ARTICLE IN PRESS

wwwelseviercomlocateijpsycho

DTD 5

International Journal of Psychoph

Brain oscillatory responses to an auditory-verbal working memory task

in mild cognitive impairment and Alzheimerrsquos disease

Mira Karrasch ab Matti Laine ab Juha O Rinne c Pekka Rapinoja d

Eija Sinerva b Christina M Krause d

aDepartment of Psychology Abo Akademi University FIN-20500 Abo FinlandbCentre for Cognitive Neuroscience University of Turku Finland

cNational PET-centre University of Turku FinlanddCognitive Science Department of Psychology University of Helsinki Finland

Received 9 December 2004 received in revised form 4 April 2005 accepted 26 April 2005

Abstract

We report preliminary findings on EEG oscillatory correlates of working memory in mild cognitive impairment (MCI) and Alzheimerrsquos

disease (AD) Event-related desynchronization (ERD) and synchronization (ERS) of the 1ndash20 Hz EEG frequencies were studied using

wavelet transforms in elderly controls MCI patients and mild probable AD patients performing an auditory-verbal Sternberg memory task

Behaviourally the AD patients made more errors than the controls and the MCI group Statistically significant differences during the

encoding of the memory set were found between the controls and the MCI group such that the latter group showed ERD in the uml10ndash20 Hz

frequencies The findings may reflect different compensatory encoding strategies in MCI During retrieval the most obvious differences

were observed between the controls and the AD group the ERD in the uml7ndash17 Hz frequencies was absent in the AD group particularly in

anterior and left temporal electrode locations This finding might indicate that AD is associated with deficient lexical-semantic processing

during the retrieval phase in working memory tasks Future studies with larger patient groups are needed to establish the diagnostic value of

ERDERS patterns in MCI and AD

D 2005 Elsevier BV All rights reserved

Keywords Event-related desynchronization Event-related synchronization Mild cognitive impairment Alzheimerrsquos disease Memory 1ndash20 Hz EEG

1 Introduction

The aging individual faces an increased risk of develop-

ing neurological diseases leading to dementia The most

common form Alzheimerrsquos disease (AD) accounts for over

half of dementia cases Given the recent developments in

drug treatment of early AD it has become increasingly

important to identify these individuals as early as possible

Limited cognitive deterioration coined as mild cognitive

impairment (MCI) has been considered as a risk zone for

0167-8760$ - see front matter D 2005 Elsevier BV All rights reserved

doi101016jijpsycho200504006

Corresponding author Department of Psychology Abo Akademi

University FIN-20500 Abo Finland Tel +358 2 2154405 fax +358 2

2154833

E-mail address mirakarraschabofi (M Karrasch)

incipient AD (Petersen et al 2001) In the present study we

sought for neurophysiological correlates of MCI and early

AD by studying the patterns of EEG oscillatory responses

during a working memory task performance

In most EEG studies on AD quantitative evaluation of

fixed periods of spontaneous EEG has been used This

method discards the temporal sequences of task-related EEG

changes Another widely used method is the temporal

summation of EEG responses over a number of frequency

bands (event-related potentials ERPs) but in this method

the functional significance of the responses in different

frequency bands is lost

It has been proposed that EEG oscillatory responses of

different frequency bands of the human EEG reflect

different aspects of information processing and that the

ysiology xx (2005) xxx ndash xxx

INTPSY-09494 No of Pages 11

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx2

oscillatory changes are basic phenomena in the EEG (Basar

et al 2001ab Karakas et al 2000) One way to assess

event-related oscillatory EEG responses is the event-related

desynchronization-method (ERD) A relative decrease in the

power of any given frequency band during either external or

internal stimulus processing is called event-related desynch-

ronization (ERD) while a relative increase in the power is

called synchronization (Pfurtscheller and Lopes da Silva

1999) The ERDERS phenomenon is quantified by

comparing two different conditions often a resting state

and the presentation of a stimulus and expressed as a

percentage power decrease or increase The time-resolution

of this method is good and it is thus suitable for studying

cognitive processes that are dynamic and evolve over time

Different frequencies in the EEG have been found to

stem from different areas in the brain The hippocampal

theta rhythm in rodents has been extensively studied It

has been found to be related to long-term potentiation and

learning (Kahana et al 2001) Theta activity has

however also been recorded from the neocortex by using

intracranial EEG in humans and primates (Caplan et al

2000 Kahana et al 1999 Lee et al 2005 Raghavachari

et al 2001) Even though the neurophysiological mech-

anisms and generators of the theta rhythm are still debated

the evidence for its role in information processing is

mounting Event-related changes in the scalp-recorded

human theta activity (uml4ndash6 Hz) have been found to

reflect brain processes associated with both attention

(Kahana et al 2001) working memory (Bastiaansen et

al 2002a Jensen and Tesche 2002) and episodic memory

(Barbeau et al in press Bastiaansen et al 2002b

Klimesch et al 1997a 2001)

Alpha activity (uml7ndash13 Hz) has been suggested to be

generated in thalamo-cortical networks The lower alpha

components reflect alertness and attention and the upper

alpha is modulated mainly by stimulus-related aspects and

semantic memory processes (Jensen et al 2002 Klimesch

1999 Klimesch et al 1997a) Utilizing cognitive tasks with

auditory stimuli (words instrument sounds) Karrasch et al

(1998 2004) and Krause et al (1999 1996 2001) have

repeatedly demonstrated that memory encoding typically

elicits alpha frequency ERS in the EEG whereas retrieval

and stimulus comparison elicits alpha ERD

EEG beta activity has been extensively studied in relation

to motor processing (Pfurtscheller and Klimesch 1991)

Imagining planning and execution of movement has

repeatedly been found to elicit ERD and ERS in the

uml14ndash35 Hz frequency range over the sensorimotor areas

(Neuper and Pfurtscheller 2001) Recent findings have

however indicated that beta oscillations also might play a

role in working memory processing and attention (Vazquez

Marrufo et al 2001) Short memory retention intervals has

been reported to elicit synchronization in the uml13ndash20 Hz

frequencies (1ndash2 s) whereas retention of material during

longer delays (10 s) elicits desynchronization (Peterson and

Thaut 2002 Tallon-Baudry et al 1999) Lowered ampli-

tudes in the 20ndash245 Hz frequency and desynchronization

in the 10ndash20 Hz frequency range have also been reported

during recognition and working memory performance

(Duzel et al 2003 Karrasch et al 2004)

The effects of normal aging on oscillatory responses

during auditory working memory performance have been

reported in a recent study (Karrasch et al 2004) In that

study it was observed that encoding elicited ERS in the

uml1ndash8 Hz frequency ranges irrespective of age However in

the elderly subjects the ERS in the uml10 Hz frequency was

greater than in the young subjects and the ERS in the uml4ndash6

Hz frequency was attenuated During retrieval ERS in the

uml1ndash5 Hz frequency bands as well as ERD in the uml8ndash20

Hz frequencies were observed in all subjects but these

responses were weaker in the elderly subjects The results

indicated that the working memory-related oscillatory

processes especially during retrieval are somewhat modu-

lated by aging even though no age-related effects were

observed at the behavioural level

AD patients are known to present with lsquolsquoslowingrsquorsquo of the

EEG (Besthorn et al 1997) The peak frequency in the

extended alpha range has been reported to be uml1 Hz lower

in mild AD when compared to age-matched controls

(Lehtovirta et al 1996) In moderate AD the peak

frequency in the power spectrum has been found to be

below 6 Hz (Signorino et al 1995) Generally it has been

thought that the earliest AD-related changes in the EEG

include an increase in theta activity and decrease in beta

activity which is later on followed by a decrease in alpha

activity (Bennys et al 2001 Claus et al 1998 Coben et

al 1983 Jeong 2004 Kowalski et al 2001) An increase

in relative theta power has been found to predict which MCI

patients will progress to AD (Jelic et al 2000) The

functional reactivity of EEG oscillations in MCI and AD

has however mostly been studied in relation to eye opening

(Claus et al 1999) tone stimulation (Muller et al 1991)

and movement (Babiloni et al 2000)

11 The aim of the study

The aim of the present preliminary study was to explore

the event-related desynchronization and synchronization

patterns in the 1ndash20 Hz frequency bands during the

encoding and retrieval phase of an auditory-verbal working

memory task in mild cognitive impairment and Alzheimerrsquos

disease A similar auditory working memory paradigm have

repeatedly demonstrated that encoding elicits ERS and

retrieval ERD in the 8ndash12 Hz alpha frequency band in

young subjects (Krause 2002 Krause et al 1996 2001)

Moreover encoding and even more so retrieval has typically

elicited ERS in the 4ndash6 Hz theta band A recent study

indicated that normal aging is associated with weakened

ERD in the 8ndash20 Hz frequencies and ERS in the 1ndash5 Hz

frequencies during retrieval (Karrasch et al 2004) As

memory disturbances play a key role in AD (and MCI) it is

of interest to explore the ERDERS responses in the 1ndash20

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx 3

Hz frequency bands during memory encoding and retrieval

in these patient groups with a task paradigm that is well

established in normal subjects To our knowledge this is the

first report on EEG ERDERS patterns during auditory

memory processes in MCI and AD

2 Materials and methods

21 Subjects

Ten healthy elderly (2 males 8 females) subjects

volunteered as controls for the study They were recruited

from various community sources None of the controls

reported any neurological or psychiatric disease prior

head trauma sensory impairment or subjective cognitive

impairment These subjects also served as the elderly

subjects in a recent study on ERDERS in aging

(Karrasch et al 2004) Ten patients suffering from mild

probable Alzheimerrsquos disease according to the NINCDS-

ADRDA criteria (McKhann et al 1984) were referred to

the study by a neurologist Three of the AD patients

were excluded from the final analysis because of

excessive motor artefacts in the EEG The final number

of AD patients was thus 7 (3 males 4 females) Nine

patients suffering from amnestic MCI (Petersen et al

2001) were referred to the study by a neurologist The

specific criteria for MCI were (1) subjective memory

complaint (2) objective memory impairment for age (test

performance 15 SD or more below age and education-

corrected norms on two or more tests of episodic

memory) (3) preserved general cognitive function (4)

intact activities of daily living and (5) no dementia There

were no other neurological or psychiatric diseases

explaining the memory impairment in the MCI patients

Two MCI patients were excluded from the study because

Table 1

Means standard deviations and ranges in age years of education MMSE and selec

Mean (SD range)

Controls MCI

Age 65 (39 58ndash71) 69 (93

Education in years 108 (39 6ndash19) 77 (21

MMSE score 274 (14 25ndash29) 264 (25

WAIS-R

Digit span forward 59 (11 4ndash8) 53 (13

Digit span backward 45 (07 3ndash5) 36 (05

WMS-R

Logical memory 249 (50 17ndash33) 221 (73

Logical memory delayed 227 (55 13ndash31) 178 (74

Logical memory savings 904 (69 76ndash100) 785 (98

Verbal paired associates 149 (37 10ndash21) 144 (39

Verbal paired associates delayed 63 (14 4ndash8) 60 (08

Verbal paired associates savings 1054 (253 66ndash160) 1074 (263

Pair-wise differences between-groups were analysed with the Tukey post hoc tes

of excessive motor artefacts on the EEG The final

number of MCI patients was 7 (3 males 4 females) The

MCI and AD patients were consecutive outpatients to a

clinic Informed consent was obtained from all subjects

and the joined ethics committee of the University of

Turku and the Turku University Central Hospital ap-

proved the study

Both controls and all patients underwent a thorough

neuropsychological assessment to measure their level of

cognitive functioning Tests used in the assessment of non-

memory cognitive functions were parts of the WAIS-R

(Wechsler 1992) the Boston Naming Test (Laine et al

1997) and the Trail Making Test A+B Episodic memory

functions were assessed by the complete WMS-R (Wechs-

ler 1996) and the Benton Visual Retention Test Partic-

ularly the logical memory subtest of the WMS-R has in

previous studies been found to be sensitive to early and mild

AD (Collie and Maruff 2000 Elias et al 2000) In the

WMS-R savings scores were calculated for logical memory

verbal paired associates visual paired associates and visual

reproduction Savings scores are delayed recall scores

adjusted for initial acquisition ( of retained material) and

have been found to be sensitive to early dementia (Elias et

al 2000 Welsh et al 1991) All subjects were right-handed

native speakers of Finnish Means standard deviations and

ranges for age MMSE scores years of education and

selected neuropsychological background data for the three

groups are shown in Table 1 Only results from tests

measuring auditory-verbal working memory and verbal

episodic memory are reported since these tests are most

relevant to the current study It should be noted that despite

the inclusion criteria for the MCI patients at the group level

the performance of MCI patients did not differ from that of

the controls in most of the WMS-R verbal memory tests

This was due to the fact that memory tests showing

impairment varied between MCI patients

ted WMS-R scores in controls (n =10) MCI (n =7) and AD patients (n =7)

Pair-wise group contrasts p lt01

AD

50ndash78) 737 (52 66ndash80) ns

6ndash12) 81 (28 6ndash14) ns

22ndash30) 227 (26 18ndash26) CgtAD

4ndash7) 53 (05 5ndash6) ns

3ndash4) 37 (09 3ndash5) ns

12ndash33) 111 (50 5ndash18) CgtAD

9ndash28) 53 (66 0ndash13) CgtAD

63ndash93) 353 (449 0ndash100) CgtMCI CgtAD

9ndash19) 69 (62 0ndash17) CgtAD

5ndash7) 27 (28 0ndash7) CgtAD

71ndash150) 607 (537 0ndash150) ns

t

ARTICLE IN PRESS

1 In the registrations of 2 MCI patients and 2 AD patients the Synamps

5083 amplifier was used The sampling rate was 250 Hz The EEG data for

these subjects were downsampled to 200 Hz in the Matlab environment

M Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx4

22 Experimental procedure

The experimental task was a modified version of

Sternbergrsquos memory search paradigm (Karrasch et al

2004 Sternberg 1966) Each trial consisted of four auditory

stimuli (memory set) and a fifth auditory stimulus (probe)

The subjectrsquos task was to decide whether the probe was

present in the memory set or not and give hisher answer by

pressing a response-pad The auditory stimuli consisted of

eight Finnish nouns in base form (nominative singular) The

stimuli were read by a female voice and recorded with an

Audio-Technica AT801 microphone and digitized using the

NeuroScan 386 Stim software A total of 64 four-word

memory sets were constructed Each of the memory sets

were randomly drawn from the eight words with the

restriction that each word had to occur with equal frequency

and only once in the same memory set The order of the

presentation of the memory sets was randomized for each

subject The length of the stimulus-window for each word

was 800 ms and the average duration of one word was 520

ms The total length of a four word memory set with inter

stimulus intervals of 1000 ms was 6200 ms Three seconds

after the presentation of the memory set the probe was

presented to the subject In 50 of the cases the probe had

been presented among the four-word memory set

Each trial began with an inter-trial-interval (ITI) of 3500

ms The 2000ndash3500 ms time window within each ITI was

used as an intra-experimental reference Thereafter a red

warning signal was presented on the TV screen for 200 ms

as a signal for the subject that the memory set was to be

presented The four-word memory set was presented 3000

ms after the warning signal The probe was presented 3000

ms after the last word of the memory set The subject then

had to decide whether the probe word had appeared in the

memory set In order to avoid any muscle artefacts a green

signal was presented at the TV screen 3000 ms after the

probe indicating that the subject should answer by pressing

either lsquolsquoyesrsquorsquo or lsquolsquonorsquorsquo on a response pad (delayed response)

The subjects perceived a minimum of 64 trials and the total

registration time was about 1 h

Total response accuracy ( correct) was calculated for

each subject for the whole experiment In order to examine

possible problems with sustaining attention throughout the

experiment response accuracy was also calculated sepa-

rately for the first and second half of the experiment for each

subject The difference in response accuracy between the

first and second half of the experiment (sustained response

accuracy correct 1st halfndash correct 2nd half) will be

reported and analyzed

23 Recording

Prior to the EEG recording the MCI and AD subjects

had trial runs on the experimental task in order to ensure that

they had understood the procedure All subjects were also

shown their real time ongoing EEG on the computer screen

to demonstrate how to avoid motor artefacts EEG was

recorded from 20 AgAgCl-electrodes according to the

international 1020 system of electrode placement Two

EOG-electrodes were placed on the outer sides of the eyes

and all electrodes were referred to linked mastoids which

also served as ground electrodes The data sampling rate

was 200 Hz Raw EEG was recorded using the Neuroscan

386 Scan 30 data acquisition system with a Braintronics

CNVISO-10321 amplifier with a frequency band of 03ndash70

Hz The impedance was always below 5 kV

24 Data processing

The digital EEG data was processed in a MATLAB 61

environment (Math Works Inc 1999) The processing was

conducted using modifications of the 4-D Toolbox (Jensen

2002) The analyses resulted in time-frequency representa-

tions (TFRs) which display the power of a continuous EEG

signal as a function of both time and frequency in the same

matrix The EEG data file was epoched using a 1500 ms time

window (100 ms before and 1400 ms after stimulus onset)

The reference was epoched with a 1500 ms time window

encompassing the 2000ndash3500 ms time period of the ITI

Artefact rejection was set to T100 AV To display the

frequency content of the EEG data segments TFRs for each

subject were calculated using Morlet wavelets (width 8) for

the intra-experimental reference period and the stimulation

conditions for each EEG channel separately The TFRs for

the reference and the task conditions were averaged for each

subject separately The TFRs for the four stimuli in the

memory sets were averaged resulting in one TFR for the

memory sets (encoding) and one for the probe (retrieval) Bad

channels were excluded from further analysis by means of

visual inspections of the TFRs displaying the absolute power

values Fp1 Fp2 F7 and F8 electrodes were excluded from

the analysis since these channels had artefacts in many

subjects The relative difference in the power between the

reference interval (rest) and the two task conditions (encoding

and retrieval) was calculated as a function of time and

frequency and was expressed as percentage in ERDERS

TFRs in which negative values indicate a relative power

decrease (ERD) and positive values indicate a relative power

increase (ERS) These ERDERS TFRs were thereafter

averaged within the three groups (controls MCI and AD)

The grand average ERDERS matrices were displayed as

ERDERS TFRs for 5 electrode locations (frontal F3 Fz F4

left temporal T3 C3 T5 right temporal T4 T6 C4 central Cz

P3 Pz P4 occipital O1 Oz O2) and the ERDERS values

were displayed as a function of time (100ndash1400 ms) and

frequency (1ndash20 Hz)

The 0ndash2560 ms time window of the ITI (no stimulation

condition) was used for the calculation of individual power

ARTICLE IN PRESS

Table 2

Means standard deviations and ranges in total response accuracy sustained response accuracy and EEG alpha peak frequency (IAF) in the controls MCI and

AD patients

Controls (n =10) MCI (n =7) AD (n =7) p lt01

Total response accuracy ( correct) 941 (18 91ndash97) 875 (87 74ndash95) 764 (146 53ndash92) CgtAD

Sustained response accuracy ( correct 1st halfndash correct 2nd half) 36 (34 8 to 2) 53 (77 18 to 3) 64 (46 14 to 0) ns

EEG IAF 99 (12 8ndash12)a 98 (17 8ndash12) 87 (13 8ndash11) ns

a n =9

M Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx 5

spectra The raw EEG epochs of all artefact-free trials of

the reference interval were averaged for each channel

Individual power spectra for each channel were calculated

in the MATLAB environment using the fast Fourier

transform ranging from 1 Hz to 45 Hz The power spectra

of all channels were averaged into one grand average

power spectrum (collapsed spectrum) Individual peak

frequency within the extended alpha range (IAF) was

defined as the frequency with a power peak within the 7ndash

13 Hz range

3 Statistical analyses

The statistical significance of any differences between

the three groups (controls MCI AD) in total response

accuracy ( correct) sustained response accuracy (

correct 1st halfndash correct 2nd half) and EEG IAF was

analysed using one-way ANOVA Pair-wise comparisons

were analysed with the Tukey post hoc test

Non-parametric analyses were conducted for the ERD

ERS responses Within-subjects effects were analysed using

the Quade test (Quade 1979) which compensates for

dependencies between preceding and following points in the

time-frequency space within one channel The significance

of any differences in the ERDERS values between the

groups were analysed using the MannndashWhitney U-test for

independent samples The results of the statistical analyses

were displayed in probability matrices In order to minimize

the type 1 error risk when conducting multiple statistical

comparisons we report and discuss only those results in the

between-groups probability matrices where the temporal

duration of the statistically significant difference exceeds

100 ms

4 Results

41 Behavioural results

There was a statistically significant difference between

the groups in total response accuracy ( correct)

(F(221)=7654 p lt003) Pair-wise differences were stat-

istically significant only between the control group and the

AD group as the AD group made more errors ( p =002)

No statistically significant difference between the three

groups was observed in sustained response accuracy

(F(221)= 609 p lt553) Means standard deviations and

ranges for the response accuracy are shown in Table 2

42 Individual peak frequency in the extended alpha range

(IAF)

All subjects with the exception of one control subject

exhibited a peak within the extended alpha range (7ndash13 Hz)

during the reference interval (no stimulation condition) The

difference in IAF between the groups failed to reach

statistical significance (F(220)=1726 p lt203) Means

standard deviations and ranges in the reference interval EEG

IAFs are shown in Table 2

43 Within-subjects ERDERS effects

The significant points in the probability matrices in the

beginning of the time window (100ndash50 ms) were

technical edge-effects caused by the wavelet-transform and

will therefore not be reported or discussed

431 Controls

A statistically significant synchronization into the uml3ndash6

Hz frequency range was observed in the control group

during encoding at frontal central and right temporal

electrode sites in the uml0ndash500 ms time window In occipital

electrodes a statistically significant ERS in the uml12ndash14 Hz

frequencies was also observed in the uml300ndash1300 ms time

window Also in central electrodes a significant synchro-

nization in the uml13ndash16 Hz frequency range was elicited in

the uml300ndash500 ms time window The presentation of the

probe (retrieval) elicited a statistically significant ERS in the

uml3ndash5 Hz frequency range and ERD in the uml6ndash20 Hz

frequency ranges (Fig 1)

432 MCI

During encoding only few statistically significant

responses in the uml2ndash5 Hz frequency bands were observed

in the MCI group in central and occipital electrodes The

presentation of the probe (retrieval) elicited statistically

significant ERS in the uml2ndash5 Hz frequency bands and ERD

in the uml10ndash15 Hz frequency bands (Fig 1)

433 AD

During the presentation of the memory set (encoding) a

uml1ndash4 Hz synchronization was observed in frontal electrodes

in the uml100ndash1300 ms time window The presentation of the

ARTICLE IN PRESS

Fig 1 Grand average ERDERS and within-groups probability TFRs of the three groups (controls MCI and AD) during the presentation of (A) the memory

set (encoding) and (B) the probe (retrieval) Red colours denote ERS and blue colours denote ERD The x-axis depicts time (100 to 1400 ms) and the y-axis

depicts frequency (1ndash20 Hz) The probability matrix below each grand average ERDERS matrix shows the significance of within-groups ERDERS ( p lt05)

M Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx6

probe (retrieval) elicited a short-lasting statistically signifi-

cant ERS in theuml3ndash5 Hz frequencies in the beginning of the

time window in frontal and central electrodes ERD in the

uml8ndash12 Hz frequencies was also observed one second after

onset of the probe in frontal electrodes (Fig 1)

44 Between-subjects ERDERS effects

441 Memory set encoding

Statistically significant differences between the groups

were observed during encoding of the memory set

ARTICLE IN PRESS

Fig 2 Grand average ERDERS and between-groups probability TFRs of the three groups (controls MCI and AD) during the presentation of (A) the memory

set (encoding) and (B) the probe (retrieval) Red colours denote ERS and blue colours denote ERD The x-axis depicts time (100 to 1400 ms) and the y-axis

depicts frequency (1ndash20 Hz) The probability matrices show the significance of differences between the ERDERS responses of the three groups ( p lt05)

M Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx 7

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx8

particularly at frontal central and occipital electrode sites

The largest differences were found between the controls and

the MCI group The differences were due to the fact that the

responses in the uml10ndash20 Hz frequency ranges were

characterized by ERS in the control group and ERD in the

MCI group Statistically significant differences between the

aforementioned groups were also observed in occipital

electrodes in the uml5 Hz frequency The responses of the

MCI group also differed significantly from that of the AD

group in the uml5ndash7 Hz frequency band in central and

occipital electrodes This difference was due to the fact that

synchronization was observed in the AD group whereas

desynchronization was observed in the MCI group (Fig 2)

442 Probe retrieval

During retrieval the largest differences were observed

between the controls and the AD group These differences

were due to the fact that ERD in the uml7ndash17 Hz frequency

bands was absent in the AD group particularly in frontal and

left temporal electrode locations The ERDERS responses

of the MCI group were only minimally different from that of

the controls whereas some statistically significant differ-

ences between the MCI and AD groups were found in the

uml4ndash5 Hz and uml12ndash14 Hz frequencies in frontal central

and occipital electrodes (Fig 2) These differences were due

to fact that synchronization was elicited in the uml4ndash5 Hz

frequency range in the MCI group but not in the AD group

In the uml12ndash14 Hz frequency band ERD was observed in

the MCI group but not in the AD group

5 Discussion

The aim of this study was to explore event-related

desynchronization (ERD) and synchronization (ERS) in the

1ndash20 Hz frequency bands during the encoding and retrieval

phase of an auditory-verbal working memory task in

patients suffering from mild cognitive impairment and

Alzheimerrsquos disease At the behavioural level there were

statistically significant differences between the control

group and the AD group in response accuracy in the task

The control group and the MCI group succeeded with few

erroneous answers whereas the AD group made more

errors This finding is in line with behavioural studies where

the maintenance and rehearsal system of working memory

(the articulatory loop) as well as verbal learning has been

found to be affected in AD (Backman et al 2001 Borgo et

al 2003 Collette et al 1999) Our results are also in line

with previous studies indicating that while MCI patients

are impaired in tests measuring learning and consolidation

of episodic memory traces they do not have overt problems

in maintaining a limited memory set in mind for short time

periods (Backman et al 2001 Elias et al 2000) No

statistically significant differences were observed between

the three groups in sustained response accuracy This

indicates that the subjects were able to maintain attention

during the task even though the experiment lasted for up to

1 h

As we have recently reported (Karrasch et al 2004)

statistically significant EEG synchronization in the uml3ndash6

Hz and uml12ndash14 Hz frequency bands was observed during

encoding in the elderly control group These results are in

line with previous studies where theta and alpha synchro-

nization has been found during successful encoding of items

into short-term memory (Klimesch et al 1996 Krause et

al 1996) Statistically significant differences during encod-

ing of the memory set were observed mostly between the

controls and the MCI group in the uml10ndash20 Hz frequency

ranges The responses in the uml10ndash20 Hz frequencies were

characterized by ERS in the control group and ERD in the

MCI group even though these responses showed within-

group significance only in the controls in the occipital

electrodes It has been suggested that in the auditory

modality task demands modulate alpha ERDERS

responses such that phonological maintenance in relatively

easy tasks elicits ERS particularly in upper alpha frequen-

cies while higher-level andor semantic processing in more

demanding tasks elicits ERD (Krause et al 1996 Peterson

and Thaut 2002) One possible explanation for the results

would thus be that the MCI patients were compensating for

their memory problems by allocating higher-level cognitive

strategies to the task The differences between the control

group and the MCI group also spanned over frequencies

normally referred to as beta activity Beta responses have

been linked to motor processing and imagery (Neuper and

Pfurtscheller 1999) but recent studies have found that

increased task demands result in attenuated beta power

(Duzel et al 2003 Peterson and Thaut 2002) supporting

the hypothesis of compensatory higher-level processing in

the MCI patients

It is noteworthy and surprising that the differences during

encoding between the control group and the AD group were

minimal and that the responses of the MCI and AD group

differed in the uml5ndash7 Hz frequency band The responses in

the MCI group were characterized by ERD while ERS was

observed in the controls and AD patients It is possible that

differences between the controls and the AD patients might

exist in the temporal dimension but the wavelet width used

in the current study does not allow for good temporal

resolution in the low frequency bands Moreover the

synchronization in the uml5ndash7 Hz band might reflect

activation of different neuronal networks in the controls

and the AD patients (theta vs low alpha)

As we have recently reported (Karrasch et al 2004) the

presentation of the probe (retrieval) elicited a statistically

significant ERS in the uml3ndash5 Hz frequencies and ERD in

the uml7ndash20 Hz frequencies in the elderly controls Similar

but somewhat attenuated patterns were observed in the MCI

patients During retrieval the most prominent group differ-

ences were observed between the controls and the AD group

in the uml7ndash17 Hz frequencies in frontal central and left

temporal electrodes Some statistically significant differ-

ARTICLE IN PRESS

Fig 2 Grand average ERDERS and between-groups probability TFRs of the three groups (controls MCI and AD) during the presentation of (A) the memory

set (encoding) and (B) the probe (retrieval) Red colours denote ERS and blue colours denote ERD The x-axis depicts time (100 to 1400 ms) and the y-axis

depicts frequency (1ndash20 Hz) The probability matrices show the significance of differences between the ERDERS responses of the three groups ( p lt05)

M Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx 7

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx8

particularly at frontal central and occipital electrode sites

The largest differences were found between the controls and

the MCI group The differences were due to the fact that the

responses in the uml10ndash20 Hz frequency ranges were

characterized by ERS in the control group and ERD in the

MCI group Statistically significant differences between the

aforementioned groups were also observed in occipital

electrodes in the uml5 Hz frequency The responses of the

MCI group also differed significantly from that of the AD

group in the uml5ndash7 Hz frequency band in central and

occipital electrodes This difference was due to the fact that

synchronization was observed in the AD group whereas

desynchronization was observed in the MCI group (Fig 2)

442 Probe retrieval

During retrieval the largest differences were observed

between the controls and the AD group These differences

were due to the fact that ERD in the uml7ndash17 Hz frequency

bands was absent in the AD group particularly in frontal and

left temporal electrode locations The ERDERS responses

of the MCI group were only minimally different from that of

the controls whereas some statistically significant differ-

ences between the MCI and AD groups were found in the

uml4ndash5 Hz and uml12ndash14 Hz frequencies in frontal central

and occipital electrodes (Fig 2) These differences were due

to fact that synchronization was elicited in the uml4ndash5 Hz

frequency range in the MCI group but not in the AD group

In the uml12ndash14 Hz frequency band ERD was observed in

the MCI group but not in the AD group

5 Discussion

The aim of this study was to explore event-related

desynchronization (ERD) and synchronization (ERS) in the

1ndash20 Hz frequency bands during the encoding and retrieval

phase of an auditory-verbal working memory task in

patients suffering from mild cognitive impairment and

Alzheimerrsquos disease At the behavioural level there were

statistically significant differences between the control

group and the AD group in response accuracy in the task

The control group and the MCI group succeeded with few

erroneous answers whereas the AD group made more

errors This finding is in line with behavioural studies where

the maintenance and rehearsal system of working memory

(the articulatory loop) as well as verbal learning has been

found to be affected in AD (Backman et al 2001 Borgo et

al 2003 Collette et al 1999) Our results are also in line

with previous studies indicating that while MCI patients

are impaired in tests measuring learning and consolidation

of episodic memory traces they do not have overt problems

in maintaining a limited memory set in mind for short time

periods (Backman et al 2001 Elias et al 2000) No

statistically significant differences were observed between

the three groups in sustained response accuracy This

indicates that the subjects were able to maintain attention

during the task even though the experiment lasted for up to

1 h

As we have recently reported (Karrasch et al 2004)

statistically significant EEG synchronization in the uml3ndash6

Hz and uml12ndash14 Hz frequency bands was observed during

encoding in the elderly control group These results are in

line with previous studies where theta and alpha synchro-

nization has been found during successful encoding of items

into short-term memory (Klimesch et al 1996 Krause et

al 1996) Statistically significant differences during encod-

ing of the memory set were observed mostly between the

controls and the MCI group in the uml10ndash20 Hz frequency

ranges The responses in the uml10ndash20 Hz frequencies were

characterized by ERS in the control group and ERD in the

MCI group even though these responses showed within-

group significance only in the controls in the occipital

electrodes It has been suggested that in the auditory

modality task demands modulate alpha ERDERS

responses such that phonological maintenance in relatively

easy tasks elicits ERS particularly in upper alpha frequen-

cies while higher-level andor semantic processing in more

demanding tasks elicits ERD (Krause et al 1996 Peterson

and Thaut 2002) One possible explanation for the results

would thus be that the MCI patients were compensating for

their memory problems by allocating higher-level cognitive

strategies to the task The differences between the control

group and the MCI group also spanned over frequencies

normally referred to as beta activity Beta responses have

been linked to motor processing and imagery (Neuper and

Pfurtscheller 1999) but recent studies have found that

increased task demands result in attenuated beta power

(Duzel et al 2003 Peterson and Thaut 2002) supporting

the hypothesis of compensatory higher-level processing in

the MCI patients

It is noteworthy and surprising that the differences during

encoding between the control group and the AD group were

minimal and that the responses of the MCI and AD group

differed in the uml5ndash7 Hz frequency band The responses in

the MCI group were characterized by ERD while ERS was

observed in the controls and AD patients It is possible that

differences between the controls and the AD patients might

exist in the temporal dimension but the wavelet width used

in the current study does not allow for good temporal

resolution in the low frequency bands Moreover the

synchronization in the uml5ndash7 Hz band might reflect

activation of different neuronal networks in the controls

and the AD patients (theta vs low alpha)

As we have recently reported (Karrasch et al 2004) the

presentation of the probe (retrieval) elicited a statistically

significant ERS in the uml3ndash5 Hz frequencies and ERD in

the uml7ndash20 Hz frequencies in the elderly controls Similar

but somewhat attenuated patterns were observed in the MCI

patients During retrieval the most prominent group differ-

ences were observed between the controls and the AD group

in the uml7ndash17 Hz frequencies in frontal central and left

temporal electrodes Some statistically significant differ-

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx8

particularly at frontal central and occipital electrode sites

The largest differences were found between the controls and

the MCI group The differences were due to the fact that the

responses in the uml10ndash20 Hz frequency ranges were

characterized by ERS in the control group and ERD in the

MCI group Statistically significant differences between the

aforementioned groups were also observed in occipital

electrodes in the uml5 Hz frequency The responses of the

MCI group also differed significantly from that of the AD

group in the uml5ndash7 Hz frequency band in central and

occipital electrodes This difference was due to the fact that

synchronization was observed in the AD group whereas

desynchronization was observed in the MCI group (Fig 2)

442 Probe retrieval

During retrieval the largest differences were observed

between the controls and the AD group These differences

were due to the fact that ERD in the uml7ndash17 Hz frequency

bands was absent in the AD group particularly in frontal and

left temporal electrode locations The ERDERS responses

of the MCI group were only minimally different from that of

the controls whereas some statistically significant differ-

ences between the MCI and AD groups were found in the

uml4ndash5 Hz and uml12ndash14 Hz frequencies in frontal central

and occipital electrodes (Fig 2) These differences were due

to fact that synchronization was elicited in the uml4ndash5 Hz

frequency range in the MCI group but not in the AD group

In the uml12ndash14 Hz frequency band ERD was observed in

the MCI group but not in the AD group

5 Discussion

The aim of this study was to explore event-related

desynchronization (ERD) and synchronization (ERS) in the

1ndash20 Hz frequency bands during the encoding and retrieval

phase of an auditory-verbal working memory task in

patients suffering from mild cognitive impairment and

Alzheimerrsquos disease At the behavioural level there were

statistically significant differences between the control

group and the AD group in response accuracy in the task

The control group and the MCI group succeeded with few

erroneous answers whereas the AD group made more

errors This finding is in line with behavioural studies where

the maintenance and rehearsal system of working memory

(the articulatory loop) as well as verbal learning has been

found to be affected in AD (Backman et al 2001 Borgo et

al 2003 Collette et al 1999) Our results are also in line

with previous studies indicating that while MCI patients

are impaired in tests measuring learning and consolidation

of episodic memory traces they do not have overt problems

in maintaining a limited memory set in mind for short time

periods (Backman et al 2001 Elias et al 2000) No

statistically significant differences were observed between

the three groups in sustained response accuracy This

indicates that the subjects were able to maintain attention

during the task even though the experiment lasted for up to

1 h

As we have recently reported (Karrasch et al 2004)

statistically significant EEG synchronization in the uml3ndash6

Hz and uml12ndash14 Hz frequency bands was observed during

encoding in the elderly control group These results are in

line with previous studies where theta and alpha synchro-

nization has been found during successful encoding of items

into short-term memory (Klimesch et al 1996 Krause et

al 1996) Statistically significant differences during encod-

ing of the memory set were observed mostly between the

controls and the MCI group in the uml10ndash20 Hz frequency

ranges The responses in the uml10ndash20 Hz frequencies were

characterized by ERS in the control group and ERD in the

MCI group even though these responses showed within-

group significance only in the controls in the occipital

electrodes It has been suggested that in the auditory

modality task demands modulate alpha ERDERS

responses such that phonological maintenance in relatively

easy tasks elicits ERS particularly in upper alpha frequen-

cies while higher-level andor semantic processing in more

demanding tasks elicits ERD (Krause et al 1996 Peterson

and Thaut 2002) One possible explanation for the results

would thus be that the MCI patients were compensating for

their memory problems by allocating higher-level cognitive

strategies to the task The differences between the control

group and the MCI group also spanned over frequencies

normally referred to as beta activity Beta responses have

been linked to motor processing and imagery (Neuper and

Pfurtscheller 1999) but recent studies have found that

increased task demands result in attenuated beta power

(Duzel et al 2003 Peterson and Thaut 2002) supporting

the hypothesis of compensatory higher-level processing in

the MCI patients

It is noteworthy and surprising that the differences during

encoding between the control group and the AD group were

minimal and that the responses of the MCI and AD group

differed in the uml5ndash7 Hz frequency band The responses in

the MCI group were characterized by ERD while ERS was

observed in the controls and AD patients It is possible that

differences between the controls and the AD patients might

exist in the temporal dimension but the wavelet width used

in the current study does not allow for good temporal

resolution in the low frequency bands Moreover the

synchronization in the uml5ndash7 Hz band might reflect

activation of different neuronal networks in the controls

and the AD patients (theta vs low alpha)

As we have recently reported (Karrasch et al 2004) the

presentation of the probe (retrieval) elicited a statistically

significant ERS in the uml3ndash5 Hz frequencies and ERD in

the uml7ndash20 Hz frequencies in the elderly controls Similar

but somewhat attenuated patterns were observed in the MCI

patients During retrieval the most prominent group differ-

ences were observed between the controls and the AD group

in the uml7ndash17 Hz frequencies in frontal central and left

temporal electrodes Some statistically significant differ-

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx 9

ences were also observed in the uml10ndash12 Hz frequencies

between the MCI and AD patients in frontal central and

occipital electrodes The statistically significant differences

were due to the fact that ERD in the abovementioned

frequency bands was absent in the AD group This finding is

in line with a spectral MEG study showing decreased task

reactivity in the 8ndash20 Hz frequencies in AD although this

attenuated task reactivity was also observed in lower 2ndash7

Hz frequencies (Berendse et al 2000) Our current findings

may indicate that the AD pathology affects desynchroniza-

tion in the uml7ndash17 Hz frequency bands (alphabeta) during

the retrieval phase of short-term memory processing

Desynchronization in the alpha and beta frequency ranges

has been found to reflect higher level cognitive and lexical-

semantic processing (Karrasch et al 1998 Klimesch 1999

Klimesch et al 1997b Peterson and Thaut 2002)

Although the ERDERS method does not allow for exact

spatial localization it is of interest to note that the

differences between the control group and the AD group

are marked in left but not right temporal electrodes The

current findings might thus reflect deficient activation of

lexical-semantic processing during memory retrieval in the

AD patients The fact that the AD patients had lower

response accuracy than the controls and the MCI patients

might however confound the results Exclusion of the

retrieval conditions with wrong answers would have

resulted in too few trials in the AD group and thus there

are more trials with wrong answers in the grand average

ERDERS responses during retrieval in the AD patients than

in those of the controls and MCI patients The lower

response accuracy in the AD patients also indicates that the

task was more demanding for them than to the controls and

MCI patients which means that the results may be

modulated by task difficulty

The absence of differences between the controls and the

AD patients in the low uml3ndash6 Hz theta frequency range was

somewhat surprising as theta oscillations have been linked

functionally to memory processes (Jensen and Tesche 2002

Kahana et al 2001 Klimesch et al 2001 Mattia et al

2003) Although theta activity has been found to increase in

the spontaneous EEG in AD (Bennys et al 2001) the

functional reactivity of theta activity in AD patients has not

been scrutinized One recent study examined spectral EEG

during rest and the retention period of a visual working

memory task in early AD (Hogan et al 2003) In line with

our results no differences between controls and AD patients

in the theta frequency range response were found Analysis

of the evoked components might shed some more light on

this issue and we intend to analyze phase-locking of the

present data in a separate study Also the wavelet width

used in the current study does not allow for high-quality

temporal resolution in the lower frequencies and thus some

temporal aspects of the responses might be blurred out In

future studies we intend to use different wavelet widths in

order to examine functional responses in the theta range in

more detail

The results of this preliminary study were based on

small samples of individuals and further studies are

needed to validate these ERDERS patterns with larger

groups of patients An important future area of inves-

tigation is the follow-up of ERDERS responses in MCI

patients to determine which features might indicate further

cognitive decline and an AD-related pathological process

Previous studies have reported that approximately 50 of

amnestic MCI patients later develop AD (Bowen et al

1997 Meyer et al 2002) It is thus possible that some of

our MCI patients will not progress to AD and since the

group size was small this obviously affects the validity of

the results The patients in the current study were

somewhat older than the controls even though the age

difference was not statistically significant Thus age effects

cannot be ruled out with certainty Additionally in the

future one could study the ERDERS responses in MCI

and AD patients using individually determined frequency

bands in order to better control for individual differences

and possible EEG slowing due to disease (Doppelmayr et

al 1998 Klimesch et al 1998) Also the separate

analysis of trials with right and wrong answers might

further elucidate how the memory-related ERDERS

responses are modulated in AD

In summary statistically significant differences were

found in the uml10ndash20 Hz frequency ERDERS responses

between the controls and the MCI group during memory

encoding These differences were due to the fact that ERD

was observed in the MCI group This finding might reflect

compensatory memory encoding strategies in the MCI

patients During retrieval significant differences were

observed between the controls and the AD group such that

uml7ndash17 Hz ERD was absent in the AD group The findings

might indicate that AD pathology affects lexical-semantic

processing during memory retrieval

Acknowledgements

This study was financially supported by the Academy of

Finland (42536) the Finnish Alzheimer Foundation the

Miina Sillanpaa Foundation the Jenny and Antti Wihuri

Foundation the Oskar Oflund Foundation and the Paulo

Foundation Professor Christina M Krause was financially

supported by the University of Helsinki (universityrsquos

research funds) The authors wish to thank Riitta Niskanen

for help in gathering the MCI and AD patients The data

analysis was technically assisted by Marcus Alanen Tom

Pakkanen Annika Hulten Toni Auranen Saku Hamalainen

and Alina Nikitenkova

References

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G et al 2000 Movement-related electroencephalographic reactivity in

Alzheimer disease NeuroImage 12 (12) 139ndash146

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx10

Backman L Small BJ Fratiglioni L 2001 Stability of the

preclinical episodic memory deficit in Alzheimerrsquos disease Brain 124

96ndash102

Barbeau E Wendling F Regis J Duncan R Poncet M Chauvel P et

al (in press) Recollection of vivid memories after perirhinal region

stimulations synchronization in the theta range of spatially distributed

brain areas Neuropsychologia Corrected Proof

Basar E Basar-Eroglu C Karakas S Schurmann M 2001 Gamma

alpha delta and theta oscillations govern cognitive processes Interna-

tional Journal of Psychophysiology 39 241ndash248

Basar E Schurmann M Demiralp T Basar-Eroglu C Ademoglu A

2001 Event-related oscillations are Freal brain responses_-wavelet

analysis and new strategies International Journal of Psychophysiology

39 91ndash127

Bastiaansen MCM Posthuma D Groot PFC de Geus EJC 2002

Event-related alpha and theta responses in a visuo-spatial working

memory task Clinical Neurophysiology 113 1882ndash1893

Bastiaansen MCM van Berkum JJA Hagoort P 2002 Event-related

theta power increases in the human EEG during online sentence

processing Neuroscience Letters 323 13ndash16

Bennys K Rondouin G Vergnes C Touchon J 2001 Diagnostic value

of quantitative EEG in Alzheimerrsquos disease Neurophysiologie Clinique

31 153ndash160

Berendse HW Verbunt JPA Scheltens P van Dijk BW Jonkman

EJ 2000 Magnetoencephalographic analysis of cortical activity in

Alzheimerrsquos disease a pilot study Clinical Neurophysiology 111

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Besthorn C Zerfass R Geiger-Kabisch C Sattel H Daniel S

Schreiter-Gasser U et al 1997 Discrimination of Alzheimerrsquos disease

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Neurophysiology 103 241ndash248

Borgo F Giovannini L Moro R Semenza C Arcicasa M Zaramella

M 2003 Updating and inhibition processes in working memory a

comparison between Alzheimerrsquos type dementia and frontal lobe focal

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Bowen J Teri L Kukull W McCormick W McCurry SM Larson

EB 1997 Progression to dementia in patients with isolated memory

loss Lancet 349 763ndash765

Caplan JB Kahana MJ Sekuler R Kirschen MP Madsen JR

2000 Task dependence of human theta the case for multiple cognitive

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Claus JJ Kwa VIH Teunisse S Walstra GJM van Gool WA

Koelman HTM et al 1998 Slowing of quantitative spectral EEG is

a marker for rate of subsequent cognitive and functional decline in early

Alzheimer disease Alzheimer Disease and Associated Disorders 12

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Claus JJ Strijers RLM Jonkman EJ Ongerboer de Visser BW

Jonker C Walstra GJM et al 1999 The diagnostic value of

electroencephalography in mild senile Alzheimerrsquos disease Clinical

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Coben LA Danziger WL Berg L 1983 Frequency analysis of the

resting awake EEG in mild senile dementia of Alzheimer type

Electroencephalography and Clinical Neurophysiology 55 372ndash380

Collette F Van der Linden M Bechet S Salmon E 1999 Phonological

loop and central executive functioning in Alzheimerrsquos disease Neuro-

psychologia 37 905ndash918

Collie A Maruff P 2000 The neuropsychology of preclinical Alzheim-

errsquos disease and mild cognitive impairment Neuroscience and Bio-

behavioral Reviews 24 365ndash374

Doppelmayr M Klimesch W Pachinger T Ripper B 1998

Individual differences in brain dynamics important implications for

the calculation of event-related band power Biological Cybernetics

79 49ndash57

Duzel E Habib R Schott B Schoenfeld A Lobaugh N McIntosh

AR et al 2003 A multivariate spatiotemporal analysis of electro-

magnetic time-frequency data of recognition memory NeuroImage 18

185ndash197

Elias MF Beiser A Wolf PA Au R White RF DrsquoAgostino RB

2000 The preclinical phase of Alzheimer disease Archives of

Neurology 57 808ndash813

Hogan MJ Swanwick GRJ Kaiser J Rowan M Lawlor B 2003

Memory-related EEG power and coherence reductions in mild

Alzheimerrsquos disease International Journal of Psychophysiology 49

147ndash163

Jelic V Johansson S-E Almkvist O Shigeta M Julin P Nordberg A

et al 2000 Quantitative electroencephalography in mild cognitive

impairment longitudinal changes and possible prediction of Alzheimerrsquos

disease Neurobiology of Aging 21 533ndash540

Jensen O 2002 4-D Toolbox version 1112 A Matlab toolbox for

the analysis of Neuromag data Retrieved 112002 2002 from

httpboojumhutfiumlojensen4Dtools

Jensen O Tesche CD 2002 Frontal theta activity in humans increases

with memory load in a working memory task European Journal of

Neuroscience 15 1395ndash1399

Jensen O Gelfand J Kounios J Lisman JE 2002 Oscillations in the

alpha band (9ndash12 Hz) increase with memory load during retention in a

short-term memory task Cerebral Cortex 12 877ndash882

Jeong J 2004 EEG dynamics in patients with Alzheimerrsquos disease

Clinical Neurophysiology 115 1490ndash1505

Kahana MJ Sekuler R Caplan JB Kirschen MP Madsen JR

1999 Human theta oscillations exhibit task dependence during virtual

maze navigation Nature 399 781ndash784

Kahana MJ Seelig D Madsen JR 2001 Theta returns Current

Opinion in Neurobiology 11 739ndash744

Karakas S Erzengin OU Basar E 2000 A new strategy involving

multiple cognitive paradigms demonstrates that ERP components are

determined by the superposition of oscillatory signals Clinical Neuro-

physiology 111 1719ndash1732

Karrasch M Krause CM Laine M Lang AH Lehto M 1998

Event-related desynchronization and synchronization during an auditory

lexical matching task Electroencephalography and clinical Neuro-

physiology 107 112ndash121

Karrasch M Laine M Rapinoja P Krause CM 2004 Effects of

normal aging on event-related desynchronizationsynchronization dur-

ing a memory task Neuroscience Letters 366 18ndash23

Klimesch W 1999 EEG alpha and theta oscillations reflect cognitive and

memory performance a review and analysis Brain Research Reviews

29 169ndash195

Klimesch W Doppelmayr M Russegger H Pachinger T 1996 Theta

band power in the human scalp EEG and the encoding of new

information NeuroReport 7 1235ndash1240

Klimesch W Doppelmayr M Pachinger T Ripper B 1997 Brain

oscillations and human memory EEG correlated in the upper alpha and

theta band Neuroscience Letters 238 9ndash12

Klimesch W Doppelmayr M Pachinger T Russegger H 1997 Event-

related desynchronization in the alpha band and the processing of

semantic information Cognitive Brain Research 6 83ndash94

Klimesch W Russegger H Doppelmayr M Pachinger T 1998 A

method for calculation of induced band power implications for the

significance of brain oscillations Electroencephalography and Clinical

Neurophysiology 108 123ndash130

Klimesch W Doppelmayr M Stadler W Pollhuber D Sauseng P

Rohm D 2001 Episodic retrieval is reflected by a process specific

increase in human electroencephalographic theta activity Neuroscience

Letters 302 49ndash52

Kowalski JW Gawel M Pfeffer A Barcikowska M 2001 The

diagnostic value of EEG in Alzheimer disease Correlation with the

severity of mental impairment Journal of Clinical Neurophysiology 18

570ndash575

Krause CM 2002 Brain electric oscillations and cognitive processes In

Hugdahl K (Ed) Experimental Methods in Neuropsychology Kluwer

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Krause CM Lang AH Laine M Kuusisto M Porn B 1996 Event-

related EEG desynchronization and synchronization during an auditory

ARTICLE IN PRESSM Karrasch et al International Journal of Psychophysiology xx (2005) xxxndashxxx 11

memory task Electroencephalography and Clinical Neurophysiology

98 319ndash326

Krause CM Astrom T Karrasch M Laine M Sillanmaki L 1999

Cortical activation related to auditory semantic matching of concrete vs

abstract words Clinical Neurophysiology 110 1307ndash1317

Krause CM Salminen P-A Sillanmaki L Holopainen IE 2001

Event-related desynchronization and synchronization during a memory

task in children Clinical Neurophysiology 112 2233ndash2240

Laine M Koivuselka-Sallinen P Hanninen R Niemi J 1997 Bostonin

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Lee H Simpson GV Logothetis NK Rainer G 2005 Phase locking

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Lehtovirta M Partanen J Kononen M Soininen H Helisalmi S

Mannermaa A et al 1996 Spectral analysis of EEG in Alzheimerrsquos

disease relation to apolipoprotein E polymorphism Neurobiology of

Aging 17 (4) 523ndash526

Math Works Inc 1999 MATLAB The Language of Technical Computing

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Mattia D Babiloni C Romigi A Cincotti F Bianchi L Sperli F et

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McKhann G Drachman D Folstein M Katzman R Price D Stadlan

EM 1984 Clinical diagnosis of Alzheimerrsquos disease report of the

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Meyer JS Xu G Thornby J Chowdhury M Quach M 2002

Longitudinal analysis of abnormal domains comprising mild cognitive

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Muller G Richter RA Weisbrod S Klingberg F 1991 Duration of

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Neuper C Pfurtscheller G 1999 Motor imagery and ERD In

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Neuper C Pfurtscheller G 2001 Evidence for distinct beta resonance

frequencies in human EEG related to specific sensorimotor cortical

areas Clinical Neurophysiology 112 (11) 2084ndash2097

Petersen RC Doody R Kurz A Mohs RC Morris JC Rabins PV

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Peterson DA Thaut MH 2002 Delay modulated spectral correlates in

the human EEG of non-verbal auditory working memory Neuroscience

Letters 328 17ndash20

Pfurtscheller G Klimesch W 1991 Event-related desynchronization

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Pfurtscheller G Lopes da Silva FH 1999 Event-related EEGMEG

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Quade D 1979 Using weighted rankings in the analysis of complete

blocks with additive block effects Journal of the American Statistical

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Raghavachari S Kahana MJ Rizzuto DS Caplan JB Kirschen

MP Bourgeois B et al 2001 Gating of human theta oscillations by

a working memory task Journal of Neuroscience 21 3175ndash3183

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EEG spectral analysis in vascular and Alzheimer dementia Electro-

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Sternberg S 1966 High-speed scanning in human memory Science 153

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Tallon-Baudry C Kreiter A Bertrand O 1999 Sustained and transient

oscillatory responses in the gamma and beta bands in a visual short-term

memory task in humans Visual Neuroscience 16 449ndash459

Vazquez Marrufo M Vaquero E Cardoso MJ Gomez CM 2001

Temporal evolution of [alpha] and [beta] bands during visual spatial

attention Cognitive Brain Research 12 (2) 315ndash320

Wechsler D (1992) WAIS-Revised [Finnish manual] Helsinki Psykolo-

gien kustannus Oy

Wechsler D (1996) WMS-Revised [Finnish manual] Helsinki Psykolo-

gien kustannus Oy

Welsh KA Butters N Hughes J Mohs R Heyman A 1991

Detection of abnormal memory decline in mild cases of Alzheimerrsquos

disease using CERAD neuropsychological measures Archives of

Neurology 48 278ndash281