We thank Erin Douglas, Anna Evans, and Carolyn Bellion for their contributions to participant recruitment and clinical assessment. We also thank Michael Casp, Zoe Englander, Justin Woodlief, and James Carter for their contributions to data collection and analysis, and Robert M. Hamer for consultation on statistical analysis and editing of the manuscript. Finally, we thank the individuals and their families who participated in this study. 
This study was supported by Conte center grant P50 MH064065 from the National Institute of Mental Health. Dr. Hart was supported by T32 HD040127 from the National Institute of Child Health and Human Development.

טכניקות המחקר השתמשו במחקר זה אושרו על ידי לוחות הסקירה המוסדיים (IRB) של אוניברסיטת דיוק ואוניברסיטת צפון קרוליינה - צ&#39;אפל היל. 1. הדמיה משימה עיצוב <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> צור משימה התנהגותית המבוסס על אירוע שמציגה גירויים נדירים יעד (עיגול) בתוך רצף של גירויים סטנדרטיים יותר תכופים (תמונות מקושקשות). סכמטי של המשימה מוצג באיור 1. הצג את המשימה באמצעות תוכנת CIGAL 10. </li></ol><img alt="איור 1" src="/files/ftp_upload/51484/51484fig1.jpg" /> איור 1. סכמטי של משימות עיצוב. נתון זה שונה מהארט et al. 20, באישור. <a href="https://www.jove.com/files/ftp_upload/51484/51484fig1large.jpg" target="_blank">אנא לחץ כאן כדי לצפות בגרסה גדולה יותר של דמות זו.</a> <ol style="margin-left: 40px;;text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> בחר כאח של גירויים מרתיעים וסט של גירויים ניטראליים מבסיס נתוני מערכת תמונה הרגשית הבינלאומית (IAPS). תמונות IAPS מדורגות בסולם של 1-9, על מנת לשקף את הרמות של עוררות וערכיות 11. מספרים גבוהים מצביעים ערכיות חיוביות גבוה יותר והתעוררות. בחר סט של תמונות שמתאימות לגיל לקבוצת המחקר כגון תמונות של נחשים, עכבישים, או בעלי חיים אחרים. הערה: תמונות גירויים מרתיעים המשימה-רלוונטית המשמשות למחקר זה היה דירוג ממוצע של 3.38 ערכיות (SD = 1.78) ודירוג ממוצע של 6.14 עוררות (SD = 2.08). היו לי תמונות גירויים ניטרליות ערכיות ממוצעת של 6.21 (SD = 0.26) ודירוג ממוצע של 3.72 עוררות (SD = 2.15). </li><li style=";text-align:right;direction:rtl"> תכנית תסריט המשימה כזו שתמונות מוצגות בצו-אקראי מדומה ל1,500 מילים-שני עם 500 אלפיות שניים אומרת מרווח בין גירוי. גירויי הווה יעד ותמונות ניטרליות משימה-לא רלוונטית לא בתדירות גבוהה יותר מאשר בכל 15 שניות ולעשות כל כ -4% מהגירויים. ג&#39;יפעמים תחילת אירוע tter על מנת לספק רזולוציה טובה יותר של פונקצית התגובה המודינמית. </li></ol><ol start="2" style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> צור 8 סטים של תמונות, אחת לכל אחת מריצות 8 פונקציונליות כגון שהמשתתפים מוצגים עם סך של 40 מטרות ו -40 תמונות ניטרליות משימה-לא רלוונטית במהלך כל 8 הריצות. </li></ol> 2. הגדרת משתתף וסריקה <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> לגייס ילדים ובני נוער בין גילאי 9 ו -18 שהם או אנשים בקרה בריאים או שנמצאים בסיכון גבוה למשפחתי פסיכוזה. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> ודא שיש לי אנשים בריאים אין מחלות פסיכיאטריות או כל בני משפחה מדרגה ראשונה עם מחלה פסיכיאטרית. ודא שיש לי משתתפי סיכון משפחתיים יחסי לפחות אחד מהדרגה הראשונה (הורה או אח) עם סכיזופרניה. לא לכלול אותם לנוכחות של מחלות פסיכיאטריות אחרות בקרובים מהדרגה הראשונה. </li><li style=";text-align:right;direction:rtl"> משתתפים בריאים גיל ומין משחק עם משתתף קבוצה משפחתי סיכוןים. </li></ol></li><li style=";text-align:right;direction:rtl"> לרכוש הסכמה מדעת של משתתפים מעל גיל 18. לקטינים, לרכוש הסכמה מדעת מהורים / אפוטרופוסים חוקיים. בנוסף, תרכוש הסכמה בכתב מקטינים שהם לוקחים חלק במחקר. </li><li style=";text-align:right;direction:rtl"> מניחים את המשתתפים בסורק MRI מדומה כדי קראתי אותם עם הסביבה. שחק הקלטת שמע רעש של הסורק ובהם להשלים ריצה בפועל של המשימה התנהגותיות כדי להבטיח שהם מבינים את הוראות המשימה. </li><li style=";text-align:right;direction:rtl"> מניחים את המשתתף בסורק MRI ולרכוש כל סריקות המוח הכרחיות לוקליזציה ו / או תמונות אנטומיים. </li><li style=";text-align:right;direction:rtl"> שימוש בתיבת קלט MRI-בטוח, לספר משתתפים ללחוץ על כפתור אחד עם האצבע שלהם בתגובה לכל גירויי היעד ועוד כפתור עם האצבע האמצעית שלהם לכל גירויים האחרים. </li><li style=";text-align:right;direction:rtl"> בעקבות סריקת fMRI, לאסוף דירוגים סובייקטיבית של עוררות וערכיות לתמונות השתמשו במחקר מקבוצת משנה של משתתפים. Currenמחקר לא השיג דירוגים מ -15 בקרות ועם 13 משפחתי סיכון גבוה. </li></ol> 3. תמונת רכישה <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> משתתפי מקום לסורק MRI טסלה 3.0. ראשית, לרכוש סט של תמונות מבניות כולל 3D coplanar תמונת T1-ניגוד אנטומיים באמצעות רצף דופק מפונק-נזכר שיפוע רכישה (TR: 5.16 אלפיות השני; TE: 2.04 אלפיות השני; FOV: 24 סנטימטר; מטריצת תמונה: 256 × 256; Flip זווית: 20; גודל voxel: 0.94 מ&quot;מ × 0.94 מ&quot;מ × 1.9 מ&quot;מ; 68 פרוסות ציריות). </li><li style=";text-align:right;direction:rtl"> רוכשים את נתוני הדמיה תפקודיות באמצעות רצף הדמיה שיפוע הד הד מישורי עם כיסוי מלא של מוח (TR: 2,000 אלפיות השני; TE: 27 אלפיות שני; FOV: 24 סנטימטר; מטריצת תמונה: 64 × 64; Flip זווית: 60; גודל voxel: 3.75 מ&quot;מ × 3.75 מ&quot;מ × 3.8 מ&quot;מ; 34 פרוסות ציריות) כך שפעילות המוח ניתן למדוד בזמן ההופעה של המשימה התנהגותיות. הפעל רצף הדמיה זו לכל ריצה של המשימה התנהגותיות. כל ריצה צריכה להיות מורכבת של 120 נקודות זמן הדמיה. </li><li style=";text-align:right;direction:rtl"> להציג את ת&quot;אSK ב 8 ריצות פונקציונליות, כל שנמשך כ -4 דקות. </li></ol> 4. ניתוח <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> עיבוד מקדים תמונה: להרחיב fMRI מומחה כלי ניתוח (feat) ב -12 FSL. בחר ניתוח ברמה הראשונה וטרום-סטטיסטי. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;נתונים&quot;, בחר את מספר תמונות קלט והזן את הנתיב לכל אחת מתמונות MR אתה הולך לעבד. הגדר את ספריית הפלט. הזן את סה&quot;כ הכרכים, מספר הרכישות שהושלכו, וTR. </li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;פרה-סטטיסטי&quot;, קבע תיקון תנועה לMCFLIRT, מרחבי החלקת FWHM 5 MMS, ו&quot; תיקון עיתוי Slice &quot;. בחר באפשרות&quot; חילוץ BET מוח &quot;וסינון זמני&quot; Highpass &quot;אך לא תבחר unwarping B0 (uness יש לך מפת שדה שיפוע) או&quot; אני ntensitiy normaization &quot;. 12,14. </li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;רישום&quot;, בחר &quot;stru ראשיתמונת ctural &quot;. הזן את הנתיב לתמונה משוקלל T1-הפשיט את גולגולתו של הנושא. השתמש בחיפוש רגיל ליניארי עם לפחות 6 DOF. בחר בתיבת סימון השטח רגילה. הזן את הנתיב לתמונת אטלס משרד התשתיות הלאומיות. השתמש נורמלי, ליניארי חיפוש עם 12 DOF. לחץ על בצע. </li><li style=";text-align:right;direction:rtl"> תכלול משתתפים עם תנועה גדולה יותר מ -3 מ&quot;מ הראש בX, Y, Z או כיוונים. </li></ol></li><li style=";text-align:right;direction:rtl"> רמת 1: השוואת נתונים בין תנאי משימה בתוך טווח אחת. FEAT הפתוח. בחר &quot;ניתוח ברמה הראשונה&quot; ו- &quot;סטטיסטיקה + פוסט-סטטיסטי&quot;. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> בכרטיסייה נתונים, להגדיר את מספר הכניסות והזן את הנתיב לכל אחת מתמונות MR. הזן את נתיב עבור &quot;ספריית הפלט&quot;. הזן &quot;סה&quot;כ הכרכים&quot;, מספר הרכישות שהושלכו, וTR. </li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;סטטיסטיקה&quot;, בחר את &quot;להשתמש בסרט prewhitening&quot; תיבת סימון 16. לחץ על &quot;המודל מלא seכפתור איל &quot;. הגדר את &quot;מספר של כלי רכב חשמליים המקוריים&quot; למספר תנאי משימה. עבור כל מצב, בחר &quot;(פורמט 3 טור) מותאמים אישית&quot; מתפריט הצורה הבסיסית הנפתח ו&quot; פעמיים גאמה HRF מ&quot; &quot;התפריט הנפתח פיתול 17,18 ובחר קובץ טקסט המכיל את עיתוי המשימה. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> פורמט קובץ טקסט זה ב 3 עמודים בכניסה אחת לכל &quot;אירוע&quot; מהסוג המסוים. העמודה הראשונה צריכה להכיל את זמן תחילת (בשניות), השני צריך להכיל את המשך (בשניות), ושלישית צריך להכיל את משקל האירוע. בכרטיסייה הניגודים &amp; F-בדיקות, ליצור ניגוד אחד לכל מצב משימה ואחד לכל השוואה. </li></ol></li><li style=";text-align:right;direction:rtl"> על &quot;פוסט-הסטטיסטיים&quot; כרטיסייה, בחר &quot;האשכול&quot; בתפריט &quot;ערכי סף&quot; הנפתח ולהגדיר את &quot;סף Z&quot; ולא P אשכולhreshold 2.3 ו 0.05 בהתאמה 8,19. </li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;רישום&quot;, בחר &quot;תמונה מבנית עיקרית&quot;. הזן את הנתיב לתמונה משוקלל T1-הפשיט את גולגולתו של הנושא. השתמש בחיפוש רגיל ליניארי עם לפחות 6 DOF. בחר בתיבת הסימון &quot;המרחב רגילה&quot;. הזן את הנתיב לתמונת אטלס משרד התשתיות הלאומיות. השתמש בחיפוש רגיל, ליניארי עם עומק שדה 12. לחץ על &quot;Go&quot;. </li></ol></li><li style=";text-align:right;direction:rtl"> רמה 2: השוואת נתונים בין ריצות לכל מצב משימה. FEAT הפתוח. בחר &quot;ניתוח ברמה גבוהה&quot; ו- &quot;סטטיסטיקה + פוסט-סטטיסטי&quot; מתפריט הנפתח. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> בכרטיסייה נתונים, בחר &quot;תשומות מדריכים FEAT ברמה נמוכה יותר&quot;. הגדר את מספר הכניסות והזן את הנתיב לכל אחת מתמונות MR. הזן את נתיב עבור &quot;ספריית הפלט&quot;. </li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;סטטיסטיקה&quot;, לשנות את &quot;השפעות מעורבות: FLAME1&quot; תיבת בחירה ל&quot; קבוע Effects &quot;. לחץ על&quot; דגם אשף הגדרה &quot;הכפתור. בחר&quot; ממוצע קבוצה אחת &quot;ולחץ על הכפתור&quot; תהליך &quot;. </li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;פוסט-סטטיסטי&quot;, בחר &quot;אשכול&quot; בתפריט &quot;ערכי סף&quot; הנפתח ולהגדיר את &quot;סף Z&quot; וסף &quot;אשכול P&quot; 2.3 ו 0.05 בהתאמה 8,19. לחץ על &quot;Go&quot;. </li></ol></li><li style=";text-align:right;direction:rtl"> רמה 3: השוואת נתונים בין נושאים לכל מצב משימה בכל הריצות. FEAT הפתוח. בחר &quot;ניתוח ברמה גבוהה&quot; ו- &quot;סטטיסטיקה + פוסט-סטטיסטי&quot; מתפריט הנפתח. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> בכרטיסייה נתונים, בחר &quot;תשומות הן 3D להתמודד תמונות מספריות Feat.&quot; הגדר את מספר הכניסות והזן את הנתיב לכל אחת מתמונות MR. הזן את נתיב עבור &quot;ספריית הפלט&quot;. </li><li style=";text-align:right;direction:rtl"> על T &quot;סטטיסטיקה&quot;ab, לחץ על &quot;התקנת מודל מלאה&quot;. הגדר את מספר כלי הרכב החשמליים שווה למספר משתני קבוצה ומשתנים כגון קבוצת אבחון, גיל, מין, וכו &#39;הזינו את הערכים לכל נושא (קלט 1 - n קלט) עבור כל EV. אתה יכול להשתמש בחלון &quot;הדבק&quot; כדי להעתיק גיליון אלקטרוני של ערכים אלה. <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;הניגודים &amp; F-בדיקות&quot;, מוסיף ניגוד לכל משתנה מבחן ולכל ניגוד (למשל, קבוצת אבחון). לכל אחד ממשתני בדיקה, להגדיר את הניגוד ידי בחירת הערך 1 בעמודה תחת EV המתאים. לכל לעומת זאת, לקבוע את הערך הראשון 1 והשני ל-1. בחר &quot;בוצע&quot;. </li></ol></li><li style=";text-align:right;direction:rtl"> בכרטיסייה &quot;פוסט-סטטיסטי&quot;, בחר &quot;האשכול&quot; בתפריט &quot;ערכי סף&quot; הנפתח ולהגדיר את &quot;סף Z&quot; וסף &quot;אשכול P&quot; 2.3 ו 0.05 בהתאמה 8,19 </sup&gt;. לחץ על &quot;Go&quot;. </li></ol></li></ol>

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S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Premorbid+cognitive+deficits+in+young+relatives+of+schizophrenia+patients.">Premorbid cognitive deficits in young relatives of schizophrenia patients.</a> Front Hum Neurosc. 3 (62), (2010).</li><li>Kiehl, K. A., Liddle, P. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+event-related+functional+magnetic+resonance+imaging+study+of+an+auditory+oddball+task+in+schizophrenia.">An event-related functional magnetic resonance imaging study of an auditory oddball task in schizophrenia.</a> Schizophr Re. 48, 159-171 (2001).</li><li>Bramon, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Is+the+P300+wave+an+endophenotype+for+schizophrenia?+A+meta-analysis+and+a+family+study.">Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study.</a> Neuroimag. 27, 960-968 (2005).</li><li>Dichter, G. S., Bellion, C., Casp, M., Belger, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+modulation+of+attention+and+emotion+in+schizophrenia.">Impaired modulation of attention and emotion in schizophrenia.</a> Schizophr Bul. 36, 595-606 (2010).</li><li>Fichtenholtz, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emotion-attention+network+interactions+during+a+visual+oddball+task.">Emotion-attention network interactions during a visual oddball task.</a> Brain Res Cogn Brain Re. 20, 67-80 (2004).</li><li>Voyvodic, J. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real-time+fMRI+paradigm+control,+physiology,+and+behavior+combined+with+near+real-time+statistical+analysis.">Real-time fMRI paradigm control, physiology, and behavior combined with near real-time statistical analysis.</a> Neuroimag. 10, 91-106 (1999).</li><li>Lang, P. J., Bradley, M. M., Cuthbert, B. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> International affective picture system (IAPS): Digitized photographs, instruction manual and affective ratings. Technical Report A-6. , (2005).</li><li>Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Advances+in+functional+and+structural+MR+image+analysis+and+implementation+as+FSL.">Advances in functional and structural MR image analysis and implementation as FSL.</a> Neuroimag. 23, 208-219 (2004).</li><li>Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fast+robust+automated+brain+extraction.">Fast robust automated brain extraction.</a> Hum Brain Map. 17, 143-155 (2002).</li><li>Jenkinson, M., Bannister, P., Brady, M., Smith, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+optimization+for+the+robust+and+accurate+linear+registration+and+motion+correction+of+brain+images.">Improved optimization for the robust and accurate linear registration and motion correction of brain images.</a> Neuroimag. 17, 825-841 (2002).</li><li>Jenkinson, M., Smith, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+global+optimisation+method+for+robust+affine+registration+of+brain+images.">A global optimisation method for robust affine registration of brain images.</a> Med Image Ana. 5, 143-156 (2001).</li><li>Woolrich, M. W., Ripley, B. D., Brady, M., Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Temporal+autocorrelation+in+univariate+linear+modeling+of+FMRI+data.">Temporal autocorrelation in univariate linear modeling of FMRI data.</a> Neuroimag. 14, 1370-1386 (2001).</li><li>Beckmann, C. F., Jenkinson, M., Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=General+multilevel+linear+modeling+for+group+analysis+in+FMRI.">General multilevel linear modeling for group analysis in FMRI.</a> Neuroimag. 20, 1052-1063 (2003).</li><li>Woolrich, M. W., Behrens, T. E., Beckmann, C. F., Jenkinson, M., Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multilevel+linear+modelling+for+FMRI+group+analysis+using+Bayesian+inference.">Multilevel linear modelling for FMRI group analysis using Bayesian inference.</a> Neuroimag. 21, 1732-1747 (2004).</li><li>Genovese, C. R., Lazar, N. A., Nichols, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thresholding+of+statistical+maps+in+functional+neuroimaging+using+the+false+discovery+rate.">Thresholding of statistical maps in functional neuroimaging using the false discovery rate.</a> Neuroimag. 15, 870-878 (2002).</li><li>Hart, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Altered+fronto-limbic+activity+in+children+and+adolescents+with+familial+high+risk+for+schizophrenia..">Altered fronto-limbic activity in children and adolescents with familial high risk for schizophrenia..</a> Psychiatry Re. 212, 19-27 (2013).</li><li>Hariri, A. R., Bookheimer, S. Y., Mazziotta, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Modulating+emotional+responses:+effects+of+a+neocortical+network+on+the+limbic+system.">Modulating emotional responses: effects of a neocortical network on the limbic system.</a> Neurorepor. 11, 43-48 (2000).</li><li>Gottesman, I. I., Gould, T. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+endophenotype+concept+in+psychiatry:+etymology+and+strategic+intentions.">The endophenotype concept in psychiatry: etymology and strategic intentions.</a> Am J Psyc. 160, 636-645 (2003).</li><li>Glahn, D. C., Thompson, P. M., Blangero, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuroimaging+endophenotypes:+strategies+for+finding+genes+influencing+brain+structure+and+function.">Neuroimaging endophenotypes: strategies for finding genes influencing brain structure and function.</a> Hum Brain Map. 28, 488-501 (2007).</li></ol>

Dr. Perkins is currently receiving grant support from Janssen, and is a consultant to Dainippon. In the past, Dr. Perkins is or has been on speaker's bureau for Eli Lilly and AstraZeneca. Dr. Perkins has previously received grants from AstraZeneca, Bristol-Myers Squibb, Otsuka, Eli Lilly, Janssen and Pfizer; and consulting and educational fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Glaxo Smith Kline, Forest Labs, Pfizer and Shire. All other authors declare no biomedical financial interests or potential conflict of interest.

The modified emotional oddball paradigm in the current study has been shown to elicit differences in neural recruitment during selective attention and emotional processing in children and adolescents at risk for schizophrenia. While existing paradigms using the emotional oddball task have been used to investigate neural changes in adult populations with psychiatric illness8, the current paradigm may be particularly useful for measurement of vulnerability markers in younger age groups. 
<p class='jove_conte...

Schizophrenia is a neurodevelopmental disorder with a known genetic component1,2 and with symptoms including deficits in both executive and emotional processing3,4. First-degree relatives are thought to be at an increased risk of developing schizophrenia, and have been shown to share some of these same neurocognitive deficits in both cognitive and social-emotional domains5. We therefore expect that brain activity in regions associated with executive and emotional processing may be altered in at-risk family members preceding the onset of clinical symptoms. 
Previous studies have indicated that both adults with schizophrenia and adults at familial high risk show aberrant activity within executive and emotional processing networks; however it remains unclear how these changes come about during development. Demonstrating that these changes occur early in life will be a critical first step in understanding the pathophysiology of the disorder. Therefore, this study utilizes an emotional oddball paradigm during functional MRI (fMRI) scanning in order to measure brain activity during the completion of a task that requires both executive and emotional processing in adolescents who are at risk for developing schizophrenia. Oddball paradigms are frequently used to examine the function of fronto-striate circuitry in schizophrenia6 and in individuals with familial high risk7 by measuring selective attention processes allocated to task-relevant target stimuli. Here, a standard oddball task has been modified to include task-irrelevant aversive and neutral stimuli that have been shown to elicit changes in brain activity in patients with schizophrenia8. 
This paper measures functional differences between healthy adolescents and adolescents at high familial risk for schizophrenia using an emotional oddball task. The task design is similar to that used by Fichtenholtz and colleagues9, but the selection of aversive emotional images has been modified to be appropriate for children between the ages of 9-18. The use of this task during functional MRI allowed for the identification of specific brain regions that showed patterns of hyperactivation and hypoactivation in children and adolescents with FHR for schizophrenia, in addition to age-related changes in neural activity during adolescent development.

<table border="0" cellpadding="0" cellspacing="0">
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			<td class="xl63">3T MRI scanner</td>
			<td class="xl63">GE</td>
			<td class="xl63"></td>
			<td class="xl63">BIAC 3T scanner (replaced)</td>
		</tr>
	</tbody>
</table>

measurement of fronto-limbic activity using an emotional oddball task in children with familial high risk for schizophrenia

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with schizophrenia who are at familial high risk (FHR) may show similar cognitive and emotional changes. However, the neurological changes underlying the emergence of these symptoms remain unclear. This study sought to identify differences in frontal, striatal, and limbic regions in children and adolescents with FHR using functional magnetic resonance imaging. Groups of 21 children and adolescents at FHR and 21 healthy controls completed an emotional oddball task that relied on selective attention and the suppression of task-irrelevant emotional information. The standard oddball task was modified to include aversive and neutral distractors in order to examine potential group differences in both emotional and executive processing. This task was designed specifically to allow for children and adolescents to complete by keeping the difficulty and emotional image content age-appropriate. Furthermore, we demonstrate a technique for suitable fMRI registration for children and adolescent participants. This paradigm may also be applied in future studies to measure changes in neural activity in other populations with hypothesized developmental changes in executive and emotional processing.

לא היו הבדלים בין קבוצות על בסיס מאפיינים דמוגרפיים 20. הנתונים מצביעים על כך שהתנהגות משימת איתור היעד היא ברמה מתאימה של קושי לילדים ובני נוער בגילאי 9-18. במחקר הנוכחי, בקרות זיהו 82.36% מיעדים (SD = 0.14), וקבוצת הסיכון המשפחתית זיהתה 76.8% מיעדים (SD = 0.17). שני הק?...

Watch this Scientific Journal Video about Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia at JoVE.com

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR).&#160;FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

מדידה של פעילות פרונטו-הלימבית שימוש מוזר משימה רגשית בילדים בסיכון גבוה לסכיזופרניה משפחתי

Adolescence is a critical developmental period where the early symptoms of schizophrenia frequently emerge. First-degree relatives of people with ...

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8.8K Views.  University of North Carolina at Chapel Hill School of Medicine. This paper describes how to use the emotional oddball task and fMRI to measure brain activation in children and adolescents at familial high risk for schizophrenia (FHR). FMRI was used to measure differences in fronto-striato-limbic regions during an emotional oddball task. Children with FHR exhibited abnormal functional activation during adolescence.

Video: Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia

Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant. The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. These are infants who are at increased risk for poor developmental outcome because of insults during prenatal development, such as substance exposure or prematurity or factors such as poverty, poor nutrition or lack of prenatal care that can have adverse effects on the intrauterine environment and affect the developing fetus. The NNNS assesses the full range of infant neurobehavioral performance including neurological integrity, behavioral functioning, and signs of stress/abstinence. The NNNS is a noninvasive neonatal assessment tool with demonstrated validity as a predictor, not only of medical outcomes such as cerebral palsy diagnosis, neurological abnormalities, and diseases with risks to the brain, but also of developmental outcomes such as mental and motor functioning, behavior problems, school readiness, and IQ. The NNNS can identify infants at high risk for abnormal developmental outcome and is an important clinical tool that enables medical researchers and health practitioners to identify these infants and develop intervention programs to optimize the development of these infants as early as possible. The video shows the NNNS procedures, shows examples of normal and abnormal performance and the various clinical populations in which the exam can be used.

The NICU Network Neurobehavioral Scale (NNNS) was developed as an assessment for the at-risk infant. The purpose of this article is to describe the NNNS, provide video examples of the NNNS procedures and discuss the ways in which the exam has been used.

המדידה וההערכה של הסיכון גבוה הילוד: Scale פגיית רשת נוירו-התנהגותיות

There has been a long-standing interest in the assessment of the neurobehavioral integrity of the newborn infant.  The NICU Network Neurobehavioral Scale ...

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&#239;ve Adolescents at High Risk for Psychosis

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of impaired neuromodulation of dopamine in fronto-striatal pathways. The traditional methods for identifying movement abnormalities include observer-based reports and force stability gauges. The drawbacks of these methods are long training times for raters, experimenter bias, large site differences in instrumental apparatus, and suboptimal reliability. Taking these drawbacks into account has guided the development of better&#160;standardized and more efficient procedures to examine movement abnormalities through handwriting analysis software and tablet. Individuals at&#160;risk for psychosis showed significantly more dysfluent pen movements (a proximal measure for dyskinesia) in a handwriting task. Handwriting kinematics offers a great advance over previous methods of assessing dyskinesia, which could clearly be beneficial for understanding the etiology of psychosis.

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&amp;#239;ve Adolescents at High Risk for Psychosis

Handwriting analysis software significantly improves upon existing instruments measuring movement disorders. Individuals at&#160;risk for psychosis and healthy controls completed handwriting tasks to test for dyskinesia. Results suggest that youth at&#160;risk for psychosis exhibit dyskinesia and that handwriting analysis could significantly contribute to wider dissemination of early identification efforts

כתב יד ניתוח מציין dyskinesias ספונטני במתבגרים הנאיביים נוירולפטיות בסיכון גבוה לפסיכוזה

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of ...

Cortical Source Analysis of High-Density EEG Recordings in Children

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and signal processing make it possible to exploit information from other imaging modalities like structural MRI that provide high spatial resolution to overcome this constraint1. This is especially useful for investigations that require high resolution in the temporal as well as spatial domain. In addition, due to the easy application and low cost of EEG recordings, EEG is often the method of choice when working with populations, such as young children, that do not tolerate functional MRI scans well. However, in order to investigate which neural substrates are involved, anatomical information from structural MRI is still needed. Most EEG analysis packages work with standard head models that are based on adult anatomy. The accuracy of these models when used for children is limited2, because the composition and spatial configuration of head tissues changes dramatically over development3.&#160;
In the present paper, we provide an overview of our recent work in utilizing head models based on individual structural MRI scans or age specific head models to reconstruct the cortical generators of high density EEG. This article describes how&#160;EEG recordings are acquired, processed, and analyzed with pediatric populations at the London Baby Lab, including laboratory setup, task design, EEG preprocessing, MRI processing, and EEG channel level and source analysis.&#160;

In recent years, there has been increasing interest in estimating the cortical sources of scalp measured electrical activity for cognitive neuroscience experiments. This article describes how high density EEG is acquired and how recordings are processed for cortical source estimation in children from the age of 2 years at the London Baby Lab.

קליפת המוח ניתוח מקור בצפיפות גבוהה הקלטות EEG בילדים

EEG is traditionally described as a neuroimaging technique with high temporal and low spatial resolution. Recent advances in biophysical modelling and ...

Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aim to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of &#8220;to-be-suppressed&#8221; thoughts (&#8220;popping&#8221; back into conscious awareness) with a button press. During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.

We aim to identify the neural correlates underlying sustained and transient thought suppression, and thought re-emergence in controls, at-risk and depressed individuals. Activation was greatest for controls compared to the at-risk and the depressed group in the dorsolateral prefrontal cortex during thought suppression and anterior cingulate cortex during thought re-emergence.

תכנון ויישום של מחקר fMRI בחינה חשבו דיכוי בנשים צעירות עם, ובסיכון, לדיכאון

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the ...

Measuring Delay Discounting in Humans Using an Adjusting Amount Task

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. Delay discounting tasks are used to identify indifference points, which reflect equal preference for two dichotomous reward alternatives differing in both delay and magnitude. Indifference points are key to assessing the shape of a delay-discounting gradient because they allow us to isolate the effect of delay on value. For example, if at a 1 week delay and a maximum of $1,000, the indifference point is at $700 we know that, for that participant, a 1-week delay corresponds to a 30% reduction in value. This video outlines an adjusting amount delay-discounting task that identifies indifference points relatively quickly and is inexpensive and easy to administer. Once data have been collected, non-linear regression techniques are typically used to generate discounting curves. The steepness of the discounting curve reflects the degree of impulsive choice of a group or individual. These techniques have been used with a wide range of commodities and have identified populations that are relatively impulsive. For example, people with substance abuse problems discount delayed rewards more steeply than control participants. Although degree of discounting varies as a function of the commodity examined, discounting of one commodity correlates with discounting of other commodities, which suggests that discounting may be a persistent pattern of behavior1.

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. We outline a computer-based delay discounting task that is easy to implement and allows for the quantification of the degree of delay discounting in human participants.

מדידת עיכוב היוון בבני אדם באמצעות משימות סכום התאמה

Delay discounting refers to a decline in the value of a reward when it is delayed relative to when it is immediately available. Delay discounting tasks ...

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The difference shows that people are affected by the emotional content conveyed by the carrier words even though they are irrelevant to the color-naming task at hand. The ESE has been widely deployed with patient populations, as well as with non-selected populations, because the emotion words can be selected to match the tested pathology. The ESE is a powerful tool, yet it is vulnerable to various threats to its validity. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them. The most prevalent threat to the validity of existing ESE studies is sustained effects and habituation wrought about by repeated exposure to emotion stimuli. Consequently, the order of exposure to emotion and neutral stimuli is of utmost importance. We show that in the standard design, only one specific order produces the ESE.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than those of neutral words. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them.

משימתו שטרופ הרגשית: הערכת ביצועים קוגניטיביים תחת חשיפת תוכן רגשי

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The ...

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug&#39;s pharmacology and identify potentially suitable therapeutic populations. The need to use a comprehensive battery of pain models is highlighted by studies whereby only a single pain model, thought to relate to the clinical situation, demonstrates lack of efficacy. No single experimental model can mimic the complex nature of clinical pain. The integrated, multi-modal pain task&#160;battery presented here encompasses the electrical stimulation task, pressure stimulation task, cold pressor task, the UVB inflammatory model which includes a thermal task and a paradigm for inhibitory conditioned pain modulation. These human pain models have been tested for predicative validity and reliability both in their own right and in combination, and can be used repeatedly, quickly, in short succession, with minimum burden for the subject and with a modest quantity of equipment. This allows a drug to be fully characterized and profiled for analgesic effect which is especially useful for drugs with a novel or untested mechanism of action.

Human pain models are valuable tools used to assess the analgesic potential of novel compounds and predict their clinical efficacy, especially when used in an integrated manner. Although implementation of these models is complex, with proper execution, the pain models described in this protocol can provide predictive and reliable results.

קביעת איתור כאב ספי סובלנות שימוש משולב, רב מודלי סוללת משימות כאב

Human pain models are useful in the assessing the analgesic effect of drugs, providing information about a drug&#39;s pharmacology and identify ...

Using the Visual World Paradigm to Study Sentence Comprehension in Mandarin-Speaking Children with Autism

Sentence comprehension relies on the ability to rapidly integrate different types of linguistic and non-linguistic information. However, there is currently a paucity of research exploring how preschool children with autism understand sentences using different types of cues. The mechanisms underlying sentence comprehension remains largely unclear. The present study presents a protocol to examine the sentence comprehension abilities of preschool children with autism. More specifically, a visual world paradigm of eye-tracking is used to explore the moment-to-moment sentence comprehension in the children. The paradigm has multiple advantages. First, it is sensitive to the time course of sentence comprehension and thus can provide rich information about how sentence comprehension unfolds over time. Second, it requires minimal task and communication demands, so it is ideal for testing children with autism. To further minimize the computational burden of children, the present study measures eye movements that arise as automatic responses to linguistic input rather than measuring eye movements that accompany conscious responses to spoken instructions.

We present a protocol to examine the use of morphological cues during real-time sentence comprehension by children with autism.

באמצעות הפרדיגמה העולם הויזואלי ללמוד משפט הבנה בקרב דוברי מנדרינית ילדים עם אוטיזם

Sentence comprehension relies on the ability to rapidly integrate different types of linguistic and non-linguistic information. However, there is ...

Impact of High-intensity Interval Exercise and Moderate-Intensity Continuous Exercise on the Cardiac Troponin T Level at an Early Stage of Training

An elevation in cardiac troponin T (cTnT), as a highly specific biomarker of cardiomyocyte damage, after moderate-intensity continuous exercise (MCE) has been described. The exercise-induced cTnT response distorts the diagnostic role of the cTnT assay. Although high-intensity interval exercise (HIE) is growing in popularity and concerns remain about its safety, available data related to cTnT release after HIE is limited, which hampers the use of HIE as a health intervention. Here, we present three representative HIE protocols [traditional HIE (repeated 4 min cycling at 90% V&#775;O2max interspersed with 3 min rest, 200 kJ/session); sprint interval exercise (SIE, repeated 1 min cycling at 120% V&#775;O2max interspersed with 1.5 min rest, 200 kJ/session); and repeated sprint exercise (RSE, 40 x 6 s all-out sprints interspersed with 9 s rest)] and one representative MCE protocol (continuous cycling exercise at an intensity of 60% V&#775;O2max, 200 kJ/session). Forty-seven sedentary, overweight young women were randomly assigned to one of four groups (HIE, SIE, RSE, and MCE). Six bouts of respective exercise were performed by every single group, with each being 48 h apart. Meanwhile, for four groups, the duration of the entire testing period was identical, being 10 days. Before and after the first and final exercise bouts, an assessment was conducted of cTnT. The current study provides a frame of reference giving a clear picture of how a specific exercise session affects the circulating cTnT concentration at the early stage of training. The information may assist with clinical interpretations of post-exercise cTnT elevation and guide the prescription of exercise, especially for HIE.

Here, we present protocols of high-intensity interval and moderate-intensity continuous exercise to observe the response of circulating cardiac troponin T (cTnT) concentration to acute exercise over 10 days. The information may assist with clinical interpretations of post-exercise cTnT elevation and guide the prescription of exercise.

ההשפעה של פעילות גופנית מרווח גבוה בעוצמה בינונית-עוצמה רציפה פעילות ברמה של הלב Troponin T בשלב מוקדם של האימון

An elevation in cardiac troponin T (cTnT), as a highly specific biomarker of cardiomyocyte damage, after moderate-intensity continuous exercise (MCE) has ...

A Within-Subject Experimental Design using an Object Location Task in Rats

Object place recognition is a prominent method used to investigate spatial memory in rodents. This object place recognition memory forms the basis of the object location task. This paper provides an extensive protocol to guide the establishment of an object location task with the option of up to four repetitions using the same cohort of rats. Both weak and strong encoding protocols can be used to study short- and long-term spatial memories of varying strength and to enable the implementation of relevant memory-inhibiting or -enhancing manipulations. In addition, repetition of the test with the counterbalancing presented here allows the combination of results from two or more tests for within-subject comparison to reduce variability between rats. This method helps to increase statistical power and is strongly recommended, particularly when running experiments that produce high variation in individual behavior. This directly refines the study by increasing the data obtained from each animal and reducing the overall number of animals needed.&#160;Finally, implementation of the repeated object location task increases the efficiency of studies that involve surgical procedures by saving time and labor.

This protocol provides detailed steps for an object location task with four repetitions using the same cohort of rats. Weak and strong encoding can produce short- and long-term memories. The flexibility of the protocol with repetition can be beneficial for studies involving surgical operations by saving time and labor.

עיצוב ניסיוני בתוך נושא באמצעות משימת מיקום אובייקט בחולדות

Object place recognition is a prominent method used to investigate spatial memory in rodents. This object place recognition memory forms the basis of the ...