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Neuropsychological disturbances in hemiparkinson's disease
Abstract
Nine parkinsonian patients with main unilateral symptoms on the right side (RHP) and nine with symptoms on the left side (LHP) were assessed through a comprehensive neuropsychological battery. RHP performed at a lower level than LHP on the WAIS verbal subtests. Although both groups scored poorly on a test of frontal lobe functions, RHP performed significantly lower than LHP. On a line bisection task, LHP showed a mild left hemispatial neglect. In conclusion, mild but significant intergroup differences were observed, tending to correlate with predominantly hemispheric functional deficits.
... As far as neuropsychological functions are concerned, reduced cognitive performances in patients with predominantly right-sided motor symptoms (RPD) have been previously documented in comparison to patients with predominantly left-sided motor symptoms (LPD) (Agosta et al., 2020;Huber et al., 1992;Katzen et al., 2006). These deficits concern global cognitive efficiency (Agosta et al., 2020), long-term verbal memory (Amick et al., 2006;Cubo et al., 2010;Foster et al., 2010;Huber et al., 1992;Starkstein et al., 1987;Starkstein and Leiguarda, 1993), language (Blonder et al., 1989;Mohr et al., 1992;Spicer et al., 1988;Starkstein et al., 1987) and for some specific authors, executive functions (Huber et al., 1992;Voruz et al., 2020;Voruz et al., 2022). Some have even suggested that RPD patients may be more vulnerable to the onset of dementia associated with PD in the long term (Harris et al., 2013). ...
... As far as neuropsychological functions are concerned, reduced cognitive performances in patients with predominantly right-sided motor symptoms (RPD) have been previously documented in comparison to patients with predominantly left-sided motor symptoms (LPD) (Agosta et al., 2020;Huber et al., 1992;Katzen et al., 2006). These deficits concern global cognitive efficiency (Agosta et al., 2020), long-term verbal memory (Amick et al., 2006;Cubo et al., 2010;Foster et al., 2010;Huber et al., 1992;Starkstein et al., 1987;Starkstein and Leiguarda, 1993), language (Blonder et al., 1989;Mohr et al., 1992;Spicer et al., 1988;Starkstein et al., 1987) and for some specific authors, executive functions (Huber et al., 1992;Voruz et al., 2020;Voruz et al., 2022). Some have even suggested that RPD patients may be more vulnerable to the onset of dementia associated with PD in the long term (Harris et al., 2013). ...
... functions, such as executive or visuospatial functions (for review see, Riederer, et al., 2018;Verreyt et al., 2011). Some studies failed to report any significant differences for visuospatial functions (Kurlawala et al., 2021;Verreyt et al., 2011), while others studies have observed worsened visuo-spatial performances in LPD patients as compared to RPD (Amick et al., 2006;Starkstein et al., 1987;Tomer et al., 1993). In this sense, the literature also suggested that inhibitory functions were underpinned by networks in the right hemisphere, thus implying a possible effect of motor symptom asymmetry in PD, with potentially greater deficits in LPD patients. ...
Introduction
The longitudinal trajectories of cognitive-neuropsychiatric symptoms from the early stages of Parkinson's disease, as a function of motor symptom asymmetry at the onset of the disease, remain to be fully explored. Moreover, the relationship to biomarkers warrants further investigation.
Method
ology: Non-motor and biospecimen data from 413 patients with Parkinson's disease, dissociating predominantly left-sided motor symptoms patients (n = 179) and predominantly right-sided motor symptoms patients (n = 234), and matched healthy controls (n = 196), were extracted from the Parkinson's Progression Marker Initiative database during a 3-Year follow-up. Non-parametric and conservative correction for multivariate comparison were carried out on neuropsychiatric and biomarker data.
Results
A decline for global cognitive efficiency scores in predominantly right-sided motor symptoms patients was observed, whereas depressive and anxiety symptoms were greater overtime for predominantly left-sided motor symptoms patients. Biomarkers analysis revealed that predominantly right-sided patients expressed decreased levels of total-tau and phospho-tau over time, while left-sided patients didn't differ from healthy controls.
Conclusion
From the early course of the disease, the existence of different clinical phenotypes is proposed, associated to emerging evidences of distinct pathological pathways and a left-hemispheric vulnerability for cognitive decline.
... In how far these findings are related to impairment of general attentional and oculomotor control is still not well understood. Overt and covert visuospatial biases have mainly been reported for patients with left hemibody onset of motor symptoms (Villardita et al., 1983; Starkstein et al., 1987; Ebersbach et al., 1996; Lee et al., 2001; Laudate et al., 2013). Left-dominant expression of parkinsonian symptoms is related to more severe neurodegeneration in the contralateral (right) basal ganglia and is often accompanied by orientation biases toward the right. ...
... In agreement with previous research showing attentional biases in patients with left-dominant symptoms in other tasks (Villardita et al., 1983; Starkstein et al., 1987; Ebersbach et al., 1996; Lee et al., 2001; Laudate et al., 2013), our patients also showed a slight rightward bias during free-viewing. The difference to control subjects was most pronounced during the first eye movements, which are usually biased to the left in healthy right-handers (Ossandón et al., 2014). ...
... This discrepancy may be explained by the small size of the bias, which became evident only by comparison with a control group. Moreover, Schmalbach et al. (2014) included patients with both left-and right-dominant symptoms whereas we evaluated only patients with left hemibody onset of symptoms, who are more likely to show attentional bias (Villardita et al., 1983; Starkstein et al., 1987; Ebersbach et al., 1996; Lee et al., 2001; Laudate et al., 2013). As mentioned above, the bias was not improved by clinical bilateral stimulation like some of the oculomotor parameters, potentially suggesting differences in the role of the basal ganglia in skeletomotor, oculomotor and attentional functions. ...
... Overt and covert visuospatial biases have mainly been reported for patients with left hemibody onset of motor symptoms (Villardita et al., 1983;Starkstein et al., 1987;Ebersbach et al., 1996;Lee et al., 2001;Laudate et al., 2013). Left-dominant expression of parkinsonian symptoms is related to more severe neurodegeneration in the contralateral (right) basal ganglia and is often accompanied by orientation biases toward the right. ...
... In agreement with previous research showing attentional biases in patients with left-dominant symptoms in other tasks (Villardita et al., 1983;Starkstein et al., 1987;Ebersbach et al., 1996;Lee et al., 2001;Laudate et al., 2013), our patients also showed a slight rightward bias during free-viewing. The difference to control subjects was most pronounced during the first eye movements, which are usually biased to the left in healthy right-handers (Ossandón et al., 2014). ...
... This discrepancy may be explained by the small size of the bias, which became evident only by comparison with a control group. Moreover, Schmalbach et al. (2014) included patients with both left-and right-dominant symptoms whereas we evaluated only patients with left hemibody onset of symptoms, who are more likely to show attentional bias (Villardita et al., 1983;Starkstein et al., 1987;Ebersbach et al., 1996;Lee et al., 2001;Laudate et al., 2013). As mentioned above, the bias was not improved by clinical bilateral stimulation like some of the oculomotor parameters, potentially suggesting differences in the role of the basal ganglia in skeletomotor, oculomotor and attentional functions. ...
In contrast to its well-established role in alleviating skeleto-motor symptoms in Parkinson´s disease, little is known about the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on oculomotor control and attention. Eye-tracking data of 17 patients with left-hemibody symptom onset was compared with 17 age- matched control subjects. Free-viewing of natural images was assessed without stimulation as baseline and during bilateral DBS. To examine the involvement of ventral STN territories in oculomotion and spatial attention, we employed unilateral stimulation via the left and right ventralmost contacts respectively. When DBS was off, patients showed shorter saccades and a rightward viewing bias compared with controls. Bilateral stimulation in therapeutic settings improved saccadic hypometria but not the visuospatial bias. At a group level, unilateral ventral stimulation yielded no consistent effects. However, the evaluation of electrode position within normalized MNI coordinate space revealed that the extent of early exploration bias correlated with the precise stimulation site within the left subthalamic area. These results suggest that oculomotor impairments but not higher-level exploration patterns are effectively ameliorable by DBS in therapeutic settings. Our findings highlight the relevance of the STN topography in selecting contacts for chronic stimulation especially upon appearance of visuospatial attention deficits.
... Some investigators note deficits in working memory, semantic fluency, setformation, cognitive sequencing, and visuomotor construction in newly diagnosed, untreated PD patients, which suggests these deficits occur independently of medication effects (Cooper et al., 1991). The most common cognitive changes involve attention and memory deficits, cognitive inflexibility, and difficulty learning new information (Direnfeld et al., 1984;Muslimovic et al., 2005;Starkstein et al., 1987;Williams-Gray et al., 2006). ...
... Other studies have shown a relationship between lateralization of PD symptoms and hemisphere specific cognitive dysfunction. Several studies reported that predominant right-sided parkinsonian symptoms (reflecting left-hemisphere dysfunction) correlate with impaired performance on verbal fluency and verbal memory, (Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989;Spicer, Roberts, & LeWitt, 1988;Starkstein et al., 1987;Taylor, Saint-Cyr, & Lang, 1986). Left-sided symptoms have been associated with visuospatial impairments (Direnfeld et al., 1984;Finali, Piccirilli, & Rizzuto, 1994) and mild left hemispatial neglect (Starkstein et al., 1987). ...
... Several studies reported that predominant right-sided parkinsonian symptoms (reflecting left-hemisphere dysfunction) correlate with impaired performance on verbal fluency and verbal memory, (Huber, Freidenberg, Shuttleworth, Paulson, & Clapp, 1989;Spicer, Roberts, & LeWitt, 1988;Starkstein et al., 1987;Taylor, Saint-Cyr, & Lang, 1986). Left-sided symptoms have been associated with visuospatial impairments (Direnfeld et al., 1984;Finali, Piccirilli, & Rizzuto, 1994) and mild left hemispatial neglect (Starkstein et al., 1987). ...
The current study examined cognitive effects of unilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients. Neuropsychological evaluations were conducted at baseline and follow-up. Data was collected from 28 unilateral STN DBS patients (15 English- and 13 Spanish-speaking), and 15 English-speaking matched PD control patients. English-speaking DBS patients demonstrated significant declines in verbal fluency and attention/executive function, whereas PD control patients did not experience significant cognitive decline. Cognitive performance did not differ based on side of DBS. Spanish-speaking DBS patients experienced significant declines in verbal fluency, confrontational naming and visuospatial abilities. Among Spanish-speaking DBS patients, older age and later age of disease onset predicted verbal fluency decline, even after controlling for education.
... Dopamine neuromodulation is intrinsic to processes of movement and motor learning, cognition, reward processing, food intake, nociception, and endocrine and autonomic regulation. Studies on the lateralization of cognitive functions in patients with PD yielded conflicting results: some reported that neuropsychological deficits are consistent with the lateralization of motor symptoms [4][5][6][7][8][9][10], whilst others failed to find a correlation [11][12][13][14][15]. A limitation of several of these studies is that they prevalently investigated global lateralized brain functions in patients with variable disease severity. ...
... Our data on cognition confirm a number of earlier studies reporting no association between laterality of motor impairment and executive functions [12,13,15] and challenge other studies suggesting that patients with left hemisphere involvement have a reduced performance in verbal fluency [7,9,10], digit span [7], and Wisconsin Card Sorting Test [8,10]. The strict inclusion criteria of this protocol probably accounts for the observed normal cognitive features. ...
... The strict inclusion criteria of this protocol probably accounts for the observed normal cognitive features. Some earlier studies included patients with different degrees of disease severity [7][8][9], whereas others also included patients Behavior, personality in lateralized PD with dementia [10]. In keeping with our observation, previous studies that matched patient groups for disease severity and overall intellectual impairment failed to find cognitive differences in lateralization [12,13,15]. ...
Dopamine neurotransmission plays a key role in several brain activities, including motor, cognitive, and behavioral functions. Parkinson's disease (PD) typically begins with asymmetrical motor features related to asymmetrical dopamine denervation. This study was designed to examine whether distinct cognitive, behavioral, and personality features are related to this asymmetry.
Fifty-six patients with mild PD and lateralized motor features were grouped according to dominant side of motor features and evaluated using a neuropsychological assessment focused on attention and executive functions, impulse control disorders, and personality inventory.
There were no differences in neuropsychological functions between patients with right and left lateralized PD, but differences occurred in personality features. Patients with motor impairment predominant on the left-hand side had prevalence of hypomania and conversion profile.
This study suggests that side dominance of dopaminergic denervation may be related to personality features in patients with PD that could influence behavioral aspects.
... These results were in line with previous findings showing that Parkinsonian patients with left-sided symptoms did not exhibit the expected displacement of the visual vertical to the left when the body was bent to the right (Proctor, Riklan, Cooper, & Teuber, 1964;Starkstein, Leiguarda, Gershanik, & Berthier, 1987). In addition, they are consistent with data in normal subjects (Schneider & Bartley, 1962 showing atypical displacement errors of the subjective vertical when the neck muscle tone was altered experimentally (the bias was in the direction of the altered muscle). ...
... Thus, the observation of a specific directional bias in association with a specific form of the disease, for example toward the affected side as shown in focal limb dystonia (Ricci et al., , 2015, or opposite to it, as reported in Parkinson's disease (Proctor et al., 1964;Starkstein et al., 1987), might provide important insights into the mechanisms underlying differences in patients with CD, and then be crucial to the design of effective rehabilitation treatments. ...
Objectives:
There is increasing evidence of non-motor, sensory symptoms, mainly involving the spatial domain, in cervical dystonia (CD). These manifestations are likely driven by dysfunctional overactivity of the parietal cortex during the execution of a sensory task. Few studies also suggest the possibility that visuospatial attention might be specifically affected in patients with CD. Therefore, we asked whether non-motor manifestations in CD might also comprise impairment of higher level visuospatial processing.
Methods:
To this end, we investigated visuospatial attention in 23 CD patients and 12 matched healthy controls (for age, gender, education, and ocular dominance). The patients were identified according to the dystonia pattern type (laterocollis vs. torticollis). Overall, participants were right-handers, and the majority of them was right-eye dominant. Visuospatial attention was assessed using a line bisection task. Participants were asked to bisect horizontal lines, using their right or left hand.
Results:
Participants bisected more to the left of true center when using their left hand to perform the task than when using their right hand. However, overall, torticollis patients produced a significantly greater leftward deviation than controls.
Conclusions:
These data are consistent with preliminary findings suggesting the presence of biased spatial attention in patients with idiopathic cervical dystonia. The presence of an attentional bias in patients with torticollis seem to indicate that alterations of attentional circuits might be implicated in the pathophysiology of this type of CD. (JINS, 2017, 23, 1-11).
... Auf der Basis der vorangegangenen umfassenden Darstellung der Hintergründe zu spatialen [Starkstein et al. 1987;Villardita et al. 1983]. [Gainotti et al. 1991], chimerischen Gesichter [Mattingley et al. 1994], die Wundt-Jastrow-Illusion [Pizzamiglio et al. 1992 [Bryden 1977;Tapley and Bryden 1983] jedes der zehn Items, welche auf fünf Stufen variieren konnten, mit einem Punktwert kodiert (Tabelle 2). ...
... Bei den in der vorliegenden Arbeit durchgeführten konventionellen Standarduntersuchungen für [Starkstein, Leiguarda, Gershanik, and Berthier 1987] veröffentlicht. Diese Autoren fanden eine mäßige rechtsgerichtete Abweichung bei LPD- ...
In der vorliegenden Arbeit wurde das spontane visuelle Explorationsverhalten von 31 Patienten mit einem idiopathischen Parkinson-Syndrom und von 17 gesunden Kontrollpersonen aus der gleichen Altersgruppe systematisch untersucht. Die Analyse der initialen visuellen Exploration (IVE) wurde mit Hilfe von Texturvorlagen durchgeführt, die aus Elementen der Texton-Forschung aufgebaut waren und die einen attentiven okulomotorischen Suchvorgang voraussetzten. Da ein Teil der Vorlagen differente Zielelemente in der linken und rechten Hälfte beinhaltete, konnte aus den Antworten der Versuchspersonen über das zuerst entdeckte Zielelement, auf die Seite der initialen Exploration geschlossen werden. In einer vorherigen Studie konnte gezeigt werden, dass die Mehrzahl der Normalpersonen ihre Exploration in der linken Hälfte der Vorlagen beginnt, während die meisten Neglect-Patienten mit rechtshemisphäralen Läsionen auf der rechten Seite anfangen. Standarduntersuchungen auf Neglect-Symptome (Linienteilungstest, Ausstreichtest, doppelseitige simultane Stimulation) wurden bei unseren Versuchspersonen als Referenztests ebenfalls durchgeführt. Bei der IVE-Aufgabe starteten 65 Prozent der gesunden Kontrollpersonen und 64 Prozent der Parkinson-Patienten mit überwiegender Beeinträchtigung der rechten Körperhälfte (RPD) und linkshemisphäral betontem Dopamindefizit den Suchvorgang erwartungsgemäß auf der linken Seite des Texturenfeldes. Im Gegensatz zu dieser Verteilung zeigten nur 12 Prozent der Parkinson-Patienten mit vornehmlicher linksseitiger Beteiligung (LPD) eine linksgerichtete IVE, während der Rest keine (35%) bzw. eine rechtsseitige (53%) Bevorzugung bei der initialen Exploration aufwies, die damit IVE-Veränderungen bei Neglect-Patienten glich. Die Ergebnisse der Referenztests ergaben bei keiner Untersuchungsgruppe einen Hinweis auf eine spatiale Vernachlässigung. Das atypische Explorationsverhalten der vornehmlich linksbetroffenen Parkinsongruppe sollte im Zusammenhang mit jüngst entwickelten Konzepten zur Aufmerksamkeitsregulation interpretiert werden, welche eine frühe automatische Orientierung in Richtung des ipsiläsionalen Halbraumes als milde Neglect-Manifestation bzw. als Residualzustand nach einem Hemineglect ansehen. Da dieser subtile Orientierungsvorzug, verglichen mit schwereren und offensichtlicheren klinischen Symptomen des Neglects, weniger einem Kompensationsmechanismus unterliegt, ist die Sensitivität der IVE-Untersuchung bei Patienten mit einem aus chronischen Störungen resultierenden subklinischen Neglect höher, als die der konventionellen Tests. Die vorliegenden Ergebnisse steuern dem komplexen Bild der kognitiven und visuospatialen Veränderungen bei Parkinson-Patienten wichtige neue Aspekte bei. Des weiteren ergänzen unsere Resultate das bisherige Wissen über Neglect-Mechanismen sowie über die Rolle dopaminerger Transmittersysteme bei der Regulation von Aufmerksamkeit. Über dies ermutigen die vorliegenden Ergebnisse zu systematischen Untersuchungen von Effekten dopaminerger Medikamente auf Neglect-Phänomene.
... Direnfeld et al. (1984) demonstrated greater cognitive impairment in people with PD who had more severe left-sided hemibody symptoms, as compared to people with PD who had more severe right-sided hemibody symptoms. People with PD who have left-sided hemibody predominant symptoms can exhibit left-sided, right-sided, or bilateral neglect on a visual cancellation test (Villardita, Smirni, & Zappalà, 1983) and mild left-sided neglect on a line bisection test (Starkstein, Leiguarda, Gershanik, & Berthier, 1987;Lee, Harris, Atkinson, & Fowler, 2001). It is not known to what extent these results reflect inattention to the left space versus reduced intention to move the hand within or toward the left space, as it is necessary to bring the pen to the middle of the line for line bisection or over to the left side of the page to complete the cancellation test (Coslett, Bowers, Fitzpatrick, Haws, & Heilman, 1990;Na et al., 1994). ...
... Judgment of line bisections has been associated with right parietal activation on functional magnetic resonance imaging (Fink et al., 2000). Starkstein et al. (1987) and Lee et al. (2001) demonstrated that left hemispatial neglect with rightward deviation during a line bisection test is associated with left hemibody-right hemisphere disease in people with PD. ...
Global attention requires disengagement from focal elements of stimuli. Since people with Parkinson's disease (PD) may reveal impaired disengagement, this study attempted to learn if people with PD may be impaired at allocating global attention. Healthy adults and people with PD attempted to bisect lines of uniform thickness and lines composed of two segments of unequal thickness and length. When the longer line segment was to the right of the shorter segment, the group with PD demonstrated an increased deviation toward the longer segment, supporting the postulate that people with PD have an impaired ability to disengage focal attention and engage global spatial attention.
... Ein ähnliches Paradigma wurde von Watson und Mitarbeitern [Watson, Miller, and Heilman 1978] bei unterbunden werden [Corwin, Kanter, Watson, Heilman, Valenstein, and Hashimoto 1986;Marshall and Gotthelf 1979]. Deuel und Collins [Deuel and Collins 1984] Vor diesem Hintergrund ist es erstaunlich und bemerkenswert, dass direktionale Phänomene eines Neglect-Syndroms bisher jedoch nur selten bei Parkinson-Patienten berichtet wurden [Starkstein et al. 1987;Villardita et al. 1983]. Darstellung dieses Bias benutzt wurden, umfassen Aufgaben mit überlappenden Figuren [Gainotti et al. 1991], chimerischen Gesichter [Mattingley et al. 1994] , die Wundt-Jastrow- Illusion [Pizzamiglio et al. 1992] und Texturfelder zur visuellen Exploration [Hattig 1992]. ...
... Im Mittel zeigte das auch die schon zitierte Arbeit von Schwartz und Koautoren [Schwartz, Adair, Na, Williamson, and Heilman 1997], und intentionalen Anteilen dissoziieren kann und aufgabenspezifisch ist [Schwartz, Adair, Na, Williamson, and Heilman 1997]. konnte von der Gruppe um Starkstein [Starkstein, Leiguarda, Gershanik, and Berthier 1987] veröffentlicht ...
... Furthermore, patterns of attentional asymmetry on chimeric tests have been shown to be highly sensitive to unilateral hemispheric damage, as in stroke (Mattingley et al., 1994). Although little work using chimeric stimuli has been conducted in patients with PD, an accumulating literature has provided compelling evidence for lateralized perceptual bias in patients with PD on range of visuospatial tasks without a facial or affective component (Ebersbach et al., 1996;Harris, Atkinson, Lee, Nithi, & Fowler, 2003;Lee, Harris, Atkinson, & Fowler, 2001;Starkstein, Leiguarda, Gershanik, & Berthier, 1987). In general, patients who suffer from motor symptoms predominantly on their left side (LPD), thought to reflect a greater loss of dopamine in the right basal ganglia, appear to be more vulnerable to perceptual asymmetries than patients with greater dopamine loss in the left basal ganglia whose symptoms are predominantly on their right side (RPD). ...
... In general, patients who suffer from motor symptoms predominantly on their left side (LPD), thought to reflect a greater loss of dopamine in the right basal ganglia, appear to be more vulnerable to perceptual asymmetries than patients with greater dopamine loss in the left basal ganglia whose symptoms are predominantly on their right side (RPD). For example, in two early studies, LPD groups exhibited signs of left spatial neglect in line bisection and tasks involving saccades to a target in the face of near-normal performance in RPD (Starkstein et al., 1987;Ventre, Zee, Papageorgiou, & Reich, 1992). In a later study of horizontal line bisection, which involved adjusting the position of a cursor on a large screen with remote switches, RPD patients and controls both evidenced pseudoneglect (a mild left hemispace bias), whereas LPD patients demonstrated left hemispatial neglect (i.e., bisected lines to the right of the midpoints), a bias that was small but nonetheless significant (Lee et al., 2001). ...
Objective: To relate lateralized impairments of visual perception in Parkinson's disease to asymmetries in the severity of motor symptoms. Method: Ten patients with worse left-sided motor symptoms (LPD), 15 with worse right-sided (RPD), and 13 healthy age-matched controls (all right-handed) viewed mirror-imaged pairs of emotional chimeric faces, (left side smiling, right neutral, and vice versa), of greyscales (strips whose luminance varied smoothly from black on the left to white on the right, and vice versa) and of gender chimeric faces (left side male, right female, and vice versa). Participants signaled which stimulus appeared happier, brighter, or more feminine, respectively, so showing which side received more attention. Results: For emotional chimeras, controls and LPD showed little bias, whereas RPD showed a strong bias to left hemispace (p = .018, r = .45). Across all patients, this bias was associated with severity of right-sided motor impairment (p = .018, r = .49). The bias was much weaker and insignificant for greyscales (p = .72, r = .14). For gender chimeras, RPD again showed a significantly greater left hemispace bias than did LPD (p = .037, r = .47), although neither patient group differed significantly from controls. Across all patients, this bias correlated with ratio of right-to-left symptom severity (p = .044, r = .48). Conclusions: The left hemispace bias in RPD is greater for facial than for luminance judgments, and is amplified for emotional judgments. Asymmetrical degeneration of the striatum, particularly involving the left side, appears to underlie this deficit in visual processing.
... A final consideration was undertaken in this study due to the wellknown asymmetry of motor symptoms at PD onset, as well as a growing body of research that suggests a perceptual asymmetry exists (Ebersbach et al., 1996;Harris et al., 2003;Hovestadt et al., 1987;Starkstein et al., 1987;Wright et al., 2007a). We recently found a leftward perceptuomotor asymmetry in PD during reaching tasks, which occurred independent of the side of disease onset (Wright et al., 2007a), however, many others have found evidence for perceptual left-neglect that occurs predominantly in patients with left-sided PD onset (LPD) (Davidsdottir et al., 2005;Ebersbach et al., 1996;Harris et al., 2003;Lee et al., 2001). ...
... Our findings that LPD have greater kinesthetic deficits than RPD, suggest a causal link with the perceptual deficits that many others have described in LPD. However, most of the prior evidence comes from visual and visuospatial tasks (Davidsdottir et al., 2005;Ebersbach et al., 1996;Harris et al., 2003;Lee et al., 2001;Starkstein et al., 1987). In our study, we are focused on a purely proprioceptive input that does not need to be mapped to exocentric coordinates, i.e. deciding between clockwise or counterclockwise rotation could be made entirely within an egocentric mapping. ...
Integration of sensory and motor inputs has been shown to be impaired in appendicular muscles and joints of Parkinson's disease (PD) patients. As PD advances, axial symptoms such as gait and balance impairments appear, which often progresses to complete inability stand or walk unaided. The current study evaluates kinesthesia in the axial musculature of PD patients during active postural control to determine whether impairments similar to those found in the appendages are also present in the hip and trunk. Using axial twisting, we quantified the detection threshold and directional accuracy of the hip relative to the feet (i.e. Hip Kinesthesia) and the hip relative to the shoulders (i.e. Trunk Kinesthesia). The relation of kinesthetic threshold to disease progression as measured by UPDRS and the effect of levodopa treatment on kinesthesia were assessed in 12 PD compared to age-matched controls. Subjects stood unaided while passively twisted at a very low constant rotational velocity (1 degrees /s). The results showed that accuracy in determining the direction of axial twisting was reduced in PD relative to healthy control subjects in the hip (PD-ON: 81%; PD-OFF: 91%; CTL=96%) and trunk (PD-ON: 81%; PD-OFF: 88%; CTL=95%). Thresholds for perception of axial twisting were increased when PD subjects were ON levodopa versus OFF in both the hip (p<0.01) and the trunk (p<0.05). The magnitude of decrease in sensitivity due to being ON levodopa was significantly correlated with the increase in UPDRS motor scores (Hip: r=0.90, p<0.01 and Trunk: r=0.60, p<0.05). This effect was not significantly correlated with equivalent levodopa dosage. PD subjects with disease onset on the left side of their body showed significantly higher axial thresholds than subjects with right PD onset (p<0.05). In conclusion, deficits in axial kinesthesia seem to contribute to the functional impairments of posture and locomotion in PD. Although levodopa has been shown to improve appendicular kinesthesia, we observed the opposite in the body axis. These findings underscore the dissociable neurophysiological circuits and dopaminergic pathways that are known to innervate these functionally distinct muscle groups.
... Patients with signs lateralized to the right were reportedly more impaired on dominant hemisphere function (e.g. WAIS verbal subtests 47 and serial digit learning, confrontation naming and verbal associative fluency 20 ). Conversely, it was contended that those with predominantly left-sided involvement evidenced mild left hemispatial neglect, 47 but showed no differences on tests of non-dominant hemisphere function. ...
Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson’s disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education, were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex, decreasing glucose metabolism was positively associated with neurobehavioral function; in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates.
... Most previous studies revealed no significant differences between LPD and RPD group performance of the digit span test; 12,13 whereas two studies found results similar to ours. 14,15 The 'digit span forward' task has been suggested as being a task of working memory and simple verbal fluency. 16 In RPD, the left hemisphere would presumably be affected more than the right hemisphere would be, given that the cognitive battery weighted on language might be influenced. ...
Background and Purpose
The relationship between the side of motor symptoms and cognitive impairment has rarely been reported in Parkinson’s disease (PD). We aimed to estimate the influence of motor laterality on cognition in PD patients.
Methods
We enrolled 67 patients with PD, and they were divided into two groups according to side of symptom onset or predominant motor symptom presentation (right and left). Right-sided PD (RPD, 40) and left-sided PD (LPD, 27) patients underwent a neuropsychological battery exploring memory, attention/working memory, frontal/executive, visuospatial, and language functions. Student's t-test and Chi-square test have been carried out to compare the clinical and neuropsychological data between two groups.
Results
There were no significant differences in any neuropsychological test between the RPD and LPD groups, except for digit forward span test. RPD patients scored lower on the digit forward span test than LPD patients (5.43±9.49 vs. 6.15±1.38, p=0.045).
Conclusions
RPD patients seem to experience more difficulties in attention and working memory than did LPD patients. The laterality of motor symptoms is not a major determinant for cognitive impairment in PD patients but, we should consider differences of cognitive deficits depending on the side of motor symptoms to treat patients with PD.
... It is possible that these task differences also lead to the discrepancies between our findings and those of Villardita et al. (1983). Obviously, more research is needed to delineate further the differential attentional impairments of PD patients experiencing literalized motor dysfunction, especially in light of' the controversy in the literature pertaining to cognitive deficits in unilateral PD (e.g., Starkstein, Leiguarda, Gershanik, & Berthier, 1987;Tomer, Levin, & Weiner, 1993). Furtlmrrnore, the suggestion that left-hemisphere dysfunction is associated with omission errors should be considered tentative, given that left-hemisphere dysfunction was determined based solely on a single measure (i.e., Grooved Pegboard performance). ...
Nondemented patients with Parkinson's disease (PD) and a group of age and education matched controls were administered a modified version of the Visual Search and Attention Test (VSAT). This task measures subjects' speed at localizing letter or symbol targets based on either a single-feature or a dual-feature search. Three indices were derived from the VSAT: (a) the amount of time taken to complete each of the trials (completion time), (b) the number of target items not crossed out (omissions), and (c) the number of nontarget items crossed out (commissions). The results indicated that, in terms of completion time, the PD patients were impaired on the single-feature search conditions but not on the dual-feature search conditions, suggesting that PD patients are impaired in selective attention processes. It was also found that the number of target items omitted by the normal controls on the VSAT varied as a function of the nature of the target (letter or form) and the search requirements (single-feature or dual-feature search), whereas the number of targets omitted by the PD patients was not affected by these factors. Correlational analyses suggested that the three measures derived from the VSAT assessed different components of attentional performance in these patients. Overall, the results of this study suggest that the VSAT can be used to detect subtle attentional impairments in nondemented PD patients, and that the pattern of their impairment on this clinical test is similar to that found on experimental attentional measures. © 1997 National Academy of Neuropsychology. Published by Elsevier Science Ltd
... This finding could also have implications for face processing, which is considered to rely on rather global, holistic processing (Kanwisher and Yovel, 2006). In line with the proposal to consider PD a disconnection syndrome, in which the less affected hemisphere gains dominance over the more degenerated one (Cronin-Golomb, 2010), the bigger picture in the literature suggests that visuospatial deficits are a prominent phenomenon in LPD (Amick et al., 2006;Karádi et al., 2015;Laudate et al., 2013, Lee et al., 2015Tomer et al., 1993), while in RPD there is a tendency to be impaired in verbal tasks (Amick et al., 2006;Starkstein et al., 1987). Facial emotion recognition experiments have yielded equivocal results: LPD patients showed deficits in recognizing sad faces in one study (Ariatti et al., 2008), while anger recognition was compromised in two other studies (Clark et al., 2008(Clark et al., , 2010. ...
We describe a method for evaluating facial expressivity in order to improve related clinical assessments of Parkinson’s Disease (PD). There is a controversial evidence in the literature that PD facial impairment can be detected on certain emotional expressions. This study aimed to investigate the feasibility of discriminative and quantitive measures of PD from the ability of a subject to express facial expressions. Video clips of 8 subjects (4 healthy controls and 4 with patients with PD) were recorded during daily sessions over several weeks. Observations covered emotion variation over one week for control subjects and six weeks for patients with PD. A statistical shape model was used to track facial expressions and to measure the amount of expressivity exhibited by each subject. The study suggests that measures of the amount of movement during happiness, disgust and anger expressions are the most discriminative, with PD patients exhibiting less movement than controls. This work demonstrates that it may be possible to measure day-to-day variations in symptoms of PD automatically.
... This finding could also have implications for face processing, which is considered to rely on rather global, holistic processing (Kanwisher & Yovel, 2006). In line with the proposal to consider PD a disconnection syndrome, in which the less affected hemisphere gains dominance over the more degenerated one (Cronin-Golomb, 2010), the bigger picture in the literature suggests that visuospatial deficits are a prominent phenomenon in LPD (Amick et al., 2006;Karádi et al., 2015;Laudate et al., 2013, Lee et al., 2015Tomer et al., 1993), while in RPD there is a tendency to be impaired in verbal tasks (Amick et al., 2006;Starkstein et al., 1987). Facial emotion recognition experiments have yielded equivocal results: LPD patients showed deficits in recognizing sad faces in one study (Ariatti et al., 2008), while anger recognition was compromised in two other studies (Clark et al., 2008(Clark et al., , 2010. ...
Parkinson's disease (PD) affects patients beyond the motor domain. According to previous evidence, one mechanism that may be impaired in the disease is face processing. However, few studies have investigated this process at the neural level in PD. Moreover, research using dynamic facial displays rather than static pictures is scarce, but highly warranted due to the higher ecological validity of dynamic stimuli. In the present study we aimed to investigate how PD patients process emotional and non-emotional dynamic face stimuli at the neural level using event-related potentials. Since the literature has revealed a predominantly right-lateralized network for dynamic face processing, we divided the group into patients with left (LPD) and right (RPD) motor symptom onset (right versus left cerebral hemisphere predominantly affected, respectively). Participants watched short video clips of happy, angry, and neutral expressions and engaged in a shallow gender decision task in order to avoid confounds of task difficulty in the data. In line with our expectations, the LPD group showed significant face processing deficits compared to controls. While there were no group differences in early, sensory-driven processing (fronto-central N1 and posterior P1), the vertex positive potential, which is considered the fronto-central counterpart of the face-specific posterior N170 component, had a reduced amplitude and delayed latency in the LPD group. This may indicate disturbances of structural face processing in LPD. Furthermore, the effect was independent of the emotional content of the videos. In contrast, static facial identity recognition performance in LPD was not significantly different from controls, and comprehensive testing of cognitive functions did not reveal any deficits in this group. We therefore conclude that PD, and more specifically the predominant right-hemispheric affection in left-onset PD, is associated with impaired processing of dynamic facial expressions, which could be one of the mechanisms behind the often reported problems of PD patients in their social lives.
... While one study reported poorer performance in RPD patients, another study did not find any difference between the groups. [26,30] The discrepancies in the above studies may be due to different neuropsychological tests applied as well as due to inclusion of patients with varying duration of PD. Our study and the study by Erro et al., did not find any difference between the RPD versus LPD, which may be due to the fact that both studies used early PD as the inclusion criteria. ...
Aims:
Though impaired cognition in Parkinson's disease (PD) is well known, data in early PD is sparse. This study was designed to assess the cognitive profile in patients with early PD (motor symptoms <5 years and Hoehn and Yahr stage <2), and to compare the cognitive profile between these patients with right versus left side onset of motor symptoms.
Materials and methods:
National Institute of National Health and Neurosciences (NIMHANS) neuropsychological battery was used to assess the cognitive profile in 50 patients with early PD and compared with 50 age-, education-, and gender-matched healthy controls. Within the PD group, the cognitive profile was also compared between patients with right side onset motor symptoms (RPD) versus those with left side onset (LPD). The neuropsychological tests assessed the executive functions, memory, attention, visuospatial functions, and psychomotor speed.
Results:
Among the 50 patients, 25 each were RPD and LPD. The two subgroups were matched for age, gender, education, age at disease onset, disease duration, and degree of motor disability. There was no significant difference between the groups on Hoehn and Yahr staging or Unified Parkinson Disease Rating Scale (UPDRS) motor score. Patients with early PD performed significantly worse in the tasks involving memory, executive functions, and attention compared to controls. However, there was no difference in the cognitive profile between RPD and LPD subgroups.
Conclusions:
Patients with early PD have cognitive dysfunction with predominant involvement of frontal and temporal lobes. Side of onset of motor symptoms probably does not have significant role in future development or profile of cognitive dysfunction in PD.
... Individuals with Parkinson's disease (PD) without dementia exhibit deficits in multiple domains of visuospatial functioning (reviewed in Cronin-Golomb, 2010), including line bisection (Barber, Tomer, Sroka, & Myslobodsky, 1985;Davidsdottir, Wagenaar, Young, & Cronin-Golomb, 2008;Lee, Harris, Atkinson, & Fowler, 2001a;Lee, Harris, Atkinson, Nithi, & Fowler 2002;Starkstein, Leiguarda, Gershanik, & Berthier, 1987). It has been found that PD patients with initial motor symptoms on the right side of the body (RPD; predominant left basal ganglia dysfunction) perform similarly to healthy control adults, whereas those whose initial symptoms originate on the left side of the body (LPD; predominant right basal ganglia dysfunction) tend to deviate to the right of center on horizontal line bisection tasks (Lee et al., 2001a;Davidsdottir et al., 2008) and downward on vertical line bisection tasks (Lee et al., 2002). ...
Parkinson's disease (PD) is characterized by disorders of visuospatial function that can impact everyday functioning. Visuospatial difficulties are more prominent in those whose motor symptoms begin on the left body side (LPD) than the right body side (RPD) and have mainly been attributed to parietal dysfunction. The source of visuospatial dysfunction is unclear, as in addition to subcortical-cortical changes, there are irregularities of visual scanning and potentially of retinal-level vision in PD. To assess these potential contributors, performance on a visuospatial task-line bisection-was examined together with retinal structure (nerve fiber layer thickness, measured by optical coherence tomography [OCT]), retinal function (contrast sensitivity, measured by frequency-doubling technology [FDT]), and visual scanning patterns. Participants included 20 nondemented patients (10 LPD, 10 RPD) and 11 normal control (NC) adults. Relative to the other groups, LPD were expected to show rightward bias on horizontal line bisection, especially within the left visual hemispace, and downward bias on vertical bisection. LPD relative rightward bias was confirmed, though not mainly within the left hemispace and not correlated with retinal structure or function. Retinal thinning was seen in LPD relative to RPD. Qualitative visualization of eye movements suggested greater LPD exploration of the right than left side of the line during horizontal bisection, and some overall compression of scanning range in RPD (both orientations) and LPD (primarily vertical). Results indicated that rightward visuospatial bias in our LPD sample arose not from abnormalities at the retinal level but potentially from attentional biases, reflected in eye movement patterns. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
... Many studies have focused on the differences between PD patients with left-sided and right-sided symptoms on neuropsychological tasks, and the results are very conflicting [11]. Since Starkstein and colleagues have reported mild but significant intergroup (right vs. left hemi-parkinsonism) neuropsychological differences [21], it has been further reported that patients with leftsided symptoms (reflecting right hemisphere dysfunction) perform worse in tasks of orientation, mental imagery and visuospatial memory, and patients with right-sided symptoms perform worse on verbal memory tasks, whereas there are few evidences for differences in attention and executive functioning with respect to inhibition, fluency, or set shifting [22]. However, these findings were not confirmed by Katzen et al, who suggested that patients developing bradykinesia or rigidity as their initial signs are more likely to develop cognitive dysfunction regardless of the laterality of their symptoms, whereas patients with tremor dominant phenotype show neuropsychological impairments only when tremor is left-sided [19]. ...
... PD has been viewed by many experts as a lateralised disorder with each hemisphere having designated motor and cognitive responsibilities. Thus, the side of symptom onset may carry differential effects on cognitive, visuospatial and perceptuo-motor functions [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Although some studies did not demonstrate a hemispheric difference on cognitive functioning [8,11] the majority of studies revealed some association with cognitive functions, especially those known to be located in a specific hemisphere [4,6,9,10,13,14]. ...
Researchers have consistently observed in right-handed individuals across normal and disease states that the 'dominant' left hemisphere has greater ipsilateral control of the left side than the right hemisphere has over the right. We sought to determine whether this ipsilateral influence of the dominant hemisphere reported in Parkinson's disease extends to treatments such as deep brain stimulation (DBS) and whether it affects outcome. We hypothesised that among Parkinson right-handers, unilateral left DBS would provide greater ipsilateral motor improvement compared with the ipsilateral motor improvement experienced on the right side.
A total of 73 Parkinson patients who underwent unilateral DBS of the subthalamic nucleus (STN) or globus palidus internus (GPi) participated. Left and right 'composite scores', were computed by separately adding all items on the left and right side from the motor section of the Unified Parkinson Disease Rating Scale. The change in the pre- and 4-month post-implantation score was the primary outcome measure. The mean motor scores improved by 4.96 ± 11.79 points (p < 0.001) post-surgery on the ipsilateral side of the DBS implantation. Regression analyses revealed that the side (left vs. right) and target (STN vs. GPi) did not significantly contribute in the effect of ipsilateral motor improvement (p = 0.3557).
While DBS on the 'dominant' left side failed to exert a greater ipsilateral influence compared with DBS on the non-dominant right side, significant ipsilateral motor improvements were observed after unilateral stimulation regardless of site of implantation and laterality.
... Finally, there also have been studies demonstrating some cognitive impairments to be associated with greater rightsided rather than left-sided symptoms. Starkstein, Leiguarda, Gershanik, and Berthier (1987) reported significantly poorer performance on the WAIS (verbal and total but not performance) and WCST for PD participants with greater right-side motor severity than PD participants with greater left-side severity. Huber, Miller, Bohaska, Christy, and Bornstein (1992) reported that PD participants with more severe right-side symptoms performed significantly more poorly than left-sided PD participants on tests of intelligence, verbal (but not visual) memory, and concentration. ...
Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N=31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the participants were analyzed with the Linguistic Inquiry and Word Count (LIWC) program. Three measures of linguistic complexity - the proportion of verbs, proportion of function words, and sentence length - were found to be affected by symptom asymmetry. Greater left-side motor severity (and hence greater right-hemisphere dysfunction) was associated with the production of significantly fewer verbs, function words, and shorter sentences. Hence, the production of linguistic complexity in a natural language context was associated with relatively greater right hemisphere involvement. The potential neurobiological mechanisms underlying this effect are discussed.
... Perhaps related is the finding that hemi-neglect in human patients is usually more prominent with right cerebral lesions. Furthermore, neuropsychological tests have shown a mild left hemispatial neglect in patients with LPD (Starkstein, 1987;Levin et al, 1991). This asymmetric defect in attention may account for the asymmetry in predictive latency in our patients with LPD. ...
We studied reflexive and predictive saccades by direct current electro-oculography in nine patients with mild hemi-Parkinson's disease (hemi-PD) and in 16 age-matched controls In five patients, the neurological syndrome was predominant on the right side of the body (RPD) and in four patients, on the left side (LPD). Reflexive saccades were elicited in response to the random appearance (timing and location) of a light-emitting diode (LED) Predictive saccades were elicited by alternatively illuminating LEDs at 10 degrees right and left, at various fixed frequencies (0 25 — 1 Hz)
In the reflexive task, latency and amplitude of the saccades were normal in both PD groups In the predictive task, mean saccade latency was not significantly different between patients and normals but there were two significant abnormalities in timing first, but only in LPD, a directional asymmetry in latency (left greater than right, e. g. at 0 25 Hz, mean difference of 90 ms); secondly, especially in RPD, an abnormal tracking pattern, reflected by more variability of the mean value (for each group of patients) of saccade latency at each point in time, throughout a period of tracking at a given frequency. Predictive saccades were also strongly hypometric in both PD groups but especially in LPD (e g for rightwards saccades controls = 19 degrees, SD = 1 6; LPD = 14 degrees, SD = 2 7; RPD = 15.7 degrees, SD = 2.3) These defects in saccadic timing and amplitude during predictive tracking were most salient at low frequencies. While these defects were largely bilateral, our findings suggest slightly different contributions of the right and left cerebral hemispheres to the spatial and timing components, respectively, that comprise optimal predictive saccadic behaviour
The interplay between uric acid, gender, and motor symptom asymmetry in the manifestation of non-motor symptomatology (NMS) remains to be better understood in early-stage Parkinson’s disease (PD). A total of 413 patients taking part in the Parkinson’s Progression Marker Initiative were divided into six groups based on their motor symptom asymmetry and gender. Clinical data was extracted over a 5-year follow-up period. Three-way interaction modeling was used to examine the moderating effects of gender and UA in the relationship between motor symptom asymmetry and NMS. The results highlighted significant moderating effects of uric acid on NMS in female PD patients, but not in male PD patients. Furthermore, female patients with right-sided motor symptom onset demonstrated the most preserved NMS functioning in the presence of lower serum uric acid levels, while their male counterparts showed the most impairment. This holds important clinical implications for symptom management in early-stage PD patients.
Introduction:
Symptom laterality is one of the main characteristics of Parkinson disease (PD) and reported to be associated with motor and nonmotor symptom severity and prognosis. This study aimed to evaluate the changes of laterality after deep brain stimulation (DBS) and the association between dopamine transporter SPECT using I FP-CIT (DAT SPECT) and symptom laterality in PD before and after DBS.
Methods:
Nineteen patients with PD who received bilateral subthalamic nucleus DBS were enrolled. The clinical scores including Unified Parkinson Disease Rating Scale (UPDRS) and Hoehn and Yahr were evaluated at baseline, 6 months, and 1 year after DBS. Also, the patients underwent DAT SPECT before and 6 months and 1 year after DBS. Symptom and DAT laterality indices were determined based on the UPDRS part 3 and DAT SPECT, respectively. The association between DAT and symptom laterality was assessed at baseline and 6 months and 1 year after DBS.
Results:
At baseline, 11, 6, and 2 among 19 patients had left-side-dominant, right-side-dominant, and symmetric motor symptom, respectively. Among 19 patients, there were 10 patients who showed changed symptom laterality within 1 year after DBS. The agreement between symptom laterality and DAT laterality was good to excellent at baseline and 6 months and 1 year after DBS (weighted κ = 0.742, 0.736, and 0.813). Furthermore, symptom and DAT laterality indices showed significant correlation at baseline (r = 0.542, P = 0.02), 6 months (r = 0.579, P = 0.01), and 1 year after DBS (r = 0.689, P = 0.02). Symptom laterality could be determined by DAT laterality index with areas under curve of 0.833 (P = 0.045), 0.982 (P < 0.001), and 1.000 (P < 0.001) at baseline and 6 and 12 months after DBS, respectively.
Conclusions:
The symptom laterality could be altered after DBS and was well correlated with laterality evaluated by DAT SPECT. An objective evaluation of laterality using DAT SPECT would be helpful for the management of patients with PD especially for adjusting the DBS programming for fine balancing of the asymmetric symptom after DBS. The large-scale study is warranted for validation of this result.
Memory dysfunction is a common problem in both organic and functional disorders and is frequently the reason for referral for psychological assessment. It is clearly necessary for the clinician to have access to reliable and accurate tests to assess the nature and severity of memory deficits in order that the patient can be appropriately treated and the effectiveness of any therapy monitored.
Sir,
We appreciate the thoughtful comments and additional contributions from Lam and colleagues with regards to our recent manuscript in Brain , which demonstrated substantial asymmetry of structural connectivity strength within the locomotor network of individuals with Parkinson’s disease who experience freezing of gait (FOG+) (Fling et al. , 2013). Specifically, we reported reduced white matter tract volume between the right pedunculopontine nucleus (PPN) and the midline of the right frontal cortex, assessed by diffusion tensor imaging. This was in contrast to those patients with Parkinson’s disease who did not have freezing issues and age-matched controls. In addition, this asymmetric reduction of the right hemisphere’s locomotor network was strongly related to inhibitory cognitive control, a process that is uniquely lateralized to the right hemisphere (Aron, 2007). In their letter, Lam and colleagues report how the …
To analyze the clinical characteristics, correlation factors and clinical heterogeneities in Parkinson's disease (PD) patients with cognitive impairment and identify whether cognitive impairment could influence the aspect of sleep.
A total of 130 PD outpatients and inpatients of sleep center at our hospital were eligible for participation. According to Montreal cognitive assessment (MOCA), they were divided into cognitive normal group (MOCA ≥ 26) (n = 51) and cognitive impairment group (MOCA < 26) (n = 79). Their clinical characteristics were mainly evaluated by unified Parkinson's disease rating scale (UPDRS) , Hoehn-Yahr (H-Y) stage, Hamilton depression scale (HAMD-24 item) and Epworth sleepiness scale (ESS). And all of them underwent video-polysomnography (PSG).
The proportion of cognitive impairment (MOCA < 26) was 60.76%. Compared to those without cognitive impairment, the PD patients with cognitive impairment had significantly higher score of HAMD (10 ± 7 vs 7 ± 4), increased incidence of hallucinations (40.50% vs 19.60%) and REM behavior disorders (RBD) (63.29% vs 39.21%), significantly higher H-Y stage [2.5(2.0-3.0) vs 2.0 (2.0-2.5)] , United Kingdom Parkinson Disease Society (UPDRS) part III (22 ± 10 vs 19 ± 10) and levodopa-equivalent daily dose (LED) (511 ± 302vs 380 ± 272) (all P < 0.05). However, no significant differences existed in the subscores of MOCA between PD patients with different sides of onset and motor subtypes of onset (all P > 0.05). Non-conditional Logistic regression analysis showed that PD duration, score of HAMD and H-Y stage were the major influencing factors of cognition. On PSG, significantly decreased sleep efficiency (57% ± 21% vs 66% ± 17%), higher percentage of non-REM sleep stage 1 (NREMS1) (37% ± 21% vs 27% ± 13%), lower percentage of NREMS2 (40% ± 17% vs 46% ± 13%) and REM sleep (39% ± 28% vs 54% ± 36%) were found for PD patients with cognitive impairment (all P < 0.05).
The PD patients with cognitive impairment have more severe disease and partial nonmotor symptoms. And the severity of disease and depression is closely associated with cognitive impairment. Cognitive impairment may also affect sleep to cause decreased sleep efficiency and severe sleep structure disorder.
The primate model of Parkinson's disease (PD) has been crucial for the evaluation of central nervous system transplantation techniques and therapeutic efforts. This chapter discusses the primate model of PD and its advantages over the rodent models. The use of primates to understand the mechanisms of host–graft interaction is applicable not only for PD, but for other neurological disorders as well. A major goal of transplantation for PD is to provide a tonic source of dopamine to the dopamine-deprived striatum. The primate model provides insight into the mechanisms by which therapies work, such as mechanisms that underlie functional recovery. The behavioral repertoire that the primate possesses provides a useful means for having meaningful comparisons between the parkinsonian model and the treated parkinsonian model. Correlation with positron emission tomography (PET) scanning needs to be studied in transplanted primates to gain more insights without the need for autopsy.
Twelve patients with idiopathic Parkinson's disease on only one side of the body were studied using various tests evaluating cognitive, memory, and psychomotor functions. All patients were untreated. The affected side was associated with impaired performance in motor and psychomotor tests but not in most of the tests to evaluate general cognitive capacity (WAIS) and memory (WMS). Patients with left hemiparkinsonism performed less well in the Picture Completion test of the WAIS and in the Stroop test (parts 3 and 3-2) than did subjects with right hemiparkinsonism. The results were interpreted as supporting the view that dopaminergic structures predominantly of the right hemisphere may be involved in the attention/activation process.
A review of the recent history, current status, and perspectives of development of neuropsychology in Latin America is presented. It is emphasized that neuropsychology represents an area of knowledge for which realistic possibilities of scientific advance exist in Latin America. Problems related with research and professional activity of neuropsychology in Latin America are examined.
Visuospatial abilities play a pivotal role in our daily living. Indeed, our survival depends, to a great extent, on our ability
to navigate sensory space. This means our ability to use spatial maps dependent on visual, tactile, and auditory information
to form and guide motor programs. Visuospatial abilities are complex brain operations requiring integration of occipital,
parietal, and frontal lobe function, as well as the contribution of subcortical structures. Consequently, it is not surprising
that visuospatial skills are often impaired in diseases with movement disorders—an impairment that depends both on the type
and on the stage of the disease in question.
At disease onset, patients with Parkinson's disease (PD) typically report one side of the body to be more affected than the other. Previous studies have reported that this motor symptom asymmetry is associated with asymmetric dopaminergic degeneration in the brain. Research on the cognitive repercussions of this asymmetric degeneration has yielded inconsistent results. Here, we review studies that reported on the cognitive performance of patients with left-sided (LPD) or right-sided (RPD) motor symptom predominance. We present evidence that patients with RPD typically experience problems with language-related tasks and verbal memory, whereas patients with LPD more often perform worse on tasks of spatial attention, visuospatial orienting and memory and mental imagery. In general, no differences were found between both groups on tasks measuring attention and executive function. The association between motor asymmetry and cognitive performance indicates that PD does not lead to one typical cognitive profile. The effect of symptom laterality on the cognitive complaints should be considered in the assessment and treatment of each individual patient.
The present study examined how asymmetrical motor symptomatology helps predict the pattern of perceptual judgements of body-scaled aperture width in lateralised Parkinson's disease (PD). Eleven patients with PD predominantly affecting the left side of their body (LPD), 16 patients with PD predominantly affecting their right side (RPD), and 16 healthy controls made forced-choice judgements about whether or not they would fit without turning their shoulders through a life-sized schematic doorway shown on a large screen. Whereas control and LPD groups made accurate estimations of body-scaled aperture width, RPD patients significantly underestimated aperture width relative to their body, perceiving doorways on average that were 12% narrower than their bodies as wide enough to allow them to pass through without rotation. Across all patients, estimates of body-scaled aperture width correlated with ratio of right-to-left symptom severity. These perceptual errors may indicate a mismatch between the neural representation of external space and that of body size in PD.
Patients with Parkinson's disease (PD) typically suffer from an asymmetric degeneration of dopaminergic cells in the substantia nigra, resulting in right-sided (RPD) or left-sided (LPD) predominance of motor symptomatology. As the dopaminergic system is also involved in attention, we examined horizontal and vertical orienting of attention in LPD (N=10), RPD (N=9) and controls (N=10). Four LPD patients demonstrated left neglect and three LPD patients demonstrated neglect for the upper visual field. LPD patients demonstrated a slower performance in detecting targets in the left hemifield and did not demonstrate a validity effect, unlike RPD patients and controls. RPD patients performed similar to controls, with the exception of one patient showing left and another showing right neglect, and two RPD patients demonstrated lower neglect. In sum, horizontal and vertical orienting of attention can be affected in Parkinson's disease - particularly in LPD - from very subtle slowing to clinically detectable horizontal and/or vertical neglect.
This investigation sought to study immediate and delayed verbal and visuospatial recall in Parkinson disease (PD) patients with left hemibody (LHO) and right hemibody (RHO) onset of motor symptoms and to examine the role of mental processing speed in recall of this information.
Research is mixed regarding material specific memory impairments in LHO and RHO PD. However, earlier research has not used a factorial approach in investigating material specific memory in LHO and RHO PD. We hypothesized that LHO PD patients would exhibit an increase in performance following the delayed verbal free recall trial and either decline or stability in performance on the delayed visuospatial free recall trial. The opposite pattern was hypothesized for RHO PD patients.
The Hopkins Verbal Learning Test-revised (HVLT-R) and the Brief Visuospatial Memory Test-revised (BVMT-R) were administered to a sample of 28 LHO PD patients and 36 RHO PD patients. The Stroop Color-word Test was administered as a measure of mental processing speed.
The results indicated that the RHO group experienced a significant decline in performance on verbal free recall from the immediate to the delayed trials and a significant improvement in performance from the immediate to the delayed visuospatial free recall trials. Additionally, a significant negative correlation was found between mental processing speed and changes in recall from the immediate to the delayed conditions for the RHO group.
These results indicate that the RHO PD group experienced a significant decline in verbal free recall and a significant improvement in visuospatial free recall from the immediate to the delayed trials and that the LHO PD patients experienced no significant changes. Further, mental processing speed appears to influence the recall of information from the immediate to the delayed conditions.
To relate sleep disturbances in Parkinson disease (PD) to hemispheric asymmetry of initial presentation.
Sleep disturbances are common in PD arising from the neurodegenerative process underlying the disease, which is usually lateralized at onset. Patients with left-side Parkinson disease onset (LPD: right hemisphere dysfunction) exhibit reduced vigilance relative to those with right-side Parkinson disease onset (RPD: left hemisphere dysfunction), leading us to hypothesize that sleep-related disturbances, particularly excessive daytime sleepiness, would be more severe for LPD than for RPD.
Thirty-one nondemented participants with PD (17 RPD and 14 LPD) and 17 age-matched control (CO) participants with chronic health conditions were administered the Parkinson Disease Sleep Scale and polysomnography was performed on a subset of the PD participants.
Both PD subgroups exhibited more nighttime motor symptoms than the CO group, but only LPD endorsed more nocturnal hallucinations and daytime dozing. Controlling for mood additionally revealed more vivid dreaming in LPD than RPD. There were no significant differences between LPD and RPD on measures of sleep architecture.
Increased dreaming, hallucinations, and daytime somnolescence in LPD may be related to changes in right-hemisphere neural networks implicated in the generation and control of visual images, arousal, and vigilance. Our results underscore the need to consider side of onset in regard to sleep disturbances in PD.
Patients with Parkinson disease (PD) have deficits in the neurotransmitter systems important for the normal allocation of attention. We sought to examine how the presence of PD influences the spatial allocation of reactive (bottom-up) and volitional (top-down) attention.
To assess the spatial allocation of attention, we used the line bisection task. When assessing "bottom-up" attention, lateral blinking lights were or were not present during the time the PD and normal subjects were attempting to perform line bisections. In the top-down condition, these subjects were asked to name the color of the laterally presented light before bisecting lines.
In the bottom-up condition, when compared with control subjects, the participants with PD were not abnormally distracted, but in the top-down condition, imperative stimuli on the right side of the line seemed to influence the PD subjects' allocation of attention.
The results suggest that when voluntarily allocating attention rightward, PD patients have difficulty disengaging and/or reallocating their attention. This disengagement deficit might be related to the frontal-executive dysfunction associated with PD.
Individuals with Parkinson's disease were compared to normal control subjects on a series of widely used neuropsychological measures. The two groups were matched for gender, handedness, age, education, and occupation. The neuropsychological tests were chosen to measure two specific functions: (a) spatial orientation (i.e., measures of personal orientation, extrapersonal orientation, right/left orientation, and mental rotation), and (b) the ability to shift mental set (e.g., generating responses from alternating categories). The tests chosen to measure spatial orientation had no set-shifting component, and the tests chosen to measure set-shifting had no spatial orientation component. Multivariate statistical analyses revealed a significant difference between the subjects with Parkinson's disease and the control subjects on the measures of set-shifting ability. In contrast, no significant difference between the groups was observed on the measures of spatial orientation. These results are discussed in terms of the current speculation in the literature regarding the relationship between set-shifting deficits and a disruption of dopaminergic fibers to the prefrontal cortex in Parkinson's disease.
Neuropsychological, neuropathological and neurochemical findings show different types of dementias. Few of them have been able to confirm a division into "subcortical" and "cortical" dementia, so this concept has to be questioned. The present clinical study compared type and severity of dementia in 12 Parkinson-patients (PD) and 12 Alzheimer-patients (AD). The age-adjusted normal value differed a significantly from both patient groups. No significant difference in pattern of neuropsychological deficits between PD- and AD-patients was apparent. However, after similar duration of illness, dementia was more severe in AD- than in PD-patients.
From the large body of empirical evidence on cognitive function in Parkinson's disease, a number of attempts have been made to describe the characteristics of the deficits and the conditions under which they are observed. This review considers descriptions limited to specific domains of cognition such as visuospatial function, memory and 'frontal' function, and more general descriptions relating to 'set-shifting', sequencing, temporal ordering and recency discrimination, the locus of cognitive control and bradyphrenia. Later in the paper an attempt is made to provide some theoretical framework for the various descriptions. Two theories are discussed representing contrasting, but complementary approaches. The first is a 'psychological' theory in which the concept of depleted processing resources is suggested as a possible mechanism to explain the observable deficits. The second is a neurobiological model that attempts to integrate information from diverse sources to provide a model for the neuroanatomical and neurochemical substrate that may underlie some of the behavioural deficits.
13 patients with PD of recent onset underwent a series of neuropsychological tests for frontal lobe associated functions (Sternberg paradigm, WCST, CVLT) before and during treatment with Artane. Test results at baseline were not significantly different from those of an age-matched control group (n = 13). Retesting after a mean of 2 weeks' treatment with trihexyphenidyl revealed only slight impairment in CVLT while performance on the other tests remained unchanged.
Unilateral lesions of the nigrostriatal dopaminergic system were induced by injecting 6-hydroxydopamine into the substantia nigra of three monkeys trained to initiate arm movements in response to stimuli randomly presented at various locations in their immediate visual space. This procedure resulted in partial reduction of dopamine content, as compared to intact side, in both the putamen and caudate nucleus, with the exception of the putamen in one monkey. A concomitant reduction in the level of dihydroxyphenylacetic acid was observed, but less systematically than the dopamine decrease in the same striatal regions. All monkeys displayed a predominant contralateral arm hypokinesia consisting of a slowness in initiating movements, little or not affected by the hemispace of presentation of the trigger stimulus. Conversely, when the monkeys responded with the arm ipsilateral to the lesion, the movement was initiated more slowly when the trigger stimulus was presented to the hemispace contralateral to the striatal dopaminergic depletion as compared to the ipsilateral hemispace. The results suggest that the visual neglect is more conspicuous when monkeys performed with the arm ipsilateral to the damaged nigrostriatal system. This neglect may be described as a disorder in the ease with which stimuli presented to the side contralateral to the impaired dopaminergic transmission are able to elicit behavioral responses, possibly as the result of a lack of selective attention or defective movement initiation.
Cognitive and cerebral blood flow (CBF) lateral asymmetries have been quantified in 23 right handed patients with lateralised idiopathic Parkinson's disease. Thirteen patients who had predominant right-sided symptoms (RPD) were compared with ten who had predominant left-sided symptoms (LPD). The patient subgroups were matched for age, education, duration of illness, disease severity and medication. Normalised asymmetries scores were calculated from the data obtained with a test battery and SPECT. No correlation was found between laterality of motor Parkinsonian symptoms and cognitive or haemodynamic asymmetry scores.
The neuropsychological effects of Parkinson's disease have gained wide recognition in recent literature. Effects have been documented in almost all areas of cognitive functioning, including general intellectual functioning, visual-spatial functioning, executive functions, attention and memory functions, language functions, and affective processes. Visual-spatial functions, memory functions, and executive functions have received particular interest. This review of the literature is an attempt to tie together the large number of studies in these cognitive areas and to present a suggestion for a comprehensive neuropsychological battery tailored to the patient with Parkinson's disease. Throughout the review, factors relevant to Parkinson's disease, e.g., dementia, motor symptoms, and hemiparkinsonism, are considered.
As anatomical studies have suggested that neglect might occur more frequently than is presently realized, and since pilot studies with dopamine agonists have suggested a possible therapy, we examined whether simple neuropsychological tests could detect neglect in the presence of a negative clinical examination. We found evidence of neglect on a simple arrow and number cancellation test in patients with lesions in either hemisphere and Parkinsonians. Clinical examination failed to identify neglect in all but three patients of the right hemisphere group. Cancellation tests are able to detect subclinical neglect, which could be important in view of possible future therapy.
Discussions of hemispheric asymmetry in psychopathology are often confounded by the effects of medication. We examined the effect of neuroleptic drugs on attention asymmetries in acutely psychotic patients admitted for the first time to a psychiatric hospital before the initiation of drug treatment and again after a period of treatment with neuroleptics. Overall performance did not change significantly; however, attention asymmetry was clearly related to the medication status of the patient: unmedicated patients showed inattention to the right hemispace, which changed to more prominent left-sided inattention when medicated. A longer time on medication or a higher daily dose were associated with a shift of inattention from the right to left hemispace. This suggests that neuroleptics may normalize left hemisphere performance, at the expense of deteriorated right hemisphere performance.
The existence of interhemispheric cortical afferent connections to the prefrontal cortex of the cat is investigated by means of the retrograde axonal transport of horseradish peroxidase technique. Labeled neurons are found in contralateral hemisphere in sites homotopical and heterotopical to the injection. The heterotopical contralateral projection arises principally from prefrontal, insular, prelimbic, premotor, cingular and retrosplenial cortices.