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AAPM 2025 - 67th Annual Meeting & Exhibition of the American Association of Physicists in Medicine

fMRI, Optogenetics Research on Brain Activity Yields Clues into Neural Circuitry

By MedImaging International staff writers
Posted on 16 Jun 2010

Combined with new optics and gene technology, functional magnetic resonance imaging (fMRI) is now being used to evaluate the brain-wide impact of changes in neural circuitry, such as ones that may underlie many neurologic and psychiatric diseases.

Similar to a motorist who realizes that the "check engine” light indicates something important but ill-defined is occurring, neuroscientists have relied heavily on an incompletely understood technology called fMRI to reveal what the brain is doing when people respond to different stimuli. The noninvasive technology offers a view into the physiology of human cognition and emotion, but--without a real clarification of how some common fMRI signals are produced--the ability of researchers to draw conclusions has been limited.

Now a Stanford University School of Medicine (Stanford, CA, USA)-led team has solved the mystery, and in doing so has discovered a new way to make fMRI signals based on increased blood flow even more useful when combined with optogenetics (a technology developed at Stanford that employs genes from microbes to allow neurons to be controlled with pulses of light).

The team's research was published May 16, 2010, in the online version of the journal Nature. The study is the first to validate what neurologists could only hope was true: that fMRI signals based on heightened levels of oxygenated blood in specific parts of the brain are caused by an increase in the excitation of specific kinds of brain cells. For example, in the past investigators could only assume that when they showed subjects a picture of someone they knew, stronger fMRI signal in a part of the brain that perhaps deals with face recognition was caused by the excitation of neurons, rather than some other factor.

These signal increases are measured using the blood oxygenation level-dependent (BOLD) technique. Because researchers have published more than 250,000 articles utilizes or building upon the BOLD technique, clarifying its true meaning is very important, according to senior author Karl Deisseroth, M.D., Ph.D., associate professor of bioengineering and of psychiatry and behavioral sciences. "It was often assumed that a positive fMRI BOLD signal can represent increased activity of excitatory neurons, but this was never really known and, in fact, became much more controversial over the years,” said Dr. Deisseroth. Now, the new study confirms those earlier suppositions.

The key experiment involved turning on genetically engineered excitatory neurons in an experimental group of rats in the presence of blue light delivered via a fiberoptic cable. The researchers then anesthetized the rats and looked at their brains with fMRI. They discovered that exciting these defined neurons with the optogenetic light generated the same kind of signals that researchers see in traditional fMRI BOLD experiments--with the same complex patterns and timing. In the control group of rats, which were not genetically modified, no such signals occurred. This showed that true neural excitation indeed produces positive fMRI BOLD signals.

To see what else this new understanding of optogenetically-enhanced fMRI BOLD might produce, the researchers took the research a few steps further, led by co-first authors Remy Durand, a Stanford bioengineering graduate student, and Jin Hyung Lee, Ph.D., a University of California Los Angeles (UCLA; USA) assistant professor and alumna of Deisseroth's lab at Stanford. They found that they could use optogenetics to produce activity in specific kinds of cells in neural circuits, and then read out the far-reaching effects with fMRI BOLD over a substantial distance in the brain.

In one experiment, for example, the investigators could see how activity they stimulated in the thalamus, a major relay center deep in the brain, could affect circuits stretching into the somatosensory cortex, a surface brain region important in processing sensation. "We can now ask what the true impact of a cell type is on global activity in the brain of a living mammal,” Dr. Deisseroth concluded. "A key to scientific inquiry is developing tools that allow us to intervene and experiment with brain circuits--engineering a reversible gain or loss of function--rather than simple observation of correlations. This points to new approaches for understanding and treatment.”

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58 (61.03515625): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

59 (97.990036010742): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

60 (49.114227294922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

61 (81.777572631836): select cover from jos_number where journalid in (5) and cover is not null order by left(issue,2)+right(issue,2)*12 desc limit 1

62 (496.86431884766): SELECT fid FROM jos_deeppockets WHERE id=294729796 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294729796 AND published='1' LIMIT 1

63 (262.02201843262): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

64 (56.028366088867): select jos_twitters.link from jos_twitters where cat=10

65 (30.040740966797): select jos_facebook.link from jos_facebook where cat=10

66 (30.994415283203): select jos_google_plus.link from jos_google_plus where cat=10

67 (28.848648071289): select jos_linkedin.link from jos_linkedin where cat=10

68 (30.994415283203): SELECT fid FROM jos_deeppockets WHERE id=294729796 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294729796 AND published='1' LIMIT 1

69 (36.001205444336): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

70 (292.06275939941): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (246.04797363281): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (73.909759521484): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

73 (47.206878662109): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (27.179718017578): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (42.915344238281): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (28.848648071289): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (31.948089599609): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

90 (47.922134399414): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (71.048736572266): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

105 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

106 (51.021575927734): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729796 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (47.206878662109): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729796 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (67.949295043945): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

109 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

110 (48.160552978516): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294729796 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (454.90264892578): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294729796 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (524.99771118164): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

113 (309.94415283203): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

114 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

115 (56.982040405273): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

116 (95.129013061523): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

117 (37.908554077148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

118 (125.88500976562): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

119 (41.007995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

120 (48.87580871582): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

121 (39.100646972656): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

122 (253.91578674316): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 22863.864898682): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7

124 (633.95500183105): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729796 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729796 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 9737.0147705078): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

126 (115.15617370605): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

127 (56.982040405273): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

128 (30.994415283203): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

129 (59.127807617188): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

130 (30.040740966797): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

131 (294.92378234863): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

132 (34.809112548828): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

133 (32.901763916016): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

134 (36.001205444336): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

135 (545.97854614258): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (!!!!! 4137.0391845703): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (!!!!! 2869.1291809082): SELECT name FROM jos_deeppockets WHERE id=212

138 (56.982040405273): SELECT name FROM jos_deeppockets WHERE id=212

139 (679.01611328125): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (528.09715270996): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (74.863433837891): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

142 (44.107437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

143 (!!!!! 16058.206558228): TRUNCATE TABLE jos_trademed_module

144 (!!!!! 1527.0709991455): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729796 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (185.01281738281): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294729796 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (280.14183044434): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

149 (39.100646972656): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

150 (984.90715026855): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6

151 (59.127807617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

152 (41.961669921875): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

153 (41.007995605469): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294729796 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294729796 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (424.86190795898): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)

155 (37.908554077148): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)

156 (31.948089599609): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (!!!!! 2861.9766235352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

158 (46.968460083008): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294729796 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294729796 AND published='1' LIMIT 1

159 (36.001205444336): select jos_twitters.link from jos_twitters where cat=10

160 (26.941299438477): select jos_facebook.link from jos_facebook where cat=10

161 (26.941299438477): select jos_google_plus.link from jos_google_plus where cat=10

162 (25.98762512207): select jos_linkedin.link from jos_linkedin where cat=10

163 (226.97448730469): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

164 (!!!!! 2737.0452880859): insert into jos_banners_delta values (14615,'2025-06-28 05:15:28','216.73.216.249','view'),(14202,'2025-06-28 05:15:28','216.73.216.249','view'),(14203,'2025-06-28 05:15:28','216.73.216.249','view')

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