Clinical trial NCT02106819: Emotional Communication Disorders in Cerebellar Disease
Official title: Disorders of Emotional Communication in Patient With Cerebellar Dysfunction
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cerebellar Diseases
Keywords: Cerebellar Ataxia
Emotions
Affective Prosody
Facial Expression
Magnetic Resonance Imaging
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2014-04-08
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The ataxia subjects will be recruited from the University of Florida Medical Center. The age matched controls have all been recruited and tested at this point.

Brief summary: The cerebellum has been linked to cognitive and emotional functions and there is increasing evidence that damage to posterior portions of the cerebellum can result in frontal-executive, visuospatial, and verbal deficits, including dysprosodia, and affective changes including blunting of affect or disinhibited and inappropriate behavior. Based on preliminary clinical observations and tests performed in the investigator's clinic, disorders of emotional communication may also be associated with cerebellar dysfunction. Emotional communication includes the production and comprehension of facial and prosodic expressions and is critical to maintaining positive and supportive relationships. Deficits in emotional communication can have devastating effects on relationships and on quality of life for those affected. Although deficits in affect and prosody have been reported in association with posterior cerebellar disorders, there are currently no studies systematically investigating emotional communication in individuals with cerebellar dysfunction. It is known that the cerebellum has strong connections with the cerebral cortex, especially the frontal lobes, and that cortical damage from stroke or neurodegenerative disease can result in disorders of emotional communication. Impairments in the integrity of cerebellar-cerebral networks from cerebellar disease may produce similar deficits in emotional communication. The purpose of this study is to systematically investigate and describe deficits in emotional communication in a series of patients with cerebellar disease. Participants will be individuals diagnosed with posterior cerebellar degeneration or damage from a non-hemorrhagic infarction, and age-matched neurologically healthy controls. Assessment will include a battery of tests of neuropsychological function as well as tests of emotional communication. Comprehension of emotional facial and prosodic expressions will be assessed as well as production of emotional communication. The expected outcomes will be to identify and describe deficits in production and comprehension of emotional prosodic and facial expressions and to describe the relationship between deficits in emotional communication and cerebellar atrophy with magnetic resonance imaging imaging (MRI) using voxel based morphometry (VBM).

Detailed description: The specific aims of this proposal will investigate the hypothesis that cerebellar damage is associated with emotional communication deficits.

* Determine whether posterior cerebellar damage results in deficits in the production or comprehension of emotional facial expressions and/or vocal prosodic expressions
* Determine whether posterior cerebellar damage results in alterations in intensity of reaction to emotionally evocative pictures or emotionally evocative words
* Investigate the relationship between performance on tests of emotional communication and left versus right cerebellar atrophy with magnetic resonance imaging imaging (MRI) using voxel based morphometry (VBM) analysis

All subjects (cerebellar and control) will be given the following testing in a single session of lasting 3 to 3 and a half hours. Included will be tests to assess reading ability, naming ability, several tests of memory, a test of ability to discriminate between faces, tests of mental flexibility, and standardized questionnaires for depression, anxiety and emotional empathy. The tests include:

1. Wechsler Test of Adult Reading
2. Montreal Cognitive Assessment
3. Beck Depression Inventory - 2
4. Wisconsin Card Sorting test
5. Toronto Alexithymia Scale
6. Multi-Dimensional Emotional Empathy Scale

All subjects will also be given tests assessing emotional communication ability. Tests of recognition and expression of emotional tones of voice and facial expression will be performed. Expression of facial expressions and tones of voice will be video recorded so that blinded raters can compare the accuracy and intensity of facial expressions and tones of voice between the participants. Training for the raters will include familiarization with the descriptions of features for each emotion with respect to changes in pitch, loudness, and rate for prosody and changes in facial features for facial expression. Both intra- and inter-judge reliability will be calculated for these blinded judges. To supplement this perceptual analysis, the participant's responses will be recorded using VisiPitch IV software, a clinical instrument that performs sound analyses and calculates the variation in the range of fundamental frequency (i.e., pitch variation) across each sentence. The ability to manipulate pitch to produce varying prosodic contours is the most salient acoustical feature of affective prosody.

We will also assess intensity ratings and descriptions of emotional pictures and words using materials that have established rating norms. Participants will be shown a series of pictures and asked to rate the emotional intensity of the picture. They will also be asked to give a brief description of the picture. They will then be given a list of words, one at a time, and asked to rate the emotional intensity of these words.

Some of the cerebellar participants will also be asked to participate in a magnetic resonance imaging (MRI) scan of the brain if the testing listed above shows deficits in understanding or producing emotional facial expressions or tones of voice and if there are no reasons that would prevent them from being able to enter a scanner (determined by a standard MRI screen form). Healthy control participants may also be asked to participate in a magnetic resonance imaging (MRI) scan of the brain and if there are no reasons that would prevent them from being able to enter a scanner. The imaging data will be used to investigate if there is a relationship between our experimental subjects' performance on tests of emotional expression and left versus right cerebellar atrophy-injury in the cerebellar lobules with MRI imaging using a voxel based morphometry (VBM) approach. The same data from controls will be used for comparison. Neuroimaging data collection will be done using a Philips Achieva 3T scanner (Amsterdam, Netherlands) and a 32-channel SENSE head coil. Imaging collected will include anatomical T1-weighted imaging scans. Structural MP-RAGE T1-weighted scans will be acquired with 130-1.0 mm sagittal slices, FOV=240 mm (AP)-180 mm (FH), matrix= 256-192, TR= 9.90 ms, TE= 4.60 ms, Flip Angle= 8, voxel size= 1.0x 0.94x 0.94 mm. Structural data will be analyzed with FSL-VBM, an optimized VBM protocol carried out with FSL tools. First, structural images will be brain-extracted and grey matter-segmented before being registered to the MNI 152 standard space using non-linear registration The resulting images will be averaged and flipped along the x-axis to create a left-right symmetric, study-specific grey matter template. Second, all native grey matter images will be non-linearly registered to this study-specific template and "modulated" to correct for local expansion (or contraction) due to the non-linear component of the spatial transformation. The modulated grey matter images were then smoothed with an isotropic Gaussian kernel with a sigma of 6 mm. Finally, voxelwise GLM will be applied using permutation-based non-parametric testing, correcting for multiple comparisons across space.

Eligibility criteria: Inclusion Criteria:

* Men and women over the age of 18
* Individuals with cerebellar ataxia

Exclusion Criteria:

* Neurological signs reflecting major pathology in extrapyramidal, brainstem, cortical and visual systems
* Symptomatic cerebellar ataxia from alcohol, toxins, vitamin deficiency, and paraneoplastic cerebellar degeneration
* Dementia
* Current symptoms of depression or severe anxiety
* Currently on any psychotropic medication other than anti-depressants or history of a psychosis
* Severe impairments of hearing or vision
* Reading level less than 10th grade and/or history of learning disability
* Chronic medical and neurological diseases other than cerebellar (e.g., cardiac failure, renal disease, hepatic failure, stroke)
* History of severe head trauma (e.g., coma for more than one hour)

Primary outcomes:
measure: Florida Affect Battery
timeFrame: baseline
Secondary outcomes:
measure: Perceptual rating of emotional expression
timeFrame: baseline
measure: Intensity and valence ratings of emotionally evocative pictures and words
timeFrame: baseline
measure: Magnetic resonance imaging of the brain
timeFrame: approximately one week post baseline
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Department of Neurology, College of Medicine, University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Kenneth M Heilman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heilman KM, Leon SA, Burtis DB, Ashizawa T, Subramony SH. Affective communication deficits associated with cerebellar degeneration. Neurocase. 2014;20(1):18-26. doi: 10.1080/13554794.2012.713496. Epub 2012 Sep 28.