A pet study of human skill learning: changes in brain activity related to learning an orientation discrimination task

Using 15O-water 3D positron emission tomography we investigated the effect of training in orientation discrimination upon cerebral activity in healthy human adults. When subjects are trained in this discrimination task, they learn the visuo-motor stimulus-response association required by the task and they increase their perceptual abilities in orientation discrimination. The present study was designed to investigate the rCBF modifications related to both these learning processes induced by training in orientation discrimination. PET data were acquired on two separate days (before and after training). Comparing the activation pattern related to orientation discrimination before and after the training period we observed activity decreases located in the left cerebellar cortex, in the right precentral gyrus and bilaterally in the fusiform gyri. The only region showing an activity increase was located in the body of the right caudate nucleus. These findings confirm the role of the neostriatum in skill learning and highlight the importance of mechanisms resulting in cortical and cerebellar neuronal activity decreases in this type of learning.     

Politics on the brain: an FMRI investigation

We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation also was associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks-one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge-cooperate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.     

Ageing affects brain activity in highly educated older adults: An ERP study using a word-stem priming task

In this event-related evoked potentials (ERP) study, the neural correlates of a group of highly educated older adults were compared with those of a group of young adults while performing a word-stem completion priming task under semantic and lexical encoding conditions. The results revealed that both age groups exhibited robust priming. The older participants showed better performance than the young adults. Both groups exhibited ERP repetition effects at posterior sites, but only the older adults showed additional frontal activity. The results suggest that highly performing older adults compensate for their lower level of parieto-occipital functioning, reflected by smaller P300 amplitude at posterior sites, by recruiting frontal sites as a mode of brain adaptation.     

Scene construction in amnesia: an FMRI study

In recent years, there has been substantial interest in how the human hippocampus not only supports recollection of past experiences, but also the construction of fictitious and future events, and the leverage this might offer for understanding the operating mechanisms of the hippocampus. Evidence that patients with bilateral hippocampal damage and amnesia cannot construct novel or future scenes/events has been influential in driving this line of research forward. There are, however, some patients with hippocampal damage and amnesia who retain the ability to construct novel scenes. This dissociation may indicate that the hippocampus is not required for scene construction, or alternatively, there could be residual function in remnant hippocampal tissue sufficient to support the basic construction of scenes. Resolving this controversy is central to current theoretical debates about the hippocampus. To investigate, we used fMRI and a scene construction task to test patient P01, who has dense amnesia, ～50% bilateral hippocampal volume loss, and intact scene construction. We found that scene construction in P01 was associated with increased activity in a set of brain areas, including medial temporal, retrosplenial, and posterior parietal cortices, that overlapped considerably with the regions engaged in control participants performing the same task. Most notably, the remnant of P01's right hippocampus exhibited increased activity during scene construction. This suggests that the intact scene construction observed in some hippocampal-damaged amnesic patients may be supported by residual function in their lesioned hippocampus, in accordance with theoretical frameworks that ascribe a vital role to the hippocampus in scene construction.     

Abnormal FMRI brain activation in euthymic bipolar disorder patients during a counting Stroop interference task

BACKGROUND: Bipolar disorder is characterized by disturbed mood homeostasis accompanied by cognitive impairments that appear to persist during euthymia. Cognitive probes, coupled with neuroimaging, provide an approach toward clarifying the neurophysiology of bipolar disorder. METHOD: Sixteen patients with euthymic bipolar disorder and 16 healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a counting Stroop interference task and a control condition. Task performance was correlated with regional brain activation differences between groups, and the effect on brain activation of receiving versus not receiving medications was evaluated. RESULTS: Bipolar patients exhibited impaired task performance relative to the healthy subjects. In addition, the two groups demonstrated significantly different patterns of brain activation during the interference task. Healthy subjects exhibited relatively increased activation in temporal cortical regions, middle frontal gyrus, putamen, and midline cerebellum. Bipolar subjects exhibited relatively greater activation in the medial occipital cortex. The groups demonstrated different associations between task performance and fMRI activation in these brain regions. No differences in activation in these regions were observed between patients who were versus those who were not receiving medications; however, patients receiving medications exhibited greater activation in the anterior cingulate and dorsolateral prefrontal cortex. CONCLUSIONS: These differences suggest that patients with euthymic bipolar disorder fail to activate brain regions associated with performance of an interference task, which may contribute to impaired task performance. Medications do not explain these differences but may influence activation of brain regions primarily associated with performing an interference task.     

Humor comprehension and appreciation: an FMRI study

Humor is a unique ability in human beings. Suls [A two-stage model for the appreciation of jokes and cartoons. In P. E. Goldstein & J. H. McGhee (Eds.), The psychology of humour. Theoretical perspectives and empirical issues. New York: Academic Press, 1972, pp. 81-100] proposed a two-stage model of humor: detection and resolution of incongruity. Incongruity is generated when a prediction is not confirmed in the final part of a story. To comprehend humor, it is necessary to revisit the story, transforming an incongruous situation into a funny, congruous one. Patient and neuroimaging studies carried out until now lead to different outcomes. In particular, patient studies found that right brain-lesion patients have difficulties in humor comprehension, whereas neuroimaging studies suggested a major involvement of the left hemisphere in both humor detection and comprehension. To prevent activation of the left hemisphere due to language processing, we devised a nonverbal task comprising cartoon pairs. Our findings demonstrate activation of both the left and the right hemispheres when comparing funny versus nonfunny cartoons. In particular, we found activation of the right inferior frontal gyrus (BA 47), the left superior temporal gyrus (BA 38), the left middle temporal gyrus (BA 21), and the left cerebellum. These areas were also activated in a nonverbal task exploring attribution of intention [Brunet, E., Sarfati, Y., Hardy-Bayle, M. C., & Decety, J. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage, 11, 157-166, 2000]. We hypothesize that the resolution of incongruity might occur through a process of intention attribution. We also asked subjects to rate the funniness of each cartoon pair. A parametric analysis showed that the left amygdala was activated in relation to subjective amusement. We hypothesize that the amygdala plays a key role in giving humor an emotional dimension.     

Measuring attachment representation in an FMRI environment: a pilot study

This exploratory study is the first to examine the neural correlates of attachment status in adults. The study examined the feasibility of assessing attachment narratives in the functional magnetic resonance imaging (fMRI) environment by challenging subjects to tell attachment stories to specific attachment pictures from the Adult Attachment Projective (AAP) while being scanned. We investigated theoretically derived hypotheses regarding predicted differences in the brain activation patterns of individuals whose attachment status was organized (resolved) versus disorganized (unresolved) with respect to attachment trauma (e.g., as associated with loss through death, abuse, threat of abandonment). Adult attachment was assessed using the AAP, a new representational attachment measure that we thought might be suitable for use in the fMRI environment. This measure was used to obtain a preliminary picture of the neural processes associated with the activation of attachment in 11 healthy female adults. Results are reported from a second-level analysis (p < 0.001 uncorrected) and confirm that the AAP is a feasible measure for use in a neuroimaging environment. Cerebral activation during continuous speech yielded results consistent with the literature. Brain activation was demonstrated in expected visual and semantic brain regions. Furthermore, we found that the rate of articulation was positively correlated with activation in the right superior temporal gyrus. The results of theoretically derived attachment hypotheses showed no differences at the chosen level of significance when comparing the 'all attachment pictures' effect between both groups (resolved vs. unresolved). More interestingly, we found a significant interaction effect between the sequence of pictures and attachment category. Only the unresolved participants showed increasing activation of medial temporal regions, including the amygdala and the hippocampus, in the course of the AAP task. This pattern was demonstrated especially at the end of the AAP task where the pictures are drawn to portray traumatic situations. We interpret these results as confirming our hypothesis, linking unresolved attachment to emotional dysregulation of the attachment system. These results are discussed in relation to assessing attachment in an fMRI environment and future research in this area.     

Behavioral and brain pattern differences between acting and observing in an auditory task

Attention Deficit Hyperactivity Disorder (ADHD) is a common and highly heritable neurodevelopmental psychiatric disorder. Here, we critically review four major psychological theories of ADHD – the Executive Dysfunction, the State Regulation, the Delay Aversion and the Dynamic Developmental – on their abilities to explain all the symptoms of ADHD, their testability and their openness to falsification. We conclude that theoreticians should focus, to a greater extent than currently practiced, on developing refutable theories of ADHD.     

Age-dependent decline of dopamine D1 receptors in human brain: A PET study

Radioligand binding studies in animals have demonstrated age-related loss of dopamine receptors in the caudate and putamen. In humans, while age-related declines in dopamine D2 receptors have been consistently reported, the effects of ageing on D1 receptors have been controversial. We used positron emission tomography (PET) with [¹¹C]SCH 23390 to investigate dopamine D1 receptor binding in 21 normal volunteers aged 22–74 years. We also assessed their motor function with a Modified Columbia Score (MCS) and the Purdue Pegboard Test (PPBT). D1 binding potentials were derived using a graphical analysis with a cerebellar tissue input function. Standard linear regression techniques were used to determine the age-related rate of decline of D1 binding. We found an age-dependent decrease of D1 receptor binding in the caudate (6.9% per decade) and putamen (7.4% per decade). There was also a significant inverse correlation between [¹¹C]SCH 23390 binding in the occipital cortex and age (8.6% decline per decade). PPBT score also decreased with age (P = 0.007). There was a direct correlation between PPBT score and D1 binding potential. We conclude that dopamine D1 receptor density declines with age and that the effects of physiological ageing may play a role in the expression of extrapyramidal disorders in the elderly. Synapse 30:56–61, 1998. Published 1998 Wiley-Liss, Inc.     

Gender differences in brain activation on a mental rotation task

ABSTRACT Few neuroimaging studies have explored gender differences on mental rotation tasks. Most studies have utilized samples with both genders, samples mainly consisting of men, or samples with six or fewer females. Graduate students in science fields or liberal arts programs (20 males, 20 females) completed a mental rotation task during functional magnetic resonance imaging (fMRI). When a pair of cube figures was shown, the participant made a keypad response based on whether the pair is the same/similar or different. Regardless of gender, the bilateral middle frontal gyrus, bilateral intraparietal sulcus (IPS), and the left precuneus were activated when a subject tried to solve the mental rotation task. Increased activation in the right inferior frontal gyrus/middle frontal gyrus, the left precuneus/posterior cingulate cortex/cuneus region, and the left middle occipital gyrus was found for men as compared to women. Better accuracy and shorter response times were correlated with an increased activation in the bilateral intraparietal sulcus. No significant brain activity differences related to mental rotation were found between academic majors. These findings suggest that networks involved in visual attention appear to be more strongly activated in the mental rotation tasks in men as compared to women. It also suggests that men use a more automatic process when analyzing complex visual reasoning tasks while women use a more top-down process.     

Functional magnetic resonance imaging of human brain activity in a verbal fluency task

OBJECTIVES—Functional MRI (fMRI) holds the promiseof non-invasive mapping of human brain function in both health anddisease. Yet its sensitivity and reliability for mapping highercognitive function are still being determined. Using verbal fluency asa task, the objective was to ascertain the consistency of fMRI on aconventional scanner for determining the anatomic substrate of languagebetween subjects and between sexes. Comparison was made with previous PET studies.
METHODS—Using a 1.5 Tesla magnet and an echoplanarpulse sequence, whole brain fMRI was obtained from 12 normal righthanded subjects (6 males and 6 females) as they performed a verbalfluency task.
RESULTS—A broadly consistent pattern of responsewas seen across subjects. Areas showing activation changes included theleft prefrontal cortex and right cerebellum, in agreement with previousPET ¹⁵O-H₂O studies. In addition, significantlydecreased responses were seen in the posterior cingulate and over anextensive area of mesial and dorsolateral parietal and superiortemporal cortices. The male cohort showed a slight asymmetry ofparietal deactivation, with more involvement on the right, whereas thefemale cohort showed a small region of activation in the rightorbitofrontal cortex. There were individual task related regionalchanges in all 12 subjects with the area showing the most significantchange being the left prefrontal cortex in all cases.
CONCLUSIONS—Magnetic resonance scanners ofconventional field strength can provide functional brain mapping datawith a sensitivity at least that of PET. Activation was seen in leftprefrontal and right cerebellar regions, as with PET. However,decremental responses were seen over a much larger area of theposterior cortex than had been anticipated by prior studies. Theability to see a response in each subject individually suggests thatfMRI may be useful in the preinterventional mapping of pathologicalstates, and offers a non-invasive alternative to the Wada test forassessment of hemispheric dominance. There were no gross differences inthe pattern of activation between male and female subjects.

     

Functional neuroanatomy of grief: an FMRI study

OBJECTIVE: In this study the authors examined the functional neuroanatomy of grief, which to their knowledge has not been studied previously in functional neuroimaging research. METHOD: Grief was elicited in eight bereaved women through photographs of the deceased versus a stranger, combined with words specific to the death event versus neutral words. Use of both pictures and words resulted in a 2x2 factorial design. RESULTS: Three brain regions were independently activated by the picture and word factors: posterior cingulate cortex, medial/superior frontal gyrus, and cerebellum. The two factors also activated distinct regions: for the picture factor, they were the cuneus, superior lingual gyrus, insula, dorsal anterior cingulate cortex, inferior temporal gyrus, and fusiform gyrus; and for the word factor, they were the precuneus, precentral gyrus, midbrain, and vermis. The interaction of the two factors showed significant activation in the cerebellar vermis. CONCLUSIONS: Grief is mediated by a distributed neural network that subserves affect processing, mentalizing, episodic memory retrieval, processing of familiar faces, visual imagery, autonomic regulation, and modulation/coordination of these functions. This neural network may account for the unique, subjective quality of grief and provide new leads in understanding the health consequences of grief and the neurobiology of attachment.     

Prefrontal activity and diagnostic monitoring of memory retrieval: FMRI of the criterial recollection task

According to the distinctiveness heuristic, subjects rely more on detailed recollections (and less on familiarity) when memory is tested for pictures relative to words, leading to reduced false recognition. If so, then neural regions that have been implicated in effortful postretrieval monitoring (e.g., dorsolateral prefrontal cortex) might be recruited less heavily when trying to remember pictures. We tested this prediction with the criterial recollection task. Subjects studied black words, paired with either the same word in red font or a corresponding colored picture. Red words were repeated at study to equate recognition hits for red words and pictures. During fMRI scanning, alternating red word memory tests and picture memory tests were given, using only white words as test stimuli (say "yes" only if you recollect a corresponding red word or picture, respectively). These tests were designed so that subjects had to rely on memory for the criterial information. Replicating prior behavioral work, we found enhanced rejection of lures on the picture test compared to the red word test, indicating that subjects had used a distinctiveness heuristic. Critically, dorsolateral prefrontal activity was reduced when rejecting familiar lures on the picture test, relative to the red word test. These findings indicate that reducing false recognition via the distinctiveness heuristic is not heavily dependent on frontally mediated postretrieval monitoring processes.     

Gender differences in brain activity toward unpleasant linguistic stimuli concerning interpersonal relationships: an fMRI study

Women are more vulnerable to psychosocial stressors such as interpersonal conflicts than men, and are more susceptible to some psychiatric disorders. We hypothesized that there are differences in the brain activity of men and women while perceiving unpleasant linguistic stimuli concerning interpersonal relationships, and that they underlie the different sensitivity toward these stressful stimuli. We carried out a functional magnetic resonance imaging (fMRI) study on 13 young female adults and 13 young male adults who performed an emotional decision task including sets of unpleasant words concerning interpersonal relationships and sets of neutral words. In the women, the unpleasant words more significantly activated the bilateral caudate nuclei and left putamen than the neutral words. However, among the men, there was no difference in the level of activation of any brain area induced by the unpleasant or neutral word stimuli. Upon performing the task, there was a significant gender difference in brain activation. Moreover, among the female subjects, the activation in the bilateral caudate nuclei and left thalamus was negatively correlated with the average rating of pleasantness of the words concerning interpersonal conflicts by the subject. These results demonstrate gender differences in brain activity in processing unpleasant linguistic stimuli related to interpersonal conflicts. Our data suggest that the bilateral caudate nuclei and left putamen play an important role in the perception of words concerning interpersonal conflicts in women. The bilateral caudate nuclei and left thalamus may regulate a woman’s sensitivity to unpleasant information about interpersonal difficulties.     

Early occipito-parietal activity in a word recognition task: an EEG and MEG study.

OBJECTIVE: We investigated early brain activity (under 200 ms after the stimulus onset) related to the encoding and the retrieval of verbal information. METHODS: First, we compared ERPs produced by words which were encoded to ERPs produced by words from following test phases (correctly identified repetitions and correctly classified new words) in two different experiments. Experiment 1 consisted of an intentional learning paradigm and experiment 2 consisted of an incidental learning paradigm. In addition, we conducted a control experiment (experiment 3), which was a continuous recognition task with two different repetition intervals. Secondly, we conducted a magnetoencephalographic (MEG) study to further investigate early brain activity (experiment 4). The same intentional learning paradigm as in experiment 1 was used. RESULTS: We found that ERPs elicited by correctly classified test words (repeated words and new words) of both experiment 1 and experiment 2 were significantly more negative going than the ERPs elicited by the study words. This effect was apparent between 100 ms and 200 ms after the stimulus onset and was distributed over occipital and parietal scalp locations. In the control task (experiment 3), these early potential differences were missing (for both repetition intervals). Early event-related fields (ERFs) were also found to depend on the situation of the study phase and the test phase. This activity difference peaked at 120 ms after the stimulus onset. The distributions of the difference magnetic fields were occipito-parietal and thus consistent with the findings of experiment 1 (EEG-experiment). CONCLUSION: Whether the effect we defined in the present study is due to an increase of activity during the test situation or due to a decrease of activity during the study situation remains unclear. However, it might reflect attentional processes within a word recognition task depending on whether a word is encoded or an effort of word retrieval has to be made.     

An FMRI analysis of the human hippocampus: inference, context, and task awareness

The hippocampus is critical for encoding and retrieving semantic and episodic memories. Animal studies indicate that the hippocampus is also required for relational learning tasks. A prototypical relational learning task, and the one investigated in this experiment, using event-related functional magnetic resonance imaging, is the transitive inference (TI) task. In the TI task, participants were to choose between A and B (A?B) and learned by trial and error to choose A (A > B). There were four such premise pairs during a training (A > B, B > C, C > D, D > E). These can be acquired distinctly or can be organized into a superordinate hierarchy (A > B > C > D > E), which would efficiently represent all the learned relations and allow inferences (e.g., B > D). At test there was no reinforcement: In addition to premise pairs, untrained pairings were introduced (e.g., A?E, B?D). Correctly inferring that B > D is taken as evidence for the formation of a superordinate hierarchy; several alternatives to the superordinate hierarchy hypothesis are considered. Awareness of the formation of this hierarchy was measured by a postscan questionnaire. Four main findings are reported: (1) Inferential performance and task awareness dissociated behaviorally and at the level of hemodynamic response; (2) As expected, performance on the inferred relation, B > D, corresponded to the ability to simultaneously acquire B > C and C > D premise pairs during training; (3) Interestingly, acquiring these "inner pairs" corresponded to greater hippocampal activation than the "outer pairs" (A > B, D > E) for all participants. However, a distinct pattern of hippocampal activity for these inner pairs differentiated those able to perform the inferential discrimination, B > D, at test. Because these inner premise pairs require contextual discrimination (e.g., C is incorrect in the context of B but correct in the context of D), we argue that the TI task is hippocampal-dependent because the premise pair acquisition necessary for inference is hippocampal-dependent; (4) We found B > D related hippocampal activity at test that is anatomically consistent with preconsolidation recall effects shown in other studies.     

Posttraumatic stress symptoms and brain function during a response-inhibition task: an fMRI study in youth

Youth who experience interpersonal trauma and have posttraumatic stress symptoms (PTSS) can exhibit difficulties in executive function and physiological hyperarousal. Response inhibition has been identified as a core component of executive function. In this study, we investigate the functional neuroanatomical correlates of response inhibition in youth with PTSS. Thirty right‐handed medication‐naïve youth between the ages of 10 and 16 years underwent a 3‐Tesla Functional Magnetic Resonance Imaging scan during a response‐inhibition (Go/No‐Go) task. Youth with PTSS (n = 16) were age and gender matched to a control group of healthy youth (n = 14). Between‐groups analyses were conducted to identify brain regions of greater activation in the No/Go‐Go contrasts. PTSS and control youth performed the task with similar accuracy and response times. Control subjects had greater middle frontal cortex activation when compared with PTSS subjects. PTSS subjects had greater medial frontal activation when compared with control subjects. A sub‐group of youth with PTSS and a history of self‐injurious behaviors demonstrated increased insula and orbitofrontal activation when compared with those PTSS youth with no self‐injurious behaviors. Insula activation correlated positively with PTSS severity. Diminished middle frontal activity and enhanced medial frontal activity during response‐inhibition tasks may represent underlying neurofunctional markers of PTSS. Depression and Anxiety 0:1–13, 2007. Published 2007 Wiley‐Liss, Inc.     

Brain activity during a motor learning task: an fMRI and skin conductance study

Measuring electrodermal activity (EDA) during fMRI is an effective means of studying the influence of task-related arousal, inferred from autonomic nervous system activity, on brain activation patterns. The goals of this study were: (1) to measure reliable EDA from healthy individuals during fMRI involving an effortful unilateral motor task, (2) to explore how EDA recordings can be used to augment fMRI data analysis. In addition to conventional hemodynamic modeling, skin conductance time series data were used as model waveforms to generate activation images from fMRI data. Activations from the EDA model produced significantly different brain regions from those obtained with a standard hemodynamic model, primarily in the insula and cingulate cortices. Onsets of the EDA changes were synchronous with the hemodynamic model, but EDA data showed additional transient features, such as a decrease in amplitude with time, and helped to provide behavioral evidence suggesting task difficulty decreased with movement repetition. Univariate statistics also confirmed that several brain regions showed early versus late session effects. Partial least squares (PLS) multivariate analysis of EDA and fMRI data provided complimentary, additional insight on how the motor network varied over the course of a single fMRI session. Brain regions identified in this manner included the insula, cingulate gyrus, pre- and postcentral gyri, putamen and parietal cortices. These results suggest that recording EDA during motor fMRI experiments provides complementary information that can be used to improve the fMRI analysis, particularly when behavioral or task effects are difficult to model a priori.     

GABA-transaminase activity in rat and human brain: regional,age and sex-related differences

Summary The activity of 4-aminobutyrate:2-oxoglutarate transaminase (GABA-T) has been investigated in the rat and human brain. Both rat and human brain GABA-T retained its full activity for at least 2 months and with a loss of less than 10% after 6 months when frozen at –20 C as tissue parts. There was a loss of activity of mouse brain GABA-T of about 15% per 24 hours postmortem. In the rat brain, GABA-T activity varied from low values in cortex and hippocampus to high in brain stem and cerebellum. There was a significant increase of GABA-T acitivity with age from 1 to 6 weeks and a significant reduction of the activity with age thereafter. Male rats had significant higher activity than female rats.In the human brain, GABA-T activities were measured in twelve regions of autopsied brains from 10 adult control subjects. No difference was found between the activities in the left and right sides. There is considerable variation in enzyme activity across the brain, with low activities in e.g. pons and medulla oblongata and high activities in e.g. caudatus, substantia nigra and hypothalamus. The acitivity of the enzyme is significantly different both between brain regions and between individuals.     

Age-dependent differences in flurothyl-induced c-fos and c-jun mRNA expression in the mouse brain

Numerous studies have examined the brain regional distribution of the immediate early gene (IEG), c-fos, following seizures induced by a variety of chemical or electrical provocations in the rat. Very little is known concerning the regional and temporal distribution of IEG expression following seizures in mice, and even less regarding the effects of development. In the present study, seizures of varying severities were induced in immature (postnatal day 17-18) and mature male (postnatal day 55-60) C3H mice with flurothyl, a volatile convulsant. In the immature mouse, neither c-fos nor c-jun mRNA were statistically elevated following any type of acute seizure activity. In the mature mouse, seizures of different severity resulted in differential effects on regional c-fos and c-jun mRNA expression. We conclude that the c-fos and c-jun are not reliable indicators of seizure activity in immature mice, whereas they remain indirect markers of neuronal activity in mature mice.