Hallucinations and conscious access to visual inputs in Parkinson’s disease
Identifieur interne : 000078 ( Pmc/Checkpoint ); précédent : 000077; suivant : 000079Hallucinations and conscious access to visual inputs in Parkinson’s disease
Auteurs : Stéphanie Lefebvre [France] ; Guillaume Baille [France] ; Renaud Jardri [France] ; Lucie Plomhause [France] ; Sébastien Szaffarczyk [France] ; Luc Defebvre [France] ; Pierre Thomas [France] ; Christine Delmaire [France] ; Delphine Pins [France] ; Kathy Dujardin [France]Source :
- Scientific Reports [ 2045-2322 ] ; 2016.
Abstract
The pathophysiology of visual hallucinations in Parkinson’s disease has yet to be characterized. Although stimulus-driven (“bottom-up”) processes are known to be impaired, the role of “top-down” processes remains to be determined. Distinguishing between conscious and non-conscious detections (i.e. access to consciousness) may be a valuable way of monitoring top-down processes. Conscious access to visual inputs was investigated to identify the neural substrates underlying susceptibility to hallucinations in Parkinson’s disease. Seventeen healthy controls, 18 Parkinson’s disease patients with minor visual hallucinations and 16 without were enrolled in the study. During functional magnetic resonance imaging, the participants performed a visual detection task. The detection threshold was significantly higher in each patient group than in healthy controls while the two groups of patients did not differ significantly. Compared with hallucination-free patients, patients with minor hallucinations displayed hyperactivation of prefrontal and right occipital cortices, and hypoactivation of the left cingulate, temporal and occipital cortices. During conscious access to visual inputs, the functional network in patients with visual hallucinations differed from that seen in patients without visual hallucinations. This suggests that the supremacy of top-down processes in visual information processing may enhance susceptibility to hallucinations in Parkinson’s disease.
Url:
DOI: 10.1038/srep36284
PubMed: 27841268
PubMed Central: 5107911
Affiliations:
- France
- Hauts-de-France, Nord-Pas-de-Calais
- Lille
- Université Lille 2, Université Lille Nord de France
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<front><div type="abstract" xml:lang="en"><p>The pathophysiology of visual hallucinations in Parkinson’s disease has yet to be characterized. Although stimulus-driven (“bottom-up”) processes are known to be impaired, the role of “top-down” processes remains to be determined. Distinguishing between conscious and non-conscious detections (i.e. access to consciousness) may be a valuable way of monitoring top-down processes. Conscious access to visual inputs was investigated to identify the neural substrates underlying susceptibility to hallucinations in Parkinson’s disease. Seventeen healthy controls, 18 Parkinson’s disease patients with minor visual hallucinations and 16 without were enrolled in the study. During functional magnetic resonance imaging, the participants performed a visual detection task. The detection threshold was significantly higher in each patient group than in healthy controls while the two groups of patients did not differ significantly. Compared with hallucination-free patients, patients with minor hallucinations displayed hyperactivation of prefrontal and right occipital cortices, and hypoactivation of the left cingulate, temporal and occipital cortices. During conscious access to visual inputs, the functional network in patients with visual hallucinations differed from that seen in patients without visual hallucinations. This suggests that the supremacy of top-down processes in visual information processing may enhance susceptibility to hallucinations in Parkinson’s disease.</p>
</div>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group><journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher><publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27841268</article-id>
<article-id pub-id-type="pmc">5107911</article-id>
<article-id pub-id-type="pii">srep36284</article-id>
<article-id pub-id-type="doi">10.1038/srep36284</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Hallucinations and conscious access to visual inputs in Parkinson’s disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Lefebvre</surname>
<given-names>Stéphanie</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baille</surname>
<given-names>Guillaume</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
<xref ref-type="author-notes" rid="n1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jardri</surname>
<given-names>Renaud</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Plomhause</surname>
<given-names>Lucie</given-names>
</name>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Szaffarczyk</surname>
<given-names>Sébastien</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Defebvre</surname>
<given-names>Luc</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thomas</surname>
<given-names>Pierre</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Delmaire</surname>
<given-names>Christine</given-names>
</name>
<xref ref-type="aff" rid="a4">4</xref>
<xref ref-type="aff" rid="a5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pins</surname>
<given-names>Delphine</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dujardin</surname>
<given-names>Kathy</given-names>
</name>
<xref ref-type="corresp" rid="c1">a</xref>
<xref ref-type="aff" rid="a3">3</xref>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<aff id="a1"><label>1</label>
<institution>Univ. Lille, CNRS, UMR 9193 - SCALab - Sciences Cognitives et Sciences Affectives</institution>
, F-59000 Lille,<country>France</country>
</aff>
<aff id="a2"><label>2</label>
<institution>CHU Lille, Clinique de Psychiatrie</institution>
, CURE, F-59000 Lille,<country>France</country>
</aff>
<aff id="a3"><label>3</label>
<institution>Department of Neurology and Movement Disorders, Lille University Medical Center</institution>
, F-59000 Lille,<country>France</country>
</aff>
<aff id="a4"><label>4</label>
<institution>Univ. Lille, Inserm, U1171 - Degenerative & vascular cognitive disorders</institution>
, F-59000 Lille,<country>France</country>
</aff>
<aff id="a5"><label>5</label>
<institution>Neuroimaging Department, Lille University Medical Center</institution>
, F-59000 Lille,<country>France</country>
</aff>
</contrib-group>
<author-notes><corresp id="c1"><label>a</label>
<email>kathy.dujardin@univ-lille2.fr</email>
</corresp>
<fn id="n1"><label>*</label>
<p>These authors contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="epub"><day>14</day>
<month>11</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><year>2016</year>
</pub-date>
<volume>6</volume>
<elocation-id>36284</elocation-id>
<history><date date-type="received"><day>08</day>
<month>06</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>13</day>
<month>10</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2016, The Author(s)</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>The Author(s)</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract><p>The pathophysiology of visual hallucinations in Parkinson’s disease has yet to be characterized. Although stimulus-driven (“bottom-up”) processes are known to be impaired, the role of “top-down” processes remains to be determined. Distinguishing between conscious and non-conscious detections (i.e. access to consciousness) may be a valuable way of monitoring top-down processes. Conscious access to visual inputs was investigated to identify the neural substrates underlying susceptibility to hallucinations in Parkinson’s disease. Seventeen healthy controls, 18 Parkinson’s disease patients with minor visual hallucinations and 16 without were enrolled in the study. During functional magnetic resonance imaging, the participants performed a visual detection task. The detection threshold was significantly higher in each patient group than in healthy controls while the two groups of patients did not differ significantly. Compared with hallucination-free patients, patients with minor hallucinations displayed hyperactivation of prefrontal and right occipital cortices, and hypoactivation of the left cingulate, temporal and occipital cortices. During conscious access to visual inputs, the functional network in patients with visual hallucinations differed from that seen in patients without visual hallucinations. This suggests that the supremacy of top-down processes in visual information processing may enhance susceptibility to hallucinations in Parkinson’s disease.</p>
</abstract>
</article-meta>
</front>
<floats-group><fig id="f1"><label>Figure 1</label>
<caption><title>The visual detection threshold Mean ± SD grating duration for each of the 70 trials and for each of the 3 groups.</title>
<p>PD-nonVH: PDpatients without visual hallucinations; PD-VH: PD patients with visual hallucinations; HC: healthy controls.</p>
</caption>
<graphic xlink:href="srep36284-f1"></graphic>
</fig>
<fig id="f2"><label>Figure 2</label>
<caption><title>Whole-brain <bold>ANCOVA</bold>
A whole-brain ANCOVA, comparing conscious access to visual inputs in the three groups [t (200) = 2.59, <italic>P</italic>
= 0.01 (corrected at the cluster level)].</title>
<p>Panel A: Comparison of conscious access to visual inputs in the HC vs. PD groups. Panel B: Comparison of conscious access to visual inputs in the PD-VH vs. PD-nonVH groups. ST: seen trials at the threshold, UT: unseen trial at the threshold, PD-nonVH: PD patients without visual hallucinations; PD-VH: PD patients with visual hallucinations; HC: healthy controls; L: left.</p>
</caption>
<graphic xlink:href="srep36284-f2"></graphic>
</fig>
<fig id="f3"><label>Figure 3</label>
<caption><title>Design of the threshold evaluation study.</title>
<p>The visual detection task consisted of 70 threshold evaluation trials. Each threshold evaluation trial began with a sound signal (duration: 200 ms; frequency: 250 Hz). The stimulus was then presented after an interval of 550 ms (the pre-stimulus interval) plus a random jitter time ranging from 0 to 1100 ms). After a second sound signal (duration: 200 ms, frequency: 500 Hz, also presented after an interval of 550 ms plus a random jitter time ranging from 0 to 1100 ms), the subject was required to press one of two buttons on the response pad with the right hand to indicate whether or not he/she had seen the stimulus. The inter-trial interval was 13300 ms.</p>
</caption>
<graphic xlink:href="srep36284-f3"></graphic>
</fig>
<table-wrap position="float" id="t1"><label>Table 1</label>
<caption><title>Demographic and clinical characteristics of the three subject groups</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom"><tr><th align="left" valign="top" charoff="50"> </th>
<th align="center" valign="top" charoff="50">PD without VHs (n = 16) Mean <italic>(SD)</italic>
</th>
<th align="center" valign="top" charoff="50">PD with minor VHs (n = 18) Mean <italic>(SD)</italic>
</th>
<th align="center" valign="top" charoff="50">Healthy controls (n = 17) Mean <italic>(SD)</italic>
</th>
<th align="center" valign="top" charoff="50">p value</th>
<th align="center" valign="top" charoff="50">Post-hoc test</th>
</tr>
</thead>
<tbody valign="top"><tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Demographics</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Gender (female/male)</td>
<td align="center" valign="top" charoff="50">4/12</td>
<td align="center" valign="top" charoff="50">7/11</td>
<td align="center" valign="top" charoff="50">7/10</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Age (y)</td>
<td align="center" valign="top" charoff="50">62.69 <italic>(4.09)</italic>
</td>
<td align="center" valign="top" charoff="50">63.50 <italic>(5.94)</italic>
</td>
<td align="center" valign="top" charoff="50">62.76 <italic>(4.19)</italic>
</td>
<td align="center" valign="top" charoff="50">0.86</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Educational level (y of full-time education)</td>
<td align="center" valign="top" charoff="50">13.38 <italic>(4.19)</italic>
</td>
<td align="center" valign="top" charoff="50">12.44 <italic>(3.33)</italic>
</td>
<td align="center" valign="top" charoff="50">13.76 <italic>(1.92)</italic>
</td>
<td align="center" valign="top" charoff="50">0.47</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Clinical characteristics</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Disease duration (y)</td>
<td align="center" valign="top" charoff="50">8.00 <italic>(5.74)</italic>
</td>
<td align="center" valign="top" charoff="50">9.06 <italic>(4.11)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">0.54</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> MDS-UPDRS3 score</td>
<td align="center" valign="top" charoff="50">21.81 <italic>(7.93)</italic>
</td>
<td align="center" valign="top" charoff="50">25 <italic>(8.44)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">0.27</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Hoehn & Yahr stage (Median; first-third quartile)</td>
<td align="center" valign="top" charoff="50"><italic>2;2–2</italic>
</td>
<td align="center" valign="top" charoff="50"><italic>2;2–2</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">0.09</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Side of onset</td>
<td align="center" valign="top" charoff="50">9 R/5 L+2 undefined</td>
<td align="center" valign="top" charoff="50">10 R/6 L + 2 undefined</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> UM-PDHQ visual modality</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">5.78 <italic>(2.07)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> VH frequency (0 to 20 on a visual analog scale)</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">3.05 <italic>(1.99)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> VH severity (0 to 20 on a visual analogue scale)</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">1.56 <italic>(2.17)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Medication</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> LEDD (mg/day)</td>
<td align="center" valign="top" charoff="50">804.25 <italic>(297.39)</italic>
</td>
<td align="center" valign="top" charoff="50">859.72 <italic>(411.08)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">0.66</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Agonist-LEDD (mg/day)</td>
<td align="center" valign="top" charoff="50">184.71 <italic>(182.49)</italic>
</td>
<td align="center" valign="top" charoff="50">166.83 <italic>(117.78)</italic>
</td>
<td align="center" valign="top" charoff="50">NA</td>
<td align="center" valign="top" charoff="50">0.58</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Neuropsychiatric</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Hamilton Depression Rating Scale</td>
<td align="center" valign="top" charoff="50">3.06 <italic>(2.88)</italic>
</td>
<td align="center" valign="top" charoff="50">3.56 <italic>(2.99)</italic>
</td>
<td align="center" valign="top" charoff="50">1.12 <italic>(1.45)</italic>
</td>
<td align="center" valign="top" charoff="50">0.02</td>
<td align="center" valign="top" charoff="50">2≠3</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Score on the PAS: persistent anxiety</td>
<td align="center" valign="top" charoff="50">2.81 <italic>(3.60)</italic>
</td>
<td align="center" valign="top" charoff="50">5.28 <italic>(5.57)</italic>
</td>
<td align="center" valign="top" charoff="50">1.35 <italic>(2.06)</italic>
</td>
<td align="center" valign="top" charoff="50">0.02</td>
<td align="center" valign="top" charoff="50">2≠3</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Score on the PAS: episodic anxiety</td>
<td align="center" valign="top" charoff="50">0.31 <italic>(0.60)</italic>
</td>
<td align="center" valign="top" charoff="50">0.83 <italic>(1.58)</italic>
</td>
<td align="center" valign="top" charoff="50">0.00 <italic>(0.00)</italic>
</td>
<td align="center" valign="top" charoff="50">0.05</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Score on the PAS: avoidance</td>
<td align="center" valign="top" charoff="50">1.00 <italic>(1.55)</italic>
</td>
<td align="center" valign="top" charoff="50">1.00 <italic>(1.64)</italic>
</td>
<td align="center" valign="top" charoff="50">0.06 <italic>(0.24)</italic>
</td>
<td align="center" valign="top" charoff="50">0.06</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Lille Apathy Rating Scale</td>
<td align="center" valign="top" charoff="50">−27.13 <italic>(4.95)</italic>
</td>
<td align="center" valign="top" charoff="50">−26.56 <italic>(3.48)</italic>
</td>
<td align="center" valign="top" charoff="50">−28.35 <italic>(4.47)</italic>
</td>
<td align="center" valign="top" charoff="50">0.46</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Visual detection threshold (ms)</td>
<td align="center" valign="top" charoff="50">163.38 <italic>129.72</italic>
</td>
<td align="center" valign="top" charoff="50">175.17 <italic>124.12</italic>
</td>
<td align="center" valign="top" charoff="50">69.29 <italic>55.99</italic>
</td>
<td align="center" valign="top" charoff="50">0.01</td>
<td align="center" valign="top" charoff="50">1≠3; 2≠3</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Overall efficiency</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Mini Mental State Examination (out of 30)</td>
<td align="center" valign="top" charoff="50">28.88 <italic>1.20</italic>
</td>
<td align="center" valign="top" charoff="50">28.00 <italic>1.24</italic>
</td>
<td align="center" valign="top" charoff="50">28.47 <italic>1.70</italic>
</td>
<td align="center" valign="top" charoff="50">0.20</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Mattis Dementia Rating Scale (out of 144)</td>
<td align="center" valign="top" charoff="50">140.44 <italic>3.22</italic>
</td>
<td align="center" valign="top" charoff="50">140.33 <italic>2.38</italic>
</td>
<td align="center" valign="top" charoff="50">142.06 <italic>1.71</italic>
</td>
<td align="center" valign="top" charoff="50">0.09</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Attention/Working memory</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> WAIS-R forward digit span</td>
<td align="center" valign="top" charoff="50">6.06 <italic>0.99</italic>
</td>
<td align="center" valign="top" charoff="50">5.67 <italic>0.91</italic>
</td>
<td align="center" valign="top" charoff="50">5.47 <italic>1.07</italic>
</td>
<td align="center" valign="top" charoff="50">0.22</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> WAIS-R backward digit span</td>
<td align="center" valign="top" charoff="50">4.31 <italic>0.70</italic>
</td>
<td align="center" valign="top" charoff="50">4.22 <italic>0.94</italic>
</td>
<td align="center" valign="top" charoff="50">4.35 <italic>0.93</italic>
</td>
<td align="center" valign="top" charoff="50">0.90</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> SDMT: number in 90 sec</td>
<td align="center" valign="top" charoff="50">48.38 <italic>9.74</italic>
</td>
<td align="center" valign="top" charoff="50">41.39 <italic>12.05</italic>
</td>
<td align="center" valign="top" charoff="50">47.06 <italic>5.39</italic>
</td>
<td align="center" valign="top" charoff="50">0.08</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Episodic Memory</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> HVLT Learn1 (out of 12)</td>
<td align="center" valign="top" charoff="50">6.50 <italic>1.93</italic>
</td>
<td align="center" valign="top" charoff="50">6.11 <italic>2.32</italic>
</td>
<td align="center" valign="top" charoff="50">7.18 <italic>1.91</italic>
</td>
<td align="center" valign="top" charoff="50">0.32</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> HVLT Learn total (out of 36)</td>
<td align="center" valign="top" charoff="50">26.63 <italic>4.18</italic>
</td>
<td align="center" valign="top" charoff="50">25.17 <italic>5.08</italic>
</td>
<td align="center" valign="top" charoff="50">28.82 <italic>3.92</italic>
</td>
<td align="center" valign="top" charoff="50">0.06</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> HVLT long-term retention (%)</td>
<td align="center" valign="top" charoff="50">92.20 <italic>12.27</italic>
</td>
<td align="center" valign="top" charoff="50">95.91 <italic>11.26</italic>
</td>
<td align="center" valign="top" charoff="50">96.84 <italic>6.24</italic>
</td>
<td align="center" valign="top" charoff="50">0.37</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> HVLT recognition hits (out of 12)</td>
<td align="center" valign="top" charoff="50">11.69 <italic>0.48</italic>
</td>
<td align="center" valign="top" charoff="50">11.50 <italic>0.79</italic>
</td>
<td align="center" valign="top" charoff="50">11.76 <italic>0.44</italic>
</td>
<td align="center" valign="top" charoff="50">0.41</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> HVLT number of intrusions</td>
<td align="center" valign="top" charoff="50">1.81 <italic>1.28</italic>
</td>
<td align="center" valign="top" charoff="50">2.22 <italic>2.84</italic>
</td>
<td align="center" valign="top" charoff="50">1.59 <italic>2.69</italic>
</td>
<td align="center" valign="top" charoff="50">0.73</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Executive functions</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Trail Making Test (time B/time A)</td>
<td align="center" valign="top" charoff="50">2.48 <italic>0.64</italic>
</td>
<td align="center" valign="top" charoff="50">3.58 <italic>1.14</italic>
</td>
<td align="center" valign="top" charoff="50">3.85 <italic>1.44</italic>
</td>
<td align="center" valign="top" charoff="50"><0.01</td>
<td align="center" valign="top" charoff="50">1 ≠ 2; 1 ≠ 3</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Stroop: interference index</td>
<td align="center" valign="top" charoff="50">1.64 <italic>0.40</italic>
</td>
<td align="center" valign="top" charoff="50">1.79 <italic>0.30</italic>
</td>
<td align="center" valign="top" charoff="50">1.78 <italic>0.27</italic>
</td>
<td align="center" valign="top" charoff="50">0.31</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Stroop: errors</td>
<td align="center" valign="top" charoff="50">0.87 <italic>0.96</italic>
</td>
<td align="center" valign="top" charoff="50">2.78 <italic>3.17</italic>
</td>
<td align="center" valign="top" charoff="50">1.00 <italic>1.50</italic>
</td>
<td align="center" valign="top" charoff="50">0.02</td>
<td align="center" valign="top" charoff="50">1≠2</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Phonemic fluency: naming in 60 sec.</td>
<td align="center" valign="top" charoff="50">14.75 <italic>3.57</italic>
</td>
<td align="center" valign="top" charoff="50">16.61 <italic>5.24</italic>
</td>
<td align="center" valign="top" charoff="50">16.71 <italic>3.79</italic>
</td>
<td align="center" valign="top" charoff="50">0.35</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Alternating fluency: naming in 60 sec</td>
<td align="center" valign="top" charoff="50">13.31 <italic>3.07</italic>
</td>
<td align="center" valign="top" charoff="50">13.11 <italic>3.50</italic>
</td>
<td align="center" valign="top" charoff="50">13.94 <italic>3.29</italic>
</td>
<td align="center" valign="top" charoff="50">0.74</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>language</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Boston naming test (out of 15)</td>
<td align="center" valign="top" charoff="50">12.94 <italic>1.57</italic>
</td>
<td align="center" valign="top" charoff="50">12.44 <italic>1.46</italic>
</td>
<td align="center" valign="top" charoff="50">13.35 <italic>1.54</italic>
</td>
<td align="center" valign="top" charoff="50">0.22</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Animal naming in 60 sec</td>
<td align="center" valign="top" charoff="50">20.88 <italic>4.69</italic>
</td>
<td align="center" valign="top" charoff="50">20.22 <italic>3.77</italic>
</td>
<td align="center" valign="top" charoff="50">20.71 <italic>3.27</italic>
</td>
<td align="center" valign="top" charoff="50">0.88</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td colspan="6" align="left" valign="top" charoff="50"><sc>Visuospatial functions</sc>
</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Judgment of line orientation (out of 15)</td>
<td align="center" valign="top" charoff="50">13.31 <italic>2.24</italic>
</td>
<td align="center" valign="top" charoff="50">12.28 <italic>1.45</italic>
</td>
<td align="center" valign="top" charoff="50">13.41 <italic>1.12</italic>
</td>
<td align="center" valign="top" charoff="50">0.09</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> Visuoconstruction (out of 12)</td>
<td align="center" valign="top" charoff="50">11.06 <italic>1.12</italic>
</td>
<td align="center" valign="top" charoff="50">11.33 <italic>1.08</italic>
</td>
<td align="center" valign="top" charoff="50">10.71 <italic>0.69</italic>
</td>
<td align="center" valign="top" charoff="50">0.18</td>
<td align="center" valign="top" charoff="50">NA</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t1-fn1"><p>VH: visual hallucination; MDS UPDRS3: Movement Disorders Society sponsored revision of the Unified Parkinson’s Disease Rating Scale-Part III (severity of motor symptoms); UM-PDHQ: University of Miami Parkinson’s Disease Hallucination Questionnaire; LEDD: levodopa equivalent daily dose; PAS: Parkinson Anxiety Scale; WAIS-R: Wechsler Adult Intelligence Scale-Revised; SDMT: symbol digit modalities test; HVLT: Hopkins Verbal Learning Test; NA: not applicable.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t2"><label>Table 2</label>
<caption><title>Whole brain ANCOVA.</title>
</caption>
<table frame="hsides" rules="groups" border="1"><colgroup><col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom"><tr><th rowspan="2" align="left" valign="bottom" charoff="50"> </th>
<th rowspan="2" align="center" valign="bottom" charoff="50">Brain area</th>
<th rowspan="2" align="center" valign="bottom" charoff="50">BA</th>
<th rowspan="2" align="center" valign="bottom" charoff="50">mean x</th>
<th rowspan="2" align="center" valign="bottom" charoff="50">mean y</th>
<th rowspan="2" align="center" valign="bottom" charoff="50">mean z</th>
<th rowspan="2" align="center" valign="bottom" charoff="50">mm<sup>3</sup>
</th>
<th align="center" valign="top" charoff="50">Activation peak</th>
</tr>
<tr><th align="center" valign="top" charoff="50">t value</th>
</tr>
</thead>
<tbody valign="top"><tr><td colspan="8" align="left" valign="top" charoff="50">[ST-UT] HCs vs PD patients: t(200) = 2.59, <italic>P</italic>
= 0.01, corrected at the cluster level</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> PD patients > HCs</td>
<td align="center" valign="top" charoff="50">R thalamus</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">22</td>
<td align="center" valign="top" charoff="50">−16</td>
<td align="center" valign="top" charoff="50">12</td>
<td align="center" valign="top" charoff="50">3 819</td>
<td align="center" valign="top" charoff="50">−4.6</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">R precuneus</td>
<td align="center" valign="top" charoff="50">7</td>
<td align="center" valign="top" charoff="50">22</td>
<td align="center" valign="top" charoff="50">−53</td>
<td align="center" valign="top" charoff="50">49</td>
<td align="center" valign="top" charoff="50">1 515</td>
<td align="center" valign="top" charoff="50">−3.17</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> HCs > PD patients</td>
<td align="center" valign="top" charoff="50">L PMd</td>
<td align="center" valign="top" charoff="50">6</td>
<td align="center" valign="top" charoff="50">−20</td>
<td align="center" valign="top" charoff="50">−10</td>
<td align="center" valign="top" charoff="50">51</td>
<td align="center" valign="top" charoff="50">1 676</td>
<td align="center" valign="top" charoff="50">3,26</td>
</tr>
<tr><td colspan="8" align="left" valign="top" charoff="50">[ST-UT] PD-VH vs PD-nonVH: t(200) = 2.59, <italic>P</italic>
= 0.01, corrected at the cluster level</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> PD-VH > PD-nonVH</td>
<td align="center" valign="top" charoff="50">R cerebellum</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">28</td>
<td align="center" valign="top" charoff="50">−57</td>
<td align="center" valign="top" charoff="50">−39</td>
<td align="center" valign="top" charoff="50">259</td>
<td align="center" valign="top" charoff="50">3,30</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">R occipital cortex</td>
<td align="center" valign="top" charoff="50">18</td>
<td align="center" valign="top" charoff="50">21</td>
<td align="center" valign="top" charoff="50">−72</td>
<td align="center" valign="top" charoff="50">−1</td>
<td align="center" valign="top" charoff="50">139</td>
<td align="center" valign="top" charoff="50">3,27</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">R prefrontal cortex</td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">9</td>
<td align="center" valign="top" charoff="50">30</td>
<td align="center" valign="top" charoff="50">52</td>
<td align="center" valign="top" charoff="50">140</td>
<td align="center" valign="top" charoff="50">2.77</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> PD-nonVH > PD-VH</td>
<td align="center" valign="top" charoff="50">L cingulate cortex</td>
<td align="center" valign="top" charoff="50">31</td>
<td align="center" valign="top" charoff="50">−20</td>
<td align="center" valign="top" charoff="50">−26</td>
<td align="center" valign="top" charoff="50">35</td>
<td align="center" valign="top" charoff="50">6 433</td>
<td align="center" valign="top" charoff="50">−4,17</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">L caudate nucleus</td>
<td align="center" valign="top" charoff="50">−23</td>
<td align="center" valign="top" charoff="50">−27</td>
<td align="center" valign="top" charoff="50">24</td>
<td align="center" valign="top" charoff="50">828</td>
<td align="center" valign="top" charoff="50">−3,5</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">L temporal cortex</td>
<td align="center" valign="top" charoff="50">22</td>
<td align="center" valign="top" charoff="50">−47</td>
<td align="center" valign="top" charoff="50">−42</td>
<td align="center" valign="top" charoff="50">4</td>
<td align="center" valign="top" charoff="50">154</td>
<td align="center" valign="top" charoff="50">−3,15</td>
</tr>
<tr><td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">L occipital cortex</td>
<td align="center" valign="top" charoff="50">19</td>
<td align="center" valign="top" charoff="50">−35</td>
<td align="center" valign="top" charoff="50">−69</td>
<td align="center" valign="top" charoff="50">−8</td>
<td align="center" valign="top" charoff="50">178</td>
<td align="center" valign="top" charoff="50">−3,13</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="t2-fn1"><p>PD-nonVH: PD patients without visual hallucinations; PD-VH: PD patients with visual hallucinations; HC: healthy controls; ST: seen at the threshold; UT: unseen at the threshold; SNT: seen not at the threshold; UNT: unseen not at the threshold; DLPFC: dorsolateral prefrontal cortex; PMd: dorsal premotor cortex; BA: Brodmann area; R: right; L: left.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>France</li>
</country>
<region><li>Hauts-de-France</li>
<li>Nord-Pas-de-Calais</li>
</region>
<settlement><li>Lille</li>
</settlement>
<orgName><li>Université Lille 2</li>
<li>Université Lille Nord de France</li>
</orgName>
</list>
<tree><country name="France"><noRegion><name sortKey="Lefebvre, Stephanie" sort="Lefebvre, Stephanie" uniqKey="Lefebvre S" first="Stéphanie" last="Lefebvre">Stéphanie Lefebvre</name>
</noRegion>
<name sortKey="Baille, Guillaume" sort="Baille, Guillaume" uniqKey="Baille G" first="Guillaume" last="Baille">Guillaume Baille</name>
<name sortKey="Defebvre, Luc" sort="Defebvre, Luc" uniqKey="Defebvre L" first="Luc" last="Defebvre">Luc Defebvre</name>
<name sortKey="Defebvre, Luc" sort="Defebvre, Luc" uniqKey="Defebvre L" first="Luc" last="Defebvre">Luc Defebvre</name>
<name sortKey="Delmaire, Christine" sort="Delmaire, Christine" uniqKey="Delmaire C" first="Christine" last="Delmaire">Christine Delmaire</name>
<name sortKey="Delmaire, Christine" sort="Delmaire, Christine" uniqKey="Delmaire C" first="Christine" last="Delmaire">Christine Delmaire</name>
<name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name>
<name sortKey="Dujardin, Kathy" sort="Dujardin, Kathy" uniqKey="Dujardin K" first="Kathy" last="Dujardin">Kathy Dujardin</name>
<name sortKey="Jardri, Renaud" sort="Jardri, Renaud" uniqKey="Jardri R" first="Renaud" last="Jardri">Renaud Jardri</name>
<name sortKey="Jardri, Renaud" sort="Jardri, Renaud" uniqKey="Jardri R" first="Renaud" last="Jardri">Renaud Jardri</name>
<name sortKey="Lefebvre, Stephanie" sort="Lefebvre, Stephanie" uniqKey="Lefebvre S" first="Stéphanie" last="Lefebvre">Stéphanie Lefebvre</name>
<name sortKey="Pins, Delphine" sort="Pins, Delphine" uniqKey="Pins D" first="Delphine" last="Pins">Delphine Pins</name>
<name sortKey="Pins, Delphine" sort="Pins, Delphine" uniqKey="Pins D" first="Delphine" last="Pins">Delphine Pins</name>
<name sortKey="Plomhause, Lucie" sort="Plomhause, Lucie" uniqKey="Plomhause L" first="Lucie" last="Plomhause">Lucie Plomhause</name>
<name sortKey="Szaffarczyk, Sebastien" sort="Szaffarczyk, Sebastien" uniqKey="Szaffarczyk S" first="Sébastien" last="Szaffarczyk">Sébastien Szaffarczyk</name>
<name sortKey="Szaffarczyk, Sebastien" sort="Szaffarczyk, Sebastien" uniqKey="Szaffarczyk S" first="Sébastien" last="Szaffarczyk">Sébastien Szaffarczyk</name>
<name sortKey="Thomas, Pierre" sort="Thomas, Pierre" uniqKey="Thomas P" first="Pierre" last="Thomas">Pierre Thomas</name>
<name sortKey="Thomas, Pierre" sort="Thomas, Pierre" uniqKey="Thomas P" first="Pierre" last="Thomas">Pierre Thomas</name>
</country>
</tree>
</affiliations>
</record>
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