Dr. Tayim: Hello, everyone, and thanks for joining me today. My name is Fadi Tayim and I’m the Division Chief of Neuropsychology and Clinical Assistant Professor of Neurology at the Wright State University and Premier Health Clinical Neuroscience Institute. Today, I’m going to discuss the role neurocognitive assessment in the context of presurgical planning. I have no conflicts to disclose.
So I wanted to give you guys an overview about what we’re going to be talking about today. Some of our listeners will have some familiarity with neuropsych testing, which is also called neurocognitive testing, but chances are a majority of you won’t. So along the way, we’re going to cover what neuropsychology is, the different cognitive domains and where they’re located in the brain, what we might see when certain parts of the brain are damaged due to traumatic brain injury or stroke and epilepsy, tumor, you name it. Also, we’ll look at how neuropsychologists use tests for presurgical planning and how we incorporate our test results with neuroimaging like CT, MRI, EEG. And lastly, how neuropsychologists with specialized training like myself use techniques like fMRI and the intracarotid sodium amobarbital procedure, which is also called the Wada, and how we use that to isolate memory and language functions.
So we have a lot of ground to cover and I know you’re anxious to get started so let’s begin. Our brains are very, very busy. They contain the accumulation of all of our emotional experiences, our education, our ability to remember things current and past, how we speak and read, not to mention all the other cognitive abilities. Yes, our brains are very, very busy. Neuropsychology is the science is the science behind taking all the things that our brains can do, as represented by this fruit bowl, and making sense of it all so it looks more like this; something that’s predictable, measurable, and understandable. Essentially, neuropsychology is the study of brain behavior relationships. A neuropsychologist deconstructs core cognitive functions into measurable parts, similar to what we just did with the fruit bowl. Our brain thrives on making sense of the world and that’s why you can read sentences like this. Essentially, neuropsychology is the study of brain behavior relationships. A neuropsychologist deconstructs core cognitive functions into measurable parts, similar to what we did with the fruit bowl. Our brain thrives on making sense of the world and that’s why you can read these sentences.
Clinical neuropsychologists assess brain function by measuring an individual’s cognitive, sensory motor, emotional, and social behavior through formalized assessment. A clinical neuropsychologist is a neuroscientist who specializes in the application of assessment and intervention principles across the life span, especially as it relates to normal and abnormal functioning of the central nervous system.
Patients may be referred for neuropsychological assessment for a number of reasons. An evaluation can provide information about the nature and severity of a patient’s cognitive difficulties, emotional status, personality characteristics, social behavior, and adaptation to their conditions. Information about their cognitive strengths and weaknesses provides a foundation for treatment planning, vocational training, competency determination, and counseling for both patients and their families. Neuropsych assessment is often requested in cases of traumatic brain injury or TBI; cerebrovascular disorders like stroke, epilepsy, tumors, Alzheimer’s disease and related dementing disorders; and other progressive diseases like Parkinson’s disease, Huntington’s disease, MS; and also, with developmental disorders and neurological infections like meningitis, as well as psychiatric disorders like depression, ADHD, anxiety, you name it.
So today, I’m going to spend a large portion talking about epilepsy, specifically, and how our evaluation plays a role in surgical planning. But before we get to that, it’s important to understand what the cognitive domains are and how they’re assessed.
One of the most important parts of a neurocognitive exam is getting a better understanding of a patient’s longstanding abilities. We do this typically through intellectual assessments, which you guys probably know as IQ tests. For example, some people are much better at verbal skills like basic reading, reading comprehension, analytical tasks, remembering historical facts, and they may even have a very large vocabulary. These are all predominantly left-brain skills. For others, they may have stronger visual skills like perceptual reasoning and visual organization. A neuropsychologist can use these data to paint a picture of that person’s longstanding skills, answering the core question of, “Does this person have greater left than right, or right than left, hemisphere functioning?” If there’s a significant difference, the neuropsychologist will want to know more information such as if this has always been the case or if this is resulting from the patient’s presenting problem; for example, left temporal lobe epilepsy.
Next is memory – and these go in no particular order. Memory is perhaps the most complex cognitive domain to discuss because of the intricacies. We have sensory memory, long term versus short term, explicit versus implicit, episodic versus semantic, procedural memory, and I’m sure there are more types that I’m forgetting; the irony of which is not lost on me. Most neuropsychological exams will assess short and long term memory, which helps us in several different ways when we’re talking about lateralizing left versus right hemisphere abilities. For most of us – about 95% – our left hemisphere is dedicated to verbal memory while our right hemisphere is dedicated to visual memory. This is grossly simplified, I know; otherwise, I would digress into detail and would spend hours talking about bilateral activation, etc. But for the purpose of this podcast, I just wanted to really make it clear that when we talk left, we think more for verbal skills. When we talk right, it’s more for visual skills. But keeping in mind left hemisphere for verbal, right for visual; neuropsychologists are able to see if a pattern develops of greater left than right hemisphere functioning as could be the case in right temporal lobe epilepsy. I’ll talk more about memory later when we get to the Wada procedure. So for now, this is just a teaser.
Next up is attention and processing speed. Attention and processing speed are routinely part of the neurocognitive evaluation and can be negatively affected in a variety of neurological and psychiatric illnesses; for example, TBI, epilepsy, tumor, schizophrenia, ADHD, and the list continues. Attention, just like memory, can be broken down into more distinctive parts; for example, simple attention versus complex versus sustained attention, or verbal versus visual attention. Processing speed often refers to the speed at which an individual can perform a task or series of tasks. Many processing speed measures involve attention, as well as visual motor and psychomotor processing speed. While these are different skills, they are regularly lumped into the same cognitive construct. What’s important here is that attention is a fundamental part of the neurocognitive assessment as many, if not all, cognitive abilities begin with the intact ability to attend to the task. For example, we would conclude that the left hemisphere; specifically, the frontal subcortical network, is more actively involved in verbal attention while greater right hemisphere involvement would be seen in visual attention.
Next up is executive functioning. This domain is another one of those complicated constructs since there’s so much that goes into it. For example, this is where we humans have our higher order frontal lobe functions like planning and organizing; judgment and decision-making; and cognitive flexibility, switching between tasks; verbal-visual abstraction; multitasking; monitoring our performance for errors; and even working memory is an executive function as we’re manipulating information so that we can encode it into our brain. Since we humans depend on these higher order abilities for our day-to-day survival, if you will, executive dysfunction is one of the most readily identifiable complaints from patients experiencing a broad range of neurological and psychiatric illnesses. Executive functions truly involve the whole brain and thus, while we refer to frontal lobes often when talking about executive functions, we see activation all over when we use fMRI. Thus, to simplify, our takeaway here is that executive functions are a very dynamic construct and we can’t really do it justice with this limited time.
Next, I’m going to talk about language, which is another broad cognitive construct. But here, I’m just going to focus on receptive and expressive language. Receptive language refers to an individual’s ability to comprehend what it is they’re hearing, seeing, and reading. Expressive language is what’s produced by the person. So that’s their ability to coherently produce speech. A neurocognitive evaluation should contain both receptive and expressive language measures as these provide a context for which the result of the exam may be viewed. For example, if an individual’s receptive language ability is poor, it’s difficult to conclude that any poor test performance was simply a result of misunderstanding the instructions. As I mentioned before, our core language skills are greatest in our – you guessed it – language dominant hemisphere. And for most of us, that’s the left hemisphere. While we know what multiple systems are involved in language, we know that receptive language is housed in the posterior superior temporal lobe. That’s Wernicke’s area. While expressive language is primarily Broca’s area so that’s the inferior frontal lobe. Knowing the neuroanatomy of language is key when I conduct the Wada procedure, as language localization is a primary goal and the other goal, of course, being a person’s memory ability.
Now, let’s talk about visuospatial skills. Neuropsychologists often administer visuospatial tasks as part of the standard battery, as deficits often present as perceptual distortions or impairment in object or facial recognition, object rotations, spatial memory, navigation difficulties, visual neglect, and how far or close objects are. Processing of visuospatial information involves multiple brain systems though typically, involving posterior areas of the right hemisphere. For example, identification of visuospatial information is heavily reliant on intact right posterior temporal systems, which is the what visual stream. Whereas localization of visual information is dependent on intact right posterior parietal systems. That’s the where visual stream. Thus, if we were to see a patient presenting with right temporal lobe epilepsy, we’d be concerned about misidentification of objects.
Next up is motor skills, which is another helpful domain within the test battery. Typically, a neuropsychologist will assess simple motor speed like finger tapping and fine motor speed and coordination separately for each hand, noting discrepancies between scores. We usually look at differences between the patient’s dominant hand and the non-dominant hand. The motor evaluation can provide valuable information with respect to the possibility of a lateralized deficit. For example, a left hemisphere motor strip deficit would likely result in right hand apraxia. Additionally, neuropsychologists use motor performance alongside other aspects of the assessment to see if any discrepancy between the left or right hand is consistent with the other discrepancies seen between lateralizing measures so verbal and visual skills or verbal and visual memory, specifically.
Lastly, I’m going to acknowledge that neuropsychologists administer performance validity measures to gauge the patient’s effort during testing but I won’t say much else about this. If a patient’s performance on PVMs is poor, then the results are probably not valid and presurgical decisions should not be made off of those results. There’s a whole host of reasons why PVMs may be poor but effort was okay, and that’s a conversation best had with really a forensic neuropsychologist and perhaps Bob Roth, who’s a great guy. He’s really into this kind of stuff.
Okay, so now that you’re all more familiar with the cognitive domains, I wanted to dive right into what neuropsychologists use to help us lateralize deficits. That is, what test results do we use to help us determine which side of the brain is better or worse? You know that the left hemisphere is associated with verbal skills, verbal memory, right hand functions; leaving the left hemisphere to be associated with visual skills, visual memory, and left hand functions. Again, this is grossly oversimplified but it remains true. As I noted in the beginning, a major factor of lateralizing includes look at the discrepancy between longstanding core verbal and core nonverbal skills. If we notice that their nonverbal skills are worse than their verbal skills, we would have to make a note of that. And while we can’t for certain say that this discrepancy is due to something like, you know, left or right temporal lobe epilepsy; we can often make the case for laterality if we see a similar pattern of laterality that has greater left than right hemisphere functioning on other lateralizing measures like memory.
So let’s talk about memory. We know that we have left hemisphere handling a large portion of verbal memory and the right side in charge of visual memory. Again, this is grossly oversimplified, I know. Using our sample patient with left temporal lobe epilepsy, let’s say that on imaging, we see significant left hippocampal volume loss resulting from mesial temporal sclerosis. Knowing the neuroanatomy and the neuroanatomical correlates for memory, we would anticipate that our patient presents with perhaps short term memory problems and likely, long term retrieval difficulties, as well. We would use this information in addition to the VCI-PRI split that I just discussed to make a case for greater left than right hemisphere impairment. Again, we don’t know for certain if they’ve always had weaker left hemisphere abilities like verbal memory but it’s at least something to go off of. And we will continue to gather this kind of information, noting the patterns that we see across the evaluation and we’ll start to formulate our working diagnosis.
Another way we lateralize is by looking at fine and simple motor dexterity and speed. This is a more gross measure of lateralizing greater left or right hemisphere functioning and it isn’t an exact science. I say that because there are a lot of extraneous influences that can negatively affect motor speed and coordination that aren’t necessarily related to neurological disease, like arthritis. Nonetheless, to change things up, let’s say our sample patient had relatively equal motor speed using both hands. That simply tells me that while our patient has greater left than right hemisphere impairment, that doesn’t translate to motor skills, and that likely means that the motor component, you know, wasn’t effectiveaffected. The motor strip is still intact. Now, if we saw worse right hand performance, we would consider this to be consistent with the overall profile that indicates greater left than right hemisphere impairment.
Some neuropsychologists, like myself, have advanced training in neuroimaging, which comes in handy when a large part of my daily activities involve integrating impressions from scans with neurocognitive tests for clinic and research. Neuroimaging is a broad term and covers a breadth of procedures. But for the purpose of neurocognitive assessment specifically, I’ll use it to refer to the procedures that I have the most experience conducting and interpreting, which in this case, is structural and functional MRI. Most often, we’ll use fMRI to help us establish which hemisphere is dominant for language. But we can also get information about spatial skills and motor functioning. The fMRI paradigms that are administered to a patient often tap into the same cognitive construct. Typically, these include measures of visual ability, visual motor integration like finger tapping, performing physical tasks that are on the screen, that kind of thing; and tasks that are done silently; that is, they’re done in your head and not out loud like listening to words being spoken, coming up with words, filling in the blanks on sentences.
FMRI tasks are excellent in helping us see the level of activation in certain brain regions that correspond to the task. For example, if the person is administered a visual task and asked to only look at the stimulus without moving, then we would anticipate seeing the visual cortex activated more than any other region. It’s why, for language tasks, we would anticipate seeing the greatest level of activation in the language dominant hemisphere.
As with any procedure, there are certain limitations that have to be taken into consideration when conducting an fMRI. Some of these limitations include understanding that activation in certain brain regions are not critical to the functions being measured, as well as understanding that the opposite is true. A lack of activation in specific brain regions may not be specific to the task being administered.
So here’s where it gets more interesting – the Wada procedure, which is also referred to as the intracarotid sodium amobarbital procedure, is a deactivating procedure while the fMRI is considered an activating procedure. This procedure is one of the most important procedures when it comes to presurgical planning. The Wada uses amobarbital, which is also called amytal, to effectively anesthetize one hemisphere of the brain in order to measure the contralateral hemisphere’s functioning. Simply put, that means injecting the left hemisphere, putting it to sleep, so we can see how the right hemisphere is functioning and visa versa. The Wada procedure accurately addresses the question of whether cognitive abilities like language and memory can be performed without the contribution of the affected brain regions. Although a specific neurological region may be involved in the task under normal circumstances; for example, the left temporal lobe in verbal memory and the right hemisphere in visual memory, we perform the Wada procedure to determine if the left hemisphere is absolutely necessary for verbal memory. By anesthetizing the left hemisphere, we’re able to measure the right hemisphere’s ability to sustain verbal memory.
A key component of the Wada procedure is the ability to determine postoperative change, particularly as it relates to memory impairment. As is often the case in left temporal lobe epilepsy, in the event that there is significant left mesial temporal sclerosis requiring a left hippocampal resection, the Wada procedure is key in determining whether the right hemisphere is capable of performing the function that is traditionally reserved for the left hemisphere, which in this case, would be verbal memory.
So I’m not going to run through the entire Wada protocol here but instead, I’m going to discuss the necessary steps that are involved in conducting this procedure. What’s so great about the Wada procedure is how this is a neuropsychological test at its most extreme. This procedure relies on an entire medical staff to perform; beside me, our neurointerventionists, our neuroradiologists, EEG technicians, medical personnel, and my assistants.
To start this procedure, I have to first determine what side we’re going to inject first. The rationale is that if we’re able to obtain results from only one hemisphere, then it’s best to capture the results from the hemisphere that we believe is more impaired. So I use the results from structural and functional MRI, EEG, and neuropsych tests to help me determine the side to inject first. Sometimes we have a clear focal point; oftentimes, we don’t. When we don’t know where the seizures are coming from, I often begin with the left side to inject, given that left temporal lobe epilepsy is the most common. The angiogram and injections are administered by our neurointervention specialists. The procedure begins with catheterization through patient’s femoral artery and an angiogram to determine the correct placement of the catheter within the internal carotid artery. A contrast dye is injected to identify any obstructions within and against the internal carotid arterial wall and to also observe if there’s any crossflow hemispherically. Once safety has been determined, then we proceed with the procedure.
As I mentioned in the previous slide, we use amobarbital, which is injected through bolus administration over the course of three to four seconds. I typically start with 125 mg and that seems to be enough for most patients. However, if we fail to achieve EEG slowing on the ipsilateral side of injection, then I’ll increase the dosage by 25 mg increments up to a maximum of 175 mg.
Despite the medical setting of this procedure, the tasks that I present to my patients aren’t that different from the tasks that I gave them when they were in my clinic. We make sure that the tasks are similar so that I can make direct comparisons on their performance based on the cognitive domain, which is, in this case, language and memory; though motor is often a part of this procedure, as well. I’ll get into how I measure language and memory on the Wada in just a minute.
But first, I wanted to mention that the Wada procedure isn’t standardized across medical centers because the protocols are not the same. Thus, we can’t do a direct point comparison between medical centers. However, our tasks are standardized to the protocol and therefore, we use the normal distribution and descriptive ranges that I’m sure you all have seen in neuropsych reports a million times. These are average, high average, superior, very superior, etc.
With that caveat noted, the tasks on the procedure are analogous to the cognitive constructs that are being measured through traditional paper and pencil assessment. The difference here is that the patient is in a medical environment reminiscent of a surgical suite and not in the traditional outpatient environment. The tasks themselves are designed to work with the surgical environment while still validly measuring core cognitive constructs that are administered in the traditional outpatient setting.
As I mentioned before, there are practically as many different ways of performing the Wada as there are medical centers. However, many procedures include something like showing the patient some objects, having the patient read words or sentences, following instructions, look at visual stimulus, free recall and recognition memory trials, and sometimes grip strength, finger tapping, or other measures of gross motor ability. The procedure that I use here at Miami Valley Hospital is one that I was trained under at Dartmouth Medical School, which has been around for a couple decades, at least. And it originally was brought to Dartmouth by faculty from the University of Pennsylvania.
With the Wada procedure complete, now we’re ready to interpret our findings. As I had mentioned before, the scores on the Wada are standardized specifically to the protocol used and do not directly translate across medical centers who may have their own Wada protocols. That said, when we’re ready to interpret the Wada results, I look at the amount of objects, words, and designs that were correctly identified. I then calculate the amount of false positives that were reported and then I come up with the total score per hemisphere that represents that hemisphere language and memory capabilities. As noted previously, the scores have a descriptor range that are similar to those seen in neuropsych tests including very superior, superior, high average, etc.
Interpreting Wada results for language is much more straightforward than interpreting results for memory. When we first inject into the left internal carotid artery, if the patient is left hemisphere dominant for language, then we would expect speech arrest that lasts for several minutes with subsequent dysarthria and articulation difficulties lasting for another couple of minutes. In contrast, we would expect no speech arrest when the right internal carotid artery is injected. If, for example, the patient demonstrates adequate slowing on EEG after the left hemisphere is injected but they’re still able to speak, then this patient may be classified as having bilateral language representation or predominantly right hemisphere lateralization for language.
But bilateral language representation is not typically uncommon; however, it is still considered somewhat rare and problematic if the question of resection involves the language hemisphere. For example, our patient with left temporal lobe epilepsy earned a left hemisphere total score of 4 and a right hemisphere total score of 9. Looking at the standardization for this protocol, I know that a score of 4 is in the moderately impaired range while a score of 9 is in the average range and is, in fact, the highest score possible. This tells me that the left hemisphere is not capable of sustaining memory when it’s compared to the right. Thus, we conclude that with resection of the left hippocampus, we should see minimal to no postoperative change.
That brings me to my last point. If we’re capable of seeing a well-lateralized temporal lobe dysfunction, this increases the chances of good surgical outcome as it relates to a reduction in the seizure severity, frequency, and duration. In one study, Loring et al found that 89% of patients were seizure free at one-year followup based on MRI hippocampal volume asymmetries and lateralization of memory as concluded by the Wada test alone.
That brings me to the conclusion of this presentation. Specially trained neuropsychologists like myself are able to integrate neuropsychological testing results, activation patterns on functional MRI paradigms, and Wada results to correctly lateralize language and memory functions, identify focal neurological deficits, and estimates of postoperative change. Using these tools, we’re able to provide detailed information to the patient’s clinical team and provide the best patient care possible. Thank you all for listening.