Investigation of the mechanisms of anxiety-related functions in the general population using brain stimulation

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李沅翰(Yuan-Han Li) 查詢紙本館藏

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認知與神經科學研究所

論文名稱

(Investigation of the mechanisms of anxiety-related functions in the general population using brain stimulation)

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摘要(中)

焦慮對一般人或是焦慮性疾患而言都是常見的問題。近年來的研究已經證明，使用腦刺激可以改善焦慮性疾患的焦慮症狀，卻很少探討在一般人上的應用。因此，我們探討腦刺激可否調節一般人的焦慮程度，並瞭解正常的功能下焦慮的基本神經機制。注意力控制理論(attentional control theory)提出，焦慮會損害認知控制並增加外在刺激的影響(Eysenck, Derakshan, Santos, & Calvo, 2007)。本文中，我們探討兩種認知控制功能，抑制(inhibition，第二章)及更新(updating，第三章)，與焦慮之間的關聯。
實驗一，我們使用一個偵測(detection)作業來確立一般人的焦慮程度與視覺搜尋效率之間的關聯。結果發現，實驗參與者對於負向評價的恐懼越高時，他們的反應時間會越長。並且，只有男性顯示這樣的關聯，而女性沒有。先前發表的研究中，招募較多的女性(約 81%實驗參與者)，因此，我們推論在作業需求上有性別差異現象。在實驗二，我們將作業從偵測作業改為定位(localization)作業。再一次，只有男性顯示焦慮程度與視覺搜尋效率之間顯著的關聯，而女性沒有顯示此關聯。因此，我們探討工作記憶歷程中的另一種認知控制功能，更新。在實驗四，我們使用問卷、呈現 n-back作業、並使用驚嚇反應作為一個與焦慮相關的測量。背外側前額葉(dorsolateral prefrontal cortex)與楔前葉(precuneus)區域已被證明，在焦慮性疾患與一般人之間有所差異。因此，在實驗四中，我們使用跨顱直流電刺激(transcranial magnetic stimulation)來調節這兩個區域的活化。然而，我們在作業表現、驚嚇反應或量表分數上沒有發現任何跨顱直流電刺激造成的改善或損傷。當我們比較過去研究與實驗四的電刺激參數後，我們推論接受背外側前額葉電刺激的組別可能是因為電刺激的參數不夠準確。但是，目前還不確定電極片的排列是否會造成楔前葉電刺激在視覺知覺上的影響。因此，實驗五我們探討楔前葉電刺激在視覺知覺上的影響，沒有發現跨顱直流電刺激在作業上的影響。最後，在實驗六中，我們在楔前葉與頂點(vertex)使用連續性高脈衝式經顱磁刺激(continuous theta burst stimulation，cTBS)。結果顯示，只有楔前葉組顯示在工作記憶上的改變(促進)，而頂點組沒有。雖然，楔前葉與頂點組在驚嚇反應上都有改善，但是只有楔前葉組在 0-back 作業(沒有記憶負荷)上有所改善。這說明了，即使在作業負荷低時，在楔前葉上使用連續性高脈衝式經顱磁刺激仍會改善驚嚇反應。並且，這些發現支持本研究在楔前葉上使用腦刺激會調節焦慮程度的想法。
總結來說，第二章顯示了在焦慮程度與視覺搜尋效率之間的關聯中有性別差異。然而，目前仍不清楚，為何只有男性顯示出此兩者之間的關聯。在第三章，我們使用了跨顱直流電刺激與跨顱磁刺激，但是我們只在跨顱磁刺激實驗中發現顯著的差異。這樣的結果有著許多的可能性，包含了跨顱磁刺激可能比跨顱直流電刺激還要精確或是有效率。然而，本研究也支持楔前葉在焦慮中扮演著重要角色。未來，如果將作業表現與驚嚇反應作為與焦慮相關的指標，需要考慮如何減少不同作業難度在這兩個指標上造成的差異。

摘要(英)

Recently, studies have demonstrated that applying brain stimulation may improve the severity of anxiety symptoms. As anxiety is common in the general population as well as those with anxiety disorders, we investigated whether brain stimulation can modulate anxiety levels for the general population with the aim of understanding the underlying mechanisms of this process in a normal system. Attentional control theory (ACT) suggests that anxiety impairs cognitive control and increases the impact of external stimuli (Eysenck, Derakshan, Santos, & Calvo, 2007). In this thesis, we investigated two cognitive control function, inhibition (in Chapter 2) and updating (in Chapter 3), in relation to anxiety.
In Experiment 1, we applied a detection task to establish the relationship between anxiety levels and visual search efficiency for the general population. We found that participants with higher fear of negative evaluation were slower in performing the task. Also, we found that only males showed such a relationship, but females did not. As a previously published study recruited more females (about 81% of participants) than males, we inferred that there may be gender differences on task demands. In Experiment 2, we changed the task from detection to localization. Again, only males showed significant correlation between anxiety levels and visual search efficiency, whereas females did not. Therefore, we turned to investigating working memory which comprises another function of attentional control, updating. In Experiment 4, we administered questionnaires, presented the n-back task, and used a startle reflex as an anxiety-related measurement. As dorsolateral prefrontal cortex (DLPFC) and precuneus (PCu) have been demonstrated to show differences between those with anxiety disorders and normal people, we applied transcranial direct current stimulation (tDCS) to modulated activities of these areas in Experiment 4. However, we did not find any significant improvement or impairment on task performance, startle reflex, nor questionnaire scores as a result of tDCS stimulation. As we compared parameters of tDCS between previous studies and ours, we inferred that one possibility was that the stimulation it might not have been precise enough for the DLPFC group. However, it was unclear whether or not the electrode arrangement led to any effect of PCu tDCS on visual perception. Therefore, we investigated the effects of PCu tDCS on a visual perception task in Experiment 5, but we did not find any significant effect on task performance. Finally, we applied continuous theta burst stimulation (cTBS) over PCu and vertex in Experiment 6. We found that only the PCu group showed a change (improvement) in working memory, but the vertex group did not. Even though both PCu and vertex groups showed an improvement in the startle reflex, only the PCu group showed this improvement on the 0-back task (i.e. no memory load). This implied that applying cTBS over PCu improves the startle reflex even when task demand was low. Also, these findings supported the idea that applying brain stimulation over this area modulates anxiety levels.
In summary, Chapter 2 showed a gender difference in the relationship between anxiety levels and visual search efficiency. However, it is still unclear why only males showed such relationship. In Chapter 3, we applied both tDCS and TMS, but observed significant differences only in the TMS experiment. There are number of possibilities for this, including, for example, that TMS may more precise or efficient than tDCS. However, the findings do support a role for precuneus in anxiety and how to both diminish the differences of task performance and in the startle reflex for different task difficulties may be important when using these as anxiety-related indices.

關鍵字(中)

★ 焦慮
★ 認知控制
★ 跨顱直流電刺激
★ 連續性高脈衝式經顱磁刺激
★ 楔前葉

關鍵字(英)

★ anxiety
★ cognitive control
★ tDCS
★ cTBS
★ precuneus

論文目次

Chapter 1 General introduction .............................................................................................. - 1 -
1.1 Anxiety ..................................................................................................................... - 1 -
1.2 Anxiety and cognitive control .................................................................................. - 2 -
1.2.1 Anxiety and attentional bias toward threat .................................................... - 2 -
1.2.2 Anxiety and dorsolateral prefrontal cortex (DLPFC) .................................... - 3 -
1.2.3 Anxiety and load manipulation ...................................................................... - 5 -
1.3 Anxiety and precuneus (PCu) ................................................................................... - 7 -
1.4 Brain stimulation ...................................................................................................... - 7 -
1.4.1 Transcranial magnetic stimulation (TMS) ..................................................... - 8 -
1.4.2 Transcranial direct current stimulation (tDCS) ............................................. - 9 -
1.4.3 Brain stimulation and anxiety disorders ........................................................ - 9 -
1.4.4 Brain stimulation and working memory ...................................................... - 10 -
1.5 Research aims ......................................................................................................... - 11 -
1.5.1 Anxiety and attentional bias for the general population .............................. - 11 -
1.5.2 Anxiety and working memory ..................................................................... - 11 -
Chapter 2 Anxiety and Visual search .................................................................................... - 14 -
2.1 Experiment 1 The effects of facial expressions on target detection ....................... - 14 -
2.1.1 Introduction ................................................................................................. - 14 -
2.1.2 Methods ....................................................................................................... - 16 -
2.1.2.1 Participants ....................................................................................... - 16 -
2.1.2.2 Questionnaires .................................................................................. - 16 -
2.1.2.3 Task ................................................................................................... - 17 -
2.1.3 Results ......................................................................................................... - 19 -
2.1.4 Discussion .................................................................................................... - 28 -
2.2 Experiment 2 The effect of facial expressions on localization ............................... - 31 -
2.2.1 Methods ....................................................................................................... - 31 -
2.2.1.1 Participants ....................................................................................... - 31 -
2.2.1.2 Procedure .......................................................................................... - 31 -
2.2.2 Results ......................................................................................................... - 32 -
2.2.3 Discussion .................................................................................................... - 43 -
2.3 Experiment 3 The effects of fearful faces on localization task performance compared
to the effects of truly neutral face presentation ............................................................ - 45 -
2.3.1 Methods ....................................................................................................... - 45 -
2.3.1.1 Participants ....................................................................................... - 45 -
2.3.2 Results ......................................................................................................... - 45 -
2.3.3 Discussion .................................................................................................... - 51 -
2.4 Conclusion .............................................................................................................. - 51 -
Chapter 3 How does the activation of anxiety-related areas modulate cognitive functions? . - 55
-
3.1 Experiment 4 The effect of tDCS over anxiety-related areas on working memory
performance .................................................................................................................. - 55 -
3.1.1 Introduction ................................................................................................. - 55 -
3.1.2 Methods ....................................................................................................... - 59 -
3.1.2.1 Participants ....................................................................................... - 59 -
3.1.2.2 Procedure .......................................................................................... - 59 -
3.1.2.3 Questionnaires .................................................................................. - 60 -
3.1.2.4 Task ................................................................................................... - 61 -
3.1.2.5 tDCS ................................................................................................. - 62 -
3.1.3 Results ......................................................................................................... - 63 -
3.1.3.1 Accuracy of judging whether or not the current letter matched the target
letter .............................................................................................................. - 64 -
3.1.3.2 Reaction times when performing the working memory tasks .......... - 67 -
3.1.3.3 Reaction times corrected for accuracy and efficacy in performing the
tasks .............................................................................................................. - 70 -
3.1.3.4 Performance of the 0-back task ........................................................ - 73 -
3.1.3.5 The startle reflex induced by the beep ..............................................- 77 -
3.1.3.6 State version of STAI (STAI-S) ........................................................ - 80 -
3.1.3.7 Trait version of STAI (STAI-T) ........................................................ - 82 -
3.1.3.8 Brief fear of negative evaluation (BFNE) scores ............................. - 84 -
3.1.3.9 BDI-II ............................................................................................... - 86 -
3.1.4 Discussion .................................................................................................... - 88 -
3.2 Experiment 5 The interaction of ocular dominance, precuneus tDCS, and electrode
arrangement, on visual perception ............................................................................. - 92 -
3.2.1 Methods ....................................................................................................... - 92 -
3.2.1.1 Participants ....................................................................................... - 92 -
3.2.1.2 Procedure .......................................................................................... - 92 -
3.2.1.3 Task ................................................................................................... - 92 -
3.2.1.4 tDCS ................................................................................................. - 93 -
3.2.2 Results ......................................................................................................... - 93 -
3.2.3 Discussion .................................................................................................... - 98 -
3.3 Experiment 6 The effect of TMS over precuneus on working memory performance and anxiety .......................................................................................................................... - 99 -
3.3.1 Introduction ................................................................................................. - 99 -
3.3.2 Methods .....................................................................................................- 100 -
3.3.2.1 Participants .....................................................................................- 100 -
3.3.2.2 Procedure ........................................................................................- 101 -
3.2.2.3 Continuous theta burst stimulation (cTBS) ....................................- 101 -
3.3.3 Results ....................................................................................................... - 102 -
3.3.3.1 Accuracy for matching the current letter with the letter n-back from the current letter ................................................................................................ - 102 -
3.3.3.2 The reaction times in performing the working memory tasks ........- 105 -
3.3.3.3 Performances of the 0-back task ..................................................... - 107 -
3.3.3.4 The startle reflex .............................................................................- 109 -
3.3.3.5 The questionnaire scores ................................................................- 112 -
3.3.4 Discussion ..................................................................................................- 114 -
Chapter 4 General discussion .............................................................................................- 116 -
4.1 Anxiety and visual search with facial expressions ...............................................- 116 -
4.2 The application of brain stimulation on modulating working memory performance, impact of external stimuli and self-reported anxiety levels ........................................- 121 -
4.3 Future directions ................................................................................................... - 127 -
References ..........................................................................................................................- 129 -

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指導教授

馬杰仁(Neil G. Muggleton)

審核日期

2015-10-29

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