Faculty Profile

Dara S. Manoach, PhD


Professor of Psychology, Harvard Medical School

See publications


Address

149 Thirteenth Street
Room 1.111
Charlestown, MA 02129
USA

Email dara@nmr.mgh.harvard.edu

Research Unit(s)

Manoach Lab
Athinoula A. Martinos Center for Biomedical Imaging
Associated Scientist, Stanley Center, Broad Institute

Research Interests

I am a neuropsychologist with a longstanding interest in cognitive neuroscience. I have devoted my career to understanding the neural basis and nature of fundamental cognitive deficits in neuropsychiatric disorders. In ongoing work, my lab is collaborating with Dr. Robert Stickgold to investigate the contribution of abnormal sleep to cognitive deficits in schizophrenia. Sleep plays a critical role in memory consolidation and renders cognitive performance faster, more accurate, and less reliant on limited capacity processing resources (i.e., more efficient and automatic). Recent evidence suggests that sleep-dependent memory consolidation is paralleled by changes in neural activity during task performance resulting in more efficient spatiotemporal patterns of brain activation. This led us to hypothesize that sleep plays a critical role in cognitive deficits and associated inefficient brain activation patterns in schizophrenia. We have repeatedly replicated our findings of deficient sleep-dependent memory consolidation schizophrenia, identified a specific mechanism (reduced sleep spindles), and in preliminary work found that eszopiclone can increase spindles. Our present projects incorporate electroencephalography, magnetoencephalography functional MRI and genetics to elucidate the links between deficient sleep-dependent memory consolidation and sleep spindles, identify effective treatments and identify genetic contributions. This research program aims to (i) substantially enhance our understanding of the pathophysiology of schizophrenia, (ii) expand current models of cognitive deficits and (iii) identify interventions that significantly improve quality of life.


Selected Publications


Original Articles:

Manoach DS, Demanuele C, Wamsley EJ, Vangel M, Montrose DM, Miewald J, Kupfer
D, Buysse D, Stickgold R, Keshavan MS. Sleep spindle deficits in antipsychotic-naïve early course schizophrenia and in non-psychotic first-degree  relatives. Front Hum Neurosci. 2014 Oct 7;8:762. doi: 10.3389/fnhum.2014.00762.eCollection 2014. PMID: 25339881; PMCID: PMC4188028.

Manoach DS, Stickgold R. Does abnormal sleep impair memory consolidation in schizophrenia? Front Hum Neurosci. 2009 Sep 1;3:21. doi: 10.3389/neuro.09.021.2009. eCollection 2009. PMID: 19750201; PMCID: PMC2741296.

Manoach DS, Thakkar KN, Stroynowski E, Ely A, McKinley SK, Wamsley E, Djonlagic I, Vangel MG, Goff DC, Stickgold R. Reduced overnight consolidation of procedural learning in chronic medicated schizophrenia is related to specific sleep stages. J Psychiatr Res. 2010 Jan;44(2):112-20. doi: 10.1016/j.jpsychires.2009.06.011. Epub 2009 Aug 8. PMID: 19665729; PMCID: PMC2813320.

Manoach DS, Cain MS, Vangel MG, Khurana A, Goff DC, Stickgold R. A failure of sleep-dependent procedural learning in chronic, medicated schizophrenia. BiolPsychiatry. 2004 Dec 15;56(12):951-6. PMID: 15601605.

Wamsley EJ, Shinn AK, Tucker MA, Ono KE, McKinley SK, Ely AV, Goff DC,
Stickgold R, Manoach DS. The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized placebo-controlled trial. Sleep.2013 Sep 1;36(9):1369-76. doi: 10.5665/sleep.2968. PMID: 23997371; PubMed PMCID: PMC3738047.

Wamsley EJ, Tucker MA, Shinn AK, Ono KE, McKinley SK, Ely AV, Goff DC,
Stickgold R, Manoach DS. Reduced sleep spindles and spindle coherence in
schizophrenia: mechanisms of impaired memory consolidation? Biol Psychiatry. 2012 Jan 15;71(2):154-61. doi:10.1016/j.biopsych.2011.08.008. Epub 2011 Oct 2. PMID: 21967958; PMCID: PMC3561714.

Gregory MD, Agam Y, Selvadurai C, Nagy A, Vangel M, Tucker M, Robertson EM, Stickgold R, Manoach DS. Resting state connectivity immediately following learning correlates with subsequent sleep-dependent enhancementof motor taskperformance. Neuroimage. 2014 Nov 15;102 Pt 2:666-73. doi:10.1016/j.neuroimage.2014.08.044. Epub 2014 Aug 28. PMID: 25173415; PMCID: PMC4252600.

Manoach DS, Lee AK, Hämäläinen MS, Dyckman KA, Friedman JS, Vangel M, Goff DC, Barton JJ. Anomalous use of context during task preparation in schizophrenia: a magnetoencephalography study. Biol Psychiatry. 2013 May 15;73(10):967-75. doi:10.1016/j.biopsych.2012.12.018. Epub 2013 Feb 4. PMID: 23380717; PMCID: PMC3641151.

Kenet T, Orekhova EV, Bharadwaj H, Shetty NR, Israeli E, Lee AK, Agam Y, Elam M, Joseph RM, Hämäläinen MS, Manoach DS. Disconnectivity of the cortical ocular motor control network in autism spectrum disorders. Neuroimage. 2012 Jul 16;61(4):1226-34. doi:10.1016/j.neuroimage.2012.03.010. Epub 2012 Mar 11. PMID: 22433660; PMCID: PMC3376722.

Agam Y, Hämäläinen MS, Lee AK, Dyckman KA, Friedman JS, Isom M, Makris N,
Manoach DS. Multimodal neuroimaging dissociates hemodynamic and electrophysiological correlates of error processing. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17556-61. doi: 10.1073/pnas.1103475108. Epub 2011 Oct 3. PMID: 21969565;  PMCID: PMC3198335.

Roffman JL, Gollub RL, Calhoun VD, Wassink TH, Weiss AP, Ho BC, White T, Clark VP, Fries J, Andreasen NC, Goff DC, Manoach DS. MTHFR 677C --> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val --> Met. Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17573-8. doi: 10.1073/pnas.0803727105. Epub 2008 Nov 6. PMID: 18988738; PMCID: PMC2582272.   

Thakkar KN, Polli FE, Joseph RM, Tuch DS, Hadjikhani N, Barton JJ, Manoach DS. Response monitoring, repetitive behaviour and anterior cingulate abnormalities in autism spectrum disorders (ASD). Brain. 2008 Sep;131(Pt 9):2464-78. doi: 10.1093/brain/awn099. Epub 2008 Jun 11. PMID: 18550622;  PMCID: PMC2525446.   

Polli FE, Barton JJ, Thakkar KN, Greve DN, Goff DC, Rauch SL, Manoach DS. Reduced error-related activation in two anterior cingulate circuits is related to impaired performance in schizophrenia. Brain. 2008 Apr;131(Pt 4):971-86. Epub 2007 Dec 24. PMID: 18158315.   

Polli FE, Barton JJ, Cain MS, Thakkar KN, Rauch SL, Manoach DS. Rostral and dorsal anterior cingulate cortex make dissociable contributions during antisaccade error commission. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15700-5. Epub 2005 Oct 14. PMID: 16227444;  PMCID: PMC1255733.   

Manoach DS. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res. 2003 Apr 1;60(2-3):285-98. Review. PMID: 12591590.   

Manoach DS, Gollub RL, Benson ES, Searl MM, Goff DC, Halpern E, Saper CB, Rauch SL. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry. 2000 Jul 15;48(2):99-109. PMID: 10903406.   

Manoach DS, Press DZ, Thangaraj V, Searl MM, Goff DC, Halpern E, Saper CB, Warach S. Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry. 1999 May 1;45(9):1128-37. PMID: 10331104.

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