The well-worn route revisited: Striatal and hippocampal system contributions to familiar route navigation.

Classic research has shown a division in the neuroanatomical structures that support flexible (e.g., short-cutting) and habitual (e.g., familiar route following) navigational behavior, with hippocampal-caudate systems associated with the former and putamen systems with the latter. There is, however, disagreement about whether the neural structures involved in navigation process particular forms of spatial information, such as associations between constellations of cues forming a cognitive map, versus single landmark-action associations, or alternatively, perform particular reinforcement learning algorithms that allow the use of different spatial strategies, so-called model-based (flexible) or model-free (habitual) forms of learning. We sought to test these theories by asking participants (N = 24) to navigate within a virtual environment through a previously learned, 9-junction route with distinctive landmarks at each junction while undergoing functional magnetic resonance imaging (fMRI). In a series of probe trials, we distinguished knowledge of individual landmark-action associations along the route versus knowledge of the correct sequence of landmark-action associations, either by having absent landmarks, or "out-of-sequence" landmarks. Under a map-based perspective, sequence knowledge would not require hippocampal systems, because there are no constellations of cues available for cognitive map formation. Within a learning-based model, however, responding based on knowledge of sequence would require hippocampal systems because prior context has to be utilized. We found that hippocampal-caudate systems were more active in probes requiring sequence knowledge, supporting the learning-based model. However, we also found greater putamen activation in probes where navigation based purely on sequence memory could be planned, supporting models of putamen function that emphasize its role in action sequencing.

Assessing combinatorial effects of HIV infection and former cocaine dependence on cognitive control processes: A functional neuroimaging study of response inhibition.

Individuals with a diagnosis of co-morbid HIV infection and cocaine use disorder are at higher risk of poor health outcomes. Active cocaine users, both with and without HIV infection, show clear deficits in response inhibition and other measures of executive function that are instrumental in maintaining drug abstinence, factors that may complicate treatment. Neuroimaging and behavioral evidence indicate normalization of executive control processes in former cocaine users as a function of the duration of drug abstinence, but it is unknown to what extent co-morbid diagnosis of HIV affects this process. To this end, we investigate the combinatorial effects of HIV and cocaine dependence on the neural substrates of cognitive control in cocaine-abstinent individuals with a history of cocaine dependence. Blood-oxygen level dependent signal changes were measured as 86 participants performed a Go/NoGo response inhibition task while undergoing functional magnetic resonance imaging (fMRI). Four groups of participants were selected based on HIV and cocaine-dependence status. Participants affected by both conditions demonstrated the lowest response accuracy of all participant groups. In a region of interest analysis, hyperactivation in the left putamen and midline-cingulate hyperactivation was observed in individuals with both HIV and cocaine dependence relative to individuals with only one condition. Results of a whole-brain analysis indicate response inhibition-related hyperactivation in the bilateral supplementary motor area, bilateral hippocampi, bilateral primary somatosensory areas, right dorsal anterior cingulate, and left insula in the CD+/HIV+ group relative to all other groups. These results indicate complex and interactive alterations in neural activation during response inhibition and highlight the importance of examining the neurocognitive effects of co-morbid conditions.

Compensatory Cross-Modal Plasticity Persists After Sight Restoration.

Sensory deprivation prompts extensive structural and functional reorganizations of the cortex resulting in the occupation of space for the lost sense by the intact sensory systems. This process, known as cross-modal plasticity, has been widely studied in individuals with vision or hearing loss. However, little is known on the neuroplastic changes in restoring the deprived sense. Some reports consider the cross-modal functionality maladaptive to the return of the original sense, and others view this as a critical process in maintaining the neurons of the deprived sense active and operational. These controversial views have been challenged in both auditory and vision restoration reports for decades. Recently with the approval of Luxturna as the first retinal gene therapy (GT) drug to reverse blindness, there is a renewed interest for the crucial role of cross-modal plasticity on sight restoration. Employing a battery of task and resting state functional magnetic resonance imaging (rsfMRI), in comparison to a group of sighted controls, we tracked the functional changes in response to auditory and visual stimuli and at rest, in a group of patients with biallelic mutations in the RPE65 gene ("RPE65 patients") before and 3 years after GT. While the sighted controls did not present any evidence for auditory cross-modal plasticity, robust responses to the auditory stimuli were found in occipital cortex of the RPE65 patients overlapping visual responses and significantly elevated 3 years after GT. The rsfMRI results showed significant connectivity between the auditory and visual areas for both groups albeit attenuated in patients at baseline but enhanced 3 years after GT. Taken together, these findings demonstrate that (1) RPE65 patients present with an auditory cross-modal component; (2) visual and non-visual responses of the visual cortex are considerably enhanced after vision restoration; and (3) auditory cross-modal functions did not adversely affect the success of vision restitution. We hypothesize that following GT, to meet the demand for the newly established retinal signals, remaining or dormant visual neurons are revived or unmasked for greater participation. These neurons or a subset of these neurons respond to both the visual and non-visual demands and further strengthen connectivity between the auditory and visual cortices.

Changes in brain activation related to visuo-spatial memory after real-time fMRI neurofeedback training in healthy elderly and Alzheimer's disease.

Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.

The potential of MR-Encephalography for BCI/Neurofeedback applications with high temporal resolution.

Real-time functional magnetic resonance imaging (rt-fMRI) enables the update of various brain-activity measures during an ongoing experiment as soon as a new brain volume is acquired. However, the recorded Blood-oxygen-level dependent (BOLD) signal also contains physiological artifacts such as breathing and heartbeat, which potentially cause misleading false positive effects especially problematic in brain-computer interface (BCI) and neurofeedback (NF) setups. The low temporal resolution of echo planar imaging (EPI) sequences (which is in the range of seconds) prevents a proper separation of these artifacts from the BOLD signal. MR-Encephalography (MREG) has been shown to provide the high temporal resolution required to unalias and correct for physiological fluctuations and leads to increased specificity and sensitivity for mapping task-based activation and functional connectivity as well as for detecting dynamic changes in connectivity over time. By comparing a simultaneous multislice echo planar imaging (SMS-EPI) sequence and an MREG sequence using the same nominal spatial resolution in an offline analysis for three different experimental fMRI paradigms (perception of house and face stimuli, motor imagery, Stroop task), the potential of this novel technique for future BCI and NF applications was investigated. First, adapted general linear model pre-whitening which accounts for the high temporal resolution in MREG was implemented to calculate proper statistical results and be able to compare these with the SMS-EPI sequence. Furthermore, the respiration- and cardiac pulsation-related signals were successfully separated from the MREG signal using independent component analysis which were then included as regressors for a GLM analysis. Only the MREG sequence allowed to clearly separate cardiac pulsation and respiration components from the signal time course. It could be shown that these components highly correlate with the recorded respiration and cardiac pulsation signals using a respiratory belt and fingertip pulse plethysmograph. Temporal signal-to-noise ratios of SMS-EPI and MREG were comparable. Functional connectivity analysis using partial correlation showed a reduced standard error in MREG compared to SMS-EPI. Also, direct time course comparisons by down-sampling the MREG signal to the SMS-EPI temporal resolution showed lower variance in MREG. In general, we show that the higher temporal resolution is beneficial for fMRI time course modeling and this aspect can be exploited in offline application but also, is especially attractive, for real-time BCI and NF applications.

Reduced cortical thickness in Heschl's gyrus as an in vivo marker for human primary auditory cortex.

The primary auditory cortex (PAC) is located in the region of Heschl's gyrus (HG), as confirmed by histological, cytoarchitectonical, and neurofunctional studies. Applying cortical thickness (CTH) analysis based on high-resolution magnetic resonance imaging (MRI) and magnetoencephalography (MEG) in 60 primary school children and 60 adults, we investigated the CTH distribution of left and right auditory cortex (AC) and primary auditory source activity at the group and individual level. Both groups showed contoured regions of reduced auditory cortex (redAC) along the mediolateral extension of HG, illustrating large inter-individual variability with respect to shape, localization, and lateralization. In the right hemisphere, redAC localized more within the medial portion of HG, extending typically across HG duplications. In the left hemisphere, redAC was distributed significantly more laterally, reaching toward the anterolateral portion of HG. In both hemispheres, redAC was found to be significantly thinner (mean CTH of 2.34 mm) as compared to surrounding areas (2.99 mm). This effect was more dominant in the right hemisphere rather than in the left one. Moreover, localization of the primary component of auditory evoked activity (P1), as measured by MEG in response to complex harmonic sounds, strictly co-localized with redAC. This structure-function link was found consistently at the group and individual level, suggesting PAC to be represented by areas of reduced cortex in HG. Thus, we propose reduced CTH as an in vivo marker for identifying shape and localization of PAC in the individual brain.

Cognitive Improvement and Brain Changes after Real-Time Functional MRI Neurofeedback Training in Healthy Elderly and Prodromal Alzheimer's Disease.

BACKGROUND: Cognitive decline is characteristic for Alzheimer's disease (AD) and also for healthy ageing. As a proof-of-concept study, we examined whether this decline can be counteracted using real-time fMRI neurofeedback training. Visuospatial memory and the parahippocampal gyrus (PHG) were targeted. METHODS: Sixteen healthy elderly subjects (mean age 63.5 years, SD = 6.663) and 10 patients with prodromal AD (mean age 66.2 years, SD = 8.930) completed the experiment. Four additional healthy subjects formed a sham-feedback condition to validate the paradigm. The protocol spanned five examination days (T1-T5). T1 contained a neuropsychological pre-test, the encoding of a real-world footpath, and an anatomical MRI scan of the brain. T2-T4 included the fMRI neurofeedback training paradigm, in which subjects learned to enhance activation of the left PHG while recalling the path encoded on T1. At T5, the neuropsychological post-test and another anatomical MRI brain scan were performed. The neuropsychological battery included the Montreal Cognitive Assessment (MoCA); the Visual and Verbal Memory Test (VVM); subtests of the Wechsler Memory Scale (WMS); the Visual Patterns Test; and Trail Making Tests (TMT) A and B. RESULTS: Healthy elderly and patients with prodromal AD showed improved visuospatial memory performance after neurofeedback training. Healthy subjects also performed better in a working-memory task (WMS backward digit-span) and in the MoCA. Both groups were able to elicit parahippocampal activation during training, but no significant changes in brain activation were found over the course of the training. However, Granger-causality-analysis revealed changes in cerebral connectivity over the course of the training, involving the parahippocampus and identifying the precuneus as main driver of activation in both groups. Voxel-based morphometry showed increases in grey matter volumes in the precuneus and frontal cortex. Neither cognitive enhancements, nor parahippocampal activation were found in the control group undergoing sham-feedback. CONCLUSION: These findings suggest that cognitive decline, either related to prodromal AD or healthy ageing, could be counteracted using fMRI-based neurofeedback. Future research needs to determine the potential of this method as a treatment tool.

A Possible Role of Prolonged Whirling Episodes on Structural Plasticity of the Cortical Networks and Altered Vertigo Perception: The Cortex of Sufi Whirling Dervishes.

Although minutes of a spinning episode may induce vertigo in the healthy human, as a result of a possible perceptional plasticity, Sufi Whirling Dervishes (SWDs) can spin continuously for an hour without a vertigo perception.This unique long term vestibular system stimulation presents a potential human model to clarify the cortical networks underlying the resistance against vertigo. This study, therefore, aimed to investigate the potential structural cortical plasticity in SWDs. Magnetic resonance imaging (MRI) of 10 SWDs and 10 controls were obtained, using a 3T scanner. Cortical thickness in the whole cortex was calculated. Results demonstrated significantly thinner cortical areas for SWD subjects compared with the control group in the hubs of the default mode network (DMN), as well as in the motion perception and discrimination areas including the right dorsolateral prefrontal cortex (DLPFC), the right lingual gyrus and the left visual area 5 (V5)/middle temporal (MT) and the left fusiform gyrus. In conclusion, this is the first report that warrants the potential relationship of the motion/body perception related cortical networks and the prolonged term of whirling ability without vertigo or dizziness.

Coronary artery disease affects cortical circuitry associated with brain-heart integration during volitional exercise.

This study tested the hypothesis that coronary artery disease (CAD) alters the cortical circuitry associated with exercise. Observations of changes in heart rate (HR) and in cortical blood oxygenation level-dependent (BOLD) images were made in 23 control subjects [control; 8 women; 63 ± 11 yr; mean arterial pressure (MAP): 90 ± 9 mmHg] (mean ± SD) and 17 similarly aged CAD patients (4 women; 59 ± 9 yr; MAP: 87 ± 10 mmHg). Four repeated bouts each of 30%, 40%, and 50% of maximal voluntary contraction (MVC) force (LAB session), and seven repeated bouts of isometric handgrip (IHG) at 40% MVC force (fMRI session), were performed, with each contraction lasting 20 s and separated by 40 s of rest. There was a main effect of group (P = 0.03) on HR responses across all IHG intensities. Compared with control, CAD demonstrated less task-dependent deactivation in the posterior cingulate cortex and medial prefrontal cortex, and reduced activation in the right anterior insula, bilateral precentral cortex, and occipital lobe (P < 0.05). When correlated with HR, CAD demonstrated reduced activation in the bilateral insula and posterior cingulate cortex, and reduced deactivation in the dorsal anterior cingulate cortex, and bilateral precentral cortex (P < 0.05). The increased variability in expected autonomic regions and decrease in total cortical activation in response to the IHG task are associated with a diminished HR response to volitional effort in CAD. Therefore, relative to similarly aged and healthy individuals, CAD impairs the heart rate response and modifies the cortical patterns associated with cardiovascular control during IHG.

Neural correlates of body and face perception following bilateral destruction of the primary visual cortices.

Non-conscious visual processing of different object categories was investigated in a rare patient with bilateral destruction of the visual cortex (V1) and clinical blindness over the entire visual field. Images of biological and non-biological object categories were presented consisting of human bodies, faces, butterflies, cars, and scrambles. Behaviorally, only the body shape induced higher perceptual sensitivity, as revealed by signal detection analysis. Passive exposure to bodies and faces activated amygdala and superior temporal sulcus. In addition, bodies also activated the extrastriate body area, insula, orbitofrontal cortex (OFC) and cerebellum. The results show that following bilateral damage to the primary visual cortex and ensuing complete cortical blindness, the human visual system is able to process categorical properties of human body shapes. This residual vision may be based on V1-independent input to body-selective areas along the ventral stream, in concert with areas involved in the representation of bodily states, like insula, OFC, and cerebellum.

Increased volume and function of right auditory cortex as a marker for absolute pitch.

Absolute pitch (AP) perception is the auditory ability to effortlessly recognize the pitch of any given tone without external reference. To study the neural substrates of this rare phenomenon, we developed a novel behavioral test, which excludes memory-based interval recognition and permits quantification of AP proficiency independently of relative pitch cues. AP- and non-AP-possessing musicians were studied with morphological and functional magnetic resonance imaging (fMRI) and magnetoencephalography. Gray matter volume of the right Heschl's gyrus (HG) was highly correlated with AP proficiency. Right-hemispheric auditory evoked fields were increased in the AP group. fMRI revealed an AP-dependent network of right planum temporale, secondary somatosensory, and premotor cortices, as well as left-hemispheric "Broca's" area. We propose the right HG as an anatomical marker of AP and suggest that a right-hemispheric network mediates AP "perception," whereas pitch "labeling" takes place in the left hemisphere.

Increased sensitivity to food cues in the fasted state and decreased inhibitory control in the satiated state in the overweight.

BACKGROUND: Flexibility of food reward-related brain signaling (FRS) between food and nonfood stimuli may differ between overweight and normal-weight subjects and depend on a fasted or satiated state. OBJECTIVE: The objective was to assess this flexibility in response to visual food and nonfood cues. DESIGN: Twenty normal-weight [mean ± SEM BMI (in kg/m(2)) = 22.7 ± 0.2; mean ± SEM age = 22.4 ± 0.4 y] and 20 overweight (BMI = 28.1 ± 0.3; age = 24.0 ± 0.7 y) participants completed 2 fMRI scans. Subjects arrived in a fasted state and consumed a breakfast consisting of 20% of subject-specific energy requirements between 2 successive scans. A block paradigm and a food > nonfood contrast was used to determine FRS. RESULTS: An overall stimulus × condition × subject group effect was observed in the anterior cingulate cortex (ACC) (P < 0.006, F((1,38)) = 9.12) and right putamen (P < 0.006, F((1,38)) = 9.27). In all participants, FRS decreased from the fasted to the satiated state in the cingulate (P < 0.005, t((39)) = 3.15) and right prefrontal cortex (PFC) (P < 0.006, t((39)) = 3.00). In the fasted state, they showed FRS in the PFC (P < 0.004, t((39)) = 3.17), left insula (P < 0.009, t((39)) = 2.95), right insula (P < 0.005, t((39)) = 3.12), cingulate cortex (P < 0.004, t((39)) = 3.21), and thalamus (P < 0.006, t((39)) = 2.96). In the satiated state, FRS was limited to the left insula (P < 0.005, t((39)) = 3.21), right insula (P < 0.006, t((39)) = 3.04), and cingulate cortex (P < 0.005, t((39)) = 3.15). Regarding subject group, in the fasted state, FRS in the ACC was more pronounced in overweight than in normal-weight subjects (P < 0.005, F((1,38)) = 9.71), whereas in the satiated state, FRS was less pronounced in overweight than in normal-weight subjects in the ACC (P < 0.006, F((1,38)) = 9.18) and PFC (P < 0.006, F((1,38)) = 8.86), which suggests lower inhibitory control in the overweight. CONCLUSION: FRS was higher in the overweight in the satiated state; however, when sufficiently satiated, the overweight showed decreased inhibitory control signalling, which facilitates overeating. This trial was registered in the Dutch clinical trial register as NTR2174.

Comparison of fMRI activation patterns for test and training procedures of alertness and focused attention.

PURPOSE: Behavioural studies of attention training after brain damage have shown that only training procedures specifically related to the impaired attention function lead to significant improvements in the respective attention domain when using psychometric tests addressing these functions. The main objective of this fMRI study was to investigate specific as well as common neural correlates of alertness and focused attention and to assess the degree of neural overlap for two different tasks of the same attention function. METHODS: To investigate how different attention functions are processed, we tested 32 healthy participants using fMRI. Each participant was randomly assigned to the alertness (n = 16) or the focused attention (n = 16) group, where participants underwent two different attention tasks, one being a diagnostic computerized test procedure and the other being a computer-game like training procedure. RESULTS: The present results show similar activation patterns when assessing the same attention function with two different tasks. Activation overlap for test and training tasks of the same attention function was more clear-cut than the activation overlap for two different attention functions. CONCLUSIONS: Clinically validated diagnostic test paradigms and computer game-like training paradigms for both alertness and focused attention activated common brain systems processing the respective attention function. These findings may help to explain the beneficial effect of specifically designed attentional training procedures and the validity of related psychometric tests in detecting specific changes in performance after training of the same attention functions.

Revealing the functional neuroanatomy of intrinsic alertness using fMRI: methodological peculiarities.

Clinical observations and neuroimaging data revealed a right-hemisphere fronto-parietal-thalamic-brainstem network for intrinsic alertness, and additional left fronto-parietal activity during phasic alertness. The primary objective of this fMRI study was to map the functional neuroanatomy of intrinsic alertness as precisely as possible in healthy participants, using a novel assessment paradigm already employed in clinical settings. Both the paradigm and the experimental design were optimized to specifically assess intrinsic alertness, while at the same time controlling for sensory-motor processing. The present results suggest that the processing of intrinsic alertness is accompanied by increased activity within the brainstem, thalamus, anterior cingulate gyrus, right insula, and right parietal cortex. Additionally, we found increased activation in the left hemisphere around the middle frontal gyrus (BA 9), the insula, the supplementary motor area, and the cerebellum. Our results further suggest that rather minute aspects of the experimental design may induce aspects of phasic alertness, which in turn might lead to additional brain activation in left-frontal areas not normally involved in intrinsic alertness. Accordingly, left BA 9 activation may be related to co-activation of the phasic alertness network due to the switch between rest and task conditions functioning as an external warning cue triggering the phasic alertness network. Furthermore, activation of the intrinsic alertness network during fixation blocks due to enhanced expectancy shortly before the switch to the task block might, when subtracted from the task block, lead to diminished activation in the typical right hemisphere intrinsic alertness network. Thus, we cautiously suggest that--as a methodological artifact--left frontal activations might show up due to phasic alertness involvement and intrinsic alertness activations might be weakened due to contrasting with fixation blocks, when assessing the functional neuroanatomy of intrinsic alertness with a block design in fMRI studies.

MDMA intoxication and verbal memory performance: a placebo-controlled pharmaco-MRI study.

The aim of the present study was to identify the neural substrate underlying memory impairment due to a single dose of MDMA (3,4-methylenedioxymethamphetamine) by means of pharmaco-MRI. Based on previous behavioral results it was hypothesized that this deficit could be attributed to a specific influence of MDMA on encoding. Fourteen Ecstasy users participated in this double-blind, placebo-controlled, within-subject study with two treatment conditions: MDMA (75 mg) and placebo. Memory performance was tested by means of a word learning task including two words lists, one addressing reading processes (control task, CWL) and a second (experimental task, EWL) addressing encoding and reading processes. Behavioral data showed that under the influence of MDMA, EWL performance was worse than placebo. Imaging data showed that Encoding was situated mainly in (pre)frontal, temporal and parietal areas. MDMA by Encoding interaction was situated in three areas: the left middle frontal gyrus (BA10), the right fusiform gyrus (BA19), and the left cuneus (BA18). Behavioral and functional data only correlated in BA10. It appeared that EWL performance caused BOLD signal change in BA10 during placebo treatment but not during MDMA intoxication. It is concluded that MDMA influences middle frontal gyrus processes resulting in impoverished memory encoding.

Individualized and clinically derived stimuli activate limbic structures in depression: an fMRI study.

OBJECTIVES: In the search for neurobiological correlates of depression, a major finding is hyperactivity in limbic-paralimbic regions. However, results so far have been inconsistent, and the stimuli used are often unspecific to depression. This study explored hemodynamic responses of the brain in patients with depression while processing individualized and clinically derived stimuli. METHODS: Eighteen unmedicated patients with recurrent major depressive disorder and 17 never-depressed control subjects took part in standardized clinical interviews from which individualized formulations of core interpersonal dysfunction were derived. In the patient group such formulations reflected core themes relating to the onset and maintenance of depression. In controls, formulations reflected a major source of distress. This material was thereafter presented to subjects during functional magnetic resonance imaging (fMRI) assessment. RESULTS: Increased hemodynamic responses in the anterior cingulate cortex, medial frontal gyrus, fusiform gyrus and occipital lobe were observed in both patients and controls when viewing individualized stimuli. Relative to control subjects, patients with depression showed increased hemodynamic responses in limbic-paralimbic and subcortical regions (e.g. amygdala and basal ganglia) but no signal decrease in prefrontal regions. CONCLUSIONS: This study provides the first evidence that individualized stimuli derived from standardized clinical interviewing can lead to hemodynamic responses in regions associated with self-referential and emotional processing in both groups and limbic-paralimbic and subcortical structures in individuals with depression. Although the regions with increased responses in patients have been previously reported, this study enhances the ecological value of fMRI findings by applying stimuli that are of personal relevance to each individual's depression.

Developmental effects of aggressive behavior in male adolescents assessed with structural and functional brain imaging.

Aggressive behavior is common during adolescence. Although aggression-related functional changes in the ventromedial prefrontal cortex (vmPFC) and frontopolar cortex (FPC) have been reported in adults, the neural correlates of aggressive behavior in adolescents, particularly in the context of structural neurodevelopment, are obscure. We used functional and structural magnetic resonance imaging (MRI) to measure the blood oxygenation level-depended signal and cortical thickness. In a block-designed experiment, 14-17-year old adolescents imagined aggressive and non-aggressive interactions with a peer. We show reduced vmPFC activation associated with imagined aggressive behavior as well as enhanced aggression-related activation and cortical thinning in the FPC with increasing age. Changes in FPC activation were also associated with judgments of the severity of aggressive acts. Reduced vmPFC activation was associated with greater aggression indicating its normal function is to exert inhibitory control over aggressive impulses. Concurrent FPC activation likely reflects foresight of harmful consequences that result from aggressive acts. The correlation of age-dependent activation changes and cortical thinning demonstrates ongoing maturation of the FPC during adolescence towards a refinement of social and cognitive information processing that can potentially facilitate mature social behavior in aggressive contexts.

Involvement of inferior parietal lobules in prospective memory impairment during acute MDMA (ecstasy) intoxication: an event-related fMRI study.

Prospective memory refers to the realization of delayed intentions. Several studies have shown that 3,4-methylenedioxy-methamphetamine (MDMA) users perform worse on measures of prospective memory as compared to nondrug users. Interpretation of these data may be limited because of polydrug use, psychosocial stressors, and increased psychopathology that have been reported in MDMA users. This study was designed to directly assess the pharmacological effect of MDMA on prospective memory and brain activity in a double-blind, placebo-controlled, cross-over study. Twelve recreational MDMA users received MDMA 75 mg and placebo and performed an objective prospective memory task during functional imaging. During prospective memory task performance subjects were engaged in a foreground task that consisted of a simple reaction time to visual stimuli (Go trials) and a prospective task of withholding a response during trials that were part of a dynamic memory set (No go trials). Behavioral data showed that a single dose of MDMA increased prospective memory failures in the No go trials, and that number of prospective memory failures was positively correlated to MDMA concentration in plasma. Functional imaging showed that MDMA decreased BOLD activation during Go trials in the thalamus (left), putamen (left), precuneus (left), and the inferior parietal lobules (bilateral), as compared to placebo. During No go trials, MDMA reduced BOLD deactivation in the inferior parietal lobules (bilateral), as compared to placebo. It is concluded that the loss of deactivation in inferior parietal lobules may account for increments in memory failures observed during MDMA intoxication.

Thinner prefrontal cortex in veterans with posttraumatic stress disorder.

Structural neuroimaging studies in posttraumatic stress disorder (PTSD) have focused primarily on structural alterations in the medial temporal lobe, and only a few have examined grey matter reductions in the cortex. Recent advances in computational analysis provide new opportunities to use semi-automatic techniques to determine cortical thickness, but these techniques have not yet been applied in PTSD. Twenty-five male veterans with PTSD and twenty-five male veterans without PTSD matched for age, year and region of deployment were recruited. All the subjects were scanned using MRI. Subjects' brains were aligned using cortex-based alignment in a region of interest based approach. Individual cortical thickness maps were calculated from the MR images. Regions of interest examined included the bilateral superior frontal gyri, bilateral middle frontal gyri, bilateral inferior frontal gyri, bilateral superior temporal gyri, and bilateral middle temporal gyri. In a large number of patients and controls, IQ scores and memory scores were also obtained. Individual cortical thickness maps were calculated from the MR images. Veterans with PTSD revealed reduced cortical thickness in the bilateral superior and middle frontal gyri, the left inferior frontal gyrus, and the left superior temporal gyrus. Veterans with PTSD performed significantly worse on memory measures compared to control veterans. Cortical thickness correlated with memory measures in the veterans without PTSD, but not in the veterans with PTSD. Cortical thinning in these regions may thus correspond to functional abnormalities observed in patients with PTSD.

Neural correlates of trust.

Trust is a critical social process that helps us to cooperate with others and is present to some degree in all human interaction. However, the underlying brain mechanisms of conditional and unconditional trust in social reciprocal exchange are still obscure. Here, we used hyperfunctional magnetic resonance imaging, in which two strangers interacted online with one another in a sequential reciprocal trust game while their brains were simultaneously scanned. By designing a nonanonymous, alternating multiround game, trust became bidirectional, and we were able to quantify partnership building and maintenance. Using within- and between-brain analyses, an examination of functional brain activity supports the hypothesis that the preferential activation of different neuronal systems implements these two trust strategies. We show that the paracingulate cortex is critically involved in building a trust relationship by inferring another person's intentions to predict subsequent behavior. This more recently evolved brain region can be differently engaged to interact with more primitive neural systems in maintaining conditional and unconditional trust in a partnership. Conditional trust selectively activated the ventral tegmental area, a region linked to the evaluation of expected and realized reward, whereas unconditional trust selectively activated the septal area, a region linked to social attachment behavior. The interplay of these neural systems supports reciprocal exchange that operates beyond the immediate spheres of kinship, one of the distinguishing features of the human species.