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Christine Mohr, Ph.D.
H. Stefan Bracha, M.D.
Peter Brugger, Ph.D.
Previous research has found that animals as well It is likely that an abnormally functioning dopamine as persons with psychotic disorders preferentially (DA) system is involved in the generation of positive orient away from the cerebral hemisphere with the psychotic symptoms. This association originates fromthe observation that neuroleptic medication (DA antag- more active dopamine system. This study investi- onists) improves psychotic symptoms, especially posi- gated the modulation of spatial behavior by a tive symptoms.1 Administration of levodopa and DA mode of thinking reminiscent of the positive agonists can trigger psychotic relapse in patients with symptoms of psychosis. In a non-treatment-seek- schizophrenia2,3 and induce hallucinatory and delu- ing sample of healthy volunteers (20 women and sional episodes in nonpsychotic individuals.4,5 The re- 16men), the authors assessed the lateral biases in lationship between DA and psychosis is also apparentfrom ﬁndings in patients with parkinsonism. When turning and veering behavior and in line bisection overtreated with DA agonists, these patients may de- as a function of their magical ideation, that is, a mild form of schizotypy. Across tasks, pronounced Turning behavior in animals is a reliable marker of magical ideation was associated with reduced DA activity. Animals turn preferentially in the direction right-sided orientation preferences. This ﬁnding of the cerebral hemisphere with less DA.7 Moreover, ani- suggests a relative hyperdopaminergia of the right mals trained to turn in one direction were found to haveincreased DA concentrations in the contralateral hemi- hemisphere as the biological basis of magical idea- sphere.8 The ﬁnding that patients with schizophrenia re- veal a left-sided turning preference that is quantitatively (The Journal of Neuropsychiatry and Clinical related to the severity of psychotic symptoms9 suggests an asymmetrical DA system in this population, with theright hemisphere having a more active DA system thanthe left. Also, patients with hemiparkinsonism prefer-entially turn toward the hemisphere with the more se- Received December 5, 2001; revised March 26, 2002; accepted May 7,2002. From the Department of Neurology, University Hospital Zurich,Zurich, Switzerland (C.M., P.B.); and the National Center for PTSD,Department of Veterans Affairs, Honolulu, Hawaii (H.S.B.). Addresscorrespondence to Dr. Mohr, Functional Brain Mapping Laboratory,Neurology Clinic, University Hospital Geneva, 24, rue Micheli-du-Crest, 1211 Geneva, Switzerland. E-mail: firstname.lastname@example.org Copyright ᭧ 2003 American Psychiatric Publishing, Inc.
J Neuropsychiatry Clin Neurosci 15:2, Spring 2003 MOHR et al.
vere dopaminergic cell degeneration.10 In bisection the left hemispace in healthy subjects with high com- tasks, analogous symptom-related shifts in spatial atten- tion were reported for both patients with psychosis11and hemiparkinsonism.12 The relevance of DA for spatial awareness is further supported by patients with neglect. This populationhas an impressive tendency to direct their attention to- Subjects
ward the left hemispace, a pathological condition most A total of 36 healthy subjects (20 women and 16 men) frequently associated with impairments in right- were recruited by personal contact and ﬂyers posted at hemispheric parietal,13 temporal,14 and subcortical the University of Zurich and at the local university hos- structures.15 A study by Heilman’s group has shown pital, where the testing took place. All of them gave in- that neglect in such patients can attenuate under DA- formed consent prior to participation in the study. The agonistic treatment,16 which is thought to restore the group had a mean age of 29.6 years (SD, 6.6 years; range, speciﬁc left-sided deﬁcits in spatial attention. These 23–48 years) and had a mean of 19.0 years (ע3.5 years) ﬁndings have been replicated by an independent re- of education. Potential participants who were currently search group.17 In the case of schizophrenia, a baseline taking any medications or had a history of drug abuse hyperdopaminergia of the right hemisphere would were not enrolled in the study. Absence of a neuropsy- shift attention toward the left hemispace much in the chiatric history was assessed with an extended clinical same way as DA treatment would do in patients with interview.26 All subjects were right-handed according to neglect. Therefore, in schizophrenia, hemiparkinson- ism, and neglect, hemispatial inattention seems to re-sult from an asymmetrically organized DA system.
Magical Ideation Scale
Recent data suggest that spatial awareness in healthy The Magical Ideation scale is a 30-item questionnaire subjects may also be modulated by a psychotic-like that includes items such as “I sometimes have a feeling thinking style, namely magical ideation (MI). Subjects of gaining or losing energy when people look at me or who endorse magical beliefs evidence a right hemispa- touch me” (keyed “true”) and “Some people can make tial inattention that is qualitatively similar to that of pa- me aware of them just by thinking about me” (keyed tients with schizophrenia.18–20 MI is conceived of as a “true”). Scores on the MI scale range from 0 to 30, with mild analog to the positive symptoms reported by pa- higher scores indicating more pronounced magical tients with schizophrenia. It primarily comprises a ten- thinking. The scale is published in full in Eckblad and dency to assume hidden meanings in random conﬁgu- Chapman,22 and normative data can be found in Garety rations and to insist in a causal determination of coincidences.21 Although the concept of MI was intro-duced as an indicator of schizotypy,22 subsequent work Spatial Tasks
has unequivocally demonstrated that the continuum of Line Bisection: Six horizontal parallel lines (lengths: 13 MI is psychometrically relevant even within samples of cm, 16 cm, 18 cm, 20 cm, 24 cm, and 25 cm) were dis- healthy subjects scoring below what would be consid- played twice on a single sheet of paper. The sheet was ered indicative of a schizotypal personality disorder by placed centrally in front of the subject, who was in- commonly accepted standards. Most importantly, even structed to mark the center of each line, using a paper entirely healthy subjects with relatively high MI scores with a 29 cm ן 2 cm window to suppress visual inter- display neuropsychological abnormalities that are qual- ference from the other lines. Two trials were conducted, itatively similar to those displayed by patients with one with the left hand and one with the right hand. The schizophrenia. These comprise, among other things, im- side of the starting hand was counterbalanced between pairments of left-hemispheric temporal lobe functions,23 subjects. For each hand separately, we calculated the an enhanced reliance on right-hemisphere-mediated number of lines that were bisected to the left or right, language functions,24 and deﬁcient somatosensory abil- respectively, from the center. Possible scores thus ranged ities.25 Investigations of MI in healthy subjects thus may from 0 (all lines correctly bisected) to 12 (all 12 lines were help to specify primary brain mechanisms underlying bisected to one side; a minus point for each line left- schizophrenia, especially with regard to positive symp- bisected, a plus point for each line right-bisected).
Turning: Spontaneous turning preferences were mea- This study used a within-subject design to investigate sured with a rotometer, which is a lightweight belt- whether line bisection and axial deviations during mounted device that consists of a position sensor, an whole-body movements are directed more strongly to electronic processing circuit, and a rechargeable battery J Neuropsychiatry Clin Neurosci 15:2, Spring 2003 MAGICAL IDEATION MODULATES SPATIAL BEHAVIOR
that monitors changes in the orientation of the dorsal- years, for men, 30.5 ע 7.5 years; Z ס –0.10, P ס 0.92; ventral axis.9,10,29 Magnetic north is used as an external education for women, 19.6 ע 3.7 years, for men, 18.3 ע reference and is tracked by a compass. Full 360-degree 3.1 years; Z ס –0.93, P ס 0.35).
turns to either side were measured for each subject overa period of 20 hours over 3 consecutive days.
Veering: Subjects were asked to walk blindfolded, with The mean MI score was 9.4 (ע 5.8); no signiﬁcant dif- their ears plugged and their shoes off, along a straight ference was observed between men and women (men, line in the middle of a corridor (1.60 m wide and 20 m 8.2 ע 4.6; women, 10.4 ע 6.6; Z ס –0.81, P ס 0.42). The long). The experimenter walked in front of the subject range of MI scores was within the range reported for and counted a veer (subjects were stopped) when the normal individuals (mostly college students).28 A pre- deviation from the line was larger than 20 cm for both planned split at the median scale score9 produced a low feet. After a veer, the subjects’ bearings were restored by MI group (n ס 17 subjects, 8 of them women) and a instructing them to walk for a short distance along a high MI group (n ס 19 subjects, 12 of them women).
metal strip placed on the line between subjects’ feet. The The distribution of women and men in the high and low strip was then removed and the subjects continued to MI groups was not signiﬁcantly different (v2 ס 0.94; df walk. The start side of the corridor was counterbalanced ס 1, P ס 0.33). Neither years of education nor subjects’ between subjects. We assessed the side of the ﬁrst veer age differed between groups (education, Z ס –0.54, P and the number of veers to either side.
ס 0.59; age, Z ס –1.16, P ס 0.25). Since gender did notinteract with age, education, or MI group, data for Procedure
At a ﬁrst meeting, participants received the rotometerand instructions about its use. The instructions indicatedthat the device was to be worn all day and removed only Spatial Tasks
for sports, sleep, or activities that could result in its dam- Line Bisection: Subjects made a signiﬁcantly higher num- age. When it was removed, the subjects were instructed ber of total left (right plus left hand, 11.5 ע 3.7) than to lay the device down in such a way as to minimize right displacements (right plus left hand, 8.7 ע 4.1; Z any confounding non-body-related movements. At the ס –2.34, P ס 0.02). For the hands separately, this dif- second meeting, which took place at least 3 days later, ference was signiﬁcant for the left hand (Z ס –3.14, P subjects returned the device, ﬁlled in the questionnaires, ס 0.002) but not the right (Z ס –0.43, P ס 0.66) (Table and performed the line bisection and veering tasks, in 1). With the left hand, more subjects bisected lines to the left than to the right (v2 ס 6.43, df ס 1, P ס 0.01). Withthe right hand, neither side was preferred over the other Data Analyses
(v2 ס 0.26, df ס 1, P ס 0.61).
Shapiro-Wilk statistics revealed that most measures (dis- Line Bisection Performance and MI: Across hands, the placements in the line bisection task with the left hand high MI group did not differ from the low MI group in [W ס 0.92, P ס 0.02] and right hand [W ס 0.93, the number of left (Z ס –0.98, P ס 0.33) or right (Z ס Pס0.04], full turns to the left side [W ס 0.89, PϽ0.001], –0.48, P ס 0.63) displacements. Groups did not differ veers to the right [W ס 0.90, P ס 0.004] and left [W ס signiﬁcantly in left displacements with the left (Z ס 0.89, P ס 0.002] side) were not normally distributed, so –0.90, P ס 0.37) or right hand (Z ס –0.60, P ס 0.55) and nonparametric statistics were calculated. Group com- for right displacements with the left (Z ס –0.74, P ס parisons were assessed with the Mann-Whitney U test 0.46) or right hand (Z ס –0.22, P ס 0.83). As illustrated and single comparisons between variables with the Wil- in Figure 1A, the high MI group demonstrated a signiﬁ- coxon test. Spearman rank-correlation coefﬁcients, cor- cant preference for left-sided displacements with the left rected for continuity, were calculated to compare contin- hand (Z ס –2.70, P ס 0.007). For the right hand, the uous variables. All tests were two-tailed, and, except difference was in the same direction, but was note sta- where otherwise noted, the alpha level was set at 0.05.
tistically signiﬁcant (Z ס –0.46, P ס 0.65). The low MIgroup did not differ between left or right displacementsfor either hand (left hand, Z ס –1.66, P ס 0.10; right hand, Z ס –0.06, P ס 0.95).
The correlations between MI scores and number of left Subjects
displacements with either hand (left hand, Spearman Age and education did not differ signiﬁcantly between rank-correlation coefﬁcient [Sr] ס –0.15, P ס 0.38; right women and men (mean age for women, 29.0 ע 5.8 hand, Sr ס –0.04, P ס 0.81) or right displacements with J Neuropsychiatry Clin Neurosci 15:2, Spring 2003 MOHR et al.
either hand (left hand, Sr ס –0.05, P ס 0.78; right hand, Veering: For the whole group, the mean total number Sr ס 0.11, P ס 0.52) were not signiﬁcant.
of veers (left plus right) was 3.6 (ע 2.2). The number of Two chi-square comparisons, one for each hand, be- veers to the right did not differ signiﬁcantly from the tween the number of subjects with a right- or left-side number of veers to the left (Z ס –0.53, P ס 0.60). The bias and MI groups were not signiﬁcant (left hand, v2 number of subjects veering to the left was comparable ס 0.73, P ס 0.39; right hand, v2 ס 0.27, P ס 0.60). In to those veering to the right (v2 ס 1.50, df ס 2, P ס both groups, slightly more subjects bisected lines to the 0.47) (Table 3). With respect to the ﬁrst veer, however, left than to the right of the center (Table 1).
only three subjects walked straight ahead without any Turning: For the whole sample, the mean total number veer, and the remainder veered in almost equal numbers of turns (left plus right) was 99.2 (ע 66.3). Signiﬁcantly to the left or the right (v2 ס 10.50, df ס 2, P ס 0.005) more turns were performed to the left than to the right (Z ס –2.48, P ס 0.01), and signiﬁcantly more subjects The high and low MI groups did not differ in mean demonstrated a preference for turning to the left than to total number of veers (high MI group, 3.1 ע 2.3; and the right (v2 ס 9.0, P ס 0.003) (Table 2).
low MI group, 4.1 ע 2.0; Z ס –1.44, P ס 0.15) or in The mean total number of turns was not different be- number of veers to one side or the other (high MI group, tween the high MI (96.0 ע 72.5) and low MI (102.7 ע Z ס –1.00, P ס 0.32; low MI group, Z ס –1.64, P ס 60.5) groups (Z ס –0.56, P ס 0.59). The number of left 0.10). Figure 1C shows that subjects in the high MI group turns was signiﬁcantly higher than the number of rightturns for the subjects in the high MI (Z ס –2.90, P ס deviated less to the right than those in the low MI group 0.004) but not the low MI group (Z ס –0.85, P ס 0.39) (Z ס –2.43, P ס 0.02). The difference between MI groups (see Figure 1B and Table 2). However, the two groups for veers to the left was not signiﬁcant (Z ס –0.29, P ס did not differ from each other in the number of left (Z 0.77). Likewise, correlation analyses conﬁrmed that sub- ס –0.56, P ס 0.58) or right turns (Z ס –0.84, P ס 0.40).
jects deviated signiﬁcantly less to the right the higher No relationship was found between raw MI score and their MI scores were (Sr ס –0.43, P ס 0.01). By contrast, the number of turns to the left (Sr ס –0.02, P ס 0.93) or veers to the left were independent of MI scores (Sr ס to the right (Sr ס –0.05, P ס 0.77).
The number of subjects preferring right or left turns The number of subjects with a left, right, or no side differed between groups (v2 ס 4.5, P ס 0.03). In the high preference did not differ between MI groups (v2 ס 3.90, MI group, the number of subjects with a left turning df ס 2, P ס 0.14). With regard to the ﬁrst veer, however, preference was higher than in the low MI group (see subjects in the high MI group showed a preference for walking either straight or veering to the left, whereas Mean (ؓ SD) number of displacements to the left and right
P (Difference Between MI Groups)
Note: Asterisks indicate signiﬁcant within-group differences between right and left displacements. *PϽ0.05; **PϽ0.01 aThe high MI group consisted of 19 subjects (MI scores, 9–27) and the low MI group, 17 subjects (MI scores, 0–8). NS ס not signiﬁcant.
Mean (ؓ SD) number of full turns to the left and right
P (Difference Between MI Groups)
Note: Asterisks indicate signiﬁcant within-group differences between right and left displacements. *PϽ0.05; **PϽ0.01 J Neuropsychiatry Clin Neurosci 15:2, Spring 2003 MAGICAL IDEATION MODULATES SPATIAL BEHAVIOR
the subjects in the low MI group had a preference for Lateralized whole-body movements (turning and veering to the right (v2 ס 8.18, df ס 2, P ס 0.02).
veering) both showed that relatively high MI scores areassociated with a greater degree of inattention to theright hemispace. On the group level, we found a left- DISCUSSION
sided turning preference. Crucially, as in the line bisec-tion task, this bias remained signiﬁcant for the high MI This study investigated whether MI, a thinking style but not the low MI group. We found that high MI found in the normal population but originally intro- subjects exhibited not an increased left-sided but a de- duced as an indicator of schizotypy,22 is related to an creased right-sided preference relative to the low MI enhanced right-sided spatial inattention similar to that group. This pattern of hemispatial preferences was also reported for patients with psychosis.9,11 Three types of seen in the veering task, in which high MI subjects spatial behavior were investigated, namely, line bisec- veered less frequently to the right than low MI subjects tion, whole-body turns, and veers while attempting to walk blindfolded in a straight line. MI was assessed with Overall, the results of the spatial performance tasks a well-validated 30-item scale22 previously used to dem- resemble those reported from unmedicated patients onstrate associations between magical beliefs and hemi- with positive psychotic symptoms.9,11 In animals, the spheric processing, both in our own lab18,20,23–24,30 and preferred side for spontaneous turning has been related to an asymmetrical DA system, speciﬁcally to a greater In the line bisection task, the high MI group (those striatal DA receptor stimulation in the hemisphere con- with scores above the median) evidenced a hand differ- tralateral to the observed turning bias.7 This well- ence in bisection performance. Subjects showed a “pseu- established relationship has also been demonstrated in doneglect”33 with their left hand but not with their right.
patients,10,12 in particular in persons with tardive dys- The occurrence of pseudoneglect restricted to the left kinesia and asymmetrical neuroleptic-induced parkin- hand is known from previous investigations,33 as is the sonism,35 which supports the postulated relationship association between MI and right-sided inattention.18–20 between right-hemispheric hyperdopaminergia on the However, the ﬁnding of a left-hand pseudoneglect ex- one hand and right-sided inattention and psychosis on clusively for the high MI group but not the low MI group is new. We should note that line bisection perfor- This study extends the literature linking psychotic- mance critically depends on task conditions.33,34 Our like thinking in healthy subjects to a neurotransmitter, procedure involved a paper-and-pencil version and dif- namely, dopamine. While previous studies have found fered from that used in previous research. Brugger and evidence for conceptual similarities between MI and Graves,18 for instance, used a tactile rod bisection task, schizophrenia,18–20,23–25,30–32 DA, the major neurotrans- and Taylor et al.20 measured lateral deviations in sub- mitter linked to schizophrenia, has remained largely ne- jects’ recollections of a complex ﬁgure from memory.
glected. Although Davis et al.36 argued that comparative These procedural differences likely explain the lack of a studies of schizophrenia and its spectrum disorders are pseudoneglect for the right hand in our experiment. Our useful for generating major ideas about effective treat- ﬁnding suggests that the association between MI and ments and tools for differentiating between diagnoses, manual space exploration may be more clear if the focus few studies have investigated the DA system within the is on left-hand rather than right-hand performance. In broader spectrum.37 The experiments described here any case, the association between MI and spatial atten- provide indirect evidence for a common dopaminergic tion adds to current discussions about the involvement mediation of lateral spatial preferences and the suscep- of the parietal lobes in the genesis of psychotic-like tibility to unfounded referential thinking—that is, MI.
In analogy to previous ﬁndings from studies with pa- Mean (ؓ SD) number of veers to the left and right
P (Difference Between MI Groups)
Subjects with left preference (n with no veering) First veer: left preference (n with no veering) Note: Asterisks indicate signiﬁcant within-group differences between right and left displacements. *PϽ0.05; **PϽ0.01 J Neuropsychiatry Clin Neurosci 15:2, Spring 2003 MOHR et al.
tients and with animals, we interpret the observed ef- symptoms. Qualitatively, the observed effects were con- fects as a consequence of hemispheric asymmetries in sistent across three different tasks. However, given the dopaminergic activity. We emphasize, however, that the simplicity and cost-effectiveness of the veering task, the relationship we found between MI and right-sided spa- assessment of veering behavior may be especially rec- tial inattention suggests that a mildly hyperactive DA ommended for future use in psychiatric patients in a system in the right hemisphere may reﬂect a normal wide variety of both research and clinical settings.
neurochemical asymmetry rather than a secondary con-sequence of psychopathology. This neurochemicalasymmetry, a property of the normal brain, may be ac- Preliminary results of this study were presented at the centuated in people with schizotypal personality dis- Fourteenth International Congress on Parkinson’s Disease, orders or schizophrenia, in whom lateral biases in spa- Helsinki, Finland, July 27–August 1, 2001. This research was tial attention are reportedly associated with symptom supported by the Institut fu¨r Grenzgebiete der Psychologie und Psychohygiene, Freiburg im Breisgau (No. 690610) to In conclusion, in this report we have described a mod- Dr. Mohr and Dr. Brugger. This material is also based on work ulation of normal subjects’ spatial behavior by a mode supported in part by the Ofﬁce of Research and Development, of thinking reminiscent of the positive symptoms of psy- Medical Research Service, Department of Veterans Affairs, chotic patients. Overall, the results of the spatial perfor- and by NIMH grant MH-43537 to Dr. Bracha. The authors mance tasks resemble those previously reported in stud- are grateful to Theodor Landis for his technical and editorial ies of unmedicated patients with positive psychotic FIGURE 1.
Hemispatialbiases in three different spatialbehavioralmeasures. Low MI group subjects who scored below the median
on the MagicalIdeation scale; high MI group subjects who scored above the median.
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Taking small steps towards targets perspectives for clinical practice in diabetes, cardiometabolic disorders and beyond
Taking small steps towards targets – perspectives forclinical practice in diabetes, cardiometabolic disordersand beyondA. Golay,1 E. Brock,2 R. Gabriel,3 T. Konrad,4 N. Lalic,5 M. Laville,6 G. Mingrone,7 J. Petrie,8T.-M. Phan,9 K. H. Pietil€ainen,10,11 C.-H. Anderwald12,13,14Big changes are hard. When trying to achieve guideline targets in diabetes andLiterature review of the effects of cha