Determining the Origin Ofclustering and Switching Abilities During Verbal Fluency Tasks

DETERMINING THE ORIGIN OFCLUSTERING AND SWITCHING ABILITIES DURING VERBAL FLUENCY TASKS: A LESION STUDY

Abstract

The study “Determining the Origin of Clustering and Switching Abilities During Verbal Fluency Tasks: A Lesion Study” tried to determine which brain regions are critical to verbal fluency and its associated strategies, clustering words together and switching between clusters. The study holds importance because understanding where clustering and switching occur in the brain can serve as a way to preliminarily diagnose where tumors are in a patient’s brain. Eighty-two subjects were used with a focal lesion in the left frontal, right frontal, left temporal, or right temporal lobe. Semantic and phonemic scoring criteria for strategies were made for categorization and letter fluency tasks to score subjects’ verbal fluency tests, which were collected from the brain tumor database at Froedtert Medical Hospital. Results found that for the overall words generated, left side damage to the brain resulted in lower scores than right side damage in categorization tasks, p0.001, and letter tasks, p=0.001; in letter tasks, frontal lobe damage resulted in lower scores than temporal damage, p=0.002. All tasks showed that left side damage would lower scores for the number of clusters produced (α=0.05), and some significance was found or scores trended to suggest that left side damage would adversely affect the size of clusters and the number of switches produced. The study provides novel scoring guidelines for verbal fluency tasks, and the results imply an associative frontal-temporal network for verbal fluency in the left hemisphere where the frontal lobe is important for executive functioning and the temporal lobe provides stored information.

Thank you to everyone who supported me in this project. Every kind word and constructive criticism helped me reach my goals.

Thank you to Dr. Sabsevitz for mentoring me in this project. For every question, for all the resources you made available to me, for all the time you gave me, thank you so very much.

In addition, thank you to everyone else at Froedtert who helped me with finding files and even with reading handwriting.

Thank you to Mr. Scheuer. For the second year in a row, you have been a caring and intelligent mentor, able to guide me in the right direction and help me develop my project to its full potential.

Thank you to Dr. Swanson. As always, I greatly appreciated all your advice and support.

Thank you to Mrs. Trepte for all your interest and support in my project.

Thank you to my parents. Every step of the way, you have done everything you can to make sure I am able to pursue my love of science, and I cannot express how much your support has meant.

Thank you to Sara Miller and Seth Johnson—your support was critical to my project and your advice was invaluable.

Table of Contents

STATEMENT OF THE PROBLEM……………………………………………6
DEFINITION OF TERMS…………………………………………………………7
LITERATURE REVIEW……………………………………………………………8
RESEARCH QUESTIONS, HYPOTHESIS, AND MATERIALS...... 39
METHOD AND PRODECURE…………………………………………………40
RESULTS………………………………………………………………………………45
CONCLUSION………………………………………………………………………49
BIBLIOGRAPHY……………………………………………………………………55

Lists of Figures

FIGURES

PLANES OF THE BRAIN……………………………………………………………8
DESCRIBING THE BRAIN DIRECTIONALLY……………………………….8
MODEL OF THE BRAIN……………………………………………………………11
BRAIN MRI CONTAINING LESIONS………………………………………....38
TOTAL WORD GENERATION DURING

CATEGORIZATION AND LETTER TASKS……………………………………46

AVERAGE NUMBER OF SEMANTIC CLUSTERS

PRODUCED DURING CATEGORIZATION AND LETTER TASKS……48

AVERAGE NUMBER OF PHONEMIC CLUSTERS

PRODUCED DURING CATEGORIZATION AND LETTER TASKS…..48

Statement of the Problem

One of the greatest neurological questions is a basic one: what are the functions of different brain regions? This study seeks to determine the regions important to verbal fluency, and which brain regions function to facilitate strategies for clustering words and switching between clusters. Researching these strategies allows for a greater understanding of how words and language are organized in the brain.

Establishing the location of clustering and switching abilities can also assist in tumor detection. If a verbal fluency test is given to a patient and the scores for clustering and switching are very low, a neurologist may have a better idea of where the origin of a patient’s problem stems from. Knowing where the brain deficits may be originating can make the diagnosis and treatment process for a patient smoother and more efficient. Therefore, studies like the current one are needed to take the first step towards establishing the functions of brain regions in order for better diagnoses.

Definition of Terms

Categorization Testing—A verbal fluency test where a subject must produce words relating to a specific semantic category (ex. animals).
Clustering—The grouping of words based on a common semantic or phonemic category. Clustering is a good measure of person’s ability to organize and retrieve relevant information.
Letter Testing—A verbal fluency test where a subject must produce words starting with a specific letter. The test is usually given as a set of three separate letter tests, usually consisting of F,A,S or C,F,L for letters.
Phonemic Scoring—Scoring of verbal fluency tests based on finding clusters with words that relate by how they sound or how they are spelled.
Semantic Scoring—Scoring of verbal fluency tests based on finding clusters with words that relate categorically or by definition.
Switching—The act of moving from one cluster directly into the next. Switching is seen as a mentally effortful task and can be viewed a measure of one’s executive thinking.
Verbal Fluency Testing—Neuropsychological tests created to measure the quantity of words a subject can produce within a certain time, usually a minute. Tests are also usually restricted to certain semantic or phonemic categories, such as giving a letter or categorization test.

Literature Review

Introduction

This study examines the effect lesion location has on clustering and switching abilities during verbal fluency tasks. Considerable research was done to understand the topic before research began. The brain needed to be studied extensively, especially the cerebrum, in order to understand both the anatomies and functions of the areas that would be worked with in the study. Verbal fluency tests, the “tool” being used to measure clustering and switching abilities, needed to be studied as well, and research was collected on both semantic and phonemic fluency. Information about verbal fluency tests that looked at clustering and switching were given special attention, and general factors that could affect the outcomes of verbal fluency tests were considered as well. Finally, brief overviews on lesions and lesion studies were provided to explain the technology in the study and type of study being conducted.

The Brain

Key Information for Discussing the Brain

The three orthogonal planes, or “main views,” used for looking at the brain are axial, coronal, and sagittal planes[1]. The axial view, also called a horizontal view, is a slice of the brain parallel to the floor (if the subject is standing up). The coronal view is a vertical slice, parallel to the face. And a sagittal slice is a vertical slice as well, perpendicular to the face[2].

Figure 1[3]

Certain terms clarify the location of parts of the brain. The term “superior” refers to towards the top, while “inferior” refers to towards the bottom[4]. “Anterior” refers to the front of a structure, while “posterior” refers to towards the rear of a structure[5]. Above the midbrain, superior means dorsal, inferior means ventral, anterior means rostral, and posterior means caudal. But, because of the midbrain-diencephalic junction, the brain has a ninety degree shift in direction, causing naming to change. Under the midbrain, superior means rostral, inferior means caudal, anterior means ventral, and posterior means dorsal[6].

Figure 2

General Overview of the Brain

The general nervous system has two parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The central nervous system contains the spinal cord and brain and the peripheral nervous system is made up of nerves[7]. The CNS forms originally from the neuronal tube, and this tube’s cavities eventually become ventricles, which fill up with cerebrospinal fluid[8]. Two notable ventricles, one in each hemisphere of the brain, form as C-shapes[9]. In addition, both the brain and spinal cord contain gray and white matter[10]. This gray matter contains the most neurons, while white matter is composed of axons and colored white by the axons’ myelin sheathes; in the brain, the inner core is made up of white matter, while the outside of the brain contains gray matter[11].

The cells of the nervous system are neurons. They have a cell body, as well as axons and dendrites. These axons and dendrites help with communication throughout the body—dendrites receive output and axons carry/pass on output— and help with the formation of synapses[12]. The brain contains over ten billion neurons[13].

Other notable cells in the brain include glial cells and meninges. Glial cells, referred to as support cells, connect tissue within the central nervous system[14]. They hold CNS neurons in place and keep axons insulated to prevent “short circuits[15].” The cells can be classified as microglia, oligodendrocytes, and astrocytes[16]. In addition, meninges are coverings of the brain. The three layers of meninges consist of dura mater, arachnoid, and pia mater[17]. Another protector of the brain is the cerebral spinal fluid[18].

The brain is made up of three main parts: the forebrain (prosencephalon), the midbrain (mesencephalon), and the hindbrain (rhombencephalon); the midbrain connects the forebrain to the hindbrain. The forebrain can be broken up into the telencephalon, containing the cerebral hemispheres, and the diencephalon, the central part of the forebrain which contains the thalamus, hypothalamus, and epithalamus. The brain also has a left and right hemisphere—these hemispheres are separated at a midline called the interhemispheric, or longitudinal, tissue. The two hemispheres are connected by the corpus callosum, made up of white matter[19].

Different parts of the brain have separate functions. The cerebrum is generally used to formulate thoughts and actions and includes the cerebral cortex[20]. The cerebrum’s cerebral cortex is the “last receiving station…it relates the received information to past memories[21].” The cortex has four main lobes: the frontal lobe, temporal lobe, parietal lobe, and occipital lobe. The frontal lobe (generally) is used for reasoning, planning, speech, movement, emotions, and problem solving. The temporal lobe is used for perception, auditory stimuli, memory, and speech. The parietal lobe is used for movement, orientation, recognition, and perceiving stimuli. The occipital lobe is used for visual processing. Outside of the cerebrum is the cerebellum, an area of the brain associated with coordination, posture, and balance[22]. The cerebellum also has associations with learning, planning, judging time, emotional control, attention, and perception[23]. The brain contains its oldest part, the brain stem, which is up of the midbrain, pons, and medulla[24]. The brain stem controls automatic, basic life functions such as heartbeat and breathing[25].

Figure 3[26]

Anatomy of the Cerebrum and Cerebral Cortex

The gray matter on the surface layer of the cerebrum’s hemispheres is known as the cerebral cortex[27].The cerebrum’s cerebral cortex contains six layers of cell bodies: the superficial molecular layer, outer granular layer, pyramidal cell layer, inner granular layer, internal pyramid layer, and polymorphic cell layer.[28] Numerous crevices on the cerebral cortex are known as sulci, and the bumps or ridges between the sulci are called gyri[29]. When sulci are large enough, they are able to separate the cerebrum into lobes, which is why the frontal, temporal, parietal, and occipital lobes exist.

The brain also contains association fibers. These fibers usually connect regions in the same hemisphere, but can also connect regions across different hemispheres. For instance, the uncinate faciculus “connects [the] first motor speech area and the gyri on the inferior surface of the frontal lobe with the cortex of the pole of the temporal lobe.” Other association fibers connect the frontal lobes to the temporal lobes as well, including the cingulum, superior longitudinal fasciculus, and fronto-occipital fasciculus[30].

The frontal lobe is predictably in the front of the brain, anterior to the central sulcus (of Rolando)[31]. The frontal lobe is separated from the parietal lobe by the central sulcus[32]. The frontal lobe is lateral to and separated from the temporal lobe by the Sylvian fissure, also called the lateral fissure; a parieto-occipital sulcus helps to separate the frontal and temporal lobes as well[33]. Within the front lobe, notable gyri include the precentral gyrus, the superior frontal gyrus, the middle frontal gyrus, and the inferior frontal gyrus. The precentral gyrus contains posterior parts of the superior, middle, and inferior frontal gyri, and while the posterior region is a motor area monitoring individual movements, the anterior area is more of a premotor area used for storing information on how to move[34]. The inferior frontal lobe can be split into four main regions: the pars triangularis, pars orbitalis, dorsal pars opercularis, and ventral pars opercularis[35]. Within the inferior frontal region, Broca’s area is also contained—this area is associated with speech functions because it connects to primary motor areas and helps with the formation of words[36].

The other lobes of the brain, in different locations than the frontal lobe, are split up into smaller sections as well. The temporal lobe is an area inferior to the lateral sulcus. Superior and medial temporal sulci split the lobe into superior, middle, and inferior temporal gyri. The temporal gyrus also contains areas such as the primary auditory area (including the gyrus of Heschl), the secondary auditory area, and the sensory speech area of Wernicke. Next, the parietal lobe is posterior to the central sulcus and superior to the lateral sulcus, and extends back to the pareito-occipital sulcus. Notable parts of the parietal lobe include the superior parietal gyrus and the inferior parietal gyrus. The final lobe, the occipital lobe, is a small area contained posterior to the pareito-occipital sulcus[37].

Movement for one side of the body takes place in the primary motor cortex, found in the precentral/anterior gyrus of the frontal lobe; the other side of the body’s movement is controlled by the primary somatosensory cortex in the postcentral/posterior gyrus of the parietal lobe.

A higher level of sensory and motor interpretation is also found in the association cortex[38]. This cortex contains parts of the prefrontal, anterior temporal, and posterior parietal cortexes[39].

Verbal Fluency Testing

Verbal Fluency Tests

Verbal fluency tests, or tests of “Controlled Oral Word Association,” are neuropsychological tests designed to measure the timed, oral production of words when word generation is restricted[40]. Measurement is done quantitatively—the number of words produced is recorded[41]. For both semantic and phonemic verbal fluency tests, subjects need access to lexical memory, or access to memory of various words[42]. With this access to lexical memory, subjects must be able to initiate word generation, effectively search for words, and retrieve the information for executive/articulation[43]. To do well on verbal fluency tests, a subject also needs a semantic store for his or her knowledge of words and an effective search strategy to gather information quickly. Subjects do poorly when they lack either a knowledge base or efficient search process[44].

The two common types of verbal fluency tests are semantic (category) and phonemic (letter) fluency tasks (described in detail below). Although both types are measures of verbal fluency and overlap in where they take place in the brain, semantics and phonemics are said to function individually of each other in the brain[45]. Typically, examiners should expect subjects to do better on category, or semantic, tasks than letter, or phonemic, tasks; whether or not this is because semantic information for speech production is available in the brain before phonemic information has not been proven[46]. In any case, verbal fluency tasks are imperative clinically for finding cognitive deficits in patients, although “deficits on tests of verbal fluency do not by themselves provide evidence of executive dysfunction[47].” They are, however, an important step in realizing a patient may need treatment.