Cognitive and behavioral dysfunction in Parkinson's disease: neurochemical and clinicopathological contributions.

The cognitive and behavioral sequelae (i.e., nonmotor profile) of Parkinson's disease (PD), with executive dysfunction and depression being most prominent, have typically been overshadowed due to an emphasis on motor symptomatology. The apparent categorization of PD as a disorder isolated to the dopaminergic system may be a generalization of the disease pathology. Dopamine therapy, used for the treatment of motor symptoms, has not consistently been shown to resolve nonmotor impairments. Research evidence indicates that nondopaminergic neurotransmitter systems (i.e., serotonergic, noradrenergic, & cholinergic) are disrupted in PD and may contribute to cognitive and behavioral dysfunction. Furthermore, Lewy bodies within cortical and subcortical structures can add to the nonmotor profile in PD. Pharmacological interventions for the treatment of cognitive and behavioral impairments associated with PD are few, especially for nondemented patients. The current review of the literature highlights evidence that associates nonmotor dysfunctions with neurochemical and clinicopathological correlates of PD.

Effects of levodopa on cognitive functioning in moderate-to-severe Parkinson's disease (MSPD).

Although improved cognition has been reported in patients with mild Parkinson's disease (PD) following the administration of levodopa, mixed results have been found in moderately-to-severely affected PD patients (MSPD), particularly in studies conducted since 1980. In the present study, 16 MSPD patients were tested on separate days, once following overnight levodopa withdrawal and once while optimally treated. A battery of neuropsychological tests that assess a range of cognitive functions (i.e., attention, language, visuospatial, memory, and executive), as well as a measure of depression, were used. Although patients performed better on a measure of confrontation naming in the untreated than in the treated condition, there were no significant differences for any of the other cognitive variables or for the depression scale variable. Thus, these data suggest that there are generally no adverse or beneficial effects of levodopa therapy on cognition in MSPD patients.

Neuropsychological functioning following bilateral subthalamic nucleus stimulation in Parkinson's disease.

The cognitive effects of subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) have been examined. However, there are no reported studies that evaluate, by incorporating a disease control group, whether neuropsychological performance in surgical patients changes beyond the variability of the assessment measures. To examine this issue, 17 PD patients were tested before and after bilateral STN stimulator implantation, both on and off stimulation. Eleven matched PD controls were administered the same repeatable neuropsychological test battery twice. Relative to changes seen in the controls, the surgery for electrode placement mildly adversely affected attention and language functions. STN stimulation, per se, had little effect on cognition. The STN DBS procedure as a whole resulted in a mild decline in delayed verbal recall and language functions. There were no surgery, stimulation, or procedure effects on depression scale scores. In contrast to these group findings, one DBS patient demonstrated significant cognitive decline following surgery.

Differential amygdala activation during emotional decision and recognition memory tasks using unpleasant words: an fMRI study.

This study used fMRI to examine the response of the amygdala in the evaluation and short-term recognition memory of unpleasant vs. neutral words in nine right-handed healthy adult women. To establish specificity of the amygdala response, we examined the fMRI BOLD signal in one control region (visual cortex). Alternating blocks of unpleasant and neutral trials were presented. During the emotional decision task, subjects viewed sets of three unpleasant or three neutral words while selecting the most unpleasant or neutral word, respectively. During the memory task, subjects identified words that were presented during the emotional decision task (0.50 probability). Images were detrended, filtered, and coregistered to standard brain coordinates. The Talairach coordinates for the center of the amygdala were chosen before analysis. The BOLD signal at this location in the right hemisphere revealed a greater amplitude signal for the unpleasant relative to the neutral words during the emotional decision but not the memory task, confirmed by Time Course x Word Condition ANOVAs. These results are consistent with the memory modulatory view of amygdala function, which suggests that the amygdala facilitates long-term, but not short-term, memory consolidation of emotionally significant material. The control area showed only an effect for Time Course for both the emotional decision and memory tasks, indicating the specificity of the amygdala response to the evaluation of unpleasant words. Moreover, the right-sided amygdala activation during the unpleasant word condition was strongly correlated with the BOLD response in the occipital cortex. These findings corroborate those by other researchers that the amygdala can modulate early processing of visual information in the occipital cortex. Finally, an increase in subject's state anxiety (evaluated by questionnaire) while in the scanner correlated with amygdala activation under some conditions.

Lexical emotional expression across the life span: quantitative and qualitative analyses of word list generation tasks.

The current study examined the effects of age and gender on emotional and nonemotional expression using an experimental word list generation (WLG) task (also referred to in the literature as verbal fluency) from the New York Emotion Battery (Borod, Welkowitz, & Obler, 1992). Subjects were 28 young ( M = 29.6 years), 28 middle-aged (M = 49.8 years), and 28 older (M = 69.9 years) healthy adults. The WLG task consists of 8 emotional (E; 3 positive and 5 negative) and 8 nonemotional (NE) categories. We developed and present here a detailed word error-type analysis that was used to evaluate the lexical output. In this study, both quantitative (amount of output and error-types) and qualitative (accuracy and intensity) analyses were used. While subjects produced more nonemotional than emotional words and more positive than negative words, the amount of error-free output and the number of errors did not change with age. An age group by error-type interaction indicated that older adults, especially men, produced more repetition errors than younger adults. The error-free output was subsequently rated for accuracy and emotional intensity. The rating data revealed that older women's overall lexical output was less accurate than that produced by younger women. Also, negative emotional words were more accurate and intense than positive emotional words. The procedures described here have implications for research assessing word list generation and emotional expression in clinical populations.

A program for neuropsychological investigation of deep brain stimulation (PNIDBS) in movement disorder patients: development, feasibility, and preliminary data.

OBJECTIVE: This technical report and feasibility study propose a standardized method for collecting neuropsychological data in patients undergoing the deep brain stimulation (DBS) procedure. BACKGROUND: Programs for standardizing motor data collected in studies investigating surgical therapies for Parkinson disease are already widely used (e.g., Core Assessment Program for Intracerebral Transplantations). The development and rationale for the proposed Program for Neuropsychological Investigation of Deep Brain Stimulation (PNIDBS) are outlined, and support for the feasibility of these methodologies is provided via preliminary data. METHOD: The PNIDBS includes a core battery of neuropsychological tests that assesses a wide range of cognitive functions (attention, language, visuospatial, memory, and executive) as well as depression. Using the PNIDBS, three Parkinson disease and two dystonia patients were evaluated at baseline and after surgery, once with stimulation off and once with stimulation on. RESULTS: Patients with severe motor disabilities were able to complete the PNIDBS. These preliminary data suggest that the DBS procedure as a whole had a minimal impact on cognitive functioning in most patients studied. There was also some evidence that the one patient who showed cognitive decline after the DBS procedure had demographic and clinical characteristics that may have put him at risk for this decline. CONCLUSIONS: The procedures in the PNIDBS were systematically developed and are feasible to execute. The relatively brief core battery has multiple versions and can be supplemented to meet individual investigator needs. By evaluating the components of the DBS procedure (electrode placement and stimulation), the PNIDBS can address clinical questions regarding the cognitive effects of the DBS procedure as well as investigate basic scientific issues regarding how different cognitive functions are affected when subcortical-prefrontal circuits are manipulated by the DBS procedure.

Verbal pragmatics following unilateral stroke: emotional content and valence.

Verbal pragmatic aspects of discourse production were examined in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD), and 16 normal control right-handed adults. The facilitation effect of emotional content, valence hypothesis, and relationship between pragmatics and emotion were evaluated. Participants produced monologues while recollecting emotional and nonemotional experiences. Transcribed monologues were rated for appropriateness on 6 pragmatic features: conciseness, lexical selection, quantity, relevancy, specificity, and topic maintenance. Overall, brain-damaged groups were rated as significantly less appropriate than normals. Consistent with the facilitation effect, emotional content enhanced pragmatic performance of LBD aphasic participants yet suppressed performance of RBD participants. Contrary to the valence hypothesis, RBD participants were more impaired for positive emotions and LBD participants for negative emotions. Pragmatic appropriateness was not strongly correlated with a measure of emotional intensity.

Development of procedures for rating posed emotional expressions across facial, prosodic, and lexical channels.

A number of rating systems are available to evaluate emotional communication in a single modality. The main purpose of this study was to develop procedures to train human raters to evaluate posed expressions of emotion across three different channels of communication, i.e., facial, prosodic/intonational, and lexical/verbal. These procedures were used to evaluate posed emotional expressions produced by individuals with unilateral brain lesions from stroke. Posers in this preliminary report were two right brain-damaged, two left brain-damaged, and two normal control right-handed adults who were matched on demographic and neurological factors. Eight emotional expressions, both positive and negative, were produced in three channels and rated for intensity, pleasantness, and category accuracy. 15 normal adults served as raters, five per channel. The rating procedures were comparable across channels, with analogous properties, and yielded substantial interrater agreement. In this small sample of posers, it was observed that the expressions of the right brain-damaged group were rated as the least accurate and those of the left brain-damaged group as the most intense. When patterns of individual performance across the channels were examined, performance was quiet consistent for the normal controls yet variable for the right brain-damaged persons. These observations are in keeping with the notion that patients with right hemisphere pathology have difficulty in emotional communication. In summary, these findings suggest that comparison of emotional expressions across multiple channels is feasible.

Emotional versus nonemotional lexical perception in patients with right and left brain damage.

OBJECTIVE: This study examined lexical emotional perception in patients with unilateral brain damage. BACKGROUND: Hypotheses pertaining to laterality and emotion were tested. More specifically, we were interested in whether the right hemisphere is dominant for verbally-presented emotion. In addition, we examined whether emotional content improves the performance of patients with left brain damage (LBD) and language deficits. METHOD: Subjects were 11 patients with right brain damage (RBD), 10 patients with LBD, and 15 normal control adults. The subject groups did not differ significantly on demographic or basic cognitive variables; the patient groups were similar on neurologic variables. Parallel emotional experimental and nonemotional control tasks included word identification (or recognition), sentence identification, and word discrimination. There were eight emotional categories (e.g., happiness) and eight nonemotional categories (e.g., vision). RESULTS: A significant interaction among Group, Condition, and Task revealed that patients with RBD were significantly impaired relative to patients with LBD and normals within the emotional condition, particularly for the identification tasks. Furthermore, the performance of patients with LBD and language deficits was improved by emotional content for the sentence identification task. CONCLUSIONS: These findings suggest that the right hemisphere has a unique contribution in the identification of lexical emotional stimuli. Implications for rehabilitation of patients with LBD and language deficits and patients with RBD by means of emotion-based strategies are discussed.

Effects of lesion variables and emotion type on the perception of facial emotion.

The purpose of this study was to consider the effects of valence, motoric direction (i.e., approach/withdrawal), and arousal on the perception of facial emotion in patients with unilateral cortical lesions. We also examined the influence of lesion side, site, and size on emotional perception. Subjects were 30 right-hemisphere-damaged (RHD) and 30 left-hemisphere-damaged (LHD) male patients with focal lesions restricted primarily to the frontal, temporal, or parietal lobe. Patient groups were comparable on demographic and clinical neurological variables. Subjects were tested for their ability to match photographs of four facial emotional expressions: happiness, sadness, fear, and anger. Overall, RHD patients were significantly more impaired than LHD patients in perceiving facial emotion. Lesion side, but not site, was associated with motoric direction and valence dimensions. RHD patients had specific deficits relative to LHD patients in processing negative and withdrawal emotions; there were no group differences for positive/approach emotions. Lesion size was not significantly correlated with accuracy of emotional perception.

Psychometric aspects of verbal pragmatic ratings.

This study examined the psychometric aspects of a verbal pragmatic rating scale. The scale contained six pragmatic features (i.e., Conciseness, Lexical Selection, Quantity, Relevancy, Specificity, and Topic Maintenance) based on Grice's cooperative principles. Fifteen right brain-damaged (RBD), 15 left brain-damaged (LBD), and 16 healthy normal control (NC) right-handed adult participants produced narratives while recollecting emotional and nonemotional experiences. Naive raters evaluated each pragmatic feature for appropriateness on a 5-point Likert scale. When reliability was examined, the overall internal consistency of the pragmatic scale was extremely high (alpha =.96). Factor analysis was conducted to examine the theoretical relations among the six pragmatic features. Three meaningful factors involving discourse content, conceptual unity, and parsimony were identified. Findings are discussed in light of Grice's model and the construct validity of the scale.

Lateralization of facial emotional expression in schizophrenic and depressed patients.

This study examined facial emotional expressions produced by schizophrenic (SZ), unipolar depressed (UD), and normal control (NC) righthanded adults. Hypotheses regarding right-hemisphere activation in UD and suppression in SZ were addressed, as well as hypotheses about emotion and laterality. Subjects were videotaped while posing positive, neutral, and negative facial expressions to verbal command and to visual imitation. Naive judges rated hemiface stimuli for intensity in original and mirror-reversed orientations. Overall, SZs produced expressions with diminished intensity relative to UDs and NCs. Across subject groups, expressions were more intense in the visual than the verbal condition. In general, approach expressions were produced with greater right-hemiface intensity, and withdrawal expressions with greater left-hemiface intensity. UDs showed more pronounced facial asymmetry than SZs or NCs. An unanticipated right-hemispace perceptual bias among the judges may reflect the analytical, detailed rating procedure used and the presumably greater reliance by the judges on left-than right-hemisphere strategies.

The effects of age and gender on the perception of lexical emotion.

The primary purpose of this study was to examine the perception of lexical/verbal emotion across the adult life span. Secondary goals were to examine the contribution of gender and valence (i.e., pleasantness/unpleasantness) to the processing of lexical emotional stimuli. Participants were 28 young (ages 20-39), 28 middle-aged (ages 40-59), and 28 older (ages 60-85) right-handed adults; there were 14 men and 14 women in each age group. Age groups were comparable on demographic and cognitive variables. Participants made accuracy judgments and intensity ratings of emotional (both positive and negative) and nonemotional stimuli from lexical perception tasks from the New York Emotion Battery (Borod, Welkowitz, & Obler, 1992). Accuracy and intensity measures were not significantly correlated. When age was examined, older participants perceived emotional and nonemotional lexical stimuli with significantly less accuracy than did younger and middle-aged participants. On the other hand, older participants evaluated the nonemotional lexical stimuli as significantly more intense than younger participants. When gender was examined, lexical stimuli were processed more accurately by female than male participants. Further, emotional stimuli were rated more intense by female participants. Clinical implications of these findings are discussed.

Facial asymmetry during emotional expression: gender, valence, and measurement technique.

The purpose of the current study was to examine 49 extant experiments of facial asymmetry during emotional expression in normal adult males and females in regard to gender, valence, and measurement technique. When facial asymmetry was evaluated by trained judges or muscle quantification, facial expressions were left-sided, a finding implicating the right cerebral hemisphere in emotional expression. However, when self-report experiential methods were utilized, the valence hypothesis received some support. Although there was some indication in single-gender studies of greater facial lateralization for males than for females, studies involving both males and females yielded no systematic asymmetry patterns as a function of gender.

Cognitive and affective functioning in Parkinson's disease patients with lateralized motor signs.

Eleven patients with Parkinson's disease (PD) and predominantly right-sided motor signs, 12 patients with PD and predominantly left-sided signs, and 11 demographically matched healthy controls were compared on tests assessing a range of cognitive and affective functions. Assuming a novel approach, our test battery was composed of measures drawn from ones previously used in the hemiparkinson' s disease and lateralized PD literature. The two patient groups were similar in illness duration, severity of motor signs, and degree of lateralized motor deficits. Statistical analyses did not reveal significant differences between patient groups, consistent with other studies that have failed to find differences in neuropsychological functioning between PD patients with right- and left-sided motor signs.

Identification of emotion in a dichotic listening task: event-related brain potential and behavioral findings.

The lateralization of emotion perception has been examined using stimuli in both auditory and visual modalities. Studies using dichotic stimuli have generally supported the hypothesis of right-hemisphere dominance for emotion perception, whereas studies of facial and verbal emotion perception have provided evidence for the right-hemisphere and valence hypotheses. A dichotic target detection task was developed to enable acquisition of event-related potentials (ERP) from subjects engaged in emotion detection. Nonsense syllables (e.g., ba, pa) stated in seven different emotional intonations were dichotically presented to 24 young adults, in a target detection task during four separate blocks (target emotions: happiness, interest, anger, or sadness). Accuracy and reaction time and ERP measures were also collected. ERPs were recorded from 14 scalp electrodes with a nose reference and quantified for N100, sustained negativity, late positivity, and slow wave. Significantly greater left- than right-ear accuracy was obtained for the identification of target prosodic emotion. Hemispheric asymmetries of N100 and sustained negativity were found, with left-hemisphere amplitudes greater than right-hemisphere amplitudes. These ERP asymmetries were not significantly correlated with the left-ear dichotic advantage and may be related more to early phonetic processing than to emotion perception. Since the behavioral evidence supports the right-hemisphere hypothesis for emotion perception, behavioral and ERP asymmetries evident in this task reflect separable patterns of brain lateralization.

Right hemisphere emotional perception: evidence across multiple channels.

Emotional perception was examined in stroke patients across 3 communication channels: facial, prosodic, and lexical. Hemispheric specialization for emotion was tested via right-hemisphere (RH) and valence hypotheses, and relationships among channels were determined. Participants were 11 right-brain-damaged (RBD), 10 left-brain-damaged (LBD), and 15 demographically matched normal control (NC) adults. Experimental measures, with analogous psychometric properties, were identification and discrimination tasks, including a range of positive and negative emotions. Nonemotional control tasks were used for each channel. For identification, RBDs were significantly impaired relative to LBDs and NCs across channels and valences, supporting the RH hypothesis. No group differences emerged for discrimination. Findings were not influenced by demographic, clinical, or control variables. Correlations among the channels were more prominent for normal than for brain-damaged groups.

A preliminary evaluation of emotional experience and expression following unilateral brain damage.

In this preliminary study, hemispheric specialization for the experience and expression of emotion was investigated. Subjects were right-brain-damaged (RBD), left-brain-damaged (LBD), and normal control (NC) right-handed adults, carefully matched on demographic and neurological variables. Facial expressions were videotaped while subjects described recollected emotional and nonemotional experiences. Expressions were later rated by trained judges for emotional intensity and category accuracy. To examine experience, subjects evaluated the intensity and accuracy with which they had produced their monologues. RBDs produced less intense facial expressions and reported less intense emotional experiences than LBDs and NCs. LBDs rated themselves as producing expressions with less accuracy than did RBDs and NCs. These findings are consistent with research that supports the right-hemisphere hypothesis for emotion. In addition, judges' ratings and subjects' self-reports of emotional intensity were positively correlated for normal but not for brain-damaged subjects.

Social functioning and facial emotional expression in neurological and psychiatric disorders.

This study examined the relationship between facial expression and social functioning in schizophrenic, depressed, right-brain-damaged, Parkinson's disease, and normal adult participants. Raters evaluated general intensity and amount of positive and negative facial emotion while participants were producing monologues regarding pleasant and unpleasant experiences. Social functioning items were derived from three standardized inventories. Overall, patient groups displayed more negative and less positive emotion than normals, and the schizophrenic and right-brain-damaged groups showed less intense expressions than normals. Correlational analyses suggested that the more intense the facial expressions, the better the social functioning, and that the more negative emotion displayed, the poorer the social functioning.

Neuropsychological aspects of facial asymmetry during emotional expression: a review of the normal adult literature.

This review focuses on facial asymmetries during emotional expression. Facial asymmetry is defined as the expression intensity or muscular involvement on one side of the face ("hemiface") relative to the other side and has been used as a behavioral index of hemispheric specialization for facial emotional expression. This paper presents a history of the neuropsychological study of facial asymmetry, originating with Darwin. Both quantitative and qualitative aspects of asymmetry are addressed. Next, neuroanatomical bases for facial expression are elucidated, separately for posed/voluntary and spontaneous/involuntary elicitation conditions. This is followed by a comprehensive review of 49 experiments of facial asymmetry in the adult literature, oriented around emotional valence (pleasantness/unpleasantness), elicitation condition, facial part, social display rules, and demographic factors. Results of this review indicate that the left hemiface is more involved than the right hemiface in the expression of facial emotion. From a neuropsychological perspective, these findings implicate the right cerebral hemisphere as dominant for the facial expression of emotion. In spite of the compelling evidence for right-hemispheric specialization, some data point to the possibility of differential hemispheric involvement as a function of emotional valence.