Alpha amplitude and phase locking in obsessive-compulsive disorder during working memory

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Alpha amplitude and phase locking in obsessive-compulsive disorder during working memory Jin Young Park a, b , Jaewon Lee c, d , Hae-Jeong Park a, e, f , Jae-Jin Kim a, b , Kee Namkoong a, b , Se Joo Kim a, b, a Department of Psychiatry, Yonsei University, College of Medicine, Seoul, Korea b Institute of Behavioral Science in Medicine, Yonsei University, College of Medicine, Seoul, Korea c Department of Psychiatry & Neuropsychiatry Laboratory, Gongju National Hospital, Gongju, Korea d Brain Dynamics Laboratory, Department of Bio and Brain Engineering, KAIST, Daejeon, South Korea e Department of Radiology, Nuclear Medicine and Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea f BK21 Project for Medical Science, Yonsei University, College of Medicine, Seoul, Korea abstract article info Article history: Received 22 February 2011 Received in revised form 13 September 2011 Accepted 14 September 2011 Available online 28 September 2011 Keywords: Obsessive compulsive disorder (OCD) Alpha oscillation Event-related desynchronization (ERD) Alpha phase locking Memory load Alpha event-related desynchronization (ERD) and synchronization are known to reect brain activation and inhibition, respectively. Alpha phase locking seems to reect the timing in the cortical process. In a previous study, lower alpha ERD was related to working memory in obsessive-compulsive disorder (OCD) patients than in controls during the retention and retrival phases, but not in the encoding phase. However, memory decits in OCD patients are known to be related to executive failure during the encoding phase. Thus, focus- ing on the encoding phase, we tested the level of alpha amplitude and phase locking in OCD patients accord- ing to memory load. The EEGs of fteen OCD patients and fteen controls were recorded during a Sternberg working memory task. The behavioral performance of the OCD patients was normal. However, the OCD group yielded signicantly lower ERD and stronger phase locking. As memory load rose, ERD and phase locking sig- nicantly increased in both groups. A difference in event-related alpha oscillation was observed in the encod- ing phase. Lower alpha modulation in the OCD patient simplied abnormality of the excitatory/inhibitory process in the brain, and increased phase locking might reect excessive attentional excitability. © 2011 Elsevier B.V. All rights reserved. 1. Introduction 1.1. Obsessive-compulsive disorder and memory impairment Obsessive-compusive disorder (OCD) is a debilitating illness char- acterized by unwanted, intrusive, and distressing thoughts, impulses, doubts, or images, which are often associated with compulsitve be- haviors that are repetitive, time consuming, and often ritualized (Sadock et al., 2007). It was thought that impaired memory functions might lead to the repetitive thoughts and behaviors of OCD. Memory dysfunction of OCD is thought to be secondary to organizational def- icits, which implicate executive dysfunction as a primary contributor to OCD proles (Olley et al., 2007). The memory decits in OCD seem to be largely mediated by organizational decits during the encoding phase. As a result, OCD patients seem to have difculty in recall (Deckersbach et al., 2005; Purcell et al., 1998b). In addition, it was reported that OCD patients perform poorly on working memory tasks as the task difculty increases (Purcell et al., 1998a,b; van der Wee et al., 2003). 1.2. Alpha oscillations and memory Alpha oscillations (812 Hz) are thoght to be related to a neuronal mechanism of complex cognitive processes that include attention, mem- ory, and mental imagery (Klimesch, 1999; Klimesch et al., 2008; Tesche et al., 1995). Event-related modulation can be quantied by both event-related desynchronization (ERD) and even-related synchroniza- tion (ERS). ERD is a relative decrease in oscillation power compared with baseline measurements after stimulation, and ERS is an increase in oscillation power after stimulation (Pfurtscheller and Aranibar, 1977). The alpha ERS seems to be related to active inhibition, and the alpha ERD might be correlated to release from inhibition (Klimesch et al., 2007a). Alpha desynchronization is known to correlate with semantic memory performance (Klimesch et al., 1994) in normal subjects, and alpha ERD is correlated with memory performance (Doppelmayr et al., 2005; Klimesch et al., 1997a). In addition, it was reported that alpha at- tenuation corresponds to gradually increased working memory loads (Gevins and Smith, 2000; Neuper and Pfurtscheller, 2001; Pfurtscheller and Klimesch, 1992). These ndings suggested that alpha oscillations may be useful in investigating the memory process. International Journal of Psychophysiology 83 (2012) 17 Corresponding author at: Department of Psychiatry and Institute of Behavioral Sci- ence in Medicine, Yonsei University, College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120752, Korea. Tel.: +82 2 2228 1620; fax: +82 2 313 0891. E-mail address: [email protected] (S.J. Kim). 0167-8760/$ see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpsycho.2011.09.014 Contents lists available at SciVerse ScienceDirect International Journal of Psychophysiology journal homepage: www.elsevier.com/locate/ijpsycho

Transcript of Alpha amplitude and phase locking in obsessive-compulsive disorder during working memory

Page 1: Alpha amplitude and phase locking in obsessive-compulsive disorder during working memory

International Journal of Psychophysiology 83 (2012) 1–7

Contents lists available at SciVerse ScienceDirect

International Journal of Psychophysiology

j ourna l homepage: www.e lsev ie r .com/ locate / i jpsycho

Alpha amplitude and phase locking in obsessive-compulsive disorder duringworking memory

Jin Young Park a,b, Jaewon Lee c,d, Hae-Jeong Park a,e,f, Jae-Jin Kim a,b, Kee Namkoong a,b, Se Joo Kim a,b,⁎a Department of Psychiatry, Yonsei University, College of Medicine, Seoul, Koreab Institute of Behavioral Science in Medicine, Yonsei University, College of Medicine, Seoul, Koreac Department of Psychiatry & Neuropsychiatry Laboratory, Gongju National Hospital, Gongju, Koread Brain Dynamics Laboratory, Department of Bio and Brain Engineering, KAIST, Daejeon, South Koreae Department of Radiology, Nuclear Medicine and Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Koreaf BK21 Project for Medical Science, Yonsei University, College of Medicine, Seoul, Korea

⁎ Corresponding author at: Department of Psychiatryence in Medicine, Yonsei University, College of MedicineSeoul, 120–752, Korea. Tel.: +82 2 2228 1620; fax: +8

E-mail address: [email protected] (S.J. Kim).

0167-8760/$ – see front matter © 2011 Elsevier B.V. Alldoi:10.1016/j.ijpsycho.2011.09.014

a b s t r a c t

a r t i c l e i n f o

Article history:Received 22 February 2011Received in revised form 13 September 2011Accepted 14 September 2011Available online 28 September 2011

Keywords:Obsessive compulsive disorder (OCD)Alpha oscillationEvent-related desynchronization (ERD)Alpha phase lockingMemory load

Alpha event-related desynchronization (ERD) and synchronization are known to reflect brain activation andinhibition, respectively. Alpha phase locking seems to reflect the timing in the cortical process. In a previousstudy, lower alpha ERD was related to working memory in obsessive-compulsive disorder (OCD) patientsthan in controls during the retention and retrival phases, but not in the encoding phase. However, memorydeficits in OCD patients are known to be related to executive failure during the encoding phase. Thus, focus-ing on the encoding phase, we tested the level of alpha amplitude and phase locking in OCD patients accord-ing to memory load. The EEGs of fifteen OCD patients and fifteen controls were recorded during a Sternbergworking memory task. The behavioral performance of the OCD patients was normal. However, the OCD groupyielded significantly lower ERD and stronger phase locking. As memory load rose, ERD and phase locking sig-nificantly increased in both groups. A difference in event-related alpha oscillation was observed in the encod-ing phase. Lower alpha modulation in the OCD patient simplied abnormality of the excitatory/inhibitoryprocess in the brain, and increased phase locking might reflect excessive attentional excitability.

and Institute of Behavioral Sci-, 50 Yonsei-ro, Seodaemun-gu,2 2 313 0891.

rights reserved.

© 2011 Elsevier B.V. All rights reserved.

1. Introduction

1.1. Obsessive-compulsive disorder and memory impairment

Obsessive-compusive disorder (OCD) is a debilitating illness char-acterized by unwanted, intrusive, and distressing thoughts, impulses,doubts, or images, which are often associated with compulsitve be-haviors that are repetitive, time consuming, and often ritualized(Sadock et al., 2007). It was thought that impaired memory functionsmight lead to the repetitive thoughts and behaviors of OCD. Memorydysfunction of OCD is thought to be secondary to organizational def-icits, which implicate executive dysfunction as a primary contributorto OCD profiles (Olley et al., 2007). The memory deficits in OCD seemto be largely mediated by organizational deficits during the encodingphase. As a result, OCD patients seem to have difficulty in recall(Deckersbach et al., 2005; Purcell et al., 1998b). In addition, it wasreported that OCD patients perform poorly on working memory

tasks as the task difficulty increases (Purcell et al., 1998a,b; van derWee et al., 2003).

1.2. Alpha oscillations and memory

Alpha oscillations (8–12 Hz) are thoght to be related to a neuronalmechanism of complex cognitive processes that include attention,mem-ory, and mental imagery (Klimesch, 1999; Klimesch et al., 2008; Tescheet al., 1995). Event-related modulation can be quantified by bothevent-related desynchronization (ERD) and even-related synchroniza-tion (ERS). ERD is a relative decrease in oscillation power comparedwith baseline measurements after stimulation, and ERS is an increasein oscillation power after stimulation (Pfurtscheller and Aranibar,1977). The alpha ERS seems to be related to active inhibition, and thealpha ERD might be correlated to release from inhibition (Klimesch etal., 2007a). Alpha desynchronization is known to correlatewith semanticmemory performance (Klimesch et al., 1994) in normal subjects, andalpha ERD is correlated with memory performance (Doppelmayr et al.,2005; Klimesch et al., 1997a). In addition, it was reported that alpha at-tenuation corresponds to gradually increased working memory loads(Gevins and Smith, 2000; Neuper and Pfurtscheller, 2001; Pfurtschellerand Klimesch, 1992). These findings suggested that alpha oscillationsmay be useful in investigating the memory process.

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1.3. OCD and alpha modulation

Studies on OCD and alpha oscillations have focused on mostlyresting alpha rhythms (Bucci et al., 2004; Karadag et al., 2003; Shinet al., 2004). It was reported that in a resting state, lower levelsof alpha power were observed in the anterior and posterior brainregions in OCD patients (Bucci et al., 2004). The reduction of alphapower is characteristic of OCD patients with more severe symptoms(Karadag et al., 2003), but relatively increased alpha power wasobserved in good responders to serotonin-reuptake inhibitors (Prichepet al., 1993).

Recently, Ciesielski et al. (2007) reported that OCD patients showimpaired ability to modulate alpha ERD in magnetoencephalogra-phy (MEG). In this study, they investigated alpha ERD during shortterm memory tasks and observed that the occurrence of a signifi-cance difference in ERD in the presence of distractors was confinedto periods of retention and retrieval by the MEG. This finding im-plies that EEG may be beneficial for understanding the neurobiolog-ical basis of OCD.

1.4. Phase locking factor of alpha osillations

Phase locking has drawn more attention since it was reportedthat alpha activity that is phase locked to stimuli provides differentinformation than phase locked alpha amplitude (Freunberger et al.,2009; Hanslmayr et al., 2005; Herrmann et al., 2004; Kolev et al.,2001). According to the inhibition-timing hypothesis, an increasein oscillatory activity caused by two differents effects results in ageneral decrease in firing rate and an increase in rhythmic dis-charges. Stricter timing of neural activity seems to enhance alphaoscillatory activity, which results in increased inhibition tones(Klimesch et al., 2007a). It was reported that alpha phase lockingis related to attention, perception, and memory process (Klimeschet al., 2007b; Palva and Palva, 2007). Higher alpha phase lockingseems to be related to good perception and memory performancein normal subjects (Ciesielski et al., 2007; Hanslmayr et al., 2005;Klimesch et al., 2004) and good working memory performance inschizophrenia (Haenschel et al., 2010). Therefore, it is important toevaluate not only alpha amplitudes but also phase locking valuesin order to understand the neural mechanism of alpha oscillationsfor memory performance.

1.5. Aims of this study

As mentioned above, impaired memory functions of OCD mightcause obsessive-compulsive symptoms (Olley et al., 2007), whilealpha event-related osillations may reflect such memory process(Klimesch et al., 1994; Pfurtscheller and Klimesch, 1992). However,reports on the relationship between the memory function of OCDand the alpha ERD have been scarce. A recent study reported thatlower alpha modulation was observed in OCD patients during ashort-term memory task during the retention and retrieval phases,but not the encoding phase (Ciesielski et al., 2007) during whichthe main deficit of memory in OCD is thought to be derived. In thepresent study, we intened to focus on the encoding phase by usingthe Sternberg working memory task. The Sternberg working memorytask is widely used in EEG studies for observing the changes in the os-cillations during encoding as the memory load varies (Raghavachariet al., 2001; Tuladhar et al., 2007).

The aim of this study is to test whether patients with OCDshow impaired alpha power and alpha phase locking duringencoding in a short-term memory task. In addition, we hypothe-size that these abnormalities become more pronounced as mem-ory load increases.

2. Materials and Methods

2.1. Subjects

Fifteen normal subjects (4 females, mean age 23; range 19–35 years) and fifteen OCD patients (4 females, mean age 23; range17–39 years) participated in this study under the ethics guidelinesat the Institutional Review Board of Yonsei University and the Decla-ration of Helsinki (World Medical Association: Ethical Principles forMedical Research Involving Human Subjects, 1964). All OCD patientsmet the DSM-IV criteria for OCD as determined by the structured clin-ical interview for DSM-IV (SCID; First et al., 1997). Patients with apsychiatric disorder other than OCD, including medical and neurolog-ical illnesses, were excluded. Obsessive-compulsive symptoms andtheir severity were evaluated and scored by the Yale-Brown Obses-sive-Compulsive Scale (Y-BOCS; Goodman et al., 1989). The meanY-BOCS score was 21.92 (range: 12–33). Ten OCD patients (66.7%)were taking only selective serotonin reuptake inhibitors (SSRIs),and the remaining five patients (33.3%) were taking SSRIs and lowdose benzodiazepines. All patients were undergoing behavioral ther-apy consisting of exposure/response prevention. Fifteen age- and sex-matched control subjects were recruited through advertisements. Allnormal subjects had no personal or family history of OCD or otherpsychiatric disorders. The presence of psychiatric disorders wasdetermined using the SCID (First et al., 1997).

2.2. Sternberg task

Amodified Sternbergworkingmemory task using consonants of theKorean alphabet as mnemonic items was applied. The Sternberg task iswidely used for observing oscillatory changes with memory load in theencoding phase. Each trial started with the word ”blink,” encouragingthe subjects to blink in order to reduce artifacts later in the trial. Afterpresenting a small red cross for 2000 ms, we sequentially presentedmemory lists of 1 to 4 consonants, namely sequence 1 (S1), S2, S3,and S4 of encoding. Each item was presented for 1200 ms with200 ms intervals between the consonants. Following a 2000 ms delayperiod, a probe consonant was presented for 3000 ms. The subjectswere instructed to indicate as quickly and accurately as possible wheth-er or not the probematched an item on the memory list .The responseswere given by pressing one of two buttons, one by the right index fingerand the other by the left index finger. Feedback on correct and incorrectresponses and accuracy rate were presented for 1500ms at the end ofeach trial, afterwhich the next trial started (Fig. 1).The experiment con-sisted of two blocks of 60 randomly presented trials (120 trials in total).Response hands and the order of tasks were counterbalanced acrosssubjects.

2.3. EEG data recording

EEGs were recorded using a GRASS 15A54 amplifier (Grass Tech-nologies, USA) with 21 sintered Au/Ag-electrodes. According to theinternational 10–20 system, the EEG locations were as follows: AFz,Fp1, Fp2, Fz, F3, F4, F7, F8, Cz, C3, C4, T3, T4, Pz, P3, P4, T5, T6, Oz,O1, and O2. We also placed an electrode on each mastoid for thelinked reference and a ground electrode at the nasion. Eye movementactivity was monitored with two additional electrodes placed supra-orbitally on both eyes and was referenced to the linked mastoids.Electrode impedances were kept below 10 kΩ prior to data acquisi-tion. The EEGs were sampled at 1000 Hz (analogue band-pass filter0.1-100 Hz) and stored for off-line analysis.

2.4. Data analysis

We used EEGLAB software (Delorme and Makeig, 2004; Makeiget al., 2004) to reference, analyze independent components and

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Fig. 1. The Sternberg working memory task using consonants of the Korean alphabet as mnemonic items. Each trial started with a blink. After 2.0 s, 4 Korean consonants were se-quentially presented at a rate of 1.2 s per itemwith 0.2 s intervals. After a 2.0 s delay, a probe was shown. The subjects had to respond as to whether the probe consonant was on thelist or not. Feedback was given after every response. A long vertical line at the time frame means that the stimulus is on, and a short vertical line indicates that the stimulus is off.

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time frequency, and illustrate. First, data were detrended and mean-subtracted. The data were then re-referenced to a common averagereference and segmented into 10,000 ms intervals (including the1,000 ms segment preceding the encoding stimulus). The epochs, in-cluding incorrect answers, were removed as well. Independent com-ponent decomposition and visual inspection of data were performedto eliminate artifacts and bad epochs. After artifact rejection, therewas a minimum of 87 trials of the original 120 remaining for the anal-ysis of each subject.

2.4.1. Event-related spectral perturbation (ERSP) and inter-trial coherence(ITC) analysis

We used the ERSP as the alpha amplitude value and the ITC as thephase locking value. ERSP may correspond to a narrow band of ERD orERS. In short, the power spectrumwas calculated over a sliding laten-cy window on each epoch, and each was normalized by its respectivemean baseline spectra before averaging across data trials was per-formed. Each trial contained samples from −1000 ms to 9000 ms ofthe onset of the first consonant (S1). The size of the sliding windowwas 2400 data points. The ERSP image provides a color code at eachimage pixel indicating the power reached (in dB) at a given frequencyand latency relative to the stimulus onset. The pre-stimulus between−1000 and 0 sec was considered as the baseline.

ERSP f ; tð Þ ¼ 1n∑n

k−1jFk f ; tð Þj2

We calculated the mean ERSP in the alpha oscillatory area duringthe time it took to present each stimulus (S1-S4) in order to observealpha amplitude dynamics. ITC is a frequency domain measure of thepartial or exact synchronization of an activity at a particular latencyand frequency compared with a set of experimental events to whichEEG data trials are time locked. This concept is matched with thephase locking factor (Tallon-Baudry et al., 1996). The ITC in thisstudy equals the inter-trial phase coherence (ITPC).

ITPC f ; tð Þ ¼ 1n∑n

k−1

Fk f ; tð ÞjFk f ; tð Þj

The ITC measure takes values between 0 and 1: 0 indicates the ab-sence of synchronization between EEG data and the time lockingevents and 1 means perfect synchronization. We obtained the maxi-mum ITC of each stimulus in the alpha oscillations to investigate thephase locking values. We calculated the maximum ITC at the sametime as the area and electrode with ERSP. In the present study, weconfined alpha activity to the frequency range from 8 to 12 Hz. Subse-quently, the mean ERSPs and the maximum ITC in windows of0–1200 ms (S1), 1400–2600 ms (S2), 2800–4000 ms (S3), and4200–5400 ms (S4) latency in 8–12 Hz were analyzed.

Visual inspection of the ERSP plot of the alpha oscillations aver-aged across all stimulations (S1-S4) and all controls were performed.As a result, we observed ERD at the frontal area around Fz and the

occipital area around O1 and O2 in all four encoding periods in thealpha oscillation area. Thus, we designated these areas as the regionsof interest (ROIs) and analysed the alpha values of Fz, O1, and O2.

2.4.2. Behavioral analysisReaction times and accuracy of task performance (error rates)

were also measured for the behavioral analysis. These behavioralmeasures were analyzed with an independent t test.

2.4.3. Statistical analysisThe ERSP and ITC for each electrode were analyzed with a repeat-

ed measures analysis of variance (ANOVA) comprising a within-subjects factor labeled “memory load” and a between-subjects factorlabeled “group” (“normal” versus "OCD”), and Greenhouse-Geissercorrection then was applied.

3. Result

3.1. Behavior

In present study, we did not find any differences of behavioral per-formances. There was no significant difference between OCD (90.78%,SD 6.89) and controls (91.49%, SD 4.73) in the accuracy rate [t(28)=−0.331, p=0.743]. There was no significant difference between OCD( 802.71 ms, SD 255.03) and controls ( 838.32 ms, SD 175.44) in thereaction times [t(28)=−0.446, p=0.66].

3.2. ERSP of alpha

Alpha ERD, which appeared as a negative value of ERSP of OCD,was less than that of controls in Fz, O1, and O2. The alpha ERD wasmore pronounced as memory load increased. Repeated measuresANOVA of the ESRP showed a significant main effect of “memoryload” in all electrodes for analysis [Fz: F(3,84)=10.714, pb0.001,O1: F(3,84)=15.644, pb0.001, O2: F(3,84)=8.401, p=0.001], butthere was no significant interaction between “memory load” and“group” [Fz: F(3,84)=0.563, p=0.585, O1: F(3,84)=1.609, p=0.212,O2: F(3,84)=1.070, p=0.341]. In between-group analyses, there wasa significant main effect of ”group” in three electrodes of ROI [Fz: F(1,28)=11.076, p=0.02,O1: F(1,28)=6.484, p=0.017,O2: F(1,28)=4.258, p=0.048] (Fig. 2, left; Fig. 3, left).

3.3. ITC of alpha

ITC, which means alpha phase locking in OCD subjects, was moreprominent than that in control subjects, and it increased accordingto memory load like alpha ERD. Repeated measures ANOVA of ITCshowed a significant main effect of “memory load” in all electrodesof ROI [Fz: F(3,84)=12.947, pb0.001, O1: F(3,84)=15.465, pb0.001,O2: F(3,84)=10.233, pb0.001]. There was no significant interactionbetween “memory load” and “group” [Fz: F(3,84)=0.740, p=0.485,O1: F(3,84)=0.454, p=0.697, O2: F(3,84)=0.150, p=0.884].

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ERSP ITC

[ms] [ms]

CTR

OCD

[dB]

S1 S2 S3 S4 S1 S2 S3 S4

Fig. 2. ERD (right) and ITC (left) in O2 electrode. Less ERD appears as lighter blue and a high ITC value appears as deeper red in OCD patients compared with controls during encod-ing at an alpha oscillatory range (8-12 Hz). White square lines indicate areas of alpha frequency (8-12 Hz) during encoding. S1-S4 means the periods during which encoding stimuliwere presented.

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Comparison of maximum ITC values showed a significantmain effect in“group” in O1 and O2 [O1: F(1,28)=5.147, p=0.031,O2: F(1,28)=5.100, p=0.032), but not in Fz (F(1,28)=2.468, p=0.127] (Fig. 2,right; Fig. 3, right).

4. Discussion

In this study, we found less alpha ERD and stronger alpha phaselocking in the OCD patients compared with the control subjects dur-ing the encoding phase. ERD and phase locking was increased inboth the OCD patients and the controls as the memory load increased.As far as we know, this was the first study to investigate whether OCDshow differences in alpha power and phase locking during the encod-ing phase.

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O2

S1 S2 S3 S4

[dB]

Fig. 3. The event-related change in the mean ERSP and the maximum ITC across four encodincontrol group.

4.1. Reduced alpha ERD of OCD in the encoding phase

4.1.1. Event-related alpha oscillations and memory of OCD in the encodingphase

As far as we know, there has only been one study reported on therelationship between the memory function of OCD and alpha ERD.The study demonstrated less alpha ERD in OCD compared to controls(CTR) during the retention and the retrieval phase (Ciesielski et al.,2007). However, no differences were seen between the two groupsduring the endoding phase in which memory deficits were suggestedto occur in OCD patients. In the present study, we used the Sternbergworking memory test and focused on the encoding phase.We found asignificant difference in ERD between the OCD patients and controlseven during the encoding phase, which contrasts from the results of

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g phases. Note less ERD and stronger alpha phase locking in the OCD group than in the

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Ciesielski et al.( 2007). There may be several reasons for this discrep-ancy between the findings. First, in this study, comparable but notidentical tasks were given to the subjects. While previous the re-search allowed for encoding stimuli once per one encoding phase,our study required the subjects to encode stimuli four times in total.Therefore, the task was more difficult in our study, which resultedin enough cognitive load to produce the difference in ERD even dur-ing encoding. Second, our study was conducted on OCD patients onmedication, unlike those in a previous study (Ciesielski et al., 2007).Given that a previous research reported that medication can affectalpha oscillations (Bolwig et al., 2007), medication may have been afactor that influenced the difference. Lastly, unlike previous studieswhere visuo-spatial stimuli were employed, our study used verbalstimuli. Considering that most available neuropsychological test re-sults have shown that verbal memory is relatively well preservedeven in the presence of visuo-spatial memory deficits in OCD patients(Olley et al., 2007), it can be assumed that the difference in propertiesof stimuli may have caused the difference in the results.

4.1.2. Abnormality of the excitatory/inhibitory process of OCDGenerally, alpha ERD reflects active information processing in the

sense of excitatory brain processing, and alpha ERS seems to reflect atop-down, inhibitory control process (Klimesch et al., 2007a). In thisstudy, the phenomenon that alpha ERD is increased with memoryload also suggested that alpha modulation reflects excitation of thebrain in the cognitive process. On the other hand, many studiesreported that alpha oscillations are strengthened by internal tasks(Cooper et al., 2003, 2006; Shimojo et al., 1997). This increasedalpha activity is considered to reflect the inhibition of the non-taskrelevant process. OCD patients have difficulty in initiating a strategy(Deckersbach et al., 2005), so it is necessary to inhibit other ongoingcognitive activities in the initiation of verbal working memory(Savage et al., 2001). Our results of less ERD in the OCD patientsimply that there is a relative increase in alpha power in OCD becauseOCD patients make an excessive effort to inhibit intrusive thoughts orother task-irrelevant processing in the initiation of the memoryprocess.

In addition, recent series of studies proposed that low alpha am-plitudes may indicate externally oriented brain states, whereas highalpha amplitudes may indicate internally oriented brain states. In ex-ternally oriented status the brain system processes information fromthe external sensory channels. On other hand, brain states are towardinternal presentation in internally oriented status, which makes it dif-ficult to perceive stimuli from the external world. (for review seeHanslmayr et al., 2011). Intrusive thoughts or other task-irrelevantprocessing clinically associated with symptoms of OCD would inter-fere with the encoding of externally present stimuli (Olley et al.,2007). In this perspective, the recent result that the alpha ERD ofOCD was less than controls, which means higher alpha amplitude,might reflect more internally orientated brain state in OCD.

S1 S2

CTR

OCD

Fig. 4. Topography in each encoding period. Topography is at 10 Hz when 6000 ms (S1), 2000

Neurobiological models for OCD suggest dysfunction of fronto-striato-thalamo-cortical circuits (Kwon et al., 2009; Rosenberg et al.,2001). Moreover, many neuroimaging studies have implied abnor-malities of thalamocortical activation (Kwon et al., 2009; Lacerda etal., 2003). In addition, a recent study reported that decoupling be-tween slow and fast EEG rhythms in OCD might reflect a dysfunctionof subcortical-cortical interaction (Velikova et al., 2010).The thalamo-cortical loop plays a crucial role in generating alpha oscillations, whichare generated from thalamic regular bursting transferred to the cor-tex. This alpha bursting reflects the level of neuronal depolarization,which in turn reflects the imbalance between excitatory and inhibito-ry postsynaptic potentials arriving at the thalamocortical cells. If exci-tation is strong enough, the thalamocortical neurons are depolarizedand do not generate bursts (Kropotov, 2008). As a result, alpha ERDcan occur. In a series of this process, interaction between thalamocor-tical neurons and inhibitory GABAergic neurons located in the reticu-lar nucleus in the thalamus plays a crucial role. The inhibition andexcitation of thalamocortical neurons are regulated by a feedbackloop with the reticular nucleus. Activation and suppression of the cor-tical area follow, and cortical activity is performed efficiently. OCD pa-tients seem to have abnormal thalamocortical activity (Kwon et al.,2009; Lacerda et al., 2003; Velikova et al., 2010), possibly leading toabnormalities in the feedback loop in OCD. Therefore, lower corticalactivation occurs in OCD, which might reflect less alpha ERD.

On the other hand, the OCD patients in our study were takingSSRIs and/or low dose benzodiazepines. The medication effects can-not be excluded, and it was reported that benzodiazepines may affectalpha oscillatory activity (Buchsbaum et al., 1985). This could be alimitation of the present study. However, in a separate analysis, wedid not find any correlations of alpha ERD and phase locking withdosage of SSRIs and any differences between OCD patients who tookbenzodiazepine and those who did not (data not shown).

4.1.2. Enhanced alpha ERD with memory loadIn our study, there were no significant interactions between

“group” and “memory load,” but alpha ERD increased with memoryload. This result is consistent with previous studies in which as cogni-tive load increased, alpha modulation also increased in normal sub-jects (Gevins and Smith, 2000; Neuper and Pfurtscheller, 2001;Pfurtscheller and Klimesch, 1992). It was initially expected that thedifference in alpha ERD would be larger at the end of the encodingphase because a higher cognitive load produces less ERD in OCD pa-tients than in control subjects (Ciesielski et al., 2007). However, wecould not find any significant interaction between memory load andgroups. This result might be because the level of difficulty of ourtask was sensitive enough to produce different alpha modulations be-tween the OCD patients and the controls in not only later stimuli butalso initial stimuli. However, further studies need to be done to iden-tify the exact reason.

[dB]

S3 S4

ms (S2), 3400 ms (S3), and 4800 ms (S4) after the first onset of the encoding stimulus.

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6 J.Y. Park et al. / International Journal of Psychophysiology 83 (2012) 1–7

4.1.3. Reduced alpha modulation of OCD in frontal and occipital areasVisual inspection yielded information for selecting two areas: the

frontal area (Fz) and the occipital area (O1 and O2) (Fig. 4). Alphadesynchronization is a local phenomenon that occurs over task rele-vant areas in contrast to task irrelevant regions that show pro-nounced synchronization. Moreover, during visual encoding, alphadesynchonization occurred in the occipital area (Pfurtscheller andKlimesch, 1990). The frontal area is well known as essential in theworking memory process, and alpha oscillations in this area reflectshort term memory (Jensen et al., 2002). Alpha suppression was ob-served in the frontal area during a semantic memory task (Klimeschet al., 1997b, 1999). Therefore, it may have been a convincing resultthat alpha desynchronization was observed in the frontal and occipi-tal areas in our study.

4.2. Increased phase locking in OCD

In our study, alpha phase locking increased in the areas where ERDincreases were observed. In previous studies, it was reported that inthe response to stimuli, the alpha power decreased and phase lockedalpha activity increased (Herrmann and Knight, 2001; Klimesch et al.,2000), which was also observed in our study. In addition, the alphaphase locking index also increased with memory load in our study.This result is in line with a previous study in which alpha phase lock-ing increased with short-term memory load in both schizophrenicsand normal subjects (Haenschel et al., 2010).

A particularly interesting finding in our study is that alpha oscilla-tions were more phase locked in the OCD patients than in the controlsubjects. Although the meaning of the alpha phase locking is stillunclear, there is a possiblity that increased phase locking is linkedwith excessive attentional processing in OCD patients. Over focusedattention is a crucial pathology in OCD (Mavrogiorgou et al., 2002;Towey et al., 1993), and evidence suggested that alpha phase lockingis related to attention (Klimesch et al., 2007b; Palva and Palva, 2007).Our results may imply that alpha phase locking reflects excessive at-tention to a given task in OCD patients. However, to clarify whetheralpha phase locking really excessive attention, more detailed andwell designed studies are necessary.

4.3. Behavioral performance

Although OCD patients have spatial memory deficits, their verbalmemory is preserved (Olley et al., 2007). Accordingly, there was nodifference in behavioral performance in the verbal working memorytask between the OCD patients and the controls in our study.

5. Conclusion

Less alpha ERD and stronger alpha phase locking in the OCD pa-tients than in the control subjects were observed during the encodingphase. This finding implies that the excitatory/inhibitory process isabnormal in the OCD patients, and a compensational process seemsto occur in order to maintain behavioral performance. Clinical OCDpatients have difficulty in inhibiting obsessive or compulsive symp-toms, and alpha oscillations are thought to reflect such inhibition. Itis intersting that the problem of the allocation of inhibitional sourcesin OCD reflects alpha oscillations. Although the clinical utility of EEGremains limited, our result shows the possibility that the EEG methodshould be considered to illuminate the pathology of OCD.

Acknowledgements

The authors thank Byoung-Kyung Min for his valuable support. Thiswork was supported by grants from the National Research Foundationof Korea (NRF) funded by the Ministry of Education, Science andTechnology (2010–0022363).

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