Supplementary Materials s15

Supplementary Materials

This file includes:

Materials and Methods

References

Figure S1

Figure S2

Questionnaire S1

1 Materials and Methods

Ethics Statements

The Human Investigations Committee of Zhejiang Normal University approved this research. The experiment conforms to The Code of Ethics of the World Medical

Association (Declaration of Helsinki).

Participants

Forty-four valid participants (we recruited 50 participants; participants with less than 5 trials in any condition were excluded from further analysis) who were university students were recruited through advertisements. Participants were randomly assigned into one of two groups: one using an Internet-based search engine, the other using an encyclopedia. Participants’ ages (t=0.40, p=0.64) and gender composition (12 males, 11 females in Internet group; 10 males, 11 females in

Encyclopedia group) were balanced and no statistically significant differences were found between these two groups. All participants provided written informed consent and underwent structured psychiatric interviews (using the MINI)

(Lecrubier et al., 1997) performed by an experienced psychiatrist. The MINI was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiological studies. All participants were free of psychiatric disorders (including major depression, anxiety disorders, schizophrenia, and substance dependence disorders) as assessed by the MINI. All participants were medication-free and were instructed not to use any substances, including coffee, on the day of scanning.

2 Task

Before scanning, participants were asked to find the answers to 40 questions and remember these answers. One group was asked to find answers through an Internet search engine (Internet group); the other group was asked to find answers through the use of a traditional printed encyclopedia (Encyclopedia group). Participants were asked to find the results and remember all the items within 40 minutes. The duration of time was set based on a pilot study and was sufficient for subjects to perform the task. In order to avoid participants’ recitation during the waiting period after the search-remember process, participants were asked to perform a 5-minute distraction task (continuously subtract 4 from 99) and complete several questionnaires (taking about 5 minutes). Besides these 40 questions without clues, there were 20 items followed by a short paragraph of descriptions about this issue and were termed questions with clues (analyses of these trials were not included in current study).

Participants were asked to find answers to questions and remember them without taking notes in order to promote memory generation and recall processes. In the

Encyclopedia group, questions were presented on printed, laminated pages. In the

Internet group, the questions were shown on a computer screen in PDF format.

To avoid potential effects from participants’ previous knowledge, the questions selected related to uncommon topics (for example, the age of the first animal that

3 people sent to space). In addition, participants were asked to identify questions to which they already knew the answers during learning. These items were excluded from further analysis (8 trials excluded in all subjects).

During fMRI, participants were asked to perform a recall and recognition task

(Figure S1). Stimuli were presented and behavioral data were collected using E- prime software (Psychology Software Tools, Inc.). In each trial, a fixation cross was presented first for 500ms, and then a recall period lasted for up to 4000ms. In this period, one question was presented, participants were asked to read and recall the items and select ‘remember’ or ‘forget’ via button press. The stimulus turned black after the key pressing and last for (4000-RT) ms. A black screen was presented for a duration of 500 to 2500ms, with the duration jittered. A recognition stage followed

(same question as in the recall stage) in which participants were asked to choose one answer from the answers listed. This stage lasted for up to 2000ms (awaiting a button press), which was followed by a black screen with a jittered interval ranging from 1500ms to 3500ms (Figure S1). We focused analyses on the recall stage in the current study.

Participants were told that they would be paid a guaranteed 50 Yuan (≈8 US$) for participation, and to encourage their motivation to response accurately, were told they would be rewarded with additional money based on their task performance.

Specifically, if they responded ‘remember’ in the ‘recall’ stage and chose the correct answer in the ‘recognition’ stage (Remember-Correct), they would gain an extra 1

4 Yuan for each trial. If they responded ‘remember’ in the ‘recall’ stage and chose the incorrect answer in the ‘recognition’ stage (Remember-Incorrect), they would lose 1

Yuan. The other responses were not rewarded or punished. These strategies were implemented to help ensure that participants would perform the task in an honest and memory-based fashion. In this study, we focused on the comparison between these two types of trials: ‘Remember-Correct’ and ‘Remember-Incorrect’ in within the sample and within and between the two groups.

Structural images were collected using a T1-weighted three-dimensional spoiled gradient-recalled sequence covering the whole brain (176 slices, repetition time=1700 ms, echo time TE=3.93 ms, slice thickness=1.0 mm, skip=0 mm, flip angle=15, inversion time=1100ms, field of view=240*240mm, in-plane resolution=256*256). Functional MRI was performed on a 3T scanner (Siemens

Trio) with a gradient-echo EPI T2 sensitive pulse sequence in 33 slices (interleaved sequence, 3mm thickness, TR=2000ms, flip angle 90°, field of view 220x220 mm2, matrix 64x64). Stimuli were presented using an Invivo synchronous system (Invivo

Company, www.invivocorp.com) through a screen in the head coil, enabling participants to view the stimuli. The whole experiment lasted for 15 minutes.

The functional data were analyzed using SPM8 (http://www.fil.ion.ucl.ac.uk/spm), and Neuroelf (http://neuroelf.net) as described previously (DeVito et al., 2012;

Krishnan-Sarin et al., 2013). Images were slice-timed, reoriented, and realigned to the first volume, with T1-co-registered volumes used to correct for head

5 movements. Images were then normalized to MNI space and spatially smoothed using a 6mm FWHM Gaussian kernel. A general linear model (GLM) was applied to identify BOLD activation in relation to separate event types. Six head-movement parameters derived from the realignment stage were included to exclude motion- related variances. The scores on a scale assessing Internet search characteristics were included as a covariate during analyses (Questionnaire S1). A GLM approach was used to identify voxels that were significantly activated for the each event that was modeled.

Second-level analysis treated inter-subject variability as a random effect. First, we tested for voxels that showed higher or lower activity in the contrasts of different types of trials (Remember_Incorrect > Remember_Correct). Second, we compared these two groups in the comparisons (Internet group versus Encyclopedia group).

We first identified clusters of contiguously significant voxels at an uncorrected threshold p<0.05, as is also used for display purposes in the figures. We then tested these clusters for cluster-level FWE correction p<0.05 and the AlphaSim estimation indicated that clusters with 120 contiguous voxels would achieve an effective FWE threshold p<0.05. The smoothing kernel used during simulating false-positive

(noise) maps using AlphaSim was 6mm, and was estimated from the residual fields of the contrast maps being entered into the one-sample t-test. The formula used to compute the smoothness is that used in FSL (see http://www.fmrib.ox.ac.uk/analysis/techrep/tr00df1/tr00df1/node6.html for more information).

6 Correlation analysis between behavioral performance and brain response

We first compared the brain activation between ‘Remember_Incorrect’ and

‘Remember_Correct’ and then took the surviving clusters as ROIs in further analyses. For each ROI, a representative BOLD beta value was obtained by averaging the signal of all the voxels within the ROI. Because the four surviving clusters showed similar patterns , we took the mean value of the beta value from these four clusters as an index to examine in correlational analyses with response times.

Functions of identified clusters

Because the four identified brain clusters after comparison showed similar activation patterns and have each been linked to memory processing (see below), we considered them together in the ‘discussion’ section.

The middle/superior temporal gyri are thought to be involved in encoding declarative long-term memory, with declarative memory referring to all memories that are consciously available (Axmacher, Schmitz, Wagner, Elger, & Fell, 2008;

Barense et al., 2005; Cohen & Stackman Jr, 2014; Jeneson & Squire, 2012; Libby,

Hannula, & Ranganath, 2014; Simons & Spiers, 2003). Patients with damage to these areas as compared to healthy control subjects have been found to perform more poorly on explicit learning tests (Meulemans & Van der Linden, 2003; Skirrow et al.,

2014).

7 The fusiform gyrus is part of the temporal lobe and occipital lobe, which is located between the inferior temporal gyrus and the parahippocampal gyrus. This area contributes to long-term memory, especially with respect to processing of facial and body recognition (Ghuman et al., 2014; Grill-Spector, Knouf, & Kanwisher, 2004) and word recognition (Dehaene & Cohen, 2011; McCandliss, Cohen, & Dehaene,

2003).

The lentiform nucleus comprises the putamen and the globus pallidus within the basal ganglia. These regions have been associated with multiple aspects of learning and memory including procedural learning (Stocco, Lebiere, & Anderson, 2010), cognition (Lieberman, 2014) and affective speech (Fruhholz, Sander, & Grandjean,

2014; Hasson, Llano, Miceli, & Dick, 2014).

Acknowledgements This research was supported by National Science Foundation of China (31371023) and the National Center for Responsible Gaming. The authors thank Yifen Zhang and

Xiao Lin for their help in data analyzing and figure preparing.

Role of the funding Source

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The contents of the manuscript do not necessarily reflect the views of the funding agencies.

8 Contributors

Guangheng Dong wrote the first draft of the manuscript, Marc Potenza contributed in editing, interpretation and revision processes. All authors contributed to and have approved the final manuscript.

Competing Interests

The authors declared that no competing interests exist. Dr. Potenza has received financial support or compensation for the following: Dr. Potenza has consulted for and advised Somaxon, Boehringer Ingelheim, Lundbeck, Ironwood, Shire, INSYS and

RiverMend Health; has received research support from the National Institutes of

Health, Veteran’s Administration, Mohegan Sun Casino, the National Center for

Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories, Ortho-McNeil, Oy-Control/Biotie, Glaxo-SmithKline, Pfizer and Psyadon pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices, the federal public defender’s office and gambling entities on issues related to impulse control disorders; provides clinical care in the Connecticut Department of Mental Health and Addiction Services

Problem Gambling Services Program; has performed grant reviews for the National

Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts.

9 References

Axmacher, N., Schmitz, D. P., Wagner, T., Elger, C. E., & Fell, J. (2008). Interactions between medial temporal lobe, prefrontal cortex, and inferior temporal regions during visual working memory: A combined intracranial EEG and functional magnetic resonance imaging study. Journal of Neuroscience, 28(29), 7304-7312. Barense, M. D., Bussey, T. J., Lee, A. C., Rogers, T. T., Davies, R. R., Saksida, L. M., et al. (2005). Functional specialization in the human medial temporal lobe. J Neurosci, 25(44), 10239-10246. Cohen, S. J., & Stackman Jr, R. W. (2014). Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res. Dehaene, S., & Cohen, L. (2011). The unique role of the visual word form area in reading. Trends Cogn Sci, 15(6), 254-262. DeVito, E. E., Worhunsky, P. D., Carroll, K. M., Rounsaville, B. J., Kober, H., & Potenza, M. N. (2012). A preliminary study of the neural effects of behavioral therapy for substance use disorders. Drug Alcohol Depend, 122(3), 228-235. Fruhholz, S., Sander, D., & Grandjean, D. (2014). Functional neuroimaging of human vocalizations and affective speech. Behav Brain Sci, 37(6), 554-555. Ghuman, A. S., Brunet, N. M., Li, Y., Konecky, R. O., Pyles, J. A., Walls, S. A., et al. (2014). Dynamic encoding of face information in the human fusiform gyrus. Nat Commun, 5, 5672. Grill-Spector, K., Knouf, N., & Kanwisher, N. (2004). The fusiform face area subserves face perception, not generic within-category identification. Nat Neurosci, 7(5), 555-562. Hasson, U., Llano, D. A., Miceli, G., & Dick, A. S. (2014). Does it talk the talk? On the role of basal ganglia in emotive speech processing. Behav Brain Sci, 37(6), 556-557. Jeneson, A., & Squire, L. R. (2012). Working memory, long-term memory, and medial temporal lobe function. Learn Mem, 19(1), 15-25. Krishnan-Sarin, S., Balodis, I. M., Kober, H., Worhunsky, P. D., Liss, T., Xu, J. S., et al. (2013). An Exploratory Pilot Study of the Relationship Between Neural Correlates of Cognitive Control and Reduction in Cigarette Use Among Treatment-Seeking Adolescent Smokers. Psychology of Addictive Behaviors, 27(2), 526-532. Lecrubier, Y., Sheehan, D. V., Weiller, E., Amorim, P., Bonora, I., Harnett Sheehan, K., et al. (1997). The Mini International Neuropsychiatric Interview (MINI). A short diagnostic structured interview: reliability and validity according to the CIDI. European Psychiatry, 12(5), 224-231. Libby, L. A., Hannula, D. E., & Ranganath, C. (2014). Medial temporal lobe coding of item and spatial information during relational binding in working memory. J Neurosci, 34(43), 14233-14242. Lieberman, P. (2014). Why we can talk, debate, and change our minds: Neural circuits, basal ganglia operations, and transcriptional factors. Behav Brain Sci, 37(6), 561-562.

10 McCandliss, B. D., Cohen, L., & Dehaene, S. (2003). The visual word form area: expertise for reading in the fusiform gyrus. Trends Cogn Sci, 7(7), 293-299. Meulemans, T., & Van der Linden, M. (2003). Implicit learning of complex information in amnesia. Brain Cogn, 52(2), 250-257. Simons, J. S., & Spiers, H. J. (2003). Prefrontal and medial temporal lobe interactions in long-term memory. Nat Rev Neurosci, 4(8), 637-648. Skirrow, C., Cross, J. H., Harrison, S., Cormack, F., Harkness, W., Coleman, R., et al. (2014). Temporal lobe surgery in childhood and neuroanatomical predictors of long-term declarative memory outcome. Brain. Stocco, A., Lebiere, C., & Anderson, J. R. (2010). Conditional routing of information to the cortex: a model of the basal ganglia's role in cognitive coordination. Psychol Rev, 117(2), 541-574.

11 Figure S1. The timeline of one trial in the fMRI task

In each trial, a fixation was presented first for 500ms. A recall period followed, lasting for 4000ms at most. During this period, one question was presented, and participants were asked to read and recall the items and select ‘remember’ or

‘forget’ with relevant key presses. The stimulus turned black after the key pressing and lasted for (4000-RT) ms. A black screen jittered from 500 to 2500ms was presented. The recognition stage (same question as during the recall stage) followed; at this point, participants were asked to choose one answer from the listed possibilities. This stage lasted for 2000ms or until a button press, with black screen following the button press to complete the 2000ms duration. A jitter ranging from

1500ms to 3500ms followed. In this study, we focused on brain activations in the recall stage (the window in green frame) during presentation of novel stimuli.

12 Figure S2. Activation patterns in the identified four clusters.

Beta-weight values from each identified cluster are plotted. Similar patterns were observed in the four clusters with differences relating to decreased brain activation in the Internet group and increased brain activation in Encyclopedia group in the

‘Remember_Incorrect’ trials.

13 Questionnaire S1

The Questionnaire on Internet Searching (Translated from Chinese)

Hello, we are researchers in the Department of Psychology of Zhejiang Normal University. We undertake this investigation to understand your usage of Internet search engines. The results will not be open to the public; please answer the questions honestly and seriously. Please read the following information before your answering: 1. Internet search means individuals using Internet search engines (for example, Google, Baidu) to find information from the Internet. 2. The ways people use Internet search engines include computers, IPADs, smart phones and other terminal sets. Basic information: 1. Gender: Male Female 2. Age: 3. Grade: 4. Major: 5. Years from your first Internet use: 6. Years from your first Internet search: 7. The time you spend on Internet searching every day: minutes 8. Please estimate the times you search the Internet everyday: 9. Percent of your online time in using the Internet to search: %

Please provide your answers according to the following criteria. 0. Never 1. Seldom 2. Sometime 3. Usually 5. Always

14 1. When facing with debatable questions, I prefer to search Google/Baidu first. 2. I won’t take notes if I know I can search for the information on the Internet. 3. When I am asked a complex question, I usually try to abstract the key words from it. 4. When someone disagrees with my points, I usually search the Internet to provide the answer. 5. I think it is not necessary to remember a thing if we can find it from Internet searches. 6. When somebody asks me a question, I will search the Internet for answers if I cannot figure it out immediately. 7. I can abstract keywords quickly from a sentence for doing a potential Internet search. 8. I will be upset if I cannot find a complex question through an Internet search. 9. I think an Internet search can satisfy daily needs, including learning and living. 10. I usually start the search page unconsciously when I am idle. 11. I am not confident about the answers in my memory if I cannot double-check the answers through Internet searches. 12. I think we can find reliable information through Internet searching.

Thanks for your sincerely participation!