抑郁症患者面部表情搜索中的皮质连接性变化研究

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"在重度抑郁症患者面部表情的空间搜索过程中皮质连接性改变" 这篇研究探讨了抑郁症患者在处理面部表情时的皮质连接性变化，尤其是与注意力调节相关的定向定向连接。抑郁症患者在视觉搜索任务中，对中性面部表情的反应与正常人存在差异，这可能反映了他们在注意力调节方面的困难。研究采用了短窗口部分定向相干性（PDC）和事件相关的脑电势（ERP）技术，结合ERP的N2成分分析，来深入理解这一现象。 N2成分通常与认知努力和注意力分配相关，其幅度降低在抑郁症患者中尤为明显，尤其是在面对积极面部表情时。这表明抑郁症患者在调节对积极情绪的注意力时表现出不足。同时，研究发现抑郁症患者在N2时间窗口内的皮质定向连接性发生了变化：额叶内和中央内定向相互作用减弱，这可能影响了他们对情绪信息的处理效率。此外，枕叶的信息输出在抑郁症患者中增强，可能反映了他们对视觉信息的过度关注或处理。另一方面，当检测到情绪化的面部表情时，抑郁症患者内部-前向的定向相互作用没有显著减少，这可能意味着他们在处理情绪刺激时的皮质连接性并未像预期那样减弱。这些发现支持了抑郁症中注意力调节障碍与皮层连通性改变之间的关联，暗示了大脑网络的异常可能导致抑郁症患者在处理情绪信息时的困难。这项研究揭示了抑郁症患者在处理面部表情时大脑连接性的独特模式，为理解抑郁症的心理病理机制提供了新的视角。未来的研究可以进一步探索这些连接性变化如何影响患者的情绪识别和处理，以及潜在的治疗策略。同时，这也为临床实践中通过神经影像技术评估和干预抑郁症提供了理论基础。

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evoked by rare targets than frequent non-targets (Breton et al., 1988).

Larger N2 amplitude was observed when task-relevant features didn't

match and reﬂected the mismatch effect (Wang et al., 2004). The

non-targets which shared features with targets elicited larger N2,

which was located in medial frontal cortex (Azizian et al., 2006).

These investigations provided the evidence that N2 indexed the atten-

tional manipulation in the processes of cognitive control (Folstein and

Van Petten, 2008). In mood disorder, altered N2 activity was also dem-

onstrated and was related to cognitive deﬁcits (Debener et al., 2000;

Levin et al., 2007; Liotti and Mayberg, 2001; Vuilleumier and Pourtois,

2007). Decreased N2 over the right posterior in response to facial stim-

uli showed face processing anomaly in depression (Deldin et al., 2000).

N2b enhancement was involved in the selective attentional deﬁcit in

patients with major depression (Levin et al., 2007). Therefore, the al-

tered N2 amplitudes in depression met the assumption that abnormal

neural activity within the N2 time-windows might contribute to the di-

minished capacity of attentional modulation in depression. With this

consideration, our interest was conﬁned to the process during the N2

time-window. The altered directed cortical connectivity in depression

was assessed within N2 time-windows in particular.

Various quantitative electroencephalography (qEEG) methods

have been proposed to study the cortical interaction (Pereda et al.,

2005). Compared with traditional coherence analysis and mutual

synchronicity, partial directed coherence (PDC) analysis evaluated

causality in terms of directional inﬂuence between multi-channel

electrophysiological time series (Ding et al., 2000; Sun et al., 2008;

Supp et al., 2005). PDC approach was based on a multivariate autore-

gressive (MVAR) model (Baccalá and Sameshima, 2001; Ding et al.,

2000) and was a genuine multi-channel method (Pereda et al.,

2005). It could help to reveal where the information ﬂow is derived

from, transmitted to, or feedback among separated cortical regions

(Supp et al., 2005, 2007). More attention has been paid for this meth-

od in recent years, due to its success in revealing the multi-channel

directed cortical interactions (Pereda et al., 2005; Sun et al., 2008;

Supp et al., 2005; Supp et al., 2007; Zhang et al., 2009). Further, a

short-window PDC approach was offered to meet temporal require-

ment (Ding et al., 2000). Since the measured ERP trials to attain the

N2 component were reasonably assumed as different realizations of

the same process, the ﬁnal covariance matrix for the MVAR model

of the observed signal could be obtained by averaging across all the

realizations, even though the duration of each realization was short

(Ding et al., 2000; Supp et al., 2005; Zhang et al., 2009). In this

paper, we evaluated the cortical directed connectivity within the

speciﬁed N2 time-window, so as to estimate the temporo-spatial pat-

terns of the cortical directed connectivity with high temporal resolu-

tion in depression.

In this study, a visual search task for emotional facial expressions

was performed by both the depressed subjects and the normal con-

trol ones. The visual search paradigm was effective to demonstrate

the visual search strategy for emotionally biased expressions in

multi-face stimuli (Ohman et al., 2001a,b; Pegna et al., 2008; Suslow

et al., 2004; Tang et al., 2009; Williams et al., 2008). Attention modu-

lation played an important role in enhancing the visual information

relevant to the target and inhibiting the irrelevant one when per-

forming a visual search task (Lorenzo-Lopez et al., 2008). We applied

the paradigm to explore the diminished capacity in attentional mod-

ulation in depression. With short-window PDC analysis, we measured

the changes of the cortical directed connectivity within the cortical

network in depressed patients as compared to normal controls. We

hypothesized that: (1) The ERPs component N2 would demonstrate

whether the capacity of attention modulation was impaired in

depression; (2) The PDC values would demonstrate the patterns of

altered cortical directed connectivity which might contribute to the

impairments of attentional modulation in depression. A well-

recognized model of visual attention consisted of a bottom-up com-

ponent for image-based saliency processing across the posterior

visual cortex and a top-down component for task-dependent modu-

lation mainly at prefrontal and frontal cortex (Itti and Koch, 2001).

In the normal subjects, the forward bottom-up pathway transferred

the visual perceptual saliency from the occipital cortex to the frontal

cortex for high-level processing. Then the feedback top-down path-

way transferred the high-level cognitive control from anterior or cen-

tral cortex to the sensory cortex. We assumed that the balance

between these two components was disrupted in depression, the de-

creased feedback regulation in conjunction with increased forward

input, contributed to the dysfunction of attention modulation in de-

pression (Fig. 1).

To further explore whether the alteration in directed connectivity

within the network in depression was due to the some node which

ceased to ﬁre independently or to a collective phenomenon, twice

PDC analysis were performed basing on two different MVAR model-

ing. The ﬁrst modeling was established using all nodes within the net-

work while the second modeling was based on nodes excluding the

node where N2 activity has signiﬁcant changes in depression. This

step should help to understand the pathophysiological dysfunction

of attention modulation in depression.

2. Materials and methods

2.1. Subjects

A total of 25 subjects participated in this study: (1) the normal

control group included thirteen right-handed normal subjects

(male/female=7/6, 39.54±9.65 years) with no personal history of

neurological or psychiatric illness, no drug or alcohol abuse, no cur-

rent medication, and normal or corrected-to-normal vision; (2) the

depressed group: twelve right-handed depressed outpatients (male/

female=8/4, 31.67±13.55 years) were recruited in Shanghai Mental

Health Center (SMHC). All depressed subjects had no history of manic

episode, and fulﬁlled ICD-10 (the tenth revision of International Clas-

siﬁcation of Diseases) diagnosis criteria of major depressive disorder

(current episode of depression). Nine patients were ﬁrst-episode

and three patients were recurrent. Nine patients were unmedicated

and hadn't taken medicine for at least one month. Three depressed

patients had taken antidepressants for less than 2 weeks. Two pa-

tients had taken paroxetine with a dosage of 20 mg/day, and another

patient had taken ﬂuoxetine with a dosage of 20 mg/day. All subjects

including healthy controls had no history of any substance or alcohol

abuse. Each subject has normal or corrected-to-normal vision. In-

formed consent was obtained from each participant before the exper-

iments. The experimental protocol was approved by the SMHC Ethics

Committee in compliance with the Helsinki Declaration.

After taking part in the experimental testing session, all subjects

participated in an interview in which HAMD (Hamilton Rating Scale

for Depression) was administered. SAS (Self-rating Anxiety Scale)

and SDS (Self-rating Depression Scale) were self-rated. The scores of

the normal group were in the normal range showing no mood disor-

der (see Table 1).

2.2. Materials and procedure

The face-in-the-crowd task was constructed according to the ex-

periments of Thomas Suslow et al. (White, 1995; Suslow et al.,

2004). Schematic faces were used. Stimuli consisted of three types

of pictures (Fig. 2): 16 pictures with four neutral faces, namely “con-

dition without target” hereafter; 8 pictures were with one positive

face among three neutral faces, namely “condition with positive tar-

get” hereafter; and another 8 pictures were with one negative face

among three neutral faces, namely “condition with negative target”

hereafter. The faces randomly located at the eight cardinal compass

points of an imaginary circle. Therefore, there were 16 + 8 + 8 = 32

independent stimuli in total in one block. The block repeated ﬁve

1892 Y. Tang et al. / Progress in Neuro-Psychopharmacology & Biological Psychiatry 35 (2011) 1891–1900

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