10.0%).

Of the 50 articles with the highest annual citation rates, nine (9/50, 18.0%) focused on pathology/natural history; six of these were common to the 50 top-cited articles in TBI. Relative to the cohort of papers with the most absolute citations, a greater proportion of the citation rate studies were review articles (4/9, 44.4%) and involved human subjects (7/9, 77.8%). A dissection by TBI severity revealed that mild TBI was studied in three papers (3/9, 33.3%), severe TBI in another (1/9, 11.1%), while samples with heterogeneous injury severity were studied in three articles (3/9, 33.3%). TBI severity could not be determined in the remaining papers (2/9, 22.2%).


Treatment was the focus of eight of the 50 top-cited articles in TBI (8/50, 16.0%). The majority of these articles (6/8, 75.0%) involved human subjects; the remainder studied pre-clinical treatment options for TBI in animal models (2/8, 25.0%). Most articles studied treatment in the context of severe TBI (6/8, 75.0%), and many treatment articles were randomized control trials (5/8, 62.5%).

Of the 50 TBI articles with the highest annual citation rates, the subject of 11 (11/50, 22.0%) was treatment. When compared to the cohort of treatment studies with the most lifetime citations, a similar proportion of these articles involved human subjects (9/11, 81.8%) and focused on moderate-to-severe or severe TBI (9/11, 81.8%). TBI treatment studies with the highest annual citation rates, however, studied interventions, such as administration of corticosteroids (1/11, 9.1%) or progesterone (1/11, 9.1%), which the top-cited treatment articles did not. Relative to papers with the most lifetime citations, a similar percentage of papers in the citation rate cohort (7/11, 63.6%) were randomized controlled trials.

Guidelines and consensus statements

Six of the 50 top-cited TBI articles (6/50, 12.0%) were guidelines and/or consensus statements. Two-thirds (4/6, 66.7%) of these articles were a product of international collaboration. The majority of these articles (4/6, 66.7%) pertained to mild TBI, including three (3/6, 50.0%) focusing exclusively on sports-related concussion. One consensus statement (1/6, 16.7%) concerned severe TBI, and another (1/6, 16.7%) provided guidelines on how to manage TBI of all severities.

Of the 50 TBI articles with the highest annual citation rates, nine (9/50, 18.0%) were guidelines and consensus statements; six of these were common to the 50 most-cited articles in TBI. An analysis by TBI severity revealed that mild TBI was the focus of six articles (6/9, 66.7%), three of which (3/6, 50.0%) were exclusively focused on concussion. One consensus statement (1/9, 11.1%) discussed pediatric head injuries specifically.


The 50 most-cited articles in TBI included three (3/50, 6.0%) epidemiological studies. One of these articles (1/3, 33.3%) studied the full spectrum of brain injury (e.g., mild-to-severe), while another (1/3, 33.3%) provided an epidemiological context to mild TBI only. The latter study was specific to TBI in sport.

In contrast, of the 50 TBI articles with the highest annual citation rates, 10 (10/50, 20.0%) were epidemiological. Half (5/10, 50.0%) of these articles studied the full spectrum of TBI severity, with one study (1/10, 10.0%) focusing exclusively on mild TBI. The single article studying the epidemiology of mild TBI did so in the context of sports. Another article (1/10, 10.0%) investigated the epidemiology of all TBI severities in war veterans.

Assessment measures

Of the 50 top-cited articles in TBI, three (3/50, 6.0%) primarily focused on assessment measures. All three studies (3/3, 100.0%) were prospective cohort investigations of cognitive assessment measures for information processing speed, sustained attention, or post-trauma orientation and amnesia. Two of these articles (2/3, 66.7%) focused on mild TBI and the third (1/3, 33.3%) explored assessment measures for TBI of any severity. The two studies specific to mild TBI in the most lifetime citation cohort were also among the 50 articles with the highest annual citation rates.

Experimental model of TBI

Three papers (3/50, 6.0%) describing an experimental model of TBI (e.g., fluid-percussion models) were identified in the cohort of 50 most-cited TBI articles; one (1/3, 33.3%) of these was common to the citation rate cohort. All three articles were animal studies. One study (1/3, 33.3%) developed a model to explore mild TBI, whereas the others (2/3, 66.7%), which were also common to the citation rate cohort, centered on a model that permitted investigation of mild-to-severe TBI in animals.


In comparing TBI papers with the most lifetime citations to those with the highest annual citation rates, it is possible to gage, respectively, which papers have had the greatest influence in TBI, and which articles are currently discussed, referenced, and shaping the field. Below, we provide a general discussion of our findings, which is followed by a category-specific commentary where appropriate.

Our data show that studies on mild TBI are currently accumulating the most citations per year, although studies on severe TBI have been more widely cited (Table ​3). This suggests that mild TBI is presently a central point of discussion in the field of brain injury, perhaps because mild TBI is the most prevalent form of TBI (Faul et al., 2010) and has, as a result, the most scope for preventive research; is of social and public concern, given its incidence in sports and the military (Langlois et al., 2006; Chen and D’Esposito, 2010; Cusimano et al., 2013); is a risk factor for other disorders (e.g., depression and anxiety) and neurodegenerative diseases such as chronic traumatic encephalopathy and Alzheimer’s disease (Plassman et al., 2000; McCauley et al., 2001; Holsinger et al., 2002; Fleminger et al., 2003; Seel et al., 2003; Gavett et al., 2010, 2011; Masel and DeWitt, 2010; Stern et al., 2011), and thereby draws interest and citations across a number of neuroscience disciplines; may now be extensively researched to overcome some of the documented shortcomings of former studies on mild TBI (Carroll et al., 2004). Furthermore, relative to papers with the most lifetime citations, a greater proportion of articles that are accumulating the most citations annually involved human subjects (Table ​3). This suggests a shifted focus from animal to clinical research, and perhaps a piqued interest in understanding, in particular, human brain and behavior after TBI. In addition, studies with the highest annual citation rates involved, on average, more routine international collaboration than papers with the most lifetime citations (Table ​3). Increased international collaboration may ultimately benefit our understanding of TBI by facilitating comparative effectiveness treatment research, the development of brain injury biomarkers, and an improved ability to predict outcome following TBI (Tosetti et al., 2013). Moreover, the articles that comprised the citation rate cohort were, on average, authored by a greater number of individuals (Table ​3). As larger groups conducted these studies, they may, therefore, benefit from greater scientific diversity and perspective.

Speculating on future trends in TBI research would suggest a sustained focus on treatment of TBI, given that patients continue to experience persistent cognitive and emotional impairment more than 5 years following mild trauma (Konrad et al., 2011). It may also be reasonable to expect an increase in research activity on assessment measures for TBI, given the push to be able to more reliability and immediately identify brain injury in the context of sports (Charleswell et al., 2014). As TBI research evolves and new knowledge is assimilated into current understanding and practice, is also likely that there will be greater research activity surrounding guidelines and consensus statements.

We would like to note that increased research activity in one subfield may influence activity in another. For example, a shifted research focus on treatment of TBI may engender downstream epidemiological research designed to assess treatment effects at the population level. Likewise, an increased focus on treatment may result in updated guidelines or consensus statements. Below, however, only category-specific findings are discussed.

Predictor of outcome

Over a third of the 50 top-cited articles in TBI studied predictors of outcome, indicating that this subfield of brain injury has been extensively researched. Moreover, eight of the 50 articles with the highest yearly citation rates focused on predictors of outcome, and half of these were also among the 50 top-cited articles in TBI. This indicates that novel research on predictors of outcome – not only former, seminal work in this subfield – continues to be discussed and cited widely. A sustained research effort into predictors of outcome is required to inform clinicians as to which patients are at greatest risk of poor long-term outcome, and, therefore, should be targeted for a particular management strategy or therapeutic intervention. Moreover, articles with the highest annual citation rates most often predicted cognitive, gross, and neurological outcomes following TBI, and not mortality, like many of 50 most-cited publications in TBI. A reduced emphasis on predicting mortality following brain injury may be commensurate with our improved ability to save the lives of TBI patients through primary prevention (e.g., seatbelt use) and case management (Stiefel et al., 2005).

Pathology/natural history

Investigations into pathological outcome and natural history following TBI are important for understanding the recovery and progression of brain injury. The most highly cited pathology/natural history studies examined histological outcomes and physiological response to trauma; however, the articles with the highest citation rates more often investigated functional outcomes post-TBI. This suggests a shifted focus, wherein patient-centered functional outcomes have become a more central point of research. This echoes the growing appreciation for the functional sequelae of brain injuries (Morton and Wehman, 1995), and identification of barriers to functional recovery that prevent restoration of pre-morbid abilities (Powell et al., 2001).


Two treatment articles with the highest annual citation rates were not common to the 50 most-cited articles in TBI. This suggests that some TBI treatment articles, despite not yet accumulating the requisite number of citations to be among the most-cited articles in TBI, are currently being regularly discussed and referenced within the scientific community. Discussion of and research into new treatment options for TBI is necessary given the limited efficacy of many currently available brain injury treatment and management options (Maas et al., 2012; Ponsford et al., 2014a,b; Velikonja et al., 2014), despite our increased pathophysiological understanding of TBI (Zitnay et al., 2008).

Guidelines and consensus statements

The greatest number of guidelines and consensus statements specific to TBI were identified in the citation rate cohort, indicating a current increase in scientific discussion on this topic. However, it should be noted that recent research indicates that, on average, TBI guidelines are based on low levels of evidence (Maas et al., 2012). This highlights the need to design and conduct studies on TBI that can provide high-level evidence that will advance the science and inform TBI guidelines of a higher standard. Nonetheless, the guidelines and consensus statements that are currently being referenced are particular to mild TBI and concussion. The observed increase in referencing of concussion and mild TBI guidelines echoes the growing interest and research activity in this field (Table ​3).


We observed that a greater proportion of the citation rate cohort comprised epidemiological studies than the absolute citation cohort. This suggests that our epidemiological knowledge of TBI is continually developing, re-contextualizing our understanding of the prevalence of TBI and the associated scope for prevention, characteristics of vulnerable populations, and how to distribute resources to manage TBI. Continued epidemiological research into TBI is required given that the incidence of this injury is changing (Maas et al., 2012). This is largely due to increased availability and use of motor vehicles in developing nations, and, therefore, greater potential for TBIs to be caused by motor vehicle collisions in these countries (Maas et al., 2008). In developed nations, moreover, rates of TBI are also on the rise in the elderly (Faul et al., 2010), potentially due to fall-related brain injuries. Given the above, the epidemiology of TBI will continue to change and require ongoing investigation. Improving and updating our understanding of the epidemiology of TBI provides the backdrop necessary for more downstream lines of research, which require an understanding of the scale of brain injury, such as prevention, treatment, and management.


Our review, similar to other citation studies, is subject to a number of limitations. Chief among these is the possibility that our search terms, albeit comprehensive, did not permit identification of every one of the top-cited papers in TBI. However, because we used Harzing’s Publish or Perish (Harzing, 2007) for our analysis, our search was biased toward inclusivity. This is because Harzing’s Publish or Perish (Harzing, 2007) collects raw citation data through Google Scholar, which is more inclusive in terms of which journals it indexes than other search engines such as the Institute for Scientific Information (ISI) Web of Science, which indexes only ISI journals (Lipsman and Lozano, 2011). Furthermore, the citation metrics that were computed in the present review have likely changed since we completed our analyses, given that the TBI literature is being continually cited. Any recent citations of the papers included in the present review may alter the ranking of some of the top-cited articles in TBI, though the overall content of the two citation cohorts is unlikely to change substantially in short intervals of time.

Furthermore, recent years have seen a growth in the number of scientific publications related to TBI. A search of the Medical Subject Headings (MeSH) keywords “traumatic brain injury,” “traumatic brain injuries,” “concussion,” and “concussions” in PubMed shows a stable growth in the number of TBI-related publications since 2004. In particular, between 2004 and 2013, 1733 TBI-specific papers were published, more than twice the 833 papers on brain injury published from 1994-2003. Therefore, as the citation rates we present do not control for general growth in the TBI field, our findings should be interpreted with caution.

There are also other measures of citation impact, including the h-index, g-index, and e-index. Although these metrics have unique value (Zhang, 2009, 2010), we did not include them in the present review, as we were not investigating citations by author or across specialties, institutions, or countries. We also did not control for the effects of self-citation or differences in citation practices across medical specialties (Kulkarni et al., 2007). Our review is also cross-sectional, and did not permit a longitudinal investigation. Future citation studies using alternative citation metrics and/or evaluating citation trends over time may be of additional value.


The present review provides a cross-sectional summary of some of the most influential studies in TBI, highlighting areas of research that require further investigation and development. Although studies on severe brain injury and predictors of outcome following TBI have been cited most extensively, the current research focus appears to be on mild TBI and investigating treatment strategies for brain injury. Our review is not designed to supplant systematic reviews or meta-analyses in TBI, but rather synthesize the literature uniquely to permit a novel analysis of TBI research. As the TBI literature evolves, it will be important for future citation studies to re-evaluate existing patterns and trends within this growing field of research.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


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