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An fMRI investigation of short-term source memory in young and older adults.

Using functional magnetic resonance imaging (fMRI) and a working memory procedure, we compared source memory judgments (format and location) with old-new judgments in young and older adults. Consistent with previous fMRI findings, for young adults, an area of left dorsolateral prefrontal cortex showed greater activity during format than old-new judgments made immediately, as well as those made after a brief, filled delay. In contrast, for older adults, activity in this area was not greater during format than old-new judgments at either retention interval. These data provide additional evidence that left lateral prefrontal cortex is important in monitoring specific source information and new evidence that older adults' source memory deficits may be related, in part, to reduced function of this brain area.

Adult↗

Males and females differ in brain activation during cognitive tasks.

To examine the effect of gender on regional brain activity, we utilized functional magnetic resonance imaging (fMRI) during a motor task and three cognitive tasks; a word generation task, a spatial attention task, and a working memory task in healthy male (n = 23) and female (n = 10) volunteers. Functional data were examined for group differences both in the number of pixels activated, and the blood-oxygen-level-dependent (BOLD) magnitude during each task. Males had a significantly greater mean activation than females in the working memory task with a greater number of pixels being activated in the right superior parietal gyrus and right inferior occipital gyrus, and a greater BOLD magnitude occurring in the left inferior parietal lobe. However, despite these fMRI changes, there were no significant differences between males and females on cognitive performance of the task. In contrast, in the spatial attention task, men performed better at this task than women, but there were no significant functional differences between the two groups. In the word generation task, there were no external measures of performance, but in the functional measurements, males had a significantly greater mean activation than females, where males had a significantly greater BOLD signal magnitude in the left and right dorsolateral prefrontal cortex, the right inferior parietal lobe, and the cingulate. In neither of the motor tasks (right or left hand) did males and females perform differently. Our fMRI findings during the motor tasks were a greater mean BOLD signal magnitude in males in the right hand motor task, compared to females where males had an increased BOLD signal magnitude in the right inferior parietal gyrus and in the left inferior frontal gyrus. In conclusion, these results demonstrate differential patterns of activation in males and females during a variety of cognitive tasks, even though performance in these tasks may not vary, and also that variability in performance may not be reflected in differences in brain activation. These results suggest that in functional imaging studies in clinical populations it may be sensible to examine each sex independently until this effect is more fully understood.

Adult↗

Lateralized and frequency-dependent effects of prefrontal rTMS on regional cerebral blood flow.

Repetitive transcranial magnetic stimulation (rTMS) is a means to study the function and connectivity of brain areas. The present study addressed the question of hemispheric asymmetry of frontal regions and aimed to further understand the acute effects of high- and low-frequency rTMS on regional cerebral blood flow (rCBF). Sixteen healthy right-handed men were imaged using H(2)(15)O positron emission tomography (PET) immediately after stimulation. High (10 Hz)- and low (1 Hz)-frequency suprathreshold short-duration rTMS was applied over either the left or right dorsolateral prefrontal cortex (DLPFC). Slow and fast rTMS applied over the left DLPFC significantly increased CBF in the stimulated area. Compared to baseline, slow rTMS induced a significant increase in CBF contralateral to the stimulation site, in the right caudate body and in the anterior cingulum. Furthermore, slow rTMS decreased CBF in the orbitofrontal cortex (OFC, ipsilateral to stimulation side). Fast rTMS applied over the right DLPFC was associated with increased activity at the stimulation site, in the bilateral orbitofrontal cortex and in the left medial thalamus compared to 1-Hz rTMS. These results show that rCBF changes induced by prefrontal rTMS differ upon hemisphere stimulated and vary with stimulation frequency. These differential neurophysiological effects of short-train rTMS with respect to side and frequency suggest hemisphere-dependent functional circuits of frontal cortico-subcortical areas.

Adult↗

Distinct neural mechanisms of risk and ambiguity: a meta-analysis of decision-making.

Converging evidence from human and animal studies suggests that decision-making relies upon a distributed neural network based in the frontal lobes. In particular, models of decision-making emphasize the involvement of orbitofrontal cortices (OFC) and the medial wall. While decision-making has been studied broadly as a class of executive function, recent models have suggested the differentiation between risky and ambiguous decision-making. Given recent emphasis on the role of OFC in affectively laden "hot" executive function and dorsolateral prefrontal cortex (DLPFC) in more purely cognitive "cool" executive function, we hypothesize that the neural substrates of decision-making may differ depending on the nature of the decision required. To test this hypothesis, we used recently developed meta-analytic techniques to examine the existent functional neuroimaging literature. An initial meta-analysis of decision-making, both risky and ambiguous, found significantly elevated probabilities of activation in frontal and parietal regions, thalamus, and caudate. Ambiguous decision-making was associated with activity in DLPFC, regions of dorsal and subcallosal anterior cingulate cortex (ACC), and parietal cortex. Risky decision-making was associated with activity in OFC, rostral portions of the ACC, and parietal cortex. Direct statistical comparisons revealed significant differences between risky and ambiguous decision-making in frontal regions, including OFC, DLPFC, and ACC, that were consistent with study hypotheses. These findings provide evidence for the dissociation of neural circuits underlying risky and ambiguous decision-making, reflecting differential involvement of affective "hot" and cognitive "cool" processes.

Brain↗

Effects of estrogen variation on neural correlates of emotional response inhibition.

Despite behavioral evidence that variation in ovarian hormones is associated with changes in affect, the neural basis of these processes is poorly understood. We combined functional magnetic resonance imaging (fMRI) with quantitative analysis of ovarian hormones in a within-subject design to investigate brain activation patterns during affective response inhibition, comparing activation between the early follicular (low estrogen and progesterone) and mid-luteal (high estrogen and progesterone) phases of the menstrual cycle in healthy women. There was significantly increased activation in the anterior cingulate and dorsolateral prefrontal cortex (DLPFC) while inhibiting response to positive words during the luteal, compared to the follicular phase. Furthermore, luteal phase estradiol level positively correlated with DLPFC activation while inhibiting response to positive words and negatively correlated with activation in several structures while inhibiting response to negative words, supporting estrogen's modulation of affective processing.

Adult↗

The effect of gender on planning: An fMRI study using the Tower of London task.

Since the introduction of brain mapping, evidences of functional gender differences have been corroborating previous behavioral and neuropsychological results showing a sex-specific brain organization. We investigated gender differences in brain activation during the performance of the Tower of London (TOL) task which is a standardized test to assess executive functions. Eighteen healthy subjects (9 females and 9 males) underwent fMRI scanning while solving a series of TOL problems with different levels of difficulty. Data were analyzed by modeling both genders and difficulty task load. Task-elicited brain activations comprised a bilateral fronto-parietal network, common to both genders; within this network, females activated more than males in dorsolateral prefrontal cortex (DLPFC) and right parietal cortex, whereas males showed higher activity in precuneus. A prominent parietal activity was found at low level of difficulty while, with heavier task demand, several frontal regions and subcortical structures were recruited. Our results suggest peculiar gender strategies, with males relying more on visuospatial abilities and females on executive processing.

Adult↗

Diffusion tensor studies dissociated two fronto-temporal pathways in the human memory system.

Recent functional neuroimaging studies have shown that multiple cortical areas are involved in memory encoding and retrieval. However, the underlying anatomical connections among these memory-related areas in humans remain elusive due to methodological limitations. Diffusion tensor imaging (DTI) is a technique based on detecting the diffusion of water molecules from magnetic resonance images. DTI allows non-invasive mapping of anatomical connections and gives a comprehensive picture of connectivity throughout the entire brain. By combining functional magnetic resonance imaging (fMRI) and DTI, we show that memory-related areas in the left dorsolateral prefrontal cortex (DLPFC) and the left ventrolateral prefrontal cortex (VLPFC) each connect with memory-related areas in the left temporal cortex. This result suggests there are two pathways between prefrontal cortex and temporal cortex related to the human memory system.

Adult↗

Individual differences in brain dynamics across a social cognition network induced by cortico-cerebellar tDCS in adults with autism spectrum disorder (ASD).

Autism spectrum disorder (ASD) is a neurodevelopmental condition with core diagnostic domains of social communication impairments, restricted interests and repetitive behaviors. Idiosyncratic brain organization is a potential hallmark of ASD. Previous transcranial direct current stimulation (tDCS) studies often targeted dorsolateral prefrontal cortex, with changes oin brain dynamics averaged across the cohort. We utilized a magnetoencephalographic (MEG) array to characterize individual differences in brain dynamics induced by cortico-cerebellar tDCS across nodes of a social cognition network. A randomized, sham-controlled, double-blind, within-subject clinical trial was conducted in a cohort of 24 young adults with ASD or high autistic traits. Two separate sessions of computerized social learning activities were combined with verum/sham tDCS, with anodal electrode over right temporoparietal junction (TPJ) and cathode on right deltoid. Following stimulation, theta- and alpha-band activity were evaluated within nodes of a social cognition network: bilateral TPJ, fusiform, medial prefrontal cortex and Crus I/II of cerebellum. Idiosyncratic participant-specific up- and down-regulation of theta- and alpha-band activity occurred across the network. Activity in right Crus I/II, a region inundated by the stimulation current, strongly correlated with the change of activity summed across all cerebral cortical nodes in theta- but not alpha-band. Intrinsic theta-band activity is believed to mediate input/output relationships in cerebellar cortex and to drive synaptic plasticity. These results suggest that theta-band stimulation of cerebellar cortex might be an effective therapy for individuals on the autism spectrum who present with cerebellar hyperactivity.

Humans↗

The neural bases of cognitive conflict and control in moral judgment.

Traditional theories of moral psychology emphasize reasoning and "higher cognition," while more recent work emphasizes the role of emotion. The present fMRI data support a theory of moral judgment according to which both "cognitive" and emotional processes play crucial and sometimes mutually competitive roles. The present results indicate that brain regions associated with abstract reasoning and cognitive control (including dorsolateral prefrontal cortex and anterior cingulate cortex) are recruited to resolve difficult personal moral dilemmas in which utilitarian values require "personal" moral violations, violations that have previously been associated with increased activity in emotion-related brain regions. Several regions of frontal and parietal cortex predict intertrial differences in moral judgment behavior, exhibiting greater activity for utilitarian judgments. We speculate that the controversy surrounding utilitarian moral philosophy reflects an underlying tension between competing subsystems in the brain.

Brain↗

Effect of intention and visual fixation disengagement on prosaccades in Parkinson's disease patients.

In a previous study, we postulated a divergence in reflexive versus voluntary saccade behavior in Parkinson's disease (PD) patients and hypothesized a fronto-striatal dysfunction. The voluntary saccade tasks included antisaccades (AS) and remembered saccades (RemS). However, multiple cognitive processes are involved in AS and RemS and the procedures lack a visual target. The present study had two main objectives. Firstly, we wanted to extend our previous findings of disturbed AS and RemS to other intentional (endogenous, "voluntary") saccades but now with a visible target. Therefore, an intentional prosaccade (IpS) task was used. Secondly, we investigated whether there is a different saccade behavior in PD patients and controls in conditions where the central fixation stimulus is extinguished shortly before the onset of the peripheral target (the so called gap condition) to assess the role of disengagement of visual fixation. With respect to the first objective, the present study found a clear dissociation between the performances of PD patients on reflexive saccade (RS) versus IpS tasks. Patients did not differ from controls in latency or error rate of RS. However, in the IpS task, latency was longer and error rate was higher in PD patients. Thus, the present study provides evidence that PD patients are deficient in intentional saccade tasks independent from the fact whether a target is visible or not. As to the second objective, saccades of PD patients did show a shorter latency in the gap than in the no gap condition. This suggests that the gap effect is not dominantly dependent on nigro-collicular neuronal circuits that are affected in PD. In the patients, the gap effect was reliable in the RS task, but not in the IpS condition. These discordant gap findings might suggest modulation of selected neuronal circuits involved in early sensorimotor processing. The present findings do not to support the hypothesis that impaired saccade behavior in PD patients is merely dependent on the presence or the absence of visual fixation and suggests a higher order psychomotor dysfunction, presumably of intentional nature. The dorsolateral prefrontal cortex might correspond to the premotor cognitive dysfunction site. However, an additional involvement of the frontal eye field can not be excluded from the present study.

Aged↗

Changes in brain activation during the acquisition of a new bimanual coodination task.

Motor skill acquisition is associated with the development of automaticity and induces neuroplastic changes in the brain. Using functional magnetic resonance imaging (fMRI), the present study traced learning-related activation changes during the acquisition of a new complex bimanual skill, requiring a difficult spatio-temporal relationship between the limbs, i.e., cyclical flexion-extension movements of both hands with a phase offset of 90 degrees. Subjects were scanned during initial learning and after the coordination pattern was established. Kinematics of the movements were accurately registered and showed that the new skill was acquired well. Learning-related decreases in activation were found in right dorsolateral prefrontal cortex (DLPFC), right premotor, bilateral superior parietal cortex, and left cerebellar lobule VI. Conversely, learning-related increases in activation were observed in bilateral primary motor cortex, bilateral superior temporal gyrus, bilateral cingulate motor cortex (CMC), left premotor cortex, cerebellar dentate nuclei/lobule III/IV/Crus I, putamen/globus pallidus and thalamus. Accordingly, bimanual skill learning was associated with a shift in activation among cortico-subcortical regions, providing further evidence for the existence of differential cortico-subcortical circuits preferentially involved during the early and advanced stages of learning. The observed activation changes account for the transition from highly attention-demanding task performance, involving processing of sensory information and corrective action planning, to automatic performance based on memory representations and forward control.

Adult↗

Brain-based mechanisms underlying complex causal thinking.

We use functional magnetic resonance imaging (fMRI) and behavioral analyses to study the neural roots of biases in causal reasoning. Fourteen participants were given a task requiring them to interpret data relative to plausible and implausible causal theories. Encountering covariation-based data during the evaluation of a plausible theory as opposed to an implausible theory selectively recruited neural tissue in the prefrontal and occipital cortices. In addition, the plausibility of a causal theory modulated the recruitment of distinct neural tissue depending on the extent to which the data were consistent versus inconsistent with the theory provided. Specifically, evaluation of data consistent with a plausible causal theory recruited neural tissue in the parahippocampal gyrus, whereas evaluating data inconsistent with a plausible theory recruited neural tissue in the anterior cingulate, left dorsolateral prefrontal cortex, and precuneus. We suggest that these findings provide a neural instantiation of the mechanisms by which working hypotheses and evidence are integrated in the brain.

Adolescent↗

Temporal and probabilistic discounting of rewards in children and adolescents: effects of age and ADHD symptoms.

This study investigated whether age and ADHD symptoms affected choice preferences in children and adolescents when they chose between (1) small immediate rewards and larger delayed rewards and (2) small certain rewards and larger probabilistic uncertain rewards. A temporal discounting (TD) task and a probabilistic discounting (PD) task were used to measure the degree to which the subjective value of a large reward decreased as one had to wait longer for it (TD), and as the probability of obtaining it decreased (PD). Rewards used were small amounts of money. In the TD task, the large reward (10 cents) was delayed by between 0 and 30s, and the immediate reward varied in magnitude (0-10 cents). In the PD task, receipt of the large reward (10 cents) varied in likelihood, with probabilities of 0, 0.25, 0.5, 0.75, and 1.0 used, and the certain reward varied in magnitude (0-10 cents). Age and diagnostic group did not affect the degree of PD of rewards: All participants made choices so that total gains were maximized. As predicted, young children, aged 6-11 years (n = 25) demonstrated steeper TD of rewards than adolescents, aged 12-17 years (n = 21). This effect remained significant even when choosing the immediate reward did not shorten overall task duration. This, together with the lack of interaction between TD task version and age, suggests that steeper discounting in young children is driven by reward immediacy and not by delay aversion. Contrary to our predictions, participants with ADHD (n = 22) did not demonstrate steeper TD of rewards than controls (n = 24). These results raise the possibility that strong preferences for small immediate rewards in ADHD, as found in previous research, depend on factors such as total maximum gain and the use of fixed versus varied delay durations. The decrease in TD as observed in adolescents compared to children may be related to developmental changes in the (dorsolateral) prefrontal cortex. Future research needs to investigate these possibilities.

Adolescent↗

Neural correlates of auditory recognition under full and divided attention in younger and older adults.

We examined how aging affects the pattern of brain activity mediating retrieval under dual-task conditions. We used functional magnetic resonance imaging (fMRI) to measure brain activity in younger and older adults while they were engaged in an auditory verbal recognition test under either full or divided attention (FA or DA). During recognition under FA, older adults had more activity in bilateral dorsolateral prefrontal cortex (PFC). DA with a distracting task requiring animacy judgments to words disrupted memory more than did a task requiring odd-digit judgments to numbers. For both behavioural and brain measures we contrasted the two DA conditions to recognition under FA to identify interference with memory performance. Behaviourally, there were no age differences in the magnitude of memory interference from DA conditions, although recognition performance was poorer overall in older adults. During the DA animacy condition, younger adults showed an increase in recognition latency, and older adults an increase in distracting task costs. Younger adults in this condition showed an increase in left inferior PFC, coupled with a decrease in right hippocampal activity; these effects were diminished in older adults who instead showed an increase in bilateral middle frontal activity. During both DA conditions, older adults showed greater activity in posterior neocortex compared to the younger group. Results indicate that older adults are able to perform as well as younger adults on retrieval tasks under DA conditions due to two alterations in brain activity: a dampening of the changes characterizing younger adults during the DA animacy condition and greater recruitment of additional regions during both DA tasks.

Adult↗

Us versus them: Political attitudes and party affiliation influence neural response to faces of presidential candidates.

We investigated how political party affiliation and political attitudes modulate neural activity while viewing faces of presidential candidates. Ten registered Democrats and 10 registered Republicans were scanned in an event-related functional MRI paradigm while viewing pictures of the faces of George Bush, John Kerry, and Ralph Nader during the 2004 United States presidential campaign. We found that compared with viewing one's own candidate, viewing the candidate from the opposing political party produced signal changes in cognitive control circuitry in the dorsolateral prefrontal cortex and anterior cingulate, as well as in emotional regions such as the insula and anterior temporal poles. BOLD signal in these regions correlated with subjects' self-reported ratings of how they felt emotionally about the candidates. These data suggest that brain activity when viewing a politician's face is affected by the political allegiance of the viewer and that people regulate their emotional reactions to opposing candidates by activating cognitive control networks.

Adult↗

The cerebellum and emotional experience.

While the role of the cerebellum in motor coordination is widely accepted, the notion that it is involved in emotion has only recently gained popularity. To date, functional neuroimaging has not been used in combination with lesion studies to elucidate the role of the cerebellum in the processing of emotional material. We examined six participants with cerebellar stroke and nine age and education matched healthy volunteers. In addition to a complete neuropsychological, neurologic, and psychiatric examination, participants underwent [15O]water positron emission tomography (PET) while responding to emotion-evoking visual stimuli. Cerebellar lesions were associated with reduced pleasant experience in response to happiness-evoking stimuli. Stroke patients reported an unpleasant experience to frightening stimuli similar to healthy controls, yet showed significantly lower activity in the right ventral lateral and left dorsolateral prefrontal cortex, amygdala, thalamus, and retrosplenial cingulate gyrus. Frightening stimuli led to increased activity in the ventral medial prefrontal, anterior cingulate, pulvinar, and insular cortex. This suggests that alternate neural circuitry became responsible for maintaining the evolutionarily critical fear response after cerebellar damage.

Aged↗

Cortical networks of procedural learning: evidence from cerebellar damage.

The lateral cerebellum plays a critical role in procedural learning that goes beyond the strict motor control functions attributed to it. Patients with cerebellar damage show marked impairment in the acquisition of procedures, as revealed by their performance on the serial reaction time task (SRTT). Here we present the case of a patient affected by ischemic damage involving the left cerebellum who showed a selective deficit in procedural learning while performing the SRTT with the left hand. The deficit recovered when the cortical excitability of an extensive network involving both cerebellar hemispheres and the dorsolateral prefrontal cortex (DLPFC) was decreased by low-frequency repetitive transcranial magnetic stimulation (rTMS). Although inhibition of the right DLPFC or a control fronto-parietal region did not modify the patient's performance, inhibition of the right (unaffected) cerebellum and the left DLPFC markedly improved task performance. These findings could be explained by the modulation of a set of inhibitory and excitatory connections between the lateral cerebellum and the contralateral prefrontal area induced by rTMS. The presence of left cerebellar damage is likely associated with a reduced excitatory drive from sub-cortical left cerebellar nuclei towards the right DLPFC, causing reduced excitability of the right DLPFC and, conversely, unbalanced activation of the left DLPFC. Inhibition of the left DLPFC would reduce the unbalancing of cortical activation, thus explaining the observed selective recovery of procedural memory.

Adult↗

Interfering with working memory in humans.

The interference method transcranial magnetic stimulation has to be seen as a complimentary tool to the other noninvasive correlational techniques such as positron emission tomography, functional magnetic resonance imaging or electroencephalography in cognitive neuroscience. However, the combination of two methods e.g. transcranial magnetic stimulation and positron emission tomography seems to be the strongest approach to validate or postulate new hypotheses. In this review several studies using transcranial magnetic stimulation to disentangle working memory functions are presented. The conclusion is drawn that there exists a superordinated amodal central executive within the dorsolateral prefrontal cortex strongly connected with modality specific areas mainly within the prefrontal cortex.

Humans↗