Low-frequency direct cortical stimulation of left superior frontal gyrus enhances working memory performance

Sankaraleengam Alagapan, Caroline Lustenberger, Eldad Hadar, Hae Won Shin, Flavio Frӧhlich, Sankaraleengam Alagapan, Caroline Lustenberger, Eldad Hadar, Hae Won Shin, Flavio Frӧhlich

Abstract

The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3-8 Hz) and alpha (8-12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results provide evidence for SFG playing a functional role in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of using intracranial electric stimulation for restoring cognitive function.

Conflict of interest statement

Conflict of interest: FF is the lead inventor of IP filed on the topics of noninvasive brain stimulation by UNC. FF is the founder, CSO and majority owner of Pulvinar Neuro LLC. The other authors declare no competing interests

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1.
Figure 1.
(A) Surface model showing the coverage of electrodes for the three participants. (B) Schematic of a single trial of the working memory task used. The task consisted of 3 epochs - Encoding, Retention and Retrieval. Stimulation was applied through the entire trial. (C) Schematic of the periodic pulse stimulation. Stimulation consisted of train of biphasic pulses 400 μs in duration every 100 ms (P1 and P2) or 200 ms (P3) for 5s.
Figure 2.
Figure 2.
(A) Cortical model showing electrodes that exhibited task-related modulation. Red circle denotes the three electrodes in lSFG whose event related spectral perturbation are plotted. observed in left superior frontal gyrus electrodes during sham trials for P1 and baseline session trials for P2 and P3 indicating the modulation of signal in the band 3 – 12 Hz. Hot (red) colors indicate an increase and cold (blue) colors indicate a decrease in signal power relative to baseline. (B) Power spectral density of lSFG electrodes during baseline session in encoding epoch showing peaks that were used to determine stimulation frequency (dotted gray lines) in P2 and P3. (C) Modulation indices during encoding epoch across all lSFG electrodes that exhibited significant task related modulation of signal power. In P1 and P2 there was a significant difference between modulation indices for list length 3 and list length 5.
Figure 3.
Figure 3.
(A) Reaction times in trials with 5 items showing a decrease with stimulation. (B) Accuracy was not affected by stimulation (C) Stimulation did not result in any changes in modulation indices in electrodes over lSFG. (D) Differential effect of stimulation on modulation indices in electrodes that exhibited taskrelevant modulation of low frequency oscillations.

References

    1. Ackerman PL, Beier ME, Boyle MO, 2005. Working memory and intelligence: the same or different constructs? Psychol Bull 131, 30–60.
    1. Alagapan S, Schmidt SL, Lefebvre J, Hadar E, Shin HW, Frhlich F, 2016. Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State- Dependent. PLoS Biol 14, e1002424.
    1. Albouy P, Weiss A, Baillet S, Zatorre RJ, 2017. Selective Entrainment of Theta Oscillations in the Dorsal Stream Causally Enhances Auditory Working Memory Performance. Neuron.
    1. Ali MM, Sellers KK, Frohlich F, 2013. Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance. J Neurosci 33, 11262–11275.
    1. Awh E, Smith EE, Jonides J, 1995. Human rehearsal processes and the frontal lobes: PET evidence. Structure and Functions of the Human Prefrontal Cortex 769, 97–117.
    1. Bagherzadeh Y, Khorrami A, Zarrindast MR, Shariat SV, Pantazis D, 2016. Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex enhances working memory. Exp Brain Res 234, 1807–1818.
    1. Blumenfeld RS, Lee TG, D’Esposito M, 2014. The effects of lateral prefrontal transcranial magnetic stimulation on item memory encoding. Neuropsychologia 53, 197202.
    1. Bokil H, Andrews P, Kulkarni JE, Mehta S, Mitra PP, 2010. Chronux: a platform for analyzing neural signals. J Neurosci Methods 192, 146–151.
    1. Borchers S, Himmelbach M, Logothetis N, Karnath HO, 2012. Direct electrical stimulation of human cortex - the gold standard for mapping brain functions? Nat Rev Neurosci 13, 63–70.
    1. Brainard DH, 1997. The Psychophysics Toolbox. Spat Vis 10, 433–436.
    1. Braver TS, Cohen JD, Nystrom LE, Jonides J, Smith EE, Noll DC, 1997. A parametric study of prefrontal cortex involvement in human working memory. Neuroimage 5, 49–62.
    1. Campo P, Garrido MI, Moran RJ, Garcia-Morales I, Poch C, Toledano R, Gil- Nagel A, Dolan RJ, Friston KJ, 2013. Network reconfiguration and working memory impairment in mesial temporal lobe epilepsy. Neuroimage 72, 48–54.
    1. Cole MW, Schneider W, 2007. The cognitive control network: Integrated cortical regions with dissociable functions. Neuroimage 37, 343–360.
    1. Coleshill SG, Binnie CD, Morris RG, Alarcon G, van Emde Boas W, Velis DN, Simmons A, Polkey CE, van Veelen CW, van Rijen PC, 2004. Material-specific recognition memory deficits elicited by unilateral hippocampal electrical stimulation. J Neurosci 24, 1612–1616.
    1. Corbin L, Marquer J, 2009. Individual differences in Sternberg’s memory scanning task. Acta Psychol (Amst) 131, 153–162.
    1. Cornette L, Dupont P, Salmon E, Orban GA, 2001. The neural substrate of orientation working memory. J Cogn Neurosci 13, 813–828.
    1. Curtis CE, 2006. Prefrontal and parietal contributions to spatial working memory. Neuroscience 139, 173–180.
    1. Curtis CE, D’Esposito M, 2003. Persistent activity in the prefrontal cortex during working memory. Trends Cogn Sci 7, 415–423.
    1. D’Esposito M, 2007. From cognitive to neural models of working memory. Philos Trans R Soc Lond B Biol Sci 362, 761–772.
    1. D’Esposito M, Postle BR, 2015. The cognitive neuroscience of working memory. Annu Rev Psychol 66, 115–142.
    1. Delorme A, Makeig S, 2004. EEGLAB: an open source toolbox for analysis of singletrial EEG dynamics including independent component analysis. J Neurosci Methods 134, 9–21.
    1. du Boisgueheneuc F, Levy R, Volle E, Seassau M, Duffau H, Kinkingnehun S, Samson Y, Zhang S, Dubois B, 2006. Functions of the left superior frontal gyrus in humans: a lesion study. Brain 129, 3315–3328.
    1. Engle RW, Kane MJ, 2004. Executive attention, working memory capacity, and a two- factor theory of cognitive control. Psychology of Learning and Motivation: Advances in Research and Theory, Vol 44 44, 145–199.
    1. Esslinger C, Schuler N, Sauer C, Gass D, Mier D, Braun U, Ochs E, Schulze TG, Rietschel M, Kirsch P, Meyer-Lindenberg A, 2014. Induction and Quantification of Prefrontal Cortical Network Plasticity Using 5 Hz rTMS and fMRI. Hum Brain Mapp 35, 140–151.
    1. Ezzyat Y, Kragel JE, Burke JF, Levy DF, Lyalenko A, Wanda P, O’Sullivan L, Hurley KB, Busygin S, Pedisich I, Sperling MR, Worrell GA, Kucewicz MT, Davis KA, Lucas TH, Inman CS, Lega BC, Jobst BC, Sheth SA, Zaghloul K, Jutras MJ, Stein JM, Das SR, Gorniak R, Rizzuto DS, Kahana MJ, 2017. Direct Brain Stimulation Modulates Encoding States and Memory Performance in Humans. Curr Biol 27, 1251–1258.
    1. Ezzyat Y, Wanda PA, Levy DF, Kadel A, Aka A, Pedisich I, Sperling MR, Sharan AD, Lega BC, Burks A, Gross RE, Inman CS, Jobst BC, Gorenstein MA, Davis KA, Worrell GA, Kucewicz MT, Stein JM, Gorniak R, Das SR, Rizzuto DS, Kahana MJ, 2018. Closed-loop stimulation of temporal cortex rescues functional networks and improves memory. Nat Commun 9, 365.
    1. Fedorov A, Beichel R, Kalpathy-Cramer J, Finet J, Fillion-Robin JC, Pujol S, Bauer C, Jennings D, Fennessy F, Sonka M, Buatti J, Aylward S, Miller JV, Pieper S, Kikinis R, 2012. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging 30, 1323–1341.
    1. Fell J, Staresina BP, Do Lam AT, Widman G, Helmstaedter C, Elger CE, Axmacher N, 2013. Memory modulation by weak synchronous deep brain stimulation: a pilot study. Brain Stimul 6, 270–273.
    1. Fonov V, Evans AC, Botteron K, Almli CR, McKinstry RC, Collins DL, Brain Development Cooperative G, 2011. Unbiased average age-appropriate atlases for pediatric studies. Neuroimage 54, 313–327.
    1. Fonov VS, Evans AC, McKinstry RC, Almli CR, Collins DL, 2009. Unbiased nonlinear average age-appropriate brain templates from birth to adulthood. Neuroimage 47, Supplement 1, S102.
    1. Forbes NF, Carrick LA, McIntosh AM, Lawrie SM, 2009. Working memory in schizophrenia: a meta-analysis. Psychol Med 39, 889–905.
    1. Gagnon G, Blanchet S, Grondin S, Schneider C, 2010. Paired-pulse transcranial magnetic stimulation over the dorsolateral prefrontal cortex interferes with episodic encoding and retrieval for both verbal and non-verbal materials. Brain Res 1344, 148–158.
    1. Gevins A, Smith ME, McEvoy L, Yu D, 1997. High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cereb Cortex 7, 374–385.
    1. Guse B, Falkai P, Gruber O, Whalley H, Gibson L, Hasan A, Obst K, Dechent P, McIntosh A, Suchan B, Wobrock T, 2013. The effect of long-term high frequency repetitive transcranial magnetic stimulation on working memory in schizophrenia and healthy controls--a randomized placebo-controlled, double-blind fMRI study. Behav Brain Res 237, 300–307.
    1. Harding IH, Yucel M, Harrison BJ, Pantelis C, Breakspear M, 2015. Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory. Neuroimage 106, 144–153.
    1. Harms MP, Wang L, Csernansky JG, Barch DM, 2013. Structure-function relationship of working memory activity with hippocampal and prefrontal cortex volumes. Brain Struct Funct 218, 173–186.
    1. Helfrich RF, Schneider TR, Rach S, Trautmann-Lengsfeld SA, Engel AK, Herrmann CS, 2014. Entrainment of brain oscillations by transcranial alternating current stimulation. Curr Biol 24, 333–339.
    1. Hoy KE, Bailey N, Michael M, Fitzgibbon B, Rogasch NC, Saeki T, Fitzgerald PB, 2016. Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls. Cereb Cortex 26, 4563–4573.
    1. Hsieh LT, Ranganath C, 2014. Frontal midline theta oscillations during working memory maintenance and episodic encoding and retrieval. Neuroimage 85 Pt 2, 721–729.
    1. Iglesias JE, Liu CY, Thompson PM, Tu Z, 2011. Robust brain extraction across datasets and comparison with publicly available methods. IEEE Trans Med Imaging 30, 1617–1634.
    1. Jacobs J, Miller J, Lee SA, Coffey T, Watrous AJ, Sperling MR, Sharan A, Worrell G, Berry B, Lega B, Jobst BC, Davis K, Gross RE, Sheth SA, Ezzyat Y, Das SR, Stein J, Gorniak R, Kahana MJ, Rizzuto DS, 2016. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory. Neuron 92, 983–990.
    1. Jausovec N, Jausovec K, Pahor A, 2014. The influence of theta transcranial alternating current stimulation (tACS) on working memory storage and processing functions. Acta Psychol (Amst) 146, 1–6.
    1. Jensen O, Gelfand J, Kounios J, Lisman JE, 2002. Oscillations in the alpha band (912 Hz) increase with memory load during retention in a short-term memory task. Cereb Cortex 12, 877–882.
    1. Jensen O, Lisman JE, 1998. An oscillatory short-term memory buffer model can account for data on the Sternberg task. J Neurosci 18, 10688–10699.
    1. Jensen O, Mazaheri A, 2010. Shaping functional architecture by oscillatory alpha activity: gating by inhibition. Front Hum Neurosci 4, 186.
    1. Jensen O, Tesche CD, 2002. Frontal theta activity in humans increases with memory load in a working memory task. Eur J Neurosci 15, 1395–1399.
    1. Keller CJ, Huang YH, Herrero JL, Fini ME, Du V, Lado FA, Honey CJ, Mehta AD, 2018. Induction and Quantification of Excitability Changes in Human Cortical Networks. Journal of Neuroscience 38, S384–S398.
    1. Khader PH, Jost K, Ranganath C, Rosler F, 2010. Theta and alpha oscillations during working-memory maintenance predict successful long-term memory encoding. Neurosci Lett 468, 339–343.
    1. Kim K, Ekstrom AD, Tandon N, 2016. A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory. Neurobiol Learn Mem.
    1. Kim K, Schedlbauer A, Rollo M, Karunakaran S, Ekstrom AD, Tandon N, 2018. Network-based brain stimulation selectively impairs spatial retrieval. Brain Stimul 11,213221.
    1. Koubeissi MZ, Kahriman E, Syed TU, Miller J, Durand DM, 2013. Low-frequency electrical stimulation of a fiber tract in temporal lobe epilepsy. Ann Neurol 74, 223–231.
    1. Krause CM, Sillanmaki L, Koivisto M, Saarela C, Haggqvist A, Laine M, Hamalainen H, 2000. The effects of memory load on event-related EEG desynchronization and synchronization. Clin Neurophysiol 111,2071–2078.
    1. Kucewicz MT, Berry BM, Miller LR, Khadjevand F, Ezzyat Y, Stein JM, Kremen V, Brinkmann BH, Wanda P, Sperling MR, Gorniak R, Davis KA, Jobst BC, Gross RE, Lega B, Van Gompel J, Stead SM, Rizzuto DS, Kahana MJ, Worrell GA, 2018. Evidence for verbal memory enhancement with electrical brain stimulation in the lateral temporal cortex. Brain.
    1. Kuznetsova A, Brockhoff PB, Christensen RHB, 2017. lmerTest Package: Tests in Linear Mixed Effects Models. Journal of Statistical Software 82, 1–26.
    1. Lacruz ME, Valentin A, Seoane JJ, Morris RG, Selway RP, Alarcon G, 2010. Single pulse electrical stimulation of the hippocampus is sufficient to impair human episodic memory. Neuroscience 170, 623–632.
    1. Lancaster JL, Woldorff MG, Parsons LM, Liotti M, Freitas CS, Rainey L, Kochunov PV, Nickerson D, Mikiten SA, Fox PT, 2000. Automated Talairach atlas labels for functional brain mapping. Hum Brain Mapp 10, 120–131.
    1. Lee J, Park S, 2005. Working memory impairments in schizophrenia: a meta-analysis. J Abnorm Psychol 114, 599–611.
    1. Lee TW, Girolami M, Bell AJ, Sejnowski TJ, 2000. A unifying information-theoretic framework for independent component analysis. Computers & Mathematics with Applications 39, 1–21.
    1. Li G, Henriquez CS, Frohlich F, 2017. Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation. PLoS Comput Biol 13, e1005797.
    1. Li W, Qin W, Liu HG, Fan LZ, Wang JJ, Jiang TZ, Yu CS, 2013. Subregions of the human superior frontal gyrus and their connections. Neuroimage 78, 46–58.
    1. Luber B, Kinnunen LH, Rakitin BC, Ellsasser R, Stern Y, Lisanby SH, 2007. Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: Frequency- and time-dependent effects. Brain Res 1128, 120–129.
    1. Meltzer JA, Zaveri HP, Goncharova II, Distasio MM, Papademetris X, Spencer SS, Spencer DD, Constable RT, 2008. Effects of working memory load on oscillatory power in human intracranial EEG. Cereb Cortex 18, 1843–1855.
    1. Miller JP, Sweet JA, Bailey CM, Munyon CN, Luders HO, Fastenau PS, 2015. Visual-spatial memory may be enhanced with theta burst deep brain stimulation of the fornix: a preliminary investigation with four cases. Brain 138, 1833–1842.
    1. Mitchell DJ, McNaughton N, Flanagan D, Kirk IJ, 2008. Frontal-midline theta from the perspective of hippocampal “theta”. Prog Neurobiol 86, 156–185.
    1. Mottaghy FM, 2006. Interfering with working memory in humans. Neuroscience 139, 8590.
    1. Mottaghy FM, Gangitano M, Sparing R, Krause BJ, Pascual-Leone A, 2002. Segregation of areas related to visual working memory in the prefrontal cortex revealed by rTMS. Cereb Cortex 12, 369–375.
    1. Oliveri M, Turriziani P, Carlesimo GA, Koch G, Tomaiuolo F, Panella M, Caltagirone C, 2001. Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation. Cereb Cortex 11,606618.
    1. Osaka N, Otsuka Y, Hirose N, Ikeda T, Mima T, Fukuyama H, Osaka M, 2007. Transcranial magnetic stimulation (TMS) applied to left dorsolateral prefrontal cortex disrupts verbal working memory performance in humans. Neurosci Lett 418, 232–235.
    1. Owen AM, McMillan KM, Laird AR, Bullmore E, 2005. N-back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum Brain Mapp 25, 46–59.
    1. Polania R, Nitsche MA, Korman C, Batsikadze G, Paulus W, 2012. The importance of timing in segregated theta phase-coupling for cognitive performance. Curr Biol 22, 1314–1318.
    1. Postle BR, Ferrarelli F, Hamidi M, Feredoes E, Massimini M, Peterson M, Alexander A, Tononi G, 2006. Repetitive transcranial magnetic stimulation dissociates working memory manipulation from retention functions in the prefrontal, but not posterior parietal, cortex. J Cogn Neurosci 18, 1712–1722.
    1. Raghavachari S, Kahana MJ, Rizzuto DS, Caplan JB, Kirschen MP, Bourgeois B, Madsen JR, Lisman JE, 2001. Gating of human theta oscillations by a working memory task. J Neurosci 21,3175–3183.
    1. Raghavachari S, Lisman JE, Tully M, Madsen JR, Bromfield EB, Kahana MJ, 2006. Theta oscillations in human cortex during a working-memory task: evidence for local generators. J Neurophysiol 95, 1630–1638.
    1. Ranganath C, Cohen MX, Dam C, D’Esposito M, 2004. Inferior temporal, prefrontal, and hippocampal contributions to visual working memory maintenance and associative memory retrieval. J Neurosci 24, 3917–3925.
    1. Roux F, Uhlhaas PJ, 2014. Working memory and neural oscillations: alpha-gamma versus theta-gamma codes for distinct WM information? Trends Cogn Sci 18, 16–25.
    1. Rypma B, Prabhakaran V, Desmond JE, Glover GH, Gabrieli JD, 1999. Load- dependent roles of frontal brain regions in the maintenance of working memory. Neuroimage 9, 216–226.
    1. Sauseng P, Klimesch W, Heise KF, Gruber WR, Holz E, Karim AA, Glennon M, Gerloff C, Birbaumer N, Hummel FC, 2009. Brain oscillatory substrates of visual short-term memory capacity. Curr Biol 19, 1846–1852.
    1. Snyder HR, 2013. Major Depressive Disorder Is Associated With Broad Impairments on Neuropsychological Measures of Executive Function: A Meta-Analysis and Review. Psychol Bull 139, 81–132.
    1. Suthana N, Fried I, 2014. Deep brain stimulation for enhancement of learning and memory. Neuroimage 85 Pt 3, 996–1002.
    1. Suthana N, Haneef Z, Stern J, Mukamel R, Behnke E, Knowlton B, Fried I, 2012. Memory enhancement and deep-brain stimulation of the entorhinal area. N Engl J Med 366, 502–510.
    1. Tesche CD, Karhu J, 2000. Theta oscillations index human hippocampal activation during a working memory task. Proc Natl Acad Sci U S A 97, 919–924.
    1. Thut G, Schyns PG, Gross J, 2011. Entrainment of perceptually relevant brain oscillations by non-invasive rhythmic stimulation of the human brain. Front Psychol 2, 170.
    1. Uhlhaas PJ, Singer W, 2012. Neuronal dynamics and neuropsychiatric disorders: toward a translational paradigm for dysfunctional large-scale networks. Neuron 75, 963980.
    1. Unsworth N, Fukuda K, Awh E, Vogel EK, 2014. Working memory and fluid intelligence: capacity, attention control, and secondary memory retrieval. Cogn Psychol 71, 1–26.
    1. Violante IR, Li LM, Carmichael DW, Lorenz R, Leech R, Hampshire A, Rothwell JC, Sharp DJ, 2017. Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance. Elife 6.
    1. Vossen A, Gross J, Thut G, 2015. Alpha Power Increase After Transcranial Alternating Current Stimulation at Alpha Frequency (alpha-tACS) Reflects Plastic Changes Rather Than Entrainment. Brain Stimul 8, 499–508.
    1. Vosskuhl J, Huster RJ, Herrmann CS, 2015. Increase in short-term memory capacity induced by down-regulating individual theta frequency via transcranial alternating current stimulation. Front Hum Neurosci 9, 257.
    1. Wager TD, Smith EE, 2003. Neuroimaging studies of working memory: a metaanalysis. Cogn Affect Behav Neurosci 3, 255–274.
    1. Yamanaka K, Tomioka H, Kawasaki S, Noda Y, Yamagata B, Iwanami A, Mimura M, 2014. Effect of parietal transcranial magnetic stimulation on spatial working memory in healthy elderly persons--comparison of near infrared spectroscopy for young and elderly. PLoS One 9, e102306.
    1. Yamanaka K, Yamagata B, Tomioka H, Kawasaki S, Mimura M, 2010. Transcranial magnetic stimulation of the parietal cortex facilitates spatial working memory: nearinfrared spectroscopy study. Cereb Cortex 20, 1037–1045.
    1. Yushkevich PA, Piven J, Hazlett HC, Smith RG, Ho S, Gee JC, Gerig G, 2006. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage 31, 1116–1128.

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