Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease
Introduction Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation. Methods Thirty‐nine patients with mild AD who...
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| Veröffentlicht in: | Alzheimer's & dementia 2021-05, Vol.17 (5), p.777-787 |
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| creator | Germann, Jürgen Elias, Gavin J.B. Boutet, Alexandre Narang, Keshav Neudorfer, Clemens Horn, Andreas Loh, Aaron Deeb, Wissam Salvato, Bryan Almeida, Leonardo Foote, Kelly D. Rosenberg, Paul B. Tang‐Wai, David F. Wolk, David A. Burke, Anna D. Salloway, Stephen Sabbagh, Marwan N. Chakravarty, M. Mallar Smith, Gwenn S. Lyketsos, Constantine G. Okun, Michael S. Lozano, Andres M. |
| description | Introduction
Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation.
Methods
Thirty‐nine patients with mild AD who took part in a prior fx‐DBS trial (NCT01608061) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel‐wise VTA mapping to identify flashback‐associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback‐associated brain‐wide networks.
Results
A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback‐inducing stimulation exhibited greater functional connectivity to a network of memory‐evoking and autobiographical memory‐related sites.
Discussion
These results clarify the neuroanatomical substrates of stimulation‐evoked flashbacks. |
| doi_str_mv | 10.1002/alz.12238 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8247976</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2480278952</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4158-1166c2f0813b30b532e868ec2a7bba258fdf783291a15a4f58bc18fb78add0333</originalsourceid><addsrcrecordid>eNp1kbtuFDEUhkeIiFyg4AWQO6DYxJfxjLdBWiIukVaigYbG8uU4a_DYiz1DtKl4hDS8YJ4kTnZZQUFly_7Od479N81zgk8JxvRMhetTQikTj5ojwjmdcdrPH-_3HT5sjkv5hnGLBeFPmkPGWoGJ6I-a32-z8hGVMU9mnDIUpKJFEcarlL8XVA_WKRavAyCXcuX8MAU1-hRvf934aCcDFg0wpLxBLqiy0srUOjtlHy_vS6I3oAKyAGukd732jgfnIlyvwA-QX9Y6X0AVeNocOBUKPNutJ82X9-8-n3-cLT99uDhfLGemJVzMCOk6Q119FNMMa84oiE6AoarXWlEunHW9YHROFOGqdVxoQ4TTvVDWYsbYSfNm611PegBrII5ZBbnOflB5I5Py8t-b6FfyMv2Ugrb9vO-q4NVOkNOPCcooB18MhKAipKlIWv-Z9mLOaUVfb1GTUykZ3L4NwfI-RlljlA8xVvbF33PtyT-5VeBsC1z5AJv_m-Ri-XWrvAM1Xq2s</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2480278952</pqid></control><display><type>article</type><title>Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Germann, Jürgen ; Elias, Gavin J.B. ; Boutet, Alexandre ; Narang, Keshav ; Neudorfer, Clemens ; Horn, Andreas ; Loh, Aaron ; Deeb, Wissam ; Salvato, Bryan ; Almeida, Leonardo ; Foote, Kelly D. ; Rosenberg, Paul B. ; Tang‐Wai, David F. ; Wolk, David A. ; Burke, Anna D. ; Salloway, Stephen ; Sabbagh, Marwan N. ; Chakravarty, M. Mallar ; Smith, Gwenn S. ; Lyketsos, Constantine G. ; Okun, Michael S. ; Lozano, Andres M.</creator><creatorcontrib>Germann, Jürgen ; Elias, Gavin J.B. ; Boutet, Alexandre ; Narang, Keshav ; Neudorfer, Clemens ; Horn, Andreas ; Loh, Aaron ; Deeb, Wissam ; Salvato, Bryan ; Almeida, Leonardo ; Foote, Kelly D. ; Rosenberg, Paul B. ; Tang‐Wai, David F. ; Wolk, David A. ; Burke, Anna D. ; Salloway, Stephen ; Sabbagh, Marwan N. ; Chakravarty, M. Mallar ; Smith, Gwenn S. ; Lyketsos, Constantine G. ; Okun, Michael S. ; Lozano, Andres M.</creatorcontrib><description>Introduction
Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation.
Methods
Thirty‐nine patients with mild AD who took part in a prior fx‐DBS trial (NCT01608061) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel‐wise VTA mapping to identify flashback‐associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback‐associated brain‐wide networks.
Results
A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback‐inducing stimulation exhibited greater functional connectivity to a network of memory‐evoking and autobiographical memory‐related sites.
Discussion
These results clarify the neuroanatomical substrates of stimulation‐evoked flashbacks.</description><identifier>ISSN: 1552-5260</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1002/alz.12238</identifier><identifier>PMID: 33480187</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>Alzheimer's disease ; brain connectivity ; deep brain stimulation ; fornix ; magnetic resonance imaging ; memory</subject><ispartof>Alzheimer's & dementia, 2021-05, Vol.17 (5), p.777-787</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC on behalf of Alzheimer's Association</rights><rights>2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4158-1166c2f0813b30b532e868ec2a7bba258fdf783291a15a4f58bc18fb78add0333</citedby><cites>FETCH-LOGICAL-c4158-1166c2f0813b30b532e868ec2a7bba258fdf783291a15a4f58bc18fb78add0333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Falz.12238$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Falz.12238$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33480187$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Germann, Jürgen</creatorcontrib><creatorcontrib>Elias, Gavin J.B.</creatorcontrib><creatorcontrib>Boutet, Alexandre</creatorcontrib><creatorcontrib>Narang, Keshav</creatorcontrib><creatorcontrib>Neudorfer, Clemens</creatorcontrib><creatorcontrib>Horn, Andreas</creatorcontrib><creatorcontrib>Loh, Aaron</creatorcontrib><creatorcontrib>Deeb, Wissam</creatorcontrib><creatorcontrib>Salvato, Bryan</creatorcontrib><creatorcontrib>Almeida, Leonardo</creatorcontrib><creatorcontrib>Foote, Kelly D.</creatorcontrib><creatorcontrib>Rosenberg, Paul B.</creatorcontrib><creatorcontrib>Tang‐Wai, David F.</creatorcontrib><creatorcontrib>Wolk, David A.</creatorcontrib><creatorcontrib>Burke, Anna D.</creatorcontrib><creatorcontrib>Salloway, Stephen</creatorcontrib><creatorcontrib>Sabbagh, Marwan N.</creatorcontrib><creatorcontrib>Chakravarty, M. Mallar</creatorcontrib><creatorcontrib>Smith, Gwenn S.</creatorcontrib><creatorcontrib>Lyketsos, Constantine G.</creatorcontrib><creatorcontrib>Okun, Michael S.</creatorcontrib><creatorcontrib>Lozano, Andres M.</creatorcontrib><title>Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease</title><title>Alzheimer's & dementia</title><addtitle>Alzheimers Dement</addtitle><description>Introduction
Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation.
Methods
Thirty‐nine patients with mild AD who took part in a prior fx‐DBS trial (NCT01608061) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel‐wise VTA mapping to identify flashback‐associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback‐associated brain‐wide networks.
Results
A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback‐inducing stimulation exhibited greater functional connectivity to a network of memory‐evoking and autobiographical memory‐related sites.
Discussion
These results clarify the neuroanatomical substrates of stimulation‐evoked flashbacks.</description><subject>Alzheimer's disease</subject><subject>brain connectivity</subject><subject>deep brain stimulation</subject><subject>fornix</subject><subject>magnetic resonance imaging</subject><subject>memory</subject><issn>1552-5260</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp1kbtuFDEUhkeIiFyg4AWQO6DYxJfxjLdBWiIukVaigYbG8uU4a_DYiz1DtKl4hDS8YJ4kTnZZQUFly_7Od479N81zgk8JxvRMhetTQikTj5ojwjmdcdrPH-_3HT5sjkv5hnGLBeFPmkPGWoGJ6I-a32-z8hGVMU9mnDIUpKJFEcarlL8XVA_WKRavAyCXcuX8MAU1-hRvf934aCcDFg0wpLxBLqiy0srUOjtlHy_vS6I3oAKyAGukd732jgfnIlyvwA-QX9Y6X0AVeNocOBUKPNutJ82X9-8-n3-cLT99uDhfLGemJVzMCOk6Q119FNMMa84oiE6AoarXWlEunHW9YHROFOGqdVxoQ4TTvVDWYsbYSfNm611PegBrII5ZBbnOflB5I5Py8t-b6FfyMv2Ugrb9vO-q4NVOkNOPCcooB18MhKAipKlIWv-Z9mLOaUVfb1GTUykZ3L4NwfI-RlljlA8xVvbF33PtyT-5VeBsC1z5AJv_m-Ri-XWrvAM1Xq2s</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Germann, Jürgen</creator><creator>Elias, Gavin J.B.</creator><creator>Boutet, Alexandre</creator><creator>Narang, Keshav</creator><creator>Neudorfer, Clemens</creator><creator>Horn, Andreas</creator><creator>Loh, Aaron</creator><creator>Deeb, Wissam</creator><creator>Salvato, Bryan</creator><creator>Almeida, Leonardo</creator><creator>Foote, Kelly D.</creator><creator>Rosenberg, Paul B.</creator><creator>Tang‐Wai, David F.</creator><creator>Wolk, David A.</creator><creator>Burke, Anna D.</creator><creator>Salloway, Stephen</creator><creator>Sabbagh, Marwan N.</creator><creator>Chakravarty, M. Mallar</creator><creator>Smith, Gwenn S.</creator><creator>Lyketsos, Constantine G.</creator><creator>Okun, Michael S.</creator><creator>Lozano, Andres M.</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>202105</creationdate><title>Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease</title><author>Germann, Jürgen ; Elias, Gavin J.B. ; Boutet, Alexandre ; Narang, Keshav ; Neudorfer, Clemens ; Horn, Andreas ; Loh, Aaron ; Deeb, Wissam ; Salvato, Bryan ; Almeida, Leonardo ; Foote, Kelly D. ; Rosenberg, Paul B. ; Tang‐Wai, David F. ; Wolk, David A. ; Burke, Anna D. ; Salloway, Stephen ; Sabbagh, Marwan N. ; Chakravarty, M. Mallar ; Smith, Gwenn S. ; Lyketsos, Constantine G. ; Okun, Michael S. ; Lozano, Andres M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4158-1166c2f0813b30b532e868ec2a7bba258fdf783291a15a4f58bc18fb78add0333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alzheimer's disease</topic><topic>brain connectivity</topic><topic>deep brain stimulation</topic><topic>fornix</topic><topic>magnetic resonance imaging</topic><topic>memory</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Germann, Jürgen</creatorcontrib><creatorcontrib>Elias, Gavin J.B.</creatorcontrib><creatorcontrib>Boutet, Alexandre</creatorcontrib><creatorcontrib>Narang, Keshav</creatorcontrib><creatorcontrib>Neudorfer, Clemens</creatorcontrib><creatorcontrib>Horn, Andreas</creatorcontrib><creatorcontrib>Loh, Aaron</creatorcontrib><creatorcontrib>Deeb, Wissam</creatorcontrib><creatorcontrib>Salvato, Bryan</creatorcontrib><creatorcontrib>Almeida, Leonardo</creatorcontrib><creatorcontrib>Foote, Kelly D.</creatorcontrib><creatorcontrib>Rosenberg, Paul B.</creatorcontrib><creatorcontrib>Tang‐Wai, David F.</creatorcontrib><creatorcontrib>Wolk, David A.</creatorcontrib><creatorcontrib>Burke, Anna D.</creatorcontrib><creatorcontrib>Salloway, Stephen</creatorcontrib><creatorcontrib>Sabbagh, Marwan N.</creatorcontrib><creatorcontrib>Chakravarty, M. Mallar</creatorcontrib><creatorcontrib>Smith, Gwenn S.</creatorcontrib><creatorcontrib>Lyketsos, Constantine G.</creatorcontrib><creatorcontrib>Okun, Michael S.</creatorcontrib><creatorcontrib>Lozano, Andres M.</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Germann, Jürgen</au><au>Elias, Gavin J.B.</au><au>Boutet, Alexandre</au><au>Narang, Keshav</au><au>Neudorfer, Clemens</au><au>Horn, Andreas</au><au>Loh, Aaron</au><au>Deeb, Wissam</au><au>Salvato, Bryan</au><au>Almeida, Leonardo</au><au>Foote, Kelly D.</au><au>Rosenberg, Paul B.</au><au>Tang‐Wai, David F.</au><au>Wolk, David A.</au><au>Burke, Anna D.</au><au>Salloway, Stephen</au><au>Sabbagh, Marwan N.</au><au>Chakravarty, M. Mallar</au><au>Smith, Gwenn S.</au><au>Lyketsos, Constantine G.</au><au>Okun, Michael S.</au><au>Lozano, Andres M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease</atitle><jtitle>Alzheimer's & dementia</jtitle><addtitle>Alzheimers Dement</addtitle><date>2021-05</date><risdate>2021</risdate><volume>17</volume><issue>5</issue><spage>777</spage><epage>787</epage><pages>777-787</pages><issn>1552-5260</issn><eissn>1552-5279</eissn><abstract>Introduction
Fornix deep brain stimulation (fx‐DBS) is under investigation for treatment of Alzheimer's disease (AD). We investigated the anatomic correlates of flashback phenomena that were reported previously during acute diencephalic stimulation.
Methods
Thirty‐nine patients with mild AD who took part in a prior fx‐DBS trial (NCT01608061) were studied. After localizing patients’ implanted electrodes and modeling the volume of tissue activated (VTA) by DBS during systematic stimulation testing, we performed (1) voxel‐wise VTA mapping to identify flashback‐associated zones; (2) machine learning–based prediction of flashback occurrence given VTA overlap with specific structures; (3) normative functional connectomics to define flashback‐associated brain‐wide networks.
Results
A distinct diencephalic region was associated with greater flashback likelihood. Fornix, bed nucleus of stria terminalis, and anterior commissure involvement predicted memory events with 72% accuracy. Flashback‐inducing stimulation exhibited greater functional connectivity to a network of memory‐evoking and autobiographical memory‐related sites.
Discussion
These results clarify the neuroanatomical substrates of stimulation‐evoked flashbacks.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>33480187</pmid><doi>10.1002/alz.12238</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Alzheimer's disease brain connectivity deep brain stimulation fornix magnetic resonance imaging memory |
| title | Brain structures and networks responsible for stimulation‐induced memory flashbacks during forniceal deep brain stimulation for Alzheimer's disease |
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