Monthly Archives: May 2017

Information About Fragmentation That Explain Aphasia Recovery

While it is common for people who have had a stroke to experience language disturbances (aphasia), approximately 60 to 70 percent of survivors recover their ability to produce language within six months. The other 30 to 40 percent of stroke patients, however, suffer permanent aphasia.

Differences between patients in the degree to which language is eventually recovered are not well understood. Currently, the only prognostic estimate that clinicians can provide is an educated guess based largely on the size and location of the stroke lesion, which can be frustratingly inaccurate. Some researchers think variations in aphasia recovery may be caused by an undetected fragmentation or disorganization of brain networks that disrupts the transfer of information in areas that may be far from the lesion itself.

To investigate this theory, MUSC researchers, under the guidance of Leonardo Bonilha, M.D., Ph.D., associate professor of neurology, worked in close collaboration with a team led by Julius Fridriksson, Ph.D., professor of Communication Sciences and Disorders at the University of South Carolina’s Arnold School of Public Health, to map entire brain networks and assess post-event connectivity in 90 people who had suffered a left hemisphere stroke.

Barbara Marebwa, a Ph.D. candidate in MUSC’s Department of Neurology, and lead author, explains, “Not a lot is known about the underlying mechanisms behind differences in language recovery. We think disruption of the network structure might be responsible. So, we wanted to look at how the entire brain was connected after the stroke. Instead of focusing on the damaged region, we looked at areas they still had to work with, and mapped those networks to see associations with their aphasia severity.”

Study participants underwent language testing to establish a global aphasia severity score, followed by magnetic resonance image (MRI) scanning. By dividing the brain into 189 regions and mapping each participant’s stroke lesion, the investigators could identify and focus on white- and grey-matter areas outside of the directly affected region. A connectivity map (or connectome) was created for each patient reflecting existing neural networks within and between these brain areas.

The team then partitioned these connectivity maps into modules and calculated a ‘modularity metric’ for each participant. “This metric helps you see how well different brain regions are connected both within themselves and to other areas. The different brain areas are like people at a party — they sit and talk together in cliques based on some connection or shared similarity. Modularity shows us how tight those cliques are. Areas that are tightly connected within themselves but not to others have high modularity,” says Marebwa.

Bonilha adds, “The way the brain is connected is not random or haphazard — there’s a balance between how much regions need to be integrated or connected and how much they need to be separated. Modularity reflects that community structure. Isolated areas no longer work with the rest of the team. So, modularity is one number that tells you how well various brain areas are able to communicate or share information.”

Language is a highly complex function. To produce speech, distant brain areas must be able to accurately share information and translate it into sounds. The study, funded by the National Institute of Deafness and other Communication Disorders and the American Heart Association, assessed the overall brain network and summarized overall brain health based on connectivity, which provided important information about why and to what degree language abilities can recover.

Modularity was significantly correlated with patients’ aphasia scores, so that the higher the left hemisphere modularity, the more severe the aphasia (r= -0.42; p<0.00001). In addition, patients with highly fragmented left hemisphere community structure had more severe aphasia (r= -0.43; p<0.0001) — a correlation that held after controlling for white matter damage (r=-0.22; p=0.0175). Thus, patients with comparable white matter damage, lesion size, and location but different fragmentation patterns had very different language abilities. For example, one patient with a lesion volume of 76.1 cm3, mean white matter damage of 0.099, and 4 left hemisphere modules had an aphasia score of 88.1. Meanwhile, another patient with similar lesion volume (99.24 cm3) and mean white matter damage (0.096), but more left hemisphere modules (9), had an aphasia score of 58.2. The second patient, then, had a more fragmented left hemisphere and more severe aphasia (lower aphasia scores indicate more severe aphasia).

Says Marebwa, “It was surprising that even when we controlled for lesion location and size, it was still significant. Modularity was a better predictor of aphasia severity than some of the other estimates that rely on the size and location of the stroke — plus it gives us a lot of new information. Modularity helps us explain why some patients do better than others with their aphasia recovery. We hope that one day we’ll be able to use it to predict recovery and steer therapies, but we’re not quite there yet.”

A novel aspect of this study was the complex mathematical algorithms that the team used to calculate modularity. Bonilha explains, “Barbara comes to neurology research from a technical imaging background and so she has a unique ability to combine complex network mathematical models with clinical imaging studies to help us better understand brain networks. This is a new approach — there’s currently no measure of ‘brain health’. We talk about small vessel changes but we don’t know how much those affect the network and the brain’s ability to function. It’s a new frontier to have a computational method to calculate how well the brain is functioning by looking at network connectivity and to have a single number indicating that. This may be a useful new metric of brain health, which can help us understand recovery from neurological injury, or identify problems in healthy individuals long before clinical symptoms appear.”

Eventually, modularity as a measure of brain organization and function, may be put to use in other conditions, such as dementia. The team is already working on studies in people without stroke but who have other chronic conditions that are known to impact brain health. “We’re expanding the application of our imaging calculations to cardiovascular disease, hypertension, and diabetes, to try to see how these conditions may contribute to disrupting brain networks. How that may affect patients’ resilience or recovery,” says Marebwa.

Should You Know If Brain Cells Found to Control Aging

Scientists at Albert Einstein College of Medicine have found that stem cells in the brain’s hypothalamus govern how fast aging occurs in the body. The finding, made in mice, could lead to new strategies for warding off age-related diseases and extending lifespan. The paper was published online today in Nature.

The hypothalamus was known to regulate important processes including growth, development, reproduction and metabolism. In a 2013 Nature paper, Einstein researchers made the surprising finding that the hypothalamus also regulates aging throughout the body. Now, the scientists have pinpointed the cells in the hypothalamus that control aging: a tiny population of adult neural stem cells, which were known to be responsible for forming new brain neurons.

“Our research shows that the number of hypothalamic neural stem cells naturally declines over the life of the animal, and this decline accelerates aging,” says senior author Dongsheng Cai, M.D., Ph.D., (professor of molecular pharmacology at Einstein. “But we also found that the effects of this loss are not irreversible. By replenishing these stem cells or the molecules they produce, it’s possible to slow and even reverse various aspects of aging throughout the body.”

In studying whether stem cells in the hypothalamus held the key to aging, the researchers first looked at the fate of those cells as healthy mice got older. The number of hypothalamic stem cells began to diminish when the animals reached about 10 months, which is several months before the usual signs of aging start appearing. “By old age — about two years of age in mice — most of those cells were gone,” says Dr. Cai.

The researchers next wanted to learn whether this progressive loss of stem cells was actually causing aging and was not just associated with it. So they observed what happened when they selectively disrupted the hypothalamic stem cells in middle-aged mice. “This disruption greatly accelerated aging compared with control mice, and those animals with disrupted stem cells died earlier than normal,” says Dr. Cai.

Could adding stem cells to the hypothalamus counteract aging? To answer that question, the researchers injected hypothalamic stem cells into the brains of middle-aged mice whose stem cells had been destroyed as well as into the brains of normal old mice. In both groups of animals, the treatment slowed or reversed various measures of aging.

Dr. Cai and his colleagues found that the hypothalamic stem cells appear to exert their anti-aging effects by releasing molecules called microRNAs (miRNAs). They are not involved in protein synthesis but instead play key roles in regulating gene expression. miRNAs are packaged inside tiny particles called exosomes, which hypothalamic stem cells release into the cerebrospinal fluid of mice.

The researchers extracted miRNA-containing exosomes from hypothalamic stem cells and injected them into the cerebrospinal fluid of two groups of mice: middle-aged mice whose hypothalamic stem cells had been destroyed and normal middle-aged mice. This treatment significantly slowed aging in both groups of animals as measured by tissue analysis and behavioral testing that involved assessing changes in the animals’ muscle endurance, coordination, social behavior and cognitive ability.

The researchers are now trying to identify the particular populations of microRNAs and perhaps other factors secreted by these stem cells that are responsible for these anti-aging effects — a first step toward possibly slowing the aging process and treating age-related diseases.

Build Your Optimal Intra-Workout Supplement

Your body works hard during training. An intra-workout supplement that contains a high concentration of amino acids maximizes those efforts and accelerates your progress.

How? Intra-workout supplementation takes effect at the exact time your body needs it. During exercise, blood flow to your muscles and nutrient absorption are at an all-time high.

When consumed as an intra-workout supplement, amino acids promote muscle building and fights muscle breakdown. This means you’ll see improvements in both performance and recovery.

But creating the best intra-workout supplement is a matter of individual goals, preferences, and priorities.

Here, we’re breaking down the different types of amino acids, their sources, and dosage guidelines, so you have all the information you need to build your optimal intra-workout supplementation plan.


Even as healthy adults, our bodies cannot make the nine classified essential amino acids (EAAs) so we need to rely on our diets to get them. Included within these nine EAAs is the branched-chain amino acids (BCAAs)—leucine, valine, and isoleucine.

If you’ve done any reading on the topic, you’ll find plenty of conflicting information about whether you should take just the BCAAs or the full spectrum of all nine EAAs.

Related: Why Intra-Workout Supplementation Works

BCAA advocators believe that athletes already consume plenty of protein, whether it’s from food or supplements, so additional EAAs are not necessary. They support only taking the BCAAs, particularly leucine, during workouts.

But EAA advocators question this stance, wondering why BCAA advocators recommend taking the other two BCAAs (valine and isoleucine) at all if leucine is the key amino acid responsible for stimulating protein synthesis (muscle building). Using leucine alone yields the same stimulus results as taking all three BCAAs, so a middle-ground stance of taking just the three BCAAs doesn’t make sense.

Here are the facts: Research has found that taking all nine EAAs may allow for a longer stimulus on protein synthesis than just taking the BCAAs alone. To gain the largest and longest protein synthesis, include all nine EAAs in your supplement. Based on scientific research, this approach will maximize the benefits of your intra-workout supplementation.

One exception to note: Emerging research shows that under extreme training conditions, our bodies may need nonessential amino acids (NEAAs) in order to sustain elevated levels of muscle protein synthesis.

Previous research has found that those who took whey protein, which contains both EAAs and NEAAs, experienced an elevated rate of muscle protein synthesis for three to five hours post-exercise, while those who just took the EAAs kept muscle protein synthesis elevated for only one to three hours.7

Given these findings, there is a strong, growing case that taking EAAs and NEAAs together from whey is superior to taking just the EAAs, and certainly superior to taking just the BCAAs.


To optimize the effects of your intra-workout supplement without upsetting your digestive tract, focus on hydrolyzed protein and free-form amino acids. As a distant third, consider your general protein powders.

Let’s explore the pros and cons of these different sources:


Whey is currently the best source of protein that has been hydrolyzed (enzymatically broken down) into rapidly absorbing di- and tripeptides.

Peptides are chains of two or more amino acids. Your body can absorb the shortest peptides rapidly and without any digestion needed. Any peptide longer than tripeptide requires digestion to break it down to either a dipeptide, tripeptide, or a single amino acid, before it can be absorbed into the blood.

It pays to check labels. If it states the percentage of di- and tripeptides, aim for a significant amount in the 30 to 50 percent range or more.


  • Our bodies’ small intestines are naturally designed to absorb di- and tripeptides intact, so no digestion is required. Absorption is quick and easy without stomach or gastrointestinal (GI) tract discomfort.
  • Hydrolyzed protein contains both EAAs and NEAAs.
  • When mixed with water, it has a very thin, easy-to-drink consistency.
  • Di- and tripeptides may actually enhance free-form amino acid transporters, further increasing the rate of absorption and creating a higher spike of amino acids in the blood during your workout.


  • Very few protein hydrolysates in the market contain any significant amount of di- and tripeptides—and the few that do are usually very expensive.
  • Di- and tripeptides can taste bitter, so it’s a challenge to flavor products so that they taste appealing.


You’ll know that a product contains single free-form amino acids if its label lists amino acids but doesn’t note a protein source, such as whey, egg, or plant.

Related: Peri-Workout Supplements – Complete Pre, Intra & Post-Workout Guide


  • Our bodies’ small intestines house a specific transporter to absorb single free-form amino acids, leading to rapid absorption into the blood without GI distress.
  • Ingesting free-form amino acids causes an almost immediate spike in amino acids that can last up to 90 minutes.
  • Due to their rapid absorption and subsequent spike in the blood, free-form amino acids produce a rapid spike in protein synthesis stimulus (muscle building).
  • They can be mixed into water and maintain a very thin consistency, making them easy to drink during an intense workout.


  • Free-form amino acids do not contain the NEAAs.
  • These can be more expensive than intact proteins, such as whey, egg or soy.
  • Free-form amino acids are more difficult to flavor than intact proteins.


Intact protein sources include regular whey protein concentrate, isolate, milk, egg, casein, soy, and other plant-based proteins. Intact means the proteins are in long chains of amino acids called polypeptides, which must be broken down into shorter di- and tripeptides and free-form amino acids before our bodies can absorb them from the small intestine into the blood.


  • Intact protein sources contain all of the EAAs and NEAAs.
  • They are inexpensive compared to hydrolyzed proteins and free-form amino acids.
  • They’re easy to flavor and usually taste good.
  • Whey protein in particular has the highest amount of EAAs, along with the lowest amount of NEAAs. More specifically, it has the highest naturally occurring amounts of the beneficial amino acid leucine (typically 10 percent).


  • Intact protein sources require digestion prior to absorption.
  • More time is required before amino acids start appearing in the blood in significant concentrations.
  • The required digestion and slower release of amino acids into your blood may limit the acute protein synthesis (muscle building) response.
  • They mix into water with a thicker consistency than free-form amino acids or di- and tripeptides, making them impractical to drink during your workout.


For the maximum protein synthesis stimulus, anti-catabolic, and recovery benefits, utilize the dosage ranges outlined below for your intra-workout supplementation. Be sure to take into account the source you choose and the amount of essential amino acids it naturally contains. You can use single sources or combine multiple sources to reach these numbers.

  1. 6-15 grams of essential amino acids
  2. 3-5 grams of the amino acid leucine, the most important stimulating protein synthesis amino acid

Related: Should I Take High Molecular Weight Carbs During My Workout?

Example (lower end of the dosing spectrum, combined sources):

  • Free-form amino acids: 5 g, with 2.5 g coming from leucine
  • Whey protein: 5 g, providing 2.0-2.5 g of EAAs and 0.5-0.7 g coming from leucine
  • Total EAAs provided: 7 g, with 3 g of leucine making up the majority

Example (upper end of the dosing spectrum, combined sources):

  • Free-form amino acids: 10 g, with 5 g coming from leucine
  • Whey protein: 10 g, providing 4.5-4.9 g of EAAs and 1.0-1.4 g coming from leucine.
  • Total EAAs provided: 14-15 g, with 6 g of leucine making up the majority

If you use single sources of protein without the addition of free-form amino acids to reach the optimal amounts of EAAs and leucine, follow these guidelines:


  • 25-30 g needed
  • 44-49% EAAs
  • 10% leucine


  • 44 g needed
  • 35-37% EAAs
  • 8% leucine


  • 44 g needed
  • 35-37% EAAs
  • 8% leucine


  • 40 g needed
  • 42% EAAs
  • 8% leucine


  • 30-35g needed
  • 42% EAAs
  • 10% leucine

You’re willing to work hard to achieve your training goals and you know the best things in life take time, effort, and commitment. To maximize your progress and performance, rely on scientifically sound strategies like optimal intra-workout supplementation. Building a nutrition plan that aligns with your priorities and preferences means you’ll gain the edge you need to succeed.