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Imaging Shows Youth Football’s Effects on the Brain
School-age football players with a history of concussion and high impact exposure undergo brain changes after one season of play, according to two studies conducted at the University of Texas Southwestern Medical Center in Dallas and Wake Forest University in Winston-Salem, North Carolina.
Both studies analyzed the default mode network (DMN), a system of brain regions that is active during wakeful rest. Changes in the DMN are observed in patients with mental disorders. Decreased connectivity within the network is also associated with traumatic brain injury.
“The DMN exists in the deep gray matter areas of the brain,” said Elizabeth M. Davenport, PhD, a postdoctoral researcher in the Advanced NeuroScience Imaging Research (ANSIR) lab at UT Southwestern’s O’Donnell Brain Institute. “It includes structures that activate when we are awake and engaging in introspection or processing emotions, which are activities that are important for brain health.”
In the first study, researchers studied youth football players without a history of concussion to identify the effect of repeated subconcussive impacts on the DMN.
“Over a season of football, players are exposed to numerous head impacts. The vast majority of these do not result in concussion,” said Gowtham Krishnan Murugesan, a PhD student in biomedical engineering and member of the ANSIR laboratory. “This work adds to a growing body of literature indicating that subconcussive head impacts can have an effect on the brain. This is a highly understudied area at the youth and high school level.”
For the study, 26 youth football players (ages 9–13) were outfitted with the Head Impact Telemetry System (HITS) for an entire football season. HITS helmets are lined with accelerometers that measure the magnitude, location, and direction of impacts to the head. Impact data from the helmets were used to calculate a risk of concussion exposure for each player.
Players were separated into high and low concussion exposure groups. Players with a history of concussion were excluded. A third group of 13 noncontact sport controls was established. Pre- and post-season resting functional MRI (fMRI) scans were performed on all players and controls, and connectivity within the DMN subcomponents was analyzed. The researchers used machine learning to analyze the fMRI data.
“Machine learning has a lot to add to our research because it gives us a fresh perspective and an ability to analyze the complex relationships within the data,” said Mr. Murugesan. “Our results suggest an increasing functional change in the brain with increasing head impact exposure.”
Five machine learning classification algorithms were used to predict whether players were in the high-exposure, low-exposure or noncontact groups, based on the fMRI results. The algorithm discriminated between high-impact exposure and noncontact controls with 82% accuracy, and between low-impact exposure and noncontact controls with 70% accuracy. The results suggest an increasing functional change with increasing head-impact exposure.
“The brains of these youth and adolescent athletes are undergoing rapid maturation in this age range. This study demonstrates that playing a season of contact sports at the youth level can produce neuroimaging brain changes, particularly for the DMN,” Mr. Murugesan said.
In the second study, 20 high school football players (median age, 16.9) wore helmets outfitted with HITS for a season. Of the 20 players, five had experienced at least one concussion, and 15 had no history of concussion.
Before and following the season, the players underwent an eight-minute magnetoencephalography (MEG) scan, which records and analyzes the magnetic fields produced by brain activity. Researchers then analyzed the MEG power associated with the eight brain regions of the DMN.
Post-season, the five players with a history of concussion had significantly lower connectivity between DMN regions. Players with no history of concussion had, on average, an increase in DMN connectivity.
The results demonstrate that concussions from previous years can influence the changes occurring in the brain during the current season, suggesting that longitudinal effects of concussion affect brain function.
“The brain’s DMN changes differently as a result of previous concussion,” said Dr. Davenport. “Previous concussion seems to prime the brain for additional changes. Concussion history may be affecting the brain’s ability to compensate for subconcussive impacts.”
Both researchers said that larger data sets, longitudinal studies that follow young football players, and research that combines MEG and fMRI are needed to better understand the complex factors involved in concussions.
Neurofeedback May Help Treat Tinnitus
Functional MRI (fMRI) suggests that neurofeedback training has the potential to reduce the severity of tinnitus or eliminate it.
Tinnitus affects approximately one in five people. As patients focus more on the noise, they become more frustrated and anxious, which in turn makes the noise seem worse. The primary auditory cortex has been implicated in tinnitus-related distress.
Researchers examined a potential way to treat tinnitus by having people use neurofeedback training to divert their focus from the sounds in their ears. Neurofeedback is a way of training the brain by allowing an individual to view an external indicator of brain activity and attempt to exert control over it.
“The idea is that in people with tinnitus, there is an overattention drawn to the auditory cortex, making it more active than in a healthy person,” said Matthew S. Sherwood, PhD, a research engineer in the Department of Biomedical, Industrial, and Human Factors Engineering at Wright State University in Fairborn, Ohio. “Our hope is that tinnitus sufferers could use neurofeedback to divert attention away from their tinnitus and possibly make it go away.”
To determine the potential efficacy of this approach, the researchers asked 18 healthy volunteers with normal hearing to undergo five fMRI-neurofeedback training sessions. Study participants were given earplugs through which white noise could be introduced. The earplugs also blocked out the scanner noise.
To obtain fMRI results, the researchers used single-shot echoplanar imaging, an MRI technique that is sensitive to blood oxygen levels, providing an indirect measure of brain activity.
“We started with alternating periods of sound and no sound in order to create a map of the brain and find areas that produced the highest activity during the sound phase,” said Dr. Sherwood. “Then we selected the voxels that were heavily activated when sound was being played.”
The subjects then participated in the fMRI-neurofeedback training phase while inside the MRI scanner. They received white noise through their earplugs and were able to view the activity in their primary auditory cortex as a bar on a screen. Each fMRI-neurofeedback training session contained eight blocks separated into a 30-second “relax” period, followed by a 30-second “lower” period. Participants were instructed to watch the bar during the relax period and attempt to lower it by decreasing primary auditory cortex activity during the lower phase. The researchers gave the participants techniques to help them do this, such as trying to divert attention from sound to other sensations like touch and sight.
“Many focused on breathing because it gave them a feeling of control,” said Dr. Sherwood. “By diverting their attention away from sound, the participants’ auditory cortex activity went down, and the signal we were measuring also went down.”
A control group of nine individuals was provided sham neurofeedback. They performed the same tasks as the other group, but the feedback came not from them, but from a random participant. By performing the exact same procedures with both groups using either real or sham neurofeedback, the researchers were able to distinguish the effect of real neurofeedback on control of the primary auditory cortex.
The study represents the first time that fMRI-neurofeedback training has been applied to demonstrate that there is a significant relationship between control of the primary auditory cortex and attentional processes. This result is important to therapeutic development, said Dr. Sherwood, because the neural mechanisms of tinnitus are unknown, but likely related to attention.
The results represent a promising avenue of research that could lead to improvements in other areas of health, like pain management, according to Dr. Sherwood. “Ultimately, we would like to take what we learned from MRI and develop a neurofeedback program that does not require MRI to use, such as an app or home-based therapy that could apply to tinnitus and other conditions,” he said.
Migraine Is Associated With High Sodium Levels in CSF
Migraineurs have significantly higher sodium concentrations in their CSF than people without migraine, according to the first study to use a technique called sodium MRI to examine patients with migraine.
Diagnosis of migraine is challenging, as the characteristics of migraines and the types of attacks vary widely among patients. Consequently, many patients with migraine are undiagnosed and untreated. Other patients, in contrast, are treated with medications for migraines even though they have a different type of headache, such as tension-type headache.
“It would be helpful to have a diagnostic tool supporting or even diagnosing migraine and differentiating migraine from all other types of headache,” said Melissa Meyer, MD, a radiology resident at the Institute of Clinical Radiology and Nuclear Medicine at University Hospital Mannheim and Heidelberg University in Heidelberg, Germany.
Dr. Meyer and colleagues explored a technique called cerebral sodium MRI as a possible means to help in the diagnosis and understanding of migraine. While MRI most often relies on protons to generate an image, sodium can be visualized as well. Research has shown that sodium plays an important role in brain chemistry.
The researchers recruited 12 women (mean age, 34) who had been clinically evaluated for migraine. The women filled out a questionnaire regarding the length, intensity, and frequency of their migraine attacks and accompanying auras. The researchers also enrolled 12 healthy women of similar age as a control group. Both groups underwent cerebral sodium MRI. Sodium concentrations of patients with migraine and healthy controls were compared and statistically analyzed.
The researchers found no significant differences between the two groups in sodium concentrations in the gray and white matter, brainstem, and cerebellum. Significant differences emerged, however, when the researchers looked at sodium concentrations in the CSF. Overall, sodium concentrations were significantly higher in the CSF of migraineurs than in healthy controls.
“These findings might facilitate the challenging diagnosis of a migraine,” said Dr. Meyer. The researchers hope to learn more about the connection between migraine and sodium in future studies. “As this was an exploratory study, we plan to examine more patients, preferably during or shortly after a migraine attack, for further validation.”
Gadolinium May Not Cause Neurologic Harm
There is no evidence that accumulation of gadolinium in the brain speeds cognitive decline, according to researchers.
“Approximately 400 million doses of gadolinium have been administered since 1988,” said Robert J. McDonald, MD, PhD, a neuroradiologist at the Mayo Clinic in Rochester, Minnesota. “Gadolinium contrast material is used in 40% to 50% of MRI scans performed today.”
Scientists previously believed that gadolinium contrast material could not cross the blood–brain barrier. Recent studies, however, including one by Dr. McDonald and colleagues, found that traces of gadolinium could be retained in the brain for years after MRI.
On September 8, 2017, the FDA recommended adding a warning about gadolinium retention in various organs, including the brain, to labels for gadolinium-based contrast agents used during MRI. The FDA highlighted several specific patient populations at greater risk, including children and pregnant women. Yet little is known about the health effects, if any, of gadolinium that is retained in the brain.
For this study, Dr. McDonald and colleagues set out to identify the neurotoxic potential of intracranial gadolinium deposition following IV administration of gadolinium-based contrast agents during MRI. The researchers used the Mayo Clinic Study of Aging (MCSA), the world’s largest prospective population-based cohort on aging, to study the effects of gadolinium exposure on neurologic and neurocognitive function.
All MCSA participants underwent extensive neurologic evaluation and neuropsychologic testing at baseline and 15-month follow-up intervals. Neurologic and neurocognitive scores were compared using standard methods between MCSA patients with no history of prior gadolinium exposure and those who had undergone prior MRI with gadolinium-based contrast agents. Progression from normal cognitive status to mild cognitive impairment and dementia was assessed using multistate Markov model analysis.
The study included 4,261 cognitively normal men and women between ages 50 and 90 (mean age, 72). Mean length of study participation was 3.7 years. Of the 4,261 participants, 1,092 (25.6%) had received one or more doses of gadolinium-based contrast agents, with at least one participant receiving as many as 28 prior doses. Median time since first gadolinium exposure was 5.6 years.
After adjusting for age, sex, education level, baseline neurocognitive performance, and other factors, gadolinium exposure was not a significant predictor of cognitive decline, dementia, diminished neuropsychologic performance, or diminished motor performance. No dose-related effects were observed among these metrics. Gadolinium exposure was not an independent risk factor in the rate of cognitive decline from normal cognitive status to dementia in this study group.
“There is concern over the safety of gadolinium-based contrast agents, particularly relating to gadolinium retention in the brain and other tissues,” said Dr. McDonald. “This study provides useful data that at the reasonable doses [that] 95% of the population is likely to receive in their lifetime, there is no evidence at this point that gadolinium retention in the brain is associated with adverse clinical outcomes.”
Imaging Shows Youth Football’s Effects on the Brain
School-age football players with a history of concussion and high impact exposure undergo brain changes after one season of play, according to two studies conducted at the University of Texas Southwestern Medical Center in Dallas and Wake Forest University in Winston-Salem, North Carolina.
Both studies analyzed the default mode network (DMN), a system of brain regions that is active during wakeful rest. Changes in the DMN are observed in patients with mental disorders. Decreased connectivity within the network is also associated with traumatic brain injury.
“The DMN exists in the deep gray matter areas of the brain,” said Elizabeth M. Davenport, PhD, a postdoctoral researcher in the Advanced NeuroScience Imaging Research (ANSIR) lab at UT Southwestern’s O’Donnell Brain Institute. “It includes structures that activate when we are awake and engaging in introspection or processing emotions, which are activities that are important for brain health.”
In the first study, researchers studied youth football players without a history of concussion to identify the effect of repeated subconcussive impacts on the DMN.
“Over a season of football, players are exposed to numerous head impacts. The vast majority of these do not result in concussion,” said Gowtham Krishnan Murugesan, a PhD student in biomedical engineering and member of the ANSIR laboratory. “This work adds to a growing body of literature indicating that subconcussive head impacts can have an effect on the brain. This is a highly understudied area at the youth and high school level.”
For the study, 26 youth football players (ages 9–13) were outfitted with the Head Impact Telemetry System (HITS) for an entire football season. HITS helmets are lined with accelerometers that measure the magnitude, location, and direction of impacts to the head. Impact data from the helmets were used to calculate a risk of concussion exposure for each player.
Players were separated into high and low concussion exposure groups. Players with a history of concussion were excluded. A third group of 13 noncontact sport controls was established. Pre- and post-season resting functional MRI (fMRI) scans were performed on all players and controls, and connectivity within the DMN subcomponents was analyzed. The researchers used machine learning to analyze the fMRI data.
“Machine learning has a lot to add to our research because it gives us a fresh perspective and an ability to analyze the complex relationships within the data,” said Mr. Murugesan. “Our results suggest an increasing functional change in the brain with increasing head impact exposure.”
Five machine learning classification algorithms were used to predict whether players were in the high-exposure, low-exposure or noncontact groups, based on the fMRI results. The algorithm discriminated between high-impact exposure and noncontact controls with 82% accuracy, and between low-impact exposure and noncontact controls with 70% accuracy. The results suggest an increasing functional change with increasing head-impact exposure.
“The brains of these youth and adolescent athletes are undergoing rapid maturation in this age range. This study demonstrates that playing a season of contact sports at the youth level can produce neuroimaging brain changes, particularly for the DMN,” Mr. Murugesan said.
In the second study, 20 high school football players (median age, 16.9) wore helmets outfitted with HITS for a season. Of the 20 players, five had experienced at least one concussion, and 15 had no history of concussion.
Before and following the season, the players underwent an eight-minute magnetoencephalography (MEG) scan, which records and analyzes the magnetic fields produced by brain activity. Researchers then analyzed the MEG power associated with the eight brain regions of the DMN.
Post-season, the five players with a history of concussion had significantly lower connectivity between DMN regions. Players with no history of concussion had, on average, an increase in DMN connectivity.
The results demonstrate that concussions from previous years can influence the changes occurring in the brain during the current season, suggesting that longitudinal effects of concussion affect brain function.
“The brain’s DMN changes differently as a result of previous concussion,” said Dr. Davenport. “Previous concussion seems to prime the brain for additional changes. Concussion history may be affecting the brain’s ability to compensate for subconcussive impacts.”
Both researchers said that larger data sets, longitudinal studies that follow young football players, and research that combines MEG and fMRI are needed to better understand the complex factors involved in concussions.
Neurofeedback May Help Treat Tinnitus
Functional MRI (fMRI) suggests that neurofeedback training has the potential to reduce the severity of tinnitus or eliminate it.
Tinnitus affects approximately one in five people. As patients focus more on the noise, they become more frustrated and anxious, which in turn makes the noise seem worse. The primary auditory cortex has been implicated in tinnitus-related distress.
Researchers examined a potential way to treat tinnitus by having people use neurofeedback training to divert their focus from the sounds in their ears. Neurofeedback is a way of training the brain by allowing an individual to view an external indicator of brain activity and attempt to exert control over it.
“The idea is that in people with tinnitus, there is an overattention drawn to the auditory cortex, making it more active than in a healthy person,” said Matthew S. Sherwood, PhD, a research engineer in the Department of Biomedical, Industrial, and Human Factors Engineering at Wright State University in Fairborn, Ohio. “Our hope is that tinnitus sufferers could use neurofeedback to divert attention away from their tinnitus and possibly make it go away.”
To determine the potential efficacy of this approach, the researchers asked 18 healthy volunteers with normal hearing to undergo five fMRI-neurofeedback training sessions. Study participants were given earplugs through which white noise could be introduced. The earplugs also blocked out the scanner noise.
To obtain fMRI results, the researchers used single-shot echoplanar imaging, an MRI technique that is sensitive to blood oxygen levels, providing an indirect measure of brain activity.
“We started with alternating periods of sound and no sound in order to create a map of the brain and find areas that produced the highest activity during the sound phase,” said Dr. Sherwood. “Then we selected the voxels that were heavily activated when sound was being played.”
The subjects then participated in the fMRI-neurofeedback training phase while inside the MRI scanner. They received white noise through their earplugs and were able to view the activity in their primary auditory cortex as a bar on a screen. Each fMRI-neurofeedback training session contained eight blocks separated into a 30-second “relax” period, followed by a 30-second “lower” period. Participants were instructed to watch the bar during the relax period and attempt to lower it by decreasing primary auditory cortex activity during the lower phase. The researchers gave the participants techniques to help them do this, such as trying to divert attention from sound to other sensations like touch and sight.
“Many focused on breathing because it gave them a feeling of control,” said Dr. Sherwood. “By diverting their attention away from sound, the participants’ auditory cortex activity went down, and the signal we were measuring also went down.”
A control group of nine individuals was provided sham neurofeedback. They performed the same tasks as the other group, but the feedback came not from them, but from a random participant. By performing the exact same procedures with both groups using either real or sham neurofeedback, the researchers were able to distinguish the effect of real neurofeedback on control of the primary auditory cortex.
The study represents the first time that fMRI-neurofeedback training has been applied to demonstrate that there is a significant relationship between control of the primary auditory cortex and attentional processes. This result is important to therapeutic development, said Dr. Sherwood, because the neural mechanisms of tinnitus are unknown, but likely related to attention.
The results represent a promising avenue of research that could lead to improvements in other areas of health, like pain management, according to Dr. Sherwood. “Ultimately, we would like to take what we learned from MRI and develop a neurofeedback program that does not require MRI to use, such as an app or home-based therapy that could apply to tinnitus and other conditions,” he said.
Migraine Is Associated With High Sodium Levels in CSF
Migraineurs have significantly higher sodium concentrations in their CSF than people without migraine, according to the first study to use a technique called sodium MRI to examine patients with migraine.
Diagnosis of migraine is challenging, as the characteristics of migraines and the types of attacks vary widely among patients. Consequently, many patients with migraine are undiagnosed and untreated. Other patients, in contrast, are treated with medications for migraines even though they have a different type of headache, such as tension-type headache.
“It would be helpful to have a diagnostic tool supporting or even diagnosing migraine and differentiating migraine from all other types of headache,” said Melissa Meyer, MD, a radiology resident at the Institute of Clinical Radiology and Nuclear Medicine at University Hospital Mannheim and Heidelberg University in Heidelberg, Germany.
Dr. Meyer and colleagues explored a technique called cerebral sodium MRI as a possible means to help in the diagnosis and understanding of migraine. While MRI most often relies on protons to generate an image, sodium can be visualized as well. Research has shown that sodium plays an important role in brain chemistry.
The researchers recruited 12 women (mean age, 34) who had been clinically evaluated for migraine. The women filled out a questionnaire regarding the length, intensity, and frequency of their migraine attacks and accompanying auras. The researchers also enrolled 12 healthy women of similar age as a control group. Both groups underwent cerebral sodium MRI. Sodium concentrations of patients with migraine and healthy controls were compared and statistically analyzed.
The researchers found no significant differences between the two groups in sodium concentrations in the gray and white matter, brainstem, and cerebellum. Significant differences emerged, however, when the researchers looked at sodium concentrations in the CSF. Overall, sodium concentrations were significantly higher in the CSF of migraineurs than in healthy controls.
“These findings might facilitate the challenging diagnosis of a migraine,” said Dr. Meyer. The researchers hope to learn more about the connection between migraine and sodium in future studies. “As this was an exploratory study, we plan to examine more patients, preferably during or shortly after a migraine attack, for further validation.”
Gadolinium May Not Cause Neurologic Harm
There is no evidence that accumulation of gadolinium in the brain speeds cognitive decline, according to researchers.
“Approximately 400 million doses of gadolinium have been administered since 1988,” said Robert J. McDonald, MD, PhD, a neuroradiologist at the Mayo Clinic in Rochester, Minnesota. “Gadolinium contrast material is used in 40% to 50% of MRI scans performed today.”
Scientists previously believed that gadolinium contrast material could not cross the blood–brain barrier. Recent studies, however, including one by Dr. McDonald and colleagues, found that traces of gadolinium could be retained in the brain for years after MRI.
On September 8, 2017, the FDA recommended adding a warning about gadolinium retention in various organs, including the brain, to labels for gadolinium-based contrast agents used during MRI. The FDA highlighted several specific patient populations at greater risk, including children and pregnant women. Yet little is known about the health effects, if any, of gadolinium that is retained in the brain.
For this study, Dr. McDonald and colleagues set out to identify the neurotoxic potential of intracranial gadolinium deposition following IV administration of gadolinium-based contrast agents during MRI. The researchers used the Mayo Clinic Study of Aging (MCSA), the world’s largest prospective population-based cohort on aging, to study the effects of gadolinium exposure on neurologic and neurocognitive function.
All MCSA participants underwent extensive neurologic evaluation and neuropsychologic testing at baseline and 15-month follow-up intervals. Neurologic and neurocognitive scores were compared using standard methods between MCSA patients with no history of prior gadolinium exposure and those who had undergone prior MRI with gadolinium-based contrast agents. Progression from normal cognitive status to mild cognitive impairment and dementia was assessed using multistate Markov model analysis.
The study included 4,261 cognitively normal men and women between ages 50 and 90 (mean age, 72). Mean length of study participation was 3.7 years. Of the 4,261 participants, 1,092 (25.6%) had received one or more doses of gadolinium-based contrast agents, with at least one participant receiving as many as 28 prior doses. Median time since first gadolinium exposure was 5.6 years.
After adjusting for age, sex, education level, baseline neurocognitive performance, and other factors, gadolinium exposure was not a significant predictor of cognitive decline, dementia, diminished neuropsychologic performance, or diminished motor performance. No dose-related effects were observed among these metrics. Gadolinium exposure was not an independent risk factor in the rate of cognitive decline from normal cognitive status to dementia in this study group.
“There is concern over the safety of gadolinium-based contrast agents, particularly relating to gadolinium retention in the brain and other tissues,” said Dr. McDonald. “This study provides useful data that at the reasonable doses [that] 95% of the population is likely to receive in their lifetime, there is no evidence at this point that gadolinium retention in the brain is associated with adverse clinical outcomes.”
Imaging Shows Youth Football’s Effects on the Brain
School-age football players with a history of concussion and high impact exposure undergo brain changes after one season of play, according to two studies conducted at the University of Texas Southwestern Medical Center in Dallas and Wake Forest University in Winston-Salem, North Carolina.
Both studies analyzed the default mode network (DMN), a system of brain regions that is active during wakeful rest. Changes in the DMN are observed in patients with mental disorders. Decreased connectivity within the network is also associated with traumatic brain injury.
“The DMN exists in the deep gray matter areas of the brain,” said Elizabeth M. Davenport, PhD, a postdoctoral researcher in the Advanced NeuroScience Imaging Research (ANSIR) lab at UT Southwestern’s O’Donnell Brain Institute. “It includes structures that activate when we are awake and engaging in introspection or processing emotions, which are activities that are important for brain health.”
In the first study, researchers studied youth football players without a history of concussion to identify the effect of repeated subconcussive impacts on the DMN.
“Over a season of football, players are exposed to numerous head impacts. The vast majority of these do not result in concussion,” said Gowtham Krishnan Murugesan, a PhD student in biomedical engineering and member of the ANSIR laboratory. “This work adds to a growing body of literature indicating that subconcussive head impacts can have an effect on the brain. This is a highly understudied area at the youth and high school level.”
For the study, 26 youth football players (ages 9–13) were outfitted with the Head Impact Telemetry System (HITS) for an entire football season. HITS helmets are lined with accelerometers that measure the magnitude, location, and direction of impacts to the head. Impact data from the helmets were used to calculate a risk of concussion exposure for each player.
Players were separated into high and low concussion exposure groups. Players with a history of concussion were excluded. A third group of 13 noncontact sport controls was established. Pre- and post-season resting functional MRI (fMRI) scans were performed on all players and controls, and connectivity within the DMN subcomponents was analyzed. The researchers used machine learning to analyze the fMRI data.
“Machine learning has a lot to add to our research because it gives us a fresh perspective and an ability to analyze the complex relationships within the data,” said Mr. Murugesan. “Our results suggest an increasing functional change in the brain with increasing head impact exposure.”
Five machine learning classification algorithms were used to predict whether players were in the high-exposure, low-exposure or noncontact groups, based on the fMRI results. The algorithm discriminated between high-impact exposure and noncontact controls with 82% accuracy, and between low-impact exposure and noncontact controls with 70% accuracy. The results suggest an increasing functional change with increasing head-impact exposure.
“The brains of these youth and adolescent athletes are undergoing rapid maturation in this age range. This study demonstrates that playing a season of contact sports at the youth level can produce neuroimaging brain changes, particularly for the DMN,” Mr. Murugesan said.
In the second study, 20 high school football players (median age, 16.9) wore helmets outfitted with HITS for a season. Of the 20 players, five had experienced at least one concussion, and 15 had no history of concussion.
Before and following the season, the players underwent an eight-minute magnetoencephalography (MEG) scan, which records and analyzes the magnetic fields produced by brain activity. Researchers then analyzed the MEG power associated with the eight brain regions of the DMN.
Post-season, the five players with a history of concussion had significantly lower connectivity between DMN regions. Players with no history of concussion had, on average, an increase in DMN connectivity.
The results demonstrate that concussions from previous years can influence the changes occurring in the brain during the current season, suggesting that longitudinal effects of concussion affect brain function.
“The brain’s DMN changes differently as a result of previous concussion,” said Dr. Davenport. “Previous concussion seems to prime the brain for additional changes. Concussion history may be affecting the brain’s ability to compensate for subconcussive impacts.”
Both researchers said that larger data sets, longitudinal studies that follow young football players, and research that combines MEG and fMRI are needed to better understand the complex factors involved in concussions.
Neurofeedback May Help Treat Tinnitus
Functional MRI (fMRI) suggests that neurofeedback training has the potential to reduce the severity of tinnitus or eliminate it.
Tinnitus affects approximately one in five people. As patients focus more on the noise, they become more frustrated and anxious, which in turn makes the noise seem worse. The primary auditory cortex has been implicated in tinnitus-related distress.
Researchers examined a potential way to treat tinnitus by having people use neurofeedback training to divert their focus from the sounds in their ears. Neurofeedback is a way of training the brain by allowing an individual to view an external indicator of brain activity and attempt to exert control over it.
“The idea is that in people with tinnitus, there is an overattention drawn to the auditory cortex, making it more active than in a healthy person,” said Matthew S. Sherwood, PhD, a research engineer in the Department of Biomedical, Industrial, and Human Factors Engineering at Wright State University in Fairborn, Ohio. “Our hope is that tinnitus sufferers could use neurofeedback to divert attention away from their tinnitus and possibly make it go away.”
To determine the potential efficacy of this approach, the researchers asked 18 healthy volunteers with normal hearing to undergo five fMRI-neurofeedback training sessions. Study participants were given earplugs through which white noise could be introduced. The earplugs also blocked out the scanner noise.
To obtain fMRI results, the researchers used single-shot echoplanar imaging, an MRI technique that is sensitive to blood oxygen levels, providing an indirect measure of brain activity.
“We started with alternating periods of sound and no sound in order to create a map of the brain and find areas that produced the highest activity during the sound phase,” said Dr. Sherwood. “Then we selected the voxels that were heavily activated when sound was being played.”
The subjects then participated in the fMRI-neurofeedback training phase while inside the MRI scanner. They received white noise through their earplugs and were able to view the activity in their primary auditory cortex as a bar on a screen. Each fMRI-neurofeedback training session contained eight blocks separated into a 30-second “relax” period, followed by a 30-second “lower” period. Participants were instructed to watch the bar during the relax period and attempt to lower it by decreasing primary auditory cortex activity during the lower phase. The researchers gave the participants techniques to help them do this, such as trying to divert attention from sound to other sensations like touch and sight.
“Many focused on breathing because it gave them a feeling of control,” said Dr. Sherwood. “By diverting their attention away from sound, the participants’ auditory cortex activity went down, and the signal we were measuring also went down.”
A control group of nine individuals was provided sham neurofeedback. They performed the same tasks as the other group, but the feedback came not from them, but from a random participant. By performing the exact same procedures with both groups using either real or sham neurofeedback, the researchers were able to distinguish the effect of real neurofeedback on control of the primary auditory cortex.
The study represents the first time that fMRI-neurofeedback training has been applied to demonstrate that there is a significant relationship between control of the primary auditory cortex and attentional processes. This result is important to therapeutic development, said Dr. Sherwood, because the neural mechanisms of tinnitus are unknown, but likely related to attention.
The results represent a promising avenue of research that could lead to improvements in other areas of health, like pain management, according to Dr. Sherwood. “Ultimately, we would like to take what we learned from MRI and develop a neurofeedback program that does not require MRI to use, such as an app or home-based therapy that could apply to tinnitus and other conditions,” he said.
Migraine Is Associated With High Sodium Levels in CSF
Migraineurs have significantly higher sodium concentrations in their CSF than people without migraine, according to the first study to use a technique called sodium MRI to examine patients with migraine.
Diagnosis of migraine is challenging, as the characteristics of migraines and the types of attacks vary widely among patients. Consequently, many patients with migraine are undiagnosed and untreated. Other patients, in contrast, are treated with medications for migraines even though they have a different type of headache, such as tension-type headache.
“It would be helpful to have a diagnostic tool supporting or even diagnosing migraine and differentiating migraine from all other types of headache,” said Melissa Meyer, MD, a radiology resident at the Institute of Clinical Radiology and Nuclear Medicine at University Hospital Mannheim and Heidelberg University in Heidelberg, Germany.
Dr. Meyer and colleagues explored a technique called cerebral sodium MRI as a possible means to help in the diagnosis and understanding of migraine. While MRI most often relies on protons to generate an image, sodium can be visualized as well. Research has shown that sodium plays an important role in brain chemistry.
The researchers recruited 12 women (mean age, 34) who had been clinically evaluated for migraine. The women filled out a questionnaire regarding the length, intensity, and frequency of their migraine attacks and accompanying auras. The researchers also enrolled 12 healthy women of similar age as a control group. Both groups underwent cerebral sodium MRI. Sodium concentrations of patients with migraine and healthy controls were compared and statistically analyzed.
The researchers found no significant differences between the two groups in sodium concentrations in the gray and white matter, brainstem, and cerebellum. Significant differences emerged, however, when the researchers looked at sodium concentrations in the CSF. Overall, sodium concentrations were significantly higher in the CSF of migraineurs than in healthy controls.
“These findings might facilitate the challenging diagnosis of a migraine,” said Dr. Meyer. The researchers hope to learn more about the connection between migraine and sodium in future studies. “As this was an exploratory study, we plan to examine more patients, preferably during or shortly after a migraine attack, for further validation.”
Gadolinium May Not Cause Neurologic Harm
There is no evidence that accumulation of gadolinium in the brain speeds cognitive decline, according to researchers.
“Approximately 400 million doses of gadolinium have been administered since 1988,” said Robert J. McDonald, MD, PhD, a neuroradiologist at the Mayo Clinic in Rochester, Minnesota. “Gadolinium contrast material is used in 40% to 50% of MRI scans performed today.”
Scientists previously believed that gadolinium contrast material could not cross the blood–brain barrier. Recent studies, however, including one by Dr. McDonald and colleagues, found that traces of gadolinium could be retained in the brain for years after MRI.
On September 8, 2017, the FDA recommended adding a warning about gadolinium retention in various organs, including the brain, to labels for gadolinium-based contrast agents used during MRI. The FDA highlighted several specific patient populations at greater risk, including children and pregnant women. Yet little is known about the health effects, if any, of gadolinium that is retained in the brain.
For this study, Dr. McDonald and colleagues set out to identify the neurotoxic potential of intracranial gadolinium deposition following IV administration of gadolinium-based contrast agents during MRI. The researchers used the Mayo Clinic Study of Aging (MCSA), the world’s largest prospective population-based cohort on aging, to study the effects of gadolinium exposure on neurologic and neurocognitive function.
All MCSA participants underwent extensive neurologic evaluation and neuropsychologic testing at baseline and 15-month follow-up intervals. Neurologic and neurocognitive scores were compared using standard methods between MCSA patients with no history of prior gadolinium exposure and those who had undergone prior MRI with gadolinium-based contrast agents. Progression from normal cognitive status to mild cognitive impairment and dementia was assessed using multistate Markov model analysis.
The study included 4,261 cognitively normal men and women between ages 50 and 90 (mean age, 72). Mean length of study participation was 3.7 years. Of the 4,261 participants, 1,092 (25.6%) had received one or more doses of gadolinium-based contrast agents, with at least one participant receiving as many as 28 prior doses. Median time since first gadolinium exposure was 5.6 years.
After adjusting for age, sex, education level, baseline neurocognitive performance, and other factors, gadolinium exposure was not a significant predictor of cognitive decline, dementia, diminished neuropsychologic performance, or diminished motor performance. No dose-related effects were observed among these metrics. Gadolinium exposure was not an independent risk factor in the rate of cognitive decline from normal cognitive status to dementia in this study group.
“There is concern over the safety of gadolinium-based contrast agents, particularly relating to gadolinium retention in the brain and other tissues,” said Dr. McDonald. “This study provides useful data that at the reasonable doses [that] 95% of the population is likely to receive in their lifetime, there is no evidence at this point that gadolinium retention in the brain is associated with adverse clinical outcomes.”
