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Frontal deficits in alcoholism: An ERP study

Mary Reeni M. George,a,* Geoffrey Potts,a Delia Kothman,a Laura Martin,a

and C.R. Mukundanb

a Department of Psychology, Rice University, Houston, TX 77005, USAb Department of Clinical Psychology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India

Accepted 12 February 2004

Abstract

Alcoholism is a major health problem afflicting people all over the world. Understanding the neural substrates of this addictive

disorder may provide the basis for effective interventions. So-called executive processes play a role in cognitive functions like

attention and working memory, and appear to be disrupted in alcoholism (Noel et al., 2001). Event related potentials (ERPs)

provide an excellent, minimally invasive technique for exploring these neural deficits. The current study used the P300 in number

sequencing task (modified version of the Petrides & Milner, 1982) requiring working memory to compare a group of patients with

alcoholism and frontal lobe lesions to patients with subcortical lesions and normal controls to assess the relationship of alcoholism

to frontal lobe damage. The ERP paradigm was a Number Sequencing task. Electrophysiological results indicate that the frontal

lesion group had significant P300 amplitude reduction and a similar trend for alcohol dependent group but not the subcortical group

compared to the normal controls.

2004 Elsevier Inc. All rights reserved.

1. Introduction

Alcoholism is a major public health problem afflicting

people all over the world resulting in huge economic

loss. The personal cost of addictive behaviors and re-

lapse prevention to the afflicted individuals and their

immediate families are immense. Understanding the

neural substrates of addictive disorders might provide

the basis for more effective interventions.

One characteristic of an alcohol dependant is the

preoccupation with alcohol and alcohol seeking behav-

ior; items in this subset of representations (alcohol and

related items) are selected by attention, and made

available to the working memory. Models of working

memory often contain a central executive that, in

part, controls the input to the system. This executive is

closely associated with the frontal lobe and is often re-

ferred to as the frontal executive. Many recent studies

have suggested that detoxified alcohol subjects do

poorly on tasks sensitive to frontal lobe particularly on

executive tasks relating to attention and working mem-

ory (Noel et al., 2001; Pfefferbaum et al., 2001).

The current study used the P300 event-related po-

tential (ERPs) component from a number sequencing

task requiring working memory in a group of patients

with alcoholism and patients with frontal lobe lesions

compared to patients with subcortical lesions and nor-

mal controls to assess the relationship of alcoholism to

frontal lobe damage. If alcoholism has a pathophysiol-

ogy similar to frontal lobe damage, then the ERP re-

sponses of the alcoholic patients should be similar to the

frontal lobe patients and dissimilar from the subcortical

patients and the normal controls.

2. Methods

The sample consisted of 4 groups of subjects: Alcohol

dependent subjects (N 15, Mean age 36.71,

SD 4:60), frontal lesion patients (N 11, Mean

age 37.3, SD 10:30), subcortical lesion patients

(N 12, Mean age 35.00, SD 10:09) and a group of

normal controls (N 17, Mean age 38.5, SD 10:04).

All subjects were recruited from the National Institute

* Corresponding author.

E-mail address: reeni@rice.edu (M.R.M. George).

0278-2626/$ - see front matter 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.bandc.2004.02.025

Brain and Cognition 54 (2004) 245247

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of Mental Health and Neurosciences (NIMHANS),

Bangalore, India. The alcohol dependant patients were

right-handed males, age 1848, from a 4-week residen-

tial treatment facility at the De-addiction center of

NIMHANS. These subjects met ICD-10 criteria for al-

cohol dependence, had an average drinking history of 6

years, and were detoxified before taking part in thestudy. Subjects with history of other substance use,

psychiatric or neurological disorders, including head

injury, epilepsy or Korsakoffs, were excluded.

The lesion subjects were selected from the outpatient

departments of Neurology and Neurosurgery, of

NIMHANS after confirming that their lesion was well

circumscribed. In the subcortical group, the subjects

were all infarct cases (6 months to 12 years after the

vascular infarct) with lesions in the thalamus or basal

ganglia. All except 2 (cerebral infarct) in the frontal le-

sion group were tumor resection cases who were re-

cruited 15 years after the tumor resection. Subjects

with raised intracranial tension, midline shift, visual

system deficits, hemi paresis, history of psychiatric or

other neurological disorders and were excluded from the

main study. Most of the subjects had returned to their

premorbid level of occupational functioning at the time

of the study. All the subcortical lesion patients were

selected on the basis of infarction to either the thalamus

or basal ganglia. The normal control subjects were non-

paid adult volunteers (who had no prior history of

substance use, significant psychiatric or neurological

disorders) who were relatives of the inpatients admitted

to the Neurology and Neurosurgery departments of

NIMHANS, Bangalore. There were no significant dif-ferences noted for the relevant matched variables in-

cluding sex, socioeconomic status, and educational level.

Subjects were right handed, could read and write, and

had normal or corrected to normal vision. Subjects were

informed about the test procedures and consented to

participate by signing an informed consent form.

The ERP paradigm was a modified version of the

Petrides and Milner (1982) Number Sequencing task. In

this test, a set of three random digits 19 (e.g., 5, 8, 4)

was presented sequentially on a computer monitor re-

placing the fixation dot. Each number was presented for

300 ms with a interstimulus interval of 200 ms. One

thousand milliseconds after the final digit, two numbers

from the initial set would appear and the subjects were

asked to respond with a key press if the two numbers

were in the same sequence (5, 8 or 8, 4) as in the first set

[presentation time of 300 ms]. Each block consisted of 80

trials and 50% had trials with the correct sequence.

There were 10 such blocks making a total of 800 trials.

The EEG recordings were done on a Biologic Brain

Atlas system using nonpolarizable electrodes mounted

in an elastic cap (Electro cap International) referenced

to linked ear lobes. All 20 electrodes of the international

10/20 system were used. Electrooculogram (EOG) was

recorded bipolarly between electrodes situated at the

outer right canthus and above the eyebrow of the right

eye with silver tin cup electrodes. Electrical impedance

was kept below 5 kX.

Recordings were done in a dimly lit, sound attenu-

ated, and electrically shielded room. Subjects were se-

ated 100 cm. from the computer display. Practice trialswere run prior to commencing the task and the subjects

were told to minimize their eye blinks and eye move-

ments during the blocks. Continuous EEG was re-

corded, segmented 200 ms after the first stimulus

presentation and proceeded for 4000 ms till the subject

made the evaluation of the sequence. The epochs were

visually scanned offline for artifacts such as eye blinks

and movement, and averaged across trials for each

condition (2 conditions one for which the sequencing

was correct and the other incorrect), across subjects.

Grand average waveforms were created across each

group of subjects. All measurements were taken with

reference to the prestimulus base line (200 ms before the

first number presentation). The mean amplitude of P300

after the final two digits was extracted from a window

from 360 to 440 ms following the final digit presentation.

(Note: earlier ERP components related to perceptual

processing of the first three digits and the retention of

the digits between the first and second sets did not show

reliable group differences). To reduce the dimensionality

of the electrode factor with potentially 20 levels, a region

of interest (ROI) grouping of electrodes was done, by

dividing it into 6 different regions of interest as follows:

anterior (FP1, FPz, FP2, F3, Fz, F4, F7, and F8),

Central (T3, C3, Cz, C4, and T4), posterior (T5,P3, Pz,P4, P6, O1, Oz, and O2), left (FP1, F7, F3, T3, C3, T5,

P3, and O1), middle (FPz, Fz, Cz, Pz, and Oz), and right

(FPz, F4, F8, C4, T4, P4, T6, and O2). ANOVAs were

done across 4 groups and at two task levels (correct

sequence and incorrect sequence) for the ERP compo-

nents using amplitude and latency at each of the 6 re-

gional electrode arrays as dependant vectors. Means and

standard deviations were computed for the descriptive

purpose for the peak amplitude and latency values in

each of the peak amplitude and latency values in each of

the 6 lead sets that were described earlier.

All comparisons were made against the normal

controls.

3. Results and discussion

There was significant effect for the P300 like compo-

nent after the sequence was correctly identified over the

left leads (more pronounced at the centro-parietal leads)

across the 4 groups. The amplitude of this positive de-

flection was significantly different among the four

groups on the left electrodes (F 3:55;P < :01, Fig. 1).

Post hoc tests revealed that there was significant

246 M.R.M. George et al. / Brain and Cognition 54 (2004) 245247

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amplitude reduction among the frontal lesion group(P < :05) and a similar trend for alcohol dependent

group (P < :10) but not the subcortical group compared

to the control group.

This study attempted to understand the relationship

between frontal lobe function, specifically, the central

executive and its dysfunction in alcoholism. The elec-

trophysiological test was specifically designed to engage

the prefrontal executive in a number sequencing task.

Results indicated that frontal lesion group had signifi-

cant reduction in P300 amplitude in the task, as did the

alcohol dependant group, compared to the normal

controls. Despite having the structural lesion, the sub-

cortical group performed similar to the normal controlgroup.

This study thus supports the contention of Moselhy,

Georgiou, and Kahn (2001) of frontal lobe pathology in

alcoholism. The fact that the reduction in the alcohol

dependent patients in the current study was only a trend

may be due to the fact that these subjects were relatively

young detoxified subjects with an average drinking his-

tory of less than 6 years. Additional evidence that dif-ferentiated the frontal lesion group and the alcohol

dependent subjects from the subcortical lesion group

would have lent stronger evidence to this case.

References

Moselhy, H. F., Georgiou, G., & Kahn, A. (2001). Frontal lobe

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Noel, X., Van der Linden, M., Schmidt, N., Sferazza, R., Hanak, C.,

Le Bon, O., De Mol, J., Kornreich, C., Pelc, I., & Verbank, P.(2001). Supervisory attentional system in nonamnesic alcoholic

men. Archives of General Psychiatry, 58(12), 11521158.

Pfefferbaum, A., Desmond, J. E., Galloway, C., Menon, V., Glover, G.

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used by alcoholics for spatial working memory: An fMRI study.

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Fig. 1. Showing the mean amplitude of P300 (left ROI) among the 4 groups in the number sequencing task.

M.R.M. George et al. / Brain and Cognition 54 (2004) 245247 247