Freezing of Gait: Clinical, Cognitive, and Imaging Features

Dot counting is a verbal working memory task where the examinee looks at a computer screen with a mixed array of green circles, blue circles and blue squares, and instructed to count all of the blue circles on the screen one at a time and remember the final total. Once the examinee finishes counting the blue circles on one screen, the examiner switches the display to a different mixed array of green circles, blue circles and blue squares. The examinee is instructed to count the blue circles in the new display. The number of different displays presented to the examinee in each trial increases from two to seven over six trials. After counting the blue circles on all of the displays presented within a trial, the examinee recalls the total number of blue circles in each of the different displays in the order in which they were presented. The task includes six trials with possible scores ranging from 0 to 27.

The n-back paradigm is a widely used measure to assess spatial working memory. The 1-back requires maintaining and updating 1 location at a time. The examinee is shown a series of 2.4 cm white squares that appear in 15 different locations on a black computer screen. Each square is presented for 1000 ms. All of the locations are equidistant from the center of the screen. The 1-back consists of one block of 30 trials, ten of which match the location of the previous square, and 20 that are in a different location. Scoring is based on the number of accurate responses out of 30 trials.

The Flanker task assesses an individual's ability to inhibit a prepotent response. A row of five arrows is presented in the center of the screen. The examinee is required to indicate whether the centrally presented arrow is pointing either to the left or right by pressing the left or right arrow key. The examinee is presented with two different conditions during the task, incongruent and congruent. In the congruent trials, the non-target arrows point in the same direction as the target arrow and in the incongruent trials they point in the opposite direction.The stimuli are presented in a random order with each condition being presented 24 times resulting in 48 total trials. Scoring is based on the number of accurate responses out of 48 trials.

The Dimensional Set Shifting task requires the individual to alternate between responding to shape vs. color of stimuli. Examinees are required to match a stimulus on the top of the screen to one of two stimuli in the lower corners of the screen. In task-homogeneous blocks, participants perform either Task A (e.g., classifying shapes) or Task B (e.g., classifying colors). In task-heterogeneous blocks, participants alternate between the two tasks pseudo-randomly. The combination of task-homogeneous and task-heterogeneous blocks allows measurement of general switch costs (latency differences between heterogeneous and homogeneous blocks) and specific switch costs (differences between switch and non-switch trials within the heterogeneous block). Scoring is based on the number of accurate responses out of 104 trials.

The digit span test forward assesses attention and short-term memory. The digit span test backward assesses measures working memory. For the forward test, the examinee is told to listen carefully because the examiner will say a series of numbers and ask him/her to repeat them back to in the same order. For the backward test, the examiner will ask the examinee to repeat the numbers backwards, that is, by starting with the last number said and going backwards to the first number said. This process continues until the examinee can no longer remember either the full sequence of numbers or the correct order. Both forward and reverse trials are given twice. The Digit Span test is scored by the amount of numbers the examinee was able to remember in each test. The examiner must add the total number of correct sequences, backwards and forwards.

Trail A assesses scanning ability and psychomotor speed. Trail B assesses executive function. In Part A, the circles are numbered 1 - 25, and the participant should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1 - 13) and letters (A - L); as in Part A, the participant draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The participant should be instructed to connect the circles as quickly as possible. The participant is timed as he or she connects the "trail." If the participant makes an error, point it out and allow the participant to correct it. Errors affect the participant's score only in that the correction of errors is included in the completion time for the task. Participants are scored by the number of seconds taken to complete the task, with high scores revealing greater impairment.

The WCST measures cognitive flexibility and problem solving skills. The WCST consists of a pack of 4 stimulus cards and 48 response cards which are devised so that each card contains from 1 to 4 identical figures of a single color. Individually administered, it requires the participant to sort the cards according to different principles (ie, by color, form, or number). As the test progresses, there are unannounced shifts in the sorting principle which require the participant to alter his or her approach.The 'number of categories' measures the number of correct responses. The percentage of perseverative errors provides the concentration of perseverative errors in relation to the overall test performance.

Brief Visuospatial Memory Test (BVMT) is a measure of visuospatial memory. This task includes three trials of six geometric figures printed on separate pages. The participant views the stimulus page for 10 seconds and is asked to draw as many of the figures as possible in their correct location on a paget. A Delayed Recall Trial is administered after a 30-minute delay. Scoring is based on accuracy of the figure as well as its location on the page. A range of 0-12 per trial is possible (0-36 total). Higher scores are better.

Hopkins Verbal Learning Test (HVLT) provides a brief assessment of immediate recall. It is administered by reading the words aloud, then asking the participant to verbally repeat the list of words (immediately), and identify the words from a word list that is presented verbally. The participant is read a list of 12 words and is then asked to recall as many of the words as possible. Tasks include three learning trials, which, when combined produce a total recall score.The HVLT total recall score ranges from 0 to 36 with 36 being the highest and best possible score.

Hopkins Verbal Learning Test (HVLT) provides a brief assessment of delay recall. It is administered by reading the words aloud, then asking the participant to verbally repeat the list of words (after a 20-25 minute delay), and identify the words from a word list that is presented verbally. The participant is read a list of 12 words and is then asked to recall as many of the words as possible. The HVLT delayed recall score ranges from 0 to 12 with 12 being the highest and best possible score.

Morris Water Maze (MWM) Paradigm is used to study spatial memory and learning. The MWM is a virtual water maze paradigm in which the hidden platform is continually re-located. The participant has to locate a hidden platform to escape the water. The number of correct trials will be the score.

Recognition of Scenes is used to assess emotional memory. The Recognition of Scenes task requires the participant to recall various scenes that have different emotional valences. The number of correct trials will be the score.

Confrontation naming tasks are used to assess impairments of word-finding abilities in individuals with various types of neurologic impairments. Confrontation naming involves the selection of a specific label corresponding to a viewed stimulus, usually a picture, of a viewed object or action. The number of correct responses will be the score.

Fluency is measured by timed word retrieval. Participants are given 60 seconds to name as many words as possible within a given category. The more words named, the better cognition

Line orientation assesses spatial perception and orientation without requiring a motor output. The Benton Judgment of Line Orientation Test measures a person's ability to match the angle and orientation of lines in space. Participants are asked to match two angled lines to a set of 11 lines that are arranged in a semicircle and separated 18 degrees from each other.The test is a standardized test with 30 items with the minimum score being 0, indicating low visual spatial cognition and the maximum score being 30, indicating high visual spatial cognition.

Mental rotation is the ability to rotate mental representations of two-dimensional and three-dimensional objects as it is related to the visual representation of such rotation within the human mind.In a mental rotation test, the participant is asked to compare two 3D objects (or letters), often rotated in some axis, and state if they are the same image or if they are mirror images (enantiomorphs). Commonly, the test will have pairs of images each rotated a specific amount of degrees (e.g. 0°, 60°, 120° or 180°). Some pairs will be the same image rotated, and others will be mirrored. The participant will be shown a set number of the pairs. The participant will be scored on how accurately they can distinguish between the mirrored and non-mirrored pairs. The number of correct responses will be the score.

Scale for the Assessment of Positive Symptoms (SAPS) assesses the presence of psychotic symptoms. There are 34 items rated on a scale of 0-5 with 0=none and 5=severe for a minimum score of 0 and a maximum score of 170. There are 4 subscales: Hallucinations (minimum score 0; maximum score 35); Delusions (minimum score 0; maximum score 65); Bizarre Behavior (minimum score 0; maximum score 25); Positive Formal Thought Disorder (minimum score 0; maximum score 45). Each subscale contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 20). The values for the Global items are included in the Total Composite score. In each case, the higher the score, the greater the severity of symptoms.

Beck Depression Inventory (BDI) is a self-report rating inventory measuring characteristic attitudes and symptoms of depression consisting of 21 items with each item rated on a four point scale (0=not present to 3=severe). The accepted ranges are as follows: 0 to 9 indicates no depression, 10 to 18 indicates mild to moderate depression, 19 to 29 indicates moderate to severe depression and 30 to 63 indicates severe depression.

Beck Anxiety Inventory (BAI) is a self-report rating inventory measuring general anxiety consisting of 21 items with each item rated on a four point scale (0=not present to 3=severe). Scores range from 0-63, with higher scores indicating greater anxiety.

Questionnaire for Impulsive-Compulsive disorders in Parkinson's disease (QUIP) is a rating scale designed to measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in Parkinson's disease. QUIP has four primary questions (pertaining to commonly reported thoughts, urges/desires, and behaviors associated with Impulse control disorders (ICDs)), each applied to the 4 ICDs (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). It uses a 5-point Likert scale (score 0-4 for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16, with a higher score indicating greater severity (ie, frequency) of symptoms. The total QUIP score for all ICDs and related disorders combined ranges from 0 to 112.

The NFOG-Q is used to quantify FOG severity and frequency in the daily living. It is a self-report measure that begins with the presentation of a short video to illustrate FOG during walking, turning and starting gait and then follows with questions related to frequency and duration of each type of FOG episode. Part I detects the presence of FOG using a dichotomous item in which individuals are classified as a freezer (FR) or a non-freezer (NFR). Parts II and III are designed for FRs only, providing a total summed score between 0 and 28. Part II (items 2-6, scoring range 0-19) rated the severity of FOG based on its duration and frequency. Part III rates the impact of FOG on daily life (items 7-9, scoring range 0-9).

The high-resolution neuromelanin images using a magnetic resonance imaging (MRI) technique will examine noradrenergic neurons in the brain.

Positron emission tomography (PET) is a technique for measuring the 3-dimensional distribution of radioactive tracers in the living human. The norepinephrine transporter (NET) ligand, [11C]MeNER, with PET imaging will measure changes in norepinephrine terminals in key brain regions and compare FOG subtypes and non-FOG PD.

Cerebrospinal fluid (CSF) collected via lumbar puncture to measure catecholamines and proteomics.

The Montreal Cognitive Assessment (MoCA) is a brief 30-point screening instrument that identifies subjects with mild cognitive impairment. Total MoCA score represents the sum of these 30-points, with a lower score indicating greater cognitive impairment. 30 is the maximum score, with a score of 26 or higher considered normal and below 26 indicative of Mild Cognitive Impairment.