Impairment of executive performance after transcranial magnetic modulation of the left dorsal frontal‐striatal circuit

The dorsal frontal‐striatal circuit is implicated in executive functions, such as planning. The Tower of London task, a planning task, in combination with off‐line low‐frequency repetitive transcranial magnetic stimulation (rTMS), was used to investigate whether interfering with dorsolateral prefrontal function would modulate executive performance, mimicking dorsal frontal‐striatal dysfunction as found in neuropsychiatric disorders. Eleven healthy controls (seven females; mean age 25.5 years) were entered in a cross‐over design: two single‐session treatments of low‐frequency (1 Hz) rTMS (vs. sham rTMS) for 20 min on the left dorsolateral prefrontal cortex (DLPFC). Directly following the off‐line rTMS treatment, the Tower of London task was performed during MRI measurements. The low‐frequency rTMS treatment impaired performance, but only when the subjects had not performed the task before: we found a TMS condition‐by‐order effect, such that real TMS treatment in the first session led to significantly more errors (P = 0.032), whereas this TMS effect was not present in subjects who received real TMS in the second session. At the neural level, rTMS resulted in decreased activation during the rTMS versus sham condition in prefrontal brain regions (i.e., premotor, dorsolateral prefrontal and anterior prefrontal cortices) and visuospatial brain regions (i.e., precuneus/cuneus and inferior parietal cortex). The results show that low‐frequency off‐line rTMS on the DLPFC resulted in decreased task‐related activations in the frontal and visuospatial regions during the performance of the Tower of London task, with a behavioral effect only when task experience is limited. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

The effect of acute tryptophan depletion on emotional distraction and subsequent memory

Serotonin is a key neurotransmitter involved in emotional regulation and memory. A number of studies using acute tryptophan depletion (ATD) in healthy subjects have shown that a temporary serotonin reduction both induces a negative emotional bias and impairs long-term memory. However, little is known about the specific effects of ATD on emotional memory. Using functional magnetic resonance imaging (fMRI), we investigated the effect of ATD on negative memory and executive function in healthy volunteers. Our emotional oddball task required participants to distinguish infrequently presented targets from distracting negative and neutral pictures. Memory for the distracting pictures was tested 1 h following the fMRI session. ATD selectively enhanced memory for negative distractors relative to neutral distractors and increased activation in response to the negative distractors in the left orbital-inferior frontal, dorsomedial prefrontal and bilateral angular gyri. ATD also induced greater activation in the left inferior frontal gyrus and anterior cingulate across all stimuli. Stronger frontal activation to distractors was positively correlated with memory performance on ATD but not control days, indicating a possible compensatory mechanism for coping with increased task demand under the ATD challenge. These findings highlight the importance of serotonin in negative memory with implications for mood disorders.     

Meta-analysis of neuroimaging studies of the Wisconsin card-sorting task and component processes

A quantitative meta-analysis using the activation likelihood estimation (ALE) method was used to investigate the brain basis of the Wisconsin Card-Sorting Task (WCST) and two hypothesized component processes, task switching and response suppression. All three meta-analyses revealed distributed frontoparietal activation patterns consistent with the status of the WCST as an attention-demanding executive task. The WCST was associated with extensive bilateral clusters of reliable cross-study activity in the lateral prefrontal cortex, anterior cingulate cortex, and inferior parietal lobule. Task switching revealed a similar, although less robust, frontoparietal pattern with additional clusters of activity in the opercular region of the ventral prefrontal cortex, bilaterally. Response-suppression tasks, represented by studies of the go/no-go paradigm, showed a large and highly right-lateralized region of activity in the right prefrontal cortex. The activation patterns are interpreted as reflecting a neural fractionation of the cognitive components that must be integrated during the performance of the WCST.     

Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data

A meta‐analysis of 140 neuroimaging studies was performed using the activation‐likelihood‐estimate (ALE) method to explore the location and extent of activation in the brain in response to noxious stimuli in healthy volunteers. The first analysis involved the creation of a likelihood map illustrating brain activation common across studies using noxious stimuli. The left thalamus, right anterior cingulate cortex (ACC), bilateral anterior insulae, and left dorsal posterior insula had the highest likelihood of being activated. The second analysis contrasted noxious cold with noxious heat stimulation and revealed higher likelihood of activation to noxious cold in the subgenual ACC and the amygdala. The third analysis assessed the implications of using either a warm stimulus or a resting baseline as the control condition to reveal activation attributed to noxious heat. Comparing noxious heat to warm stimulation led to peak ALE values that were restricted to cortical regions with known nociceptive input. The fourth analysis tested for a hemispheric dominance in pain processing and showed the importance of the right hemisphere, with the strongest ALE peaks and clusters found in the right insula and ACC. The fifth analysis compared noxious muscle with cutaneous stimuli and the former type was more likely to evoke activation in the posterior and anterior cingulate cortices, precuneus, dorsolateral prefrontal cortex, and cerebellum. In general, results indicate that some brain regions such as the thalamus, insula and ACC have a significant likelihood of activation regardless of the type of noxious stimuli, while other brain regions show a stimulus‐specific likelihood of being activated. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Theta burst stimulation‐induced inhibition of dorsolateral prefrontal cortex reveals hemispheric asymmetry in striatal dopamine release during a set‐shifting task – a TMS–[11C]raclopride PET study

The prefrontostriatal network is considered to play a key role in executive functions. Previous neuroimaging studies have shown that executive processes tested with card‐sorting tasks requiring planning and set‐shifting [e.g. Montreal‐card‐sorting‐task (MCST)] may engage the dorsolateral prefrontal cortex (DLPFC) while inducing dopamine release in the striatum. However, functional imaging studies can only provide neuronal correlates of cognitive performance and cannot establish a causal relation between observed brain activity and task performance. In order to investigate the contribution of the DLPFC during set‐shifting and its effect on the striatal dopaminergic system, we applied continuous theta burst stimulation (cTBS) to left and right DLPFC. Our aim was to transiently disrupt its function and to measure MCST performance and striatal dopamine release during [¹¹C]raclopride PET. A significant hemispheric asymmetry was observed. cTBS of the left DLPFC impaired MCST performance and dopamine release in the ipsilateral caudate–anterior putamen and contralateral caudate nucleus, as compared to cTBS of the vertex (control). These effects appeared to be limited only to left DLPFC stimulation while right DLPFC stimulation did not influence task performance or [¹¹C]raclopride binding potential in the striatum. This is the first study showing that cTBS, by disrupting left prefrontal function, may indirectly affect striatal dopamine neurotransmission during performance of executive tasks. This cTBS‐induced regional prefrontal effect and modulation of the frontostriatal network may be important for understanding the contribution of hemisphere laterality and its neural bases with regard to executive functions, as well as for revealing the neurochemical substrate underlying cognitive deficits.     

Disorder‐specific inferior prefrontal hypofunction in boys with pure attention‐deficit/hyperactivity disorder compared to boys with pure conduct disorder during cognitive flexibility

Background. Problems with cognitive flexibility have been observed in patients with attention deficit hyperactivity disorder (ADHD) and in patients with conduct disorder (CD), characterized by the violation of societal rules and the rights of others. Functional magnetic resonance imaging (fMRI) of cognitive switching, however, has only been investigated in patients with ADHD, including comorbidity with CD, finding frontostriatal and temporoparietal underactivation. This study investigates disorder‐specific functional abnormalities during cognitive flexibility between medication‐naïve children and adolescents with noncomorbid CD and those with noncomorbid ADHD compared to healthy controls. Methods. Event‐related fMRI was used to compare brain activation of 14 boys with noncomorbid, childhood‐onset CD, 14 boys with noncomorbid ADHD, and 20 healthy comparison boys during a visual–spatial Switch task. Results. Behaviorally, children with ADHD compared to children with CD had significantly slower reaction times to switch compared to repeat trials. The fMRI comparison showed that the patients with ADHD compared to both controls and patients with CD showed underactivation in right and left inferior prefrontal cortex. No disorder‐specific brain underactivation was observed in patients with CD. Only when compared with controls alone, the disruptive behavior group showed reduced activation in bilateral temporoparietal and occipital brain regions. Conclusions. The findings extend previous evidence for disorder‐specific underactivation in patients with ADHD compared to patients with CD in inferior prefrontal cortex during tasks of inhibitory control to the domain of cognitive flexibility. Inferior prefrontal underactivation thus appears to be a disorder‐specific neurofunctional biomarker for ADHD when compared with patients with CD. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Prefrontal cortex activation in task switching: an event-related fMRI study

When a switch between two tasks has to be carried out, performance is slower than in trials where the same task is performed repeatedly. This finding has been attributed to time-consuming control processes required for task switching. Previous results of other paradigms investigating cognitive control processes suggested that prefrontal cortex is involved in executive control. We used event-related fMRI to investigate prefrontal cortex involvement in task switching. Regions in the lateral prefrontal and premotor cortex bilaterally, the anterior insula bilaterally, the left intraparietal sulcus, the SMA/pre-SMA region and the cuneus/precuneus were activated by the task repetition condition and showed additional activation in the task switch condition. This confirmed the hypothesis that lateral prefrontal cortex is involved in task switching. However, the results also showed that this region is neither the only region involved in task switching nor a region specifically involved in task switching.     

Modulation of decision‐making in a gambling task in older adults with transcranial direct current stimulation

Cognitive performance usually declines in older adults as a result of neurodegenerative processes. One of the cognitive domains usually affected is decision‐making. Based on our recent findings suggesting that non‐invasive brain stimulation can improve decision‐making in young participants, we studied whether bifrontal transcranial direct current stimulation (tDCS) applied over the right and left prefrontal cortex of older adult subjects can change balance of risky and safe responses as it can in younger individuals. Twenty‐eight subjects (age range from 50 to 85 years) performed a gambling risk task while receiving either anodal tDCS over the right and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC), anodal tDCS over the left with cathodal tDCS over the right DLPFC, or sham stimulation. Our main finding was a significant group effect showing that participants receiving left anodal/right cathodal stimulation chose more often high‐risk prospects as compared with participants receiving sham or those receiving right anodal/left cathodal stimulation. This result is contrary to previous findings in young subjects, suggesting that modulation of cortical activity in young and elderly results in opposite behavioral effects; thus supporting fundamental changes in cognitive processing in the elderly.     

Disorder‐specific dysfunction in right inferior prefrontal cortex during two inhibition tasks in boys with attention‐deficit hyperactivity disorder compared to boys with obsessive–compulsive disorder

Background:

Inhibitory dysfunction is a key behavioral and cognitive phenotype of attention‐deficit hyperactivity disorder (ADHD) and obsessive–compulsive disorder (OCD). Both disorders show neuropsychological deficits and fronto‐striatal dysfunction during tasks of motor response inhibition and cognitive flexibility. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between adolescents with ADHD and those with OCD to identify disorder‐specific neurofunctional markers that distinguish these two inhibitory disorders.

Methods:

Event‐related fMRI was used to compare brain activation between 20 healthy boys, 18 (Stop task) or 12 boys (Switch task) with ADHD, and 10 boys with OCD during a tracking Stop task that measures inhibition and stopping failure and during a visual–spatial switching task measuring cognitive flexibility.

Results:

Both patient groups shared brain dysfunction compared to healthy controls in right orbitofrontal (successful inhibition) and left dorsolateral prefrontal cortices (failed inhibition). Right inferior prefrontal dysfunction, however, was disorder‐specific to ADHD during both tasks. Left inferior prefrontal dysfunction during the Switch task was significant in children with ADHD relative to controls, but only reached a trend in patients with OCD. Patients with ADHD furthermore showed disorder‐specific dysfunction in left basal ganglia and cingulate gyrus during the Switch task.

Conclusions:

Patients with ADHD compared to those with OCD have both common and distinct dysfunctions during inhibitory control. The most consistently reported functional abnormality in children with ADHD in right inferior prefrontal cortex during inhibitory control appears to be disorder‐specific when compared to patients with OCD and may be a specific neurofunctional biomarker of ADHD. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.

     

Progressive increase of frontostriatal brain activation from childhood to adulthood during event-related tasks of cognitive control

Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence, presumably concurrent with anatomical brain maturational changes. The relatively scarce developmental functional imaging literature on cognitive control, however, has been inconsistent with respect to the neurofunctional substrates of this cognitive development, finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood. Such inconsistencies may be due to small subject numbers or confounds from age-related performance differences in block design functional MRI (fMRI). In this study, rapid, randomized, mixed-trial event-related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults. Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition (Go/no-go task), cognitive interference inhibition (Simon task), and attentional set shifting (Switch task). Adults compared with children showed increased brain activation in task-specific frontostriatal networks, including right orbital and mesial prefrontal cortex and caudate during the Go/no-go task, right mesial and inferior prefrontal cortex, parietal lobe, and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task. Whole-brain regression analyses with age across all subjects showed progressive age-related changes in similar and extended clusters of task-specific frontostriatal, frontotemporal, and frontoparietal networks. The findings suggest progressive maturation of task-specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid-adulthood.     

Short‐term language switching training tunes the neural correlates of cognitive control in bilingual language production

The present study investigated how language switching experience would modulate the neural correlates of cognitive control involved in bilingual language production. A group of unbalanced Chinese–English bilinguals undertook an 8‐day cued picture naming training during which they named pictures in either of their languages based on visually presented cues. Participants’ brain activation was scanned before and after the training in the same task. Behavioral results revealed a significant training effect such that switch costs were reduced after training. fMRI results showed that after training, activation of brain areas associated with cognitive control including the anterior cingulated cortex and the caudate was reduced. Besides, the activation reduction in the left dorsal anterior cingulated cortex positively correlated with the reduction in switch costs in response time and this training effect could be transferred to untrained stimuli. These findings suggest that neural correlates of cognitive control, especially that of the conflict monitoring process, in bilingual language production could be modulated by short‐term language switching training. Hum Brain Mapp 38:5859–5870, 2017. © 2017 Wiley Periodicals, Inc.     

Effects of multitasking‐training on gray matter structure and resting state neural mechanisms

Multitasking (MT) constitutes engaging in two or more cognitive activities at the same time. MT‐training improves performance on untrained MT tasks and alters the functional activity of the brain during MT. However, the effects of MT‐training on neural mechanisms beyond MT‐related functions are not known. We investigated the effects of 4 weeks of MT‐training on regional gray matter volume (rGMV) and functional connectivity during rest (resting‐FC) in young human adults. MT‐training was associated with increased rGMV in three prefrontal cortical regions (left lateral rostral prefrontal cortex (PFC), dorsolateral PFC (DLPFC), and left inferior frontal junction), the left posterior parietal cortex, and the left temporal and lateral occipital areas as well as decreased resting‐FC between the right DLPFC and an anatomical cluster around the ventral anterior cingulate cortex (ACC). Our findings suggest that participation in MT‐training is as a whole associated with task‐irrelevant plasticity (i.e., neural changes are not limited to certain specific task conditions) in regions and the network that are assumed to play roles in MT as well as diverse higher‐order cognitive functions. We could not dissociate the effects of each task component and the diverse cognitive processes involved in MT because of the nature of the study, and these remain to be investigated. Hum Brain Mapp 35:3646–3660, 2014. © 2013 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Resting‐state and task‐based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that “virtually lesioning” the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using 1 Hz rTMS reduced performance on a set‐shifting task. We aimed to determine whether this behavioural response was related to topological features of pre‐TMS resting‐state and task‐based functional networks. 1 Hz (inhibitory) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set‐shifting task during fMRI at baseline and directly after a single rTMS session 1–2 weeks later. Functional network topology measures were calculated from resting‐state and task‐based fMRI scans using graph theoretical analysis. The dlPFC‐stimulated group, but not the vertex group, showed reduced setshifting performance after rTMS, associated with lower task‐based betweenness centrality (BC) of the dlPFC at baseline (p = .030) and a smaller reduction in task‐based BC after rTMS (p = .024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p = .017). Our results suggest that behavioural response to 1 Hz rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to rTMS effects, while individuals with more locally well‐connected regions show greater vulnerability.     

Dynamic shifts in brain network activation during supracapacity working memory task performance

Despite significant advances in understanding how brain networks support working memory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a fine‐grained manipulation of memory load within a single trial to exceed WM capacity during functional magnetic resonance imaging to investigate how these networks respond to support task performance when WM capacity is exceeded. Analyzing correct trials only, we observed a nonmonotonic (inverted‐U) response to WM load throughout the classic WM network (including bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and presupplementary motor areas) that peaked later in individuals with greater WM capacity. We also observed a relative increase in activity in medial anterior prefrontal cortex, posterior cingulate/precuneus, and lateral temporal and parietal regions at the highest WM loads, and a set of predominantly subcortical and prefrontal regions whose activation was greatest at the lowest WM loads. At the individual subject level, the inverted‐U pattern was associated with poorer performance while expression of the early and late activating patterns was predictive of better performance. In addition, greater activation in bilateral fusiform gyrus and right occipital lobe at the highest WM loads predicted better performance. These results demonstrate dynamic and behaviorally relevant changes in the level of activation of multiple brain networks in response to increasing WM load that are not well accounted for by present models of how the brain subserves the cognitive ability to hold and manipulate information on‐line. Hum Brain Mapp 36:1245–1264, 2015. © 2014 Wiley Periodicals, Inc.     

Neural correlates of memory for object identity and object location: effects of aging

The purpose of this study was to investigate the effects of aging on memory for object identity and object location to determine whether aging affects both posterior neocortical areas that are domain-specific and other brain regions, such as pre-frontal cortex, that are involved in encoding and retrieval regardless of the information that is processed (domain-general). We used positron emission tomography (PET) to measure changes in regional cerebral blood flow (rCBF) in younger and older participants while they were engaged in encoding and retrieving information about object identity and object location. Compared to young adults, older adults showed decreased activation in domain-specific regions of inferior parietal and inferior temporal cortex while engaged in processing (encoding and retrieving) information about object location and object identity, respectively. This decreased specificity in the older adults was accompanied by greater domain-general activation in right prefrontal and premotor cortex during perceptual encoding than during retrieval. Conversely, the younger participants showed greater domain-general activation in right extrastriate cortex (Brodmann area (BA) 18) during retrieval. Moreover, we found that medial temporal and frontal lobes were synergistically activated in younger adults but not in older adults. The pattern of decreased specificity of activation in posterior neocortex with greater activation in anterior neocortex suggests that, with age, compensatory domain-general mechanisms in anterior neocortex are recruited to mitigate altered domain-specific processes. Thus, the results of the present study indicate that the relation between the presumed integrity of various structures, such as the hippocampus, prefrontal cortex, and posterior neocortex, and their pattern of activation, is a complex one that is influenced by age, by the perceptual and cognitive demands of the task and their interaction.     

Brain areas activated by uncertain reward-based decision-making in healthy volunteers

Reward-based decision-making has been found to activate several brain areas, including the ven- trolateral prefronta~ lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three de- grees of uncertainty in a reward-based decision-making task （certain, risky, and ambiguous）. The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to ana- lyze the location and intensity of activation during the reward-based decision-making task, with re- spect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ＇risk＇ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during am- biguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbi- tofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, infe- rior parietal Iobule, and cerebellar posterior lobe exhibited greater activation in the ＇risk＇ than in the ＇certain＇ condition （P 〈 0.05）. The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the ＇ambiguous＇ condition compared to the ＇risk＇ condition （P 〈 0.05）. The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during deci- sion-making about uncertain rewards. Thus, we observed different levels and regions of activation for different types of reward processing during decision-making. Specifically, when the degree of reward uncertainty increased, the number of activated brain areas increased, including greater ac- tivation of brain areas associated with loss.     

Serotonergic modulation of mismatch negativity

Neurochemical mechanisms mediating the interaction between emotional and cognitive processing are not yet fully understood. Here, we utilized acute tryptophan depletion (ATD) to reduce the brain synthesis of serotonin (5-HT), which is thought to have a central role in regulation of emotions and mood in humans. ATD effects on event-related potentials and magnetic fields were studied using a passive odd-ball paradigm in a randomized, double-blinded, controlled, cross-over design. Auditory responses were recorded simultaneously with high-resolution magnetoencephalography (MEG) and electroencephalography (EEG) in 14 healthy subjects, 5 h after ATD or a control condition. ATD significantly increased depressed mood and lowered plasma tryptophan concentration (total tryptophan decreased by 75%, free tryptophan decreased by 39%). As compared with the control condition, ATD increased the amplitudes of mismatch negativity (MMN) to duration and frequency changes and decreased the latencies of magnetic MMN to frequency changes in the hemisphere ipsilateral to the ear stimulated. Further, ATD modulated N1m latencies and decreased P2m source activity. ATD increased the interhemispheric latency difference of MMNm to frequency changes. No effects on P50 were observed. The present results suggest serotonergic modulation of preattentive auditory change detection, suggested to initiate involuntary attention shifting in the human brain.     

Interactive effects of estrogen and serotonin on brain activation during working memory and affective processing in menopausal women

While cognitive changes and mood instability are frequent symptoms reported by menopausal women, the degree to which the decline in estrogen production is responsible is not yet clear. Several lines of evidence suggest that estrogen may produce its effects on cognition and mood through modulation of serotonergic function. To test this hypothesis, we used the tryptophan depletion (TD) paradigm to lower central serotonin levels and pharmacologically manipulated estrogen levels in healthy menopausal women. We examined the individual and combined effects of estradiol and serotonin on working memory, emotion processing and task-related brain activation. Eight healthy predominantly early postmenopausal women underwent TD or sham depletion followed by functional magnetic resonance imaging (fMRI) both before and after short-term transdermal estradiol 75-150 μg/d administration. There was an estradiol treatment by TD interaction for brain activation during performance on both the N-back Task (working memory) and Emotion Identification Task (affective processing). During the 2-back condition, TD attenuated activation prior to, but not after, estradiol treatment in the right and left dorsal lateral prefrontal and middle frontal/cingulate gyrus. During emotion identification, TD heightened activation in the orbital frontal cortex and bilateral amygdala, and this effect was attenuated by estradiol treatment. These results provide preliminary evidence that serotonergic effects directly mediate the impact of estrogen on brain activation during working memory and affective processing.     

Differential impact of continuous theta‐burst stimulation over left and right DLPFC on planning

Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task‐relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta‐burst stimulation (cTBS) to investigate the supposed causal structure‐function mapping underlying this double dissociation. Two groups of healthy subjects (left‐lateralized stimulation, n = 26; right‐lateralized stimulation, n = 26) were tested within‐subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning‐parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task‐parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Magnetic resonance imaging brain activation in first‐episode bipolar mania during a response inhibition task

Aims: Impulsivity is common in bipolar disorder, especially during mania. Understanding the functional neuroanatomy of response inhibition, one component of impulsivity, might clarify the neural substrate of bipolar disorder. Methods: Sixteen DSM‐IV first‐episode, manic bipolar patients and 16 matched healthy subjects were examined during a first manic episode using functional magnetic resonance imaging while performing a response inhibition task. All subjects were studied using a 4.0 Tesla Varian Unity INOVA Whole Body MRI/MRS system. The response inhibition task was presented using non‐ferromagnetic goggles, and task performance was recorded during scan acquisition. Imaging data were analysed using analysis of functional neuroimages. Group contrasts were made for the specific response inhibition measure. Results: The groups performed the task similarly, although both demonstrated relatively poor rates of target response, but high rates of successful ‘stops’. Despite similar behavioural results, the groups showed significantly different patterns of functional magnetic resonance imaging brain activation. Specifically, during response inhibition, the healthy subjects exhibited significantly greater activation in anterior and posterior cingulate, medial dorsal thalamus, middle temporal gyrus, and precuneus. The bipolar patients exhibited prefrontal activation (BA 10) that was not observed in healthy subjects. Conclusions: Bipolar and healthy subjects exhibit different patterns of brain activation to response inhibition; these differences may reflect different functional neuroanatomic approaches to response inhibition between the two groups.