A MUCH debated question is whether sex differences exist in the functional organization of the brain for language1–4. A long-held hypothesis posits that language functions are more likely to be highly lateralized in males and to be represented in both cerebral hemispheres in females5,6, but attempts to demonstrate this have been inconclusive7–17. Here we use echo-planar functional magnetic resonance imaging18–21 to study 38 right-handed subjects (19 males and 19 females) during orthographic (letter recognition), phonological (rhyme) and semantic (semantic category) tasks. During phonological tasks, brain activation in males is lateralized to the left inferior frontal gyrus regions; in females the pattern of activation is very different, engaging more diffuse neural systems that involve both the left and right inferior frontal gyrus. Our data provide clear evidence for a sex difference in the functional organization of the brain for language and indicate that these variations exist at the level of phonological processing.

Sex differences in the functional organization of the brain for language

http://www3.uji.es/~gonzalez/neuroimage.pdf

Reading cinnamon activates olfactory brain regions

Sex differences and reproductive hormone influences on human odor perception

Background In functional brain imaging studies, exposure to cues related to cocaine, opiates, and alcohol in dependent individuals is associated with activation of the anterior cingulate gyrus, amygdala, orbitofrontal cortex, and dorsolateral prefrontal cortex. Craving for these substances positively correlates with activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula. The objective of this study was to determine changes in regional cerebral glucose metabolism and correlations between craving and regional metabolism in heavy cigarette smokers exposed to cigarette-related cues. Methods Twenty heavy smokers (who smoked ≥20 cigarettes per day) and 20 nonsmoking control subjects underwent 2 fluorine 18–fluorodeoxyglucose positron emission tomography scans 10 days apart in randomized order: one while watching a videotape that presented cigarette-related cues and handling a cigarette, and the other while watching an educational (nature) videotape and handling a neutral object (pen). Results From the neutral to the cigarette cue scan, heavy smokers had greater increases than nonsmoking controls in relative glucose metabolism in the perigenual anterior cingulate gyrus spanning the midline. Significant positive correlations were found between intensity of craving and metabolism in the orbitofrontal cortex, dorsolateral prefrontal cortex, and anterior insula bilaterally. An unexpected positive association was found between craving and metabolism in the right sensorimotor cortex. Conclusions Brain regions associated with arousal, compulsive repetitive behaviors, sensory integration, and episodic memory are activated during exposure to cigarette-related cues and cigarette craving. These regional brain activations and associations with craving are similar to findings with other addictive substances.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/206957/yoa10040.pdf

Brain metabolic changes during cigarette craving.

Olfactory system and emotion: Common substrates

Purpose: Our goal was to use functional MRI (fMRI) to measure brain activation in response to imagination of odors in humans. Method: fMR brain scans were obtained in 21 normal subjects (9 men, 12 women) using multislice FLASH MRI in response to imagination of odors of banana and peppermint and to the actual smells of the corresponding odors of amyl acetate and menthone, respectively, in three coronal sections selected from anterior to posterior temporal brain regions. Similar studies were obtained in two patients with hyposmia using FLASH MRI and in one patient with hyposmia using echo planar imaging, both before and after theophylline treatment, which returned smell function to or toward normal in each patient. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. Results: Activation was present in each section in all normal subjects and in each patient after imagination of each vapor. In normal subjects, brain activation in response to imagination of odors was significantly less than that in response to the actual smell of these odors, and activation following imagination of banana odor was significantly greater in men than in women, as was previously reported for the actual smell of the odor of amyl acetate. However, in relative terms, albeit at an absolute lower brain activation level, the ratio of brain activation by imagination of banana to activation by actual amyl acetate odor was about twice as high in women as in men. Before treatment, in patients with hyposmia, brain activation in response to odor imagination was greater than after presentation of the actual odor itself. After treatment, in patients with hyposmia in whom smell acuity returned to or toward normal, brain activation in response to odor imagination was not significantly different quantitatively from that before treatment; however, brain activation in response to the actual odor was significantly greater than that in response to imagination of the corresponding odor. Brain regions activated by both odor imagination and actual corresponding odor were similar and consistent with regions previously described as responding to odors. Conclusion: These studies indicate that (a) odors can be imagined and similar brain regions are activated by both imagined and corresponding actual odors; (b) imagination of odors elicits quantitatively less brain activation than do actual smells of corresponding odors in normal subjects; (c) absolute brain activation in men by odor imagination is greater than in women for some odors, but on a relative basis, the ratio for odor imagination to actual smell in women is twice that in men; (d) odor imagination, once the odor has been experienced, is present, recallable, and capable of inducing a relatively constant degree of brain activation even in the absence of the ability to recognize an actual corresponding odor. Index Terms: Magnetic resonance imaging-Magnetic resonance imaging, functional-Cognition-Smell-Memory-Odor memory.

Odor memory induces brain activation as measured by functional MRI.

Purpose: Our goal was to demonstrate that medical therapy in patients with smell loss (hyposmia) that restored olfactory function toward or to normal could be verified and quantitated by functional MRI (fMRI) of brain and that visual representation of these changes could be used to identify these patients. Method: Multislice FLASH MR or echo planar MR brain scans were obtained in four patients with hyposmia in response to three olfactory stimuli both before and after treatment with theophylline. Activation images were derived using correlation analysis, and ratios of brain area activated to total brain area were obtained. Results: Prior to treatment, all patients stated that they could not smell; these losses were confirmed by standard psychophysical tests. At this time, fMRI brain activation in response to odors was significantly less than that measured in normal volunteers and similar to activation measured previously in other patients with a similar type of hyposmia. After treatment, subjective smell function improved in three patients and no improvement occurred in one; results were confirmed by psychophysical tests. In each patient in whom smell acuity improved, brain activation in response to each odor increased in each section and mean activation increased significantly for each odor. Activation increased in all regions previously associated with olfactory stimulation and was particularly apparent in orbitofrontal cortex, frontal lobe component of cingulate gyri, temporal lobe gyri, and hippocampus. There also was consistent activation in superior, middle, and inferior frontal lobe gyri. There were no changes in brain activation after treatment in the patient in whom smell did not improve. Conclusion: These results demonstrate that theophylline is an effective therapeutic agent to correct hyposmia in some patients with smell loss. These changes have been documented by fMRI brain scans using olfactory stimuli. This is the first study in which this type of objective improvement following medical treatment has been demonstrated in patients with hyposmia.

Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI.

Purpose: Our goal was to use functional MRI (fMRI) to measure brain activation in response to olfactory stimuli. Method: fMRI brain scans were obtained in 17 normal subjects (9 men, 8 women) using multislice FLASH MRI in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. Results: Activation was present in each section in all subjects. Subjective estimation of vapor intensity followed relative vapor pressure of stimuli presented (pyridine > amyl acetate > menthone) and were similar for both men and women. However, brain activation did not follow subjective responsiveness order but rather pyridine > menthone > amyl acetate, a pattern demonstrated by both men and women. Brain activation in women was consistently lower than in men for all vapors in all brain sections, although regions of activation did not differ. Activation occurred in regions previously recognized as associated with olfactory stimulation, including orbitofrontal and entorhinal cortex; however, extensive regions within frontal cortex including cingulate gyrus were also activated. Brain regions activated to odors considered pleasant or unpleasant did not differ. Conclusion: The techniques used in this study demonstrated that brain activation to olfactory stimuli could be measured quantitatively such that differences between groups of subjects (in this case men and women) could be compared. Although localization of brain activation was not the major thrust of this study, activation to olfactory stimuli was found not only in brain regions previously associated with processing of olfactory information but also in several other areas of frontal cortex, in cingulate gyrus, and in several components of the limbic system. This is the first study in which activation in human brain parenchyma of normal humans to olfactory stimuli has been quantitated by fMRI.

Functional MRI of human olfaction.

Purpose: Our goal was to use functional MRI (fMRI) to develop an objective, noninvasive technique by which patients with smell loss can be identified, their abnormalities quantitated, their results compared with findings in normal subjects, and visual representation of their CNS pathology obtained. Method: Functional MR brain scans were obtained in eight patients with hyposmia in response to three olfactory stimuli (pyridine, menthone, amyl acetate) in three coronal brain sections selected from anterior to posterior temporal brain regions using multislice FLASH MRI. Results were compared with similar studies performed in 17 normal subjects. Activation images were derived using correlation analysis, and ratios of area of brain activated to total brain area were obtained. Results: Brain activation to each stimulus was lower in each section in patients compared with normal subjects and reached statistical significance for mean activation for each odor and in six of the nine individual sections studied. Activation in patients was found in regions previously associated with CNS processing of olfactory stimuli in normal subjects, but activation in patients was much less, particularly in inferior frontal and cingulate gyral regions of frontal cortex and in regions of medial and posterior temporal cortex. Conclusion: These results demonstrate quantitative CNS changes in smell function in response to olfactory stimuli in patients with hyposmia, demonstrate a novel, objective method by which these patients can be identified, and provide maps of the CNS changes associated with their smell loss.

Mapping brain activation to odorants in patients with smell loss by functional MRI.

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Odor memory induces brain activation as measured by functional MRI.

Increased brain activation in response to odors in patients with hyposmia after theophylline treatment demonstrated by fMRI.

Functional MRI of human olfaction.

Mapping brain activation to odorants in patients with smell loss by functional MRI.