Laterality in Parkinson's disease: A neuropsychological review.

Laterality of motor symptom onset in Parkinson's disease is both well-known and under-appreciated. Treatment of disorders that have asymmetric pathological features, such as stroke and epilepsy, demonstrate the importance of incorporating hemispheric lateralization and specialization into therapy and care planning. These practices could theoretically extend to Parkinson's disease, providing increased diagnostic accuracy and improved treatment outcomes. Additionally, while motor symptoms have generally received the majority of attention, non-motor features (e.g., autonomic dysfunction) also decrease quality of life and are influenced by asymmetrical neurodegeneration. Due to the laterality of cognitive and behavioral processes in the two brain hemispheres, analysis of hemibody side of onset can potentially give insight into expected symptom profile of the patient and allow for increased predictive accuracy of disease progression and outcome, thus opening the door to personalized and improved therapy in treating Parkinson's disease patients. This review discusses motor and non-motor symptoms (namely autonomic, sensory, emotional, and cognitive dysfunction) of Parkinson's disease in respect to hemispheric lateralization from a theoretical perspective in hopes of providing a framework for future research and personalized treatment.

Hostility and cognitive control: Evidence of increased cardiovascular reactivity as a function of exposure to affective stress using a dichotic listening paradigm.

Indices of cognitive control were examined in men with high and low levels of trait hostility as a function of exposure to affective and cognitive stress. A dual concurrent task paradigm was used whereby participants intentionally directed focus to the left or right ear under dichotic listening conditions before and after exposure to angry infant vocalizations. Analysis of the behavioral data supports the prediction of reduced right frontal regulatory control in men with high levels of hostility as indicated by diminished capacity to suppress report of phonemes presented to the language dominant left hemisphere (right ear) in the Focus Left condition. This diminishment in the capacity to suppress report of phonemes presented to the right ear in the Focus Left condition is suggestive of reduced cognitive control. With respect to the neurophysiological data, heart rate increased for only men with high levels of hostility in the Focus Left condition, and this was especially evident in the post-affective stress condition. This increase in right hemisphere arousal provides additional evidence of reduced cognitive control and support for the capacity model of hostility by implicating poor right frontal regulatory control over right posterior cerebral regions under dual task conditions. The results are discussed in terms of integrating the construct of cognitive control into the capacity model as well as providing implications regarding reductions in the capacity to suppress predominant aggressive responses in domestic settings.

The effect of anger expression style on cardiovascular responses to lateralized cognitive stressors.

To determine the effects of self-reported anger expression style on cerebrally lateralized physiological responses to neuropsychological stressors, changes in systolic blood pressure and heart rate were examined in response to a verbal fluency task and a figural fluency task among individuals reporting either "anger in" or "anger out" expression styles. Significant group by trial interaction effects was found for systolic blood pressure following administration of verbal fluency [F(1,54) = 5.86, p < 0.05] and nonverbal fluency stressors [F(1,54) = 13.68, p < .001]. Similar interactions were seen for systolic heart rate following administration of verbal fluency [F(1,54) = 5.86, p < .005] and nonverbal fluency stressors [F(1,54) = 13.68, p < .001]. The corresponding results are discussed in terms of functional cerebral systems and potential implications for physiological models of anger. Given the association between anger and negative physical health outcomes, there is a clear need to better understand the physiological components of anger. The results of this experiment indicate that a repressive "anger in" expression style is associated with deregulation of the right frontal region. This same region has been shown to be intimately involved in cardiovascular recovery, glucose metabolism, and blood pressure regulation.

Spreading activation in nonverbal memory networks.

Theories of spreading activation primarily involve semantic memory networks. However, the existence of separate verbal and visuospatial memory networks suggests that spreading activation may also occur in visuospatial memory networks. The purpose of the present investigation was to explore this possibility. Specifically, this study sought to create and describe the design frequency corpus and to determine whether this measure of visuospatial spreading activation was related to right hemisphere functioning and spreading activation in verbal memory networks. We used word frequencies taken from the Controlled Oral Word Association Test and design frequencies taken from the Ruff Figural Fluency Test as measures of verbal and visuospatial spreading activation, respectively. Average word and design frequencies were then correlated with measures of left and right cerebral functioning. The results indicated that a significant relationship exists between performance on a test of right posterior functioning (Block Design) and design frequency. A significant negative relationship also exists between spreading activation in semantic memory networks and design frequency. Based on our findings, the hypotheses were supported. Further research will need to be conducted to examine whether spreading activation exists in visuospatial memory networks as well as the parameters that might modulate this spreading activation, such as the influence of neurotransmitters.

Spreading activation in emotional memory networks and the cumulative effects of somatic markers.

The theory of spreading activation proposes that the activation of a semantic memory node may spread along bidirectional associative links to other related nodes. Although this theory was originally proposed to explain semantic memory networks, a similar process may be said to exist with episodic or emotional memory networks. The Somatic Marker hypothesis proposes that remembering an emotional memory activates the somatic sensations associated with the memory. An integration of these two models suggests that as spreading activation in emotional memory networks increases, a greater number of associated somatic markers would become activated. This process would then result in greater changes in physiological functioning. We sought to investigate this possibility by having subjects recall words associated with sad and happy memories, in addition to a neutral condition. The average ages of the memories and the number of word memories recalled were then correlated with measures of heart rate and skin conductance. The results indicated significant positive correlations between the number of happy word memories and heart rate (r = .384, p = .022) and between the average ages of the sad memories and skin conductance (r = .556, p = .001). Unexpectedly, a significant negative relationship was found between the number of happy word memories and skin conductance (r = -.373, p = .025). The results provide partial support for our hypothesis, indicating that increasing spreading activation in emotional memory networks activates an increasing number of somatic markers and this is then reflected in greater physiological activity at the time of recalling the memories.

Frontal lobe regulation of blood glucose levels: support for the limited capacity model in hostile violence-prone men.

Hostile men have reliably displayed an exaggerated sympathetic stress response across multiple experimental settings, with cardiovascular reactivity for blood pressure and heart rate concurrent with lateralized right frontal lobe stress (Trajanoski et al., in Diabetes Care 19(12):1412-1415, 1996; see Heilman et al., in J Neurol Neurosurg Psychiatry 38(1):69-72, 1975). The current experiment examined frontal lobe regulatory control of glucose in high and low hostile men with concurrent left frontal lobe (Control Oral Word Association Test [verbal]) or right frontal lobe (Ruff Figural Fluency Test [nonverbal]) stress. A significant interaction was found for Group × Condition, F (1,22) = 4.16, p ≤ .05 with glucose levels (mg/dl) of high hostile men significantly elevated as a function of the right frontal stressor (M = 101.37, SD = 13.75) when compared to the verbal stressor (M = 95.79, SD = 11.20). Glucose levels in the low hostile group remained stable for both types of stress. High hostile men made significantly more errors on the right frontal but not the left frontal stressor (M = 17.18, SD = 19.88) when compared to the low hostile men (M = 5.81, SD = 4.33). These findings support our existing frontal capacity model of hostility (Iribarren et al., in J Am Med Assoc 17(19):2546-2551, 2000; McCrimmon et al., in Physiol Behav 67(1):35-39, 1999; Brunner et al., in Diabetes Care 21(4):585-590, 1998), extending the role of the right frontal lobe to regulatory control over glucose mobilization.

Functional cerebral space theory: Towards an integration of theory and mechanisms of left hemineglect, anosognosia, and anosodiaphoria.

BACKGROUND: The current case study presents a 43 year old African American woman admitted to a Tertiary Care Rehabilitation unit at a major medical center for concerns over left-sided anesthesia and weakness. Head scans indicate a right middle cerebral arterial distribution infarct altering blood flow in temporal, parietal, and occipital regions in the right cerebral hemisphere. OBJECTIVE: Physician and therapist reports (i.e., speech and occupational therapists) referred the patient for a neuropsychological evaluation for concerns over the patient's capacity to recognize the severity of her deficits and self-care, with potential rule-outs indicated by the extant literature on right CVA for anosognosia, anosodiaphoria, and left hemibody/hemispace neglect. METHODS: The current case integrates interdisciplinary physician notation, magnetic resonance imaging and magnetic resonance angiogram, observations and reports from speech and occupational therapy, and neuropsychological assessment via standardized tests and neurobehavioral syndrome analysis. RESULTS: Evidence was found for co-occurring syndromes of moderate anosognosia, anosodiaphoria, and left hemibody/hemispatial neglect derived from shared functional cerebral space with overlapping temporal, parietal, and occipital damage. CONCLUSIONS: Clinical implications are discussed, including recommendations for therapy approaches based on functional cerebral space theory that may indicate the use of known techniques (e.g., for left hemibody neglect) that may also have therapeutic implications for treating other, more mercurial co-occurring syndromes of anosognosia and anosodiaphoria.

The dynamic opponent relativity model: an integration and extension of capacity theory and existing theoretical perspectives on the neuropsychology of arousal and emotion.

Arousal theory as discussed within the present paper refers to those mechanisms and neural systems involved in central nervous system activation and more specifically the systems involved in cortical activation. Historical progress in the evolution of arousal theory has led to a better understanding of the functional neural systems involved in arousal or activation processes and ultimately contributed much to our current theories of emotion. Despite evidence for the dynamic interplay between the left and right cerebral hemispheres, the concepts of cerebral balance and dynamic activation have been emphasized in the neuropsychological literature. A conceptual model is proposed herein that incorporates the unique contributions from multiple neuropsychological theories of arousal and emotion. It is argued that the cerebral hemispheres may play oppositional roles in emotion partially due to the differences in their functional specializations and in their persistence upon activation. In the presence of a threat or provocation, the right hemisphere may activate survival relevant responses partially derived from hemispheric specializations in arousal and emotional processing, including the mobilization of sympathetic drive to promote heightened blood pressure, heart rate, glucose mobilization and respiratory support necessary for the challenge. Oppositional processes and mechanisms are discussed, which may be relevant to the regulatory control over the survival response; however, the capacity of these systems is necessarily limited. A limited capacity mechanism is proposed, which is familiar within other physiological systems, including that providing for the prevention of muscular damage under exceptional demand. This capacity theory is proposed, wherein a link may be expected between exceptional stress within a neural system and damage to the neural system. These mechanisms are proposed to be relevant to emotion and emotional disorders. Discussion is provided on the possible role of currently applied therapeutic interventions for emotional disorders.

Quantitative electroencephalographic and neuropsychological investigation of an alternative measure of frontal lobe executive functions: the Figure Trail Making Test.

The most frequently used measures of executive functioning are either sensitive to left frontal lobe functioning or bilateral frontal functioning. Relatively little is known about right frontal lobe contributions to executive functioning given the paucity of measures sensitive to right frontal functioning. The present investigation reports the development and initial validation of a new measure designed to be sensitive to right frontal lobe functioning, the Figure Trail Making Test (FTMT). The FTMT, the classic Trial Making Test, and the Ruff Figural Fluency Test (RFFT) were administered to 42 right-handed men. The results indicated a significant relationship between the FTMT and both the TMT and the RFFT. Performance on the FTMT was also related to high beta EEG over the right frontal lobe. Thus, the FTMT appears to be an equivalent measure of executive functioning that may be sensitive to right frontal lobe functioning. Applications for use in frontotemporal dementia, Alzheimer's disease, and other patient populations are discussed.

Physiological and behavioural indices of hostility: an extension of the capacity model to include exposure to affective stress and right lateralized motor stress.

Right hemisphere functional cerebral systems have reliably been associated with sympathetic nervous system arousal and the perception of negative affective events. The goal of the current research was to provide additional support for the capacity model of hostility by examining changes attributable to functional cerebral systems within the right hemisphere using a dual concurrent task paradigm. To incorporate exposure to negative affective and right-lateralized motor stress using this approach, high and low hostile individuals completed a series of grip-strength tasks before and after hearing a recording of angry infant vocalizations. Results supported the capacity model in that high hostile individuals were unable to maintain regulatory control over right hemisphere activation as indicated through increased motor perseveration in the pre- and post-affective stress conditions, heightened systolic blood pressure (SBP) upon exposure to negative emotional sounds, and increased heart rate (HR) following stress. Conversely, low hostile individuals showed improved regulatory control over these regions as evidenced by reduced motor perseveration in the pre- and post-affective stress conditions, maintenance of SBP and reductions in HR following stress. The current data support the capacity model and extend its scope to include exposure to affective and right-lateralized motor stress.

Cerebral asymmetry in the control of cardiovascular functioning: evidence from lateral vibrotactile stimulation.

Research has supported hemispheric specialisation in the regulation of cardiovascular functioning, with the left hemisphere being associated with parasympathetic functioning and the right hemisphere with sympathetic functioning. We sought to investigate this relationship further using vibrotactile stimulation applied to the palms. Our prediction was that vibrotactile stimulation applied to the left hand would result in increased heart rate and blood pressure, and that stimulation applied to the right hand would result in decreased heart rate and blood pressure. The results indicated significant differences in heart rate change scores in the predicted direction. No differences were noted for systolic or diastolic blood pressure. Hence the findings provide partial support for the lateralisation of autonomic functions.

An extension of the functional cerebral systems approach to hostility: a capacity model utilizing a dual concurrent task paradigm.

Regulatory control of emotions and expressive fluency (verbal or design) have historically been associated with the frontal lobes. Moreover, research has demonstrated the importance of cerebral laterality with a prominent role of the right frontal regions in the regulation of negative affect (anger, hostility) and in the fluent production of designs rather than verbal fluency. In the present research, participants identified with high and with low levels of hostility were evaluated on a design fluency test twice in one experimental session. Before the second administration of the fluency test, each participant underwent physiological (cold pressor) stress. It was hypothesized that diminished right frontal capacity in high-hostile men would be evident through lowered performance on this cognitive stressor. Convergent validity of the capacity model was supported wherein high-hostile men evidenced reduced delta magnitude over the right frontal region after exposure to the physiological stressor but failed to maintain consistent levels of right cerebral activation across conditions. The results suggest an inability for high-hostile men to maintain stable levels of cerebral activation after exposure to physiological and cognitive stress. Moreover, low-hostiles showed enhanced cognitive performance on the design task with lower levels of arousal (heightened delta magnitude). In contrast, reduced arousal yielded increased executive deficits in high-hostiles as evidenced through increased perseverative errors on the design fluency task.

Influence of left versus right hemibody onset Parkinson's disease on cardiovascular control.

Whereas the left hemisphere is involved in regulating the parasympathetic nervous system, the right hemisphere regulates the sympathetic. Given the asymmetrical onset of motor symptoms and neuropathology in PD, differences in cardiovascular functions might be expected between PD patients with left hemibody onset (LHO) versus right hemibody onset (RHO). A total of 66 PD patients served as participants, including 31 LHO patients and 35 RHO PD patients. All participants had their resting heart rate (HR) and blood pressure (BP) recorded. Although the LHO group had lower systolic BP, it had higher resting HR than did the RHO group. The reason for this dissociation is not known but might be related to asymmetrical vagus nerve control of the heart (SA node). Future researchers might want to use additional indices of cardiovascular functioning that are more precise measures of parasympathetic and sympathetic functioning, as well as learn the influence of dopaminergic medications.

Neuropsychological effects of hostility and pain on emotion perception.

In order to examine the neuropsychological effects of hostility on emotional and pain processing, auditory emotion perception before and after cold pressor pain in high and low hostile men was examined. Additionally, quantitative electroencephalography (QEEG) was recorded between each experimental manipulation. Results indicated that identification of emotion post cold pressor differed as a function of hostility level and ear. Primary QEEG findings indicated increased left temporal activation after cold pressor exposure and increased reactivity to cold pressor pain in the high hostile group. Low hostile men had a bilateral increase in high beta magnitude at the temporal lobes and a bilateral increase in delta magnitude at the frontal lobes after the cold pressor. Taken together, results from the dichotic listening task and the QEEG suggest decreased cerebral laterality and left hemisphere activation for emotional and pain processing in high hostile men.

The memory screening outreach program: findings from a large community-based sample of middle-aged and older adults.

Few papers have been published concerning the efficacy of community-based memory and dementia screening programs. This article examines the descriptive, clinical, and outcome characteristics of participants attending the Memory Screening Outreach Program (MSOP). The program provided free screenings of participants' short-term memory processes, neurocognitive complaints, and depressive and psychiatric symptomatology. Screening results were subsequently forwarded to participants and their designated healthcare providers (HCPs), and approximately 8 weeks later, participants who received follow-up recommendations were mailed a survey assessing screening-related outcomes. One thousand community-based persons aged 44 to 91 participated in the program at 16 screening sites. Results indicated that 44.3% of the MSOP participants received follow-up recommendations secondary to age-inappropriate memory impairments, depressive or psychiatric symptomatology, significant neurocognitive complaints, need for respite, or a combination thereof. Memory impairments and depressive or psychiatric symptomatology contributed, at least in part, to the recommendations of 24.0% and 30.9% of the sample, respectively. The prevalence of impaired Wechsler Memory Scale-III subtest performances ranged from 20.5% to 5.4%, and 28.7% of the participants exhibited elevated depression inventory scores. Of the participants who returned follow-up surveys, 49.5% visited their primary HCPs regarding their screening results; of the participants who had not followed up, 36.8% indicated plans to do so. Of the participants who followed up, contributing conditions and diagnoses were identified in 50.9%, medication or supplement recommendations or regimen changes were provided to 47.1%, and 17.0% were referred to healthcare specialists. Overall, the MSOP proved efficacious in identifying age-inappropriate memory impairments, notable depressive and psychiatric symptomatology, and significant neurocognitive complaints in an appreciable portion of a large, community-based, sample of middle-aged and older adults, which, in turn, contributed to the identification and treatment of a diversity of conditions at follow-up.

Assessment of nonverbal learning and memory using the Design Learning Test.

The laterality of verbal and nonverbal learning and memory to the left and right temporal lobes, respectively, has received much empirical support. Researchers have often used the Rey Auditory Verbal Learning Test (RAVLT) as a measure of verbal learning and memory in these investigations. However, a precise analog of the RAVLT that uses stimuli difficult to encode verbally has not been reported. Further, although researchers have developed some measures that are essentially visuospatial analogs of the RAVLT, no correlational data have been reported attesting to the relation between the measures. The authors report the development of a nonverbal analog of the RAVLT, referred to as the Design Learning Test (DLT). Also, the authors present correlational data supporting a relation between the DLT and RAVLT, and they hope that the present study will stimulate research investigating whether the DLT is sensitive to right temporal lobe functioning.

Extending the functional cerebral systems theory of emotion to the vestibular modality: a systematic and integrative approach.

Throughout history, vestibular and emotional dysregulation have often manifested together in clinical settings, with little consideration that they may have a common basis. Regarding vestibular mechanisms, the role of brainstem and cerebellar structures has been emphasized in the neurological literature, whereas emotion processing in the cerebral hemispheres has been the focus in psychology. A conceptual model is proposed that links research in the 2 disparate fields by means of a functional cerebral systems framework. The claim is that frontal regions exert regulatory control over posterior systems for sensation and autonomic functions in a dense, interconnected network. Impairment at levels within the system is expected to influence vestibular and cognitive processes depending on the extent of frontal regulatory capacity. M. Kinsbourne's (1980) shared cerebral space model specifies the conditions under which dysfunction of the vestibular modality will influence higher cognitive levels. A position on laterality and associative relations within the right hemisphere is proposed to explain links among dizziness, nausea, and negative emotion.

Cerebral moderation of cardiovascular functioning: a functional cerebral systems perspective.

OBJECTIVE: Interhemispheric and intrahemispheric balance models may be integrated to gain an increased understanding of how cerebral systems are involved in the regulation of heart rate and blood pressure. We sought to examine the relationship between left and right frontal and posterior activity and resting heart rate and blood pressure. Based on this integration, we predicted that lateral (left minus right hemisphere) and longitudinal (frontal minus posterior regions) asymmetry in cerebral activity would be related to resting measures of heart rate and blood pressure. METHODS: Resting heart rate, blood pressure, and EEG (low and high beta) were obtained in a sample of 42 men. Physiological measures were obtained during an eyes closed resting period. RESULTS: Our results provided partial support, finding significant correlations between resting heart rate and not only frontal lobe lateral asymmetry but also frontal-parietal asymmetry. CONCLUSIONS: These results provide support for the relative differential associations of the left and right frontal and parietal lobes and cardiovascular activity. SIGNIFICANCE: Previous research has not examined cerebral control of cardiovascular functioning from a functional cerebral systems perspective. The results are discussed as they relate to research on aggression and hostility.

A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults.

BACKGROUND: In recent years, there has been increased interest in the potential health-related benefits of antioxidant- and phytochemical-rich dark chocolate and cocoa. OBJECTIVE: The objective of the study was to examine the short-term (6 wk) effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health in healthy older adults. DESIGN: A double-blind, placebo-controlled, fixed-dose, parallel-group clinical trial was used. Participants (n = 101) were randomly assigned to receive a 37-g dark chocolate bar and 8 ounces (237 mL) of an artificially sweetened cocoa beverage or similar placebo products each day for 6 wk. RESULTS: No significant group (dark chocolate and cocoa or placebo)-by-trial (baseline, midpoint, and end-of-treatment assessments) interactions were found for the neuropsychological, hematological, or blood pressure variables examined. In contrast, the midpoint and end-of-treatment mean pulse rate assessments in the dark chocolate and cocoa group were significantly higher than those at baseline and significantly higher than the midpoint and end-of-treatment rates in the control group. Results of a follow-up questionnaire item on the treatment products that participants believed they had consumed during the trial showed that more than half of the participants in both groups correctly identified the products that they had ingested during the experiment. CONCLUSIONS: This investigation failed to support the predicted beneficial effects of short-term dark chocolate and cocoa consumption on any of the neuropsychological or cardiovascular health-related variables included in this research. Consumption of dark chocolate and cocoa was, however, associated with significantly higher pulse rates at 3- and 6-wk treatment assessments.

Reduced verbal learning associated with posterior temporal lobe slow wave activity.

Functional imaging has revealed that during verbal-word learning there is activation of the left posterior temporo-parietal region (PTPL). The purpose of this study was to learn if differences in the ability of normal people to learn might be accounted for by differences in electrophysiological (EEG) measures of activation of their left, but not right, PTPL. The Rey Auditory Verbal Learning Test (RAVLT) was administered to 42 men without neurological diseases. Delta magnitude, as measured by quantitative electroencephalography (QEEG), was recorded from the left and right PTPL while the participants sat quietly with their eyes closed. The magnitude of delta EEG activity is inversely proportional to cerebral activation. Based on delta magnitude, comparison groups were created by separating those with low and high delta at the left and right PTPL. Cumulative word learning (CWL) on the RAVLT was computed by subtracting the number of words recalled on the first learning trial from the highest number of words recalled on the fourth or fifth trial and multiplying this difference by the total words recalled during all 5 learning trials. The group with a greater magnitude of left PTPL delta activity had a significantly poorer CWL scores than those with less delta, but the CWL scores of the group with a greater magnitude of delta of the right PTPL was no different that the group with less right-sided delta. No significant differences emerged at any frontal or parietal electrode site. Decreased activation of the left, but not right, PTPL appears to be associated with a decreased verbal leaning ability.