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ABSTRACT: Trauma-related psychopathology has been associated with an intense emotional reaction to stressful event. Emotional responses have evolved to signal the presence of risks to be avoided or of rewards to be approached in the environment. Thus, individuals' sensitivity to signals of risk and reward may affect the level of stress vulnerability. Stress, however, can modify these sensitivities as well. In the current functional magnetic resonance imaging (fMRI) study, we prospectively probed the neural correlates of such sensitivities in 24 healthy soldiers by using an interactive game that encompasses risky and rewarding intervals both pre-exposure and post-exposure to stressful military service. As expected, risky and rewarding intervals elicited selective responses in the amygdala and nucleus accumbens (Nacc), respectively. Furthermore, increased post-traumatic stress disorder symptoms post-exposure (i.e., stress vulnerability) corresponded to greater amygdala's response to risk both pre-exposure and post-exposure and to decreased NAcc response to reward only post-exposure. By combining these regional responsivities post-exposure, we accurately identified all the most vulnerable soldiers. Imbalanced neural responsivity to risk and reward following exposure to stress may therefore constitute a marker for stress vulnerability. Such identification of vulnerability biomarkers can aid future diagnostic and therapeutic efforts by allowing early detection of vulnerability as well as follow up on patient's treatment progression.
Cerebral Cortex 01/2012; · 6.54 Impact Factor
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ABSTRACT: The blood oxygenation level-dependent (BOLD) signal serves as the basis for human functional MRI (fMRI). Knowledge of the properties of the BOLD signal, such as how linear its response is to sensory stimuli, is essential for the design and interpretation of fMRI experiments. Here, we combined the cell-type and site-specific causal control provided by optogenetics and fMRI (opto-fMRI) in mice to test the linearity of BOLD signals driven by locally induced excitatory activity. We employed high-resolution mouse fMRI at 9.4 tesla to measure the BOLD response, and extracellular electrophysiological recordings to measure the effects of stimulation on single unit, multiunit, and local field potential activity. Optically driven stimulation of layer V neocortical pyramidal neurons resulted in a positive local BOLD response at the stimulated site. Consistent with a linear transform model, this locally driven BOLD response summated in response to closely spaced trains of stimulation. These properties were equivalent to responses generated through the multisynaptic method of driving neocortical activity by tactile sensory stimulation, and paralleled changes in electrophysiological measures. These results illustrate the potential of the opto-fMRI method and reinforce the critical assumption of human functional neuroimaging that--to first approximation--the BOLD response tracks local neural activity levels.
Journal of Neuroscience 10/2011; 31(42):15086-91. · 7.11 Impact Factor
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ABSTRACT: Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.
Cerebral Cortex 10/2011; 22(8):1935-49. · 6.54 Impact Factor
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ABSTRACT: Neuroimaging experiments in humans suggest that regions in parietal cortex and along the posterior midline are functionally connected to the medial temporal lobe and are active during memory retrieval. It is unknown whether macaques have a similar network. We examined functional connectivity in isoflurane-anesthetized macaques to identify a network associated with posterior parahippocampal cortex (PPHC). Functional connectivity was observed between the PPHC and retrosplenial, posterior cingulate, superior temporal gyrus, and inferior parietal cortex. PPHC correlations were distinct from regions in parietal and temporal cortex activated by an oculomotor task. Comparison of macaque and human PPHC correlations revealed similarities that suggest the temporal-parietal region identified in the macaque may share a common lineage with human Brodmann area 39, a region thought to be involved in recollection. These results suggest that macaques and humans may have homologous PPHC-parietal pathways. By specifying the location of the putative macaque homologue in parietal cortex, we provide a target for future physiological exploration of this area's role in mnemonic or alternative processes.
Journal of Neurophysiology 12/2009; 103(2):793-800. · 3.32 Impact Factor
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ABSTRACT: Studies demonstrating selective brain networks subserving motivation and mentalization (i.e. attributing states of mind to others) during social interactions have not investigated their mutual independence. We report the results of two fMRI studies using a competitive game requiring players to use implicit 'on-line' mentalization simultaneously with motivational processes of gains and losses in playing against a human or a computer opponent. We delineate a network, consisting of bilateral temporoparietal junction, temporal pole (TP), medial prefrontal cortex (MPFC) and right fusiform gyrus, which is sensitive to the opponent's response (challenging>not challenging the player) and opponent type (human>computer). This network is similar to a known explicit 'off-line' mentalization circuit, suggesting its additional involvement in implicit 'on-line' mentalization, a process more applicable to real-life social interactions. Importantly, only MPFC and TP were selective to mentalization compared to motivation, highlighting their specific operation in attributing states of mind to others during social interactions.
Brain Imaging and Behavior 03/2009; 3(1):24-37. · 1.66 Impact Factor
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ABSTRACT: Two functionally distinct, and potentially competing, brain networks have been recently identified that can be broadly distinguished by their contrasting roles in attention to the external world versus internally directed mentation involving long-term memory. At the core of these two networks are the dorsal attention system and the hippocampal-cortical memory system, a component of the brain's default network. Here spontaneous blood-oxygenation-level-dependent (BOLD) signal correlations were used in three separate functional magnetic resonance imaging data sets (n = 105) to define a third system, the frontoparietal control system, which is spatially interposed between these two previously defined systems. The frontoparietal control system includes many regions identified as supporting cognitive control and decision-making processes including lateral prefrontal cortex, anterior cingulate cortex, and inferior parietal lobule. Detailed analysis of frontal and parietal cortex, including use of high-resolution data, revealed clear evidence for contiguous but distinct regions: in general, the regions associated with the frontoparietal control system are situated between components of the dorsal attention and hippocampal-cortical memory systems. The frontoparietal control system is therefore anatomically positioned to integrate information from these two opposing brain systems.
Journal of Neurophysiology 10/2008; 100(6):3328-42. · 3.32 Impact Factor
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ABSTRACT: The hippocampus and adjacent cortical structures in the medial temporal lobe (MTL) contribute to memory through interactions with distributed brain areas. Studies of monkey and rodent anatomy suggest that parallel pathways converge on distinct subregions of the MTL. To explore the cortical areas linked to subregions of the MTL in humans, we examined cortico-cortical and hippocampal-cortical correlations using high-resolution, functional connectivity analysis in 100 individuals. MTL seed regions extended along the anterior to posterior axis and included hippocampus and adjacent structures. Results revealed two separate brain pathways that correlated with distinct subregions within the MTL. The body of the hippocampus and posterior parahippocampal cortex correlated with lateral parietal cortex, regions along the posterior midline including posterior cingulate and retrosplenial cortex, and ventral medial prefrontal cortex. By contrast, anterior hippocampus and the perirhinal/entorhinal cortices correlated with distinct regions in the lateral temporal cortex extending into the temporal pole. The present results are largely consistent with known connectivity in the monkey and provide a novel task-independent dissociation of the parallel pathways supporting the MTL memory system in humans. The cortical pathways include regions that have undergone considerable areal expansion in humans, providing insight into how the MTL memory system has evolved to support a diverse array of cognitive domains.
Journal of Neurophysiology 08/2008; 100(1):129-39. · 3.32 Impact Factor
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ABSTRACT: The ability to remember is often compromised by competition from irrelevant memories. However, acts of selective remembering can alter the competitive relationship between memories; memories that are selected against are weakened, whereas those that are retrieved are strengthened. Whereas the weakening of selected-against memories is typically evidenced by subsequently poorer recall of these memories, the present study tested the hypothesis that when previously selected-against memories can subsequently be successfully retrieved, such acts of successful retrieval are associated with engagement of neurobiological mechanisms that serve to detect and overcome competition. Consistent with this hypothesis, fMRI revealed that anteriorcingulate cortex and right ventrolateral prefrontal cortex are differentially engaged during successful retrieval of previously selected-against memories, and that their engagement is directly related to the magnitude of weakening that is induced by prior acts of selecting against these memories.
Cognitive Affective & Behavioral Neuroscience 07/2008; 8(2):211-21. · 3.57 Impact Factor
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ABSTRACT: Remembering often requires the selection of goal-relevant memories in the face of competition from irrelevant memories. Although there is a cost of selecting target memories over competing memories (increased forgetting of the competing memories), here we report neural evidence for the adaptive benefits of forgetting--namely, reduced demands on cognitive control during future acts of remembering. Functional magnetic resonance imaging during selective retrieval showed that repeated retrieval of target memories was accompanied by dynamic reductions in the engagement of functionally coupled cognitive control mechanisms that detect (anterior cingulate cortex) and resolve (dorsolateral and ventrolateral prefrontal cortex) mnemonic competition. Strikingly, regression analyses revealed that this prefrontal disengagement tracked the extent to which competing memories were forgotten; greater forgetting of competing memories was associated with a greater decline in demands on prefrontal cortex during target remembering. These findings indicate that, although forgetting can be frustrating, memory might be adaptive because forgetting confers neural processing benefits.
Nature Neuroscience 08/2007; 10(7):908-14. · 15.53 Impact Factor
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ABSTRACT: Although the parietal lobe is not traditionally thought to support declarative memory, recent event-related fMRI studies of episodic retrieval have consistently revealed a range of memory-related influences on activation in lateral posterior parietal cortex (PPC) and precuneus extending into posterior cingulate and retrosplenial cortex. This article surveys the fMRI literature on PPC activation during remembering, a literature that complements earlier electroencephalography data. We consider these recent memory-related fMRI responses within the context of classical ideas about parietal function that emphasize space-based attention and motor intention. We conclude by proposing three hypotheses concerning how parietal cortex might contribute to memory.
Trends in Cognitive Sciences 10/2005; 9(9):445-53. · 12.59 Impact Factor
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ABSTRACT: Declarative memory permits an organism to recognize stimuli that have been previously encountered, discriminating them from those that are novel. One basis for recognition is item memory strength, which may support the perception of stimulus familiarity. Though the medial temporal lobes are known to be critical for declarative memory, at present the neural mechanisms supporting perceived differences in memory strength remain poorly specified. Here, functional MRI (fMRI) and anatomically constrained magnetoencephalography (MEG) indexed correlates of graded memory strength in the human brain, focusing on medial temporal cortex. fMRI revealed a decrease in medial temporal cortical activation that tracked parametric levels of perceived memory strength. Anatomically constrained MEG current estimates revealed that strength-dependent signal reductions onset within 150-300 ms. Memory strength appears to be rapidly signaled by medial temporal cortex through repetition suppression (activation reductions), providing a basis for the subjective perception of stimulus familiarity or novelty.
Neuron 10/2005; 47(5):751-61. · 14.74 Impact Factor
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ABSTRACT: Episodic memory supports conscious remembrance of everyday experience. Prior functional neuroimaging data indicate that episodic encoding during phonological task performance is correlated with activation in bilateral posterior ventrolateral prefrontal cortex (pVLPFC), although uncertainty remains regarding whether these prefrontal regions make necessary contributions to episodic memory formation. Using functional MRI data to guide application of single-pulse transcranial magnetic stimulation (spTMS), this study examined the necessity of left and right pVLPFC for episodic encoding (as expressed through subsequent memory performance). To assess the timing of critical computations, pVLPFC function was transiently disrupted at different poststimulus onset times while subjects made syllable decisions about visually presented familiar and unfamiliar words; subsequent memory for these stimuli was measured. Results revealed that left pVLPFC disruption during encoding of familiar words impaired subsequent memory, expressed as a decline in recognition confidence, with disruption being maximal at 380 ms after stimulus onset. In contrast, right pVLPFC disruption facilitated subsequent memory for familiar words, expressed as an increase in medium confidence recognition, with this facilitation being maximal at 380 ms. Finally, phonological (syllable) decision accuracy was facilitated by right pVLPFC disruption, with this effect being maximal at 340 ms, but was unaffected by left pVLPFC disruption. These findings suggest that left pVLPFC mechanisms onset between 300 and 400 ms during phonological processing of words, with these mechanisms appearing necessary for effective episodic encoding. In contrast, disruption of correlated mechanisms in right pVLPFC facilitates encoding, perhaps by inducing a functional shift in the mechanisms engaged during learning.
Journal of Neurophysiology 08/2005; 94(1):688-98. · 3.32 Impact Factor
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ABSTRACT: Recognition decisions can be based on familiarity, the sense that an item was encountered previously (item memory), and on recollection, the conscious recovery of contextual information surrounding a previous encounter with the item (e.g., source memory). Recognition with recollection is thought to depend on multiple mechanisms, including prefrontal "control" processes that guide retrieval and recapitulation mechanisms that reactivate posterior neocortical representations that were present at encoding. However, uncertainty remains regarding the precise nature of prefrontal contributions to recollection and the selectivity of recapitulation to veridical recollection. The present event-related functional magnetic resonance imaging study sought to examine whether regions showing "old-new" effects support processes sensitive to recollection success or recollection attempt and whether recapitulation of neocortical representations emerge during veridical recollection as well as during false recognition (i.e., false alarms) or whether false recognition resembles familiarity-based responding. Results revealed that multiple left prefrontal cortical regions were engaged during attempts to recollect previous contextual (source) details, regardless of the nature of the to-be-recollected details and of source recollection outcome (successful vs unsuccessful). Recapitulation effects were observed in regions sensitive to the encoding task, suggesting that veridical recollection entails the reactivation of processes or representations present during encoding. Importantly, in contrast to leading models of recognition memory, false alarms also appeared to be based partially on recollection, as revealed through false recapitulation effects. Implications for neural and cognitive models of recognition are considered.
Journal of Neuroscience 05/2004; 24(17):4172-80. · 7.11 Impact Factor
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ABSTRACT: Behavior is often governed by abstract rules or instructions for behavior that can be abstracted from one context and applied to another. Prefrontal cortex (PFC) is thought to be important for representing rules, although the contributions of ventrolateral (VLPFC) and dorsolateral (DLPFC) regions remain under-specified. In the present study, event-related fMRI was used to examine abstract rule representation in humans. Prior to scanning, subjects learned to associate unfamiliar shapes and nonwords with particular rules. During each fMRI trial, presentation of one of these cues was followed by a delay and then by sample and probe stimuli. Match and non-match rules required subjects to indicate whether or not the sample and probe matched; go rules required subjects to make a response that was not contingent on the sample/probe relation. Left VLPFC, parietal cortex, and pre-SMA exhibited sensitivity to rule type during the cue and delay periods. Delay-period activation in these regions, but not DLPFC, was greater when subjects had to maintain response contingencies (match, non-match) relative to when the cue signaled a specific response (go). In contrast, left middle temporal cortex exhibited rule sensitivity during the cue but not delay period. These results support the hypothesis that VLPFC interacts with temporal cortex to retrieve semantic information associated with a cue and with parietal cortex to retrieve and maintain relevant response contingencies across delays. Future investigations of cross-regional interactions will enable full assessment of this account. Collectively, these results demonstrate that multiple, neurally separable processes are recruited during abstract rule representation.
Journal of Neurophysiology 12/2003; 90(5):3419-28. · 3.32 Impact Factor
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ABSTRACT: The functional anatomy of syntactic transformations, a major computational operation invoked in sentence processing, was identified through a functional magnetic resonance imaging investigation. A grammaticality judgment task was used, presented through a novel hidden-blocks design. Subjects listened to transformational and nontransformational sentences in which a host of other complexity generators (number of words, prepositions, embeddings, etc.) were kept constant. A series of analyses revealed that the neural processing of transformations is localizable, evoking a highly lateralized and localized activation in the left inferior frontal gyrus (Broca's region) and bilateral activation in the posterior superior temporal sulcus. The pattern of activation associated with transformational analysis was distinct from the one observed in neighboring regions, and anatomically separable from the effects of verb complexity, which yielded significant activation in the left posterior superior temporal sulcus. Taken together with neuropsychological evidence, these results uncover the neural reality of syntactic transformations.
Psychological Science 10/2003; 14(5):433-40. · 4.43 Impact Factor
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ABSTRACT: To what extent does emotional traumatic context affect sensory processing in the brain? A striking example of emotional impact on sensation is manifested in posttraumatic stress disorder (PTSD), in which a severe emotional trauma produces recurrent and vivid unpleasant sensory recollections. Here we report on an fMRI study exploring the sensory processing of trauma-related pictures in the visual cortex and amygdala in respect to PTSD. The impact of traumatic experience on brain responses was tested in relation to stimuli content and its level of recognition in a parametric factorial design. Twenty combat veterans, 10 with and 10 without PTSD, viewed backward-masked images of combat and noncombat content, presented at below, near, and above recognition thresholds. The response to combat content evoked more activation in the visual cortex in PTSD subjects than in non-PTSD subjects, only when images were presented at below recognition threshold. By contrast, the amygdala demonstrated increased activation in PTSD subjects irrespective of content and recognition threshold of the images. These intriguing findings are compatible with the notion that in PTSD, emotional traumatic experience could modify visual processing already at the preattentive level. On the other hand, lack of content specificity in the amygdala point to a possible predisposed mechanism for pathological processing of traumatic experience. The differential sensitivity of the amygdala and visual cortex to traumatic context implies distinct roles of limbic and sensory regions in the registration and recollection of emotional experience in the brain.
NeuroImage 08/2003; 19(3):587-600. · 5.89 Impact Factor
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ABSTRACT: Can brain activity reveal a covert choice? Making a choice often evokes distinct emotions that accompany decision processes. Amygdala has been implicated in choice behavior that is guided by a prospective negative outcome. However, its specific involvement in emotional versus cognitive processing of choice behavior has been a subject of controversy. In this study, the human amygdala was monitored by functional magnetic resonance imaging (fMRI) while subjects were playing in a naturalistic choice paradigm against the experimenter. In order to win, players had to occasionally choose to bluff their opponent, risk "getting caught," and suffer a loss. A critical period, when choice has been made but outcome was still unknown, activated the amygdala preferentially following the choice that entailed risk of loss. Thus, the response of the amygdala differentiated between subject's covert choice of either playing fair or foul. These results support a role of the amygdala in choice behavior, both in the appraisal of inherent value of choice and the signaling of prospective negative outcomes.
Neuron 04/2002; 33(6):983-94. · 14.74 Impact Factor
