Putative tests of frontal lobe function: a PET-study of brain activation during Stroop's Test and verbal fluency

Stroop's test and the Verbal Fluency test are commonly argued to be measures of the integrity of the prefrontal cortex. This assumption has only to some degree been confirmed by lesion studies. In the present study, Positron Emission Tomography (PET) with H(2)(15)O was used to further validate Stroop's test and the Verbal Fluency as measures of frontal lobe function; both tests were implemented as activation paradigms during scanning of normal middleaged individuals. Stroop interference was found to activate the left anterior cingulate cortex, the supplementary motor cortex, thalamus, and the cerebellum. Although the prominent anterior cingulate activation is in the frontal lobe, it is not prefrontal. Verbal Fluency activated the left inferior frontal cortex and the left dorsolateral prefrontal cortex, the supplementary motor cortex, the anterior cingulate cortex and the cerebellum. These results bring this latter test closer to being a specific test of prefrontal function.     

The brain basis of piano performance

Performances of memorized piano compositions unfold via dynamic integrations of motor, perceptual, cognitive, and emotive operations. The functional neuroanatomy of such elaborately skilled achievements was characterized in the present study by using (15)0-water positron emission tomography to image blindfolded pianists performing a concerto by J.S. Bach. The resulting brain activity was referenced to that for bimanual performance of memorized major scales. Scales and concerto performances both activated primary motor cortex, corresponding somatosensory areas, inferior parietal cortex, supplementary motor area, motor cingulate, bilateral superior and middle temporal cortex, right thalamus, anterior and posterior cerebellum. Regions specifically supporting the concerto performance included superior and middle temporal cortex, planum polare, thalamus, basal ganglia, posterior cerebellum, dorsolateral premotor cortex, right insula, right supplementary motor area, lingual gyrus, and posterior cingulate. Areas specifically implicated in generating and playing scales were posterior cingulate, middle temporal, right middle frontal, and right precuneus cortices, with lesser increases in right hemispheric superior temporal, temporoparietal, fusiform, precuneus, and prefrontal cortices, along with left inferior frontal gyrus. Finally, much greater deactivations were present for playing the concerto than scales. This seems to reflect a deeper attentional focus in which tonically active orienting and evaluative processes, among others, are suspended. This inference is supported by observed deactivations in posterior cingulate, parahippocampus, precuneus, prefrontal, middle temporal, and posterior cerebellar cortices. For each of the foregoing analyses, a distributed set of interacting localized functions is outlined for future test.     

Atrophy of the left dorsolateral prefrontal cortex is associated with poor performance in verbal fluency in elderly poststroke women

This study aimed to investigate the association between atrophy in the prefrontal cortex with executive function and verbal fluency in elderly male and female patients poststroke. Thirty elderly female patients with non-aphasic ischemic stroke aged ≥ 60 years and 30 age-matched non-aphasic male patients with ischemic stroke were recruited. Automatic magnetic resonance imaging segmentation was used to assess the volume of the whole prefrontal cortex, along with its subdivisions: anterior cingulate cortex, orbitofrontal cortex and dorsolateral prefrontal cortex. The Semantic Verbal Fluency Test was administered at 3 and 15 months poststroke. At 3 months poststroke, left dorsolateral prefrontal cortex volume was significantly correlated with Verbal Fluency Test score in female patients only (partial coefficient = 0.453, P = 0.045), after controlling for age, education, diabetes, neurological deficit, white matter lesions volume, as well as the location and volume of infarcts. At 15 months poststroke, there remained a significant association between the left dorsolateral prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.661, P = 0.001) and between the left prefrontal cortex volume and Verbal Fluency Test (partial coefficient = 0.573, P = 0.004) in female patients after the same adjustments. These findings indicate that atrophy of the left dorsolateral prefrontal cortex contributes to the impairment of verbal fluency in elderly female patients with stroke. Sex differences may be present in the neuropsychological mechanisms of verbal fluency impairment in patients with stroke.     

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.     

Globus pallidus stimulation reduces frontal hyperactivity in tardive dystonia.

Tardive dystonia (TD) is a disabling disorder induced by neuroleptics. Internal globus pallidus (GPi) stimulation can dramatically improve TD. The present positron emission tomography and H(2)(15)O study aimed to characterize the abnormalities of brain activation of TD and the impact of GPi stimulation on these abnormalities in five TD patients treated with GPi stimulation and eight controls. Changes of regional cerebral blood flow (rCBF) were determined: (i) at rest; (ii) when moving a joystick with the right hand in three freely chosen directions in on and off bilateral GPi stimulation. A significant increase of rCBF was found in TD patients in off-stimulation condition compared to controls: (1) during motor execution in the prefrontal, premotor lateral, and anterior cingulate cortex; (2) at rest, in the prefrontal and anterior cingulate cortex and the cerebellum. Internal globus pallidus stimulation led to a reduction of rCBF (1) during motor execution, in the primary motor and prefrontal cortex and the cerebellum; (2) at rest, in the primary motor and anterior cingulate cortex and supplementary motor area. The results are as follows: (1) TD is related to an excess of brain activity notably in the prefrontal and premotor areas; (2) GPi stimulation reduces the activation of motor, premotor, and prefrontal cortex as well as cerebellum.     

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.     

Recalling word lists reveals "cognitive dysmetria" in schizophrenia: a positron emission tomography study

OBJECTIVE: This study explored the neural circuitry used during recall of unstructured verbal material in schizophrenic patients and healthy volunteer subjects. METHOD: The subjects were 13 healthy volunteers and 14 schizophrenic patients. All patients were free of medication, and all subjects were right-handed. Two experimental cognitive conditions were used: recall of novel and practiced word lists (two 15-item lists from the Rey Auditory Verbal Learning Test). Both active recall tasks were compared with an eyes-closed resting baseline condition. A nonparametric randomization test was used to determine within- and between-group differences in regional cerebral blood flow. RESULTS: Performance on both the practiced and novel memory tasks was nonsignificantly different in the patients and control subjects. During the novel memory task, the patients showed decreased flow in the right anterior cingulate, right thalamus, and bilateral cerebellum (left greater than right) relative to the control subjects. When recalling the practiced word lists, the patients showed decreased flow in the left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left supplementary motor area, left thalamus, left cerebellar regions, anterior vermis, and right cuneus. CONCLUSIONS: Patients with schizophrenia fail to activate cortical-cerebellar-thalamic-cortical circuitry during recall of both well-learned and novel word lists.     

The Danish PET/depression project: poor verbal fluency performance despite normal prefrontal activation in patients with major depression

The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.     

Comprehensive examination of frontal regions in boys and girls with attention-deficit/hyperactivity disorder

The current study examined regional frontal lobe volumes based on functionally relevant subdivisions in contemporaneously recruited samples of boys and girls with and without attention-deficit/hyperactivity disorder (ADHD). Forty-four boys (21 ADHD, 23 control) and 42 girls (21 ADHD, 21 control), ages 8-13 years, participated. Sulcal-gyral landmarks were used to manually delimit functionally relevant regions within the frontal lobe: primary motor cortex, anterior cingulate, deep white matter, premotor regions [supplementary motor complex (SMC), frontal eye field, lateral premotor cortex (LPM)], and prefrontal cortex (PFC) regions [medial PFC, dorsolateral PFC (DLPFC), inferior PFC, lateral orbitofrontal cortex (OFC), and medial OFC]. Compared to sex-matched controls, boys and girls with ADHD showed reduced volumes (gray and white matter) in the left SMC. Conversely, girls (but not boys) with ADHD showed reduced gray matter volume in left LPM; while boys (but not girls) with ADHD showed reduced white matter volume in left medial PFC. Reduced left SMC gray matter volumes predicted increased go/no-go commission rate in children with ADHD. Reduced left LPM gray matter volumes predicted increased go/no-go variability, but only among girls with ADHD. Results highlight different patterns of anomalous frontal lobe development among boys and girls with ADHD beyond that detected by measuring whole lobar volumes.     

Frontal granular cortex input to the cingulate (M3), supplementary (M2) and primary (M1) motor cortices in the rhesus monkey

Although frontal lobe interconnections of the primary (area 4 or M1) and supplementary (area 6m or M2) motor cortices are well understood, how frontal granular (or prefrontal) cortex influences these and other motor cortices is not. Using fluorescent dyes in rhesus monkeys, we investigated the distribution of frontal lobe inputs to M1, M2, and the cingulate motor cortex (area 24c or M3, and area 23c). M1 received input from M2, lateral area 6, areas 4C and PrCO, and granular area 12. M2 received input from these same areas as well as M1; granular areas 45, 8, 9, and 46; and the lateral part of the orbitofrontal cortex. Input from the ventral part of lateral area 6, area PrCO, and frontal granular cortex targeted only the ventral portion of M1, and primarily the rostral portion of M2. In contrast, M3 and area 23c received input from M1, M2; lateral area 6 and area 4C; granular areas 8, 12, 9, 46, 10, and 32; as well as orbitofrontal cortex. Only M3 received input from the ventral part of lateral area 6 and areas PrCO, 45, 12vl, and the posterior part of the orbitofrontal cortex. This diversity of frontal lobe inputs, and the heavy component of prefrontal input to the cingulate motor cortex, suggests a hierarchy among the motor cortices studied. M1 receives the least diverse frontal lobe input, and its origin is largely from other agranular motor areas. M2 receives more diverse input, arising primarily from agranular motor and prefrontal association cortices. M3 and area 23c receive both diverse and widespread frontal lobe input, which includes agranular motor, prefrontal association, and frontal limbic cortices. These connectivity patterns suggest that frontal association and frontal limbic areas have direct and preferential access to that part of the corticospinal projection which arises from the cingulate motor cortex. © 1993 Wiley-Liss,Inc.     

Brain activity during expectancy of emotional stimuli: an fMRI study

We studied the neural activation associated with the expectancy of emotional stimuli using whole brain fMRI. Fifteen healthy subjects underwent fMRI scanning during which they performed a warned reaction task using emotional pictures carrying pleasant, unpleasant, or neutral content. The task involved an expected or unexpected condition. Data were analyzed by comparing the images acquired under the different conditions. In the expected condition, compared with the unexpected condition, significant activation was observed in the medial, inferior and dorsolateral prefrontal cortex. Whereas the expectancy of pleasant stimuli produced activation in the left dorsolateral and left medial prefrontal cortex as well as in the right cerebellum, the expectancy of unpleasant stimuli produced activation in the right inferior and right medial prefrontal cortex, the right amygdala, the left anterior cingulate cortex, and bilaterally in the visual cortex. These results suggest that the expectancy of emotional stimuli is mediated by the prefrontal area including the medial, inferior, and dorsolateral prefrontal cortex. Furthermore, our data suggest that left frontal activation is associated with the expectancy of pleasant stimuli and that right frontal activation is associated with the expectancy of unpleasant stimuli. Finally, our findings suggest that the amygdala and anterior cingulate cortex may play an important role in the expectancy of unpleasant stimuli and that the input of this negative information is modulated by these specific brain areas.     

小脑在血管性认知功能障碍中的作用

小脑不仅与运动有关,而且也参与非运动的认知功能。血管性认知功能障碍是认知功能疾病中的一个重要分支,其主要与脑血管病危险因素及高龄有关。脑组织缺血导致的神经细胞及神经纤维束损害是血管性认知功能损害的主要发病机制,其关键部位在额叶（尤其是前额区）、前扣带回、海马回、下丘脑、基底节、顶叶（特别是优势半球角回）和颞叶等,这些部位多数与小脑存在纤维联系。本文综述了近年来对小脑各部分组件式结构和功能,及其与血管性认知功能损害关系等方面的研究,探讨小脑在血管性认知功能损害中的作用。     

Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey

The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic-motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.     

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.     

Functional neuroanatomy of sustained attention in schizophrenia: contribution of parietal cortices

Deficits in sustained attention have been frequently described in schizophrenia. The neuroanatomical basis reported previously have included altered levels of activation in cingulate and prefrontal cortex, but the contribution of further regions remains unclear. We explored the full neuroanatomy underlying the sustained attentional deficits observed in naïve schizophrenics compared with controls. Participants included 10 controls and 11 patients. The experimental design included rest, auditory stimulation using clicks, and two counting tasks. Subjects were instructed to mentally count the clicks, and then to count forward at the same frequency they heard previously when listening to the clicks. Relative cerebral blood flow (relCBF) was measured by means of PET ¹⁵O‐water. Differences were observed between both groups at superior temporal cortex, superior parietal gyrus, and cerebellum during tasks requiring listening. During all counting conditions, additionally to supplementary motor area (SMA), dorsolateral prefrontal cortex (DLPCF), precentral gyrus, cingulate, cerebellum, and inferior parietal (IP) gyrus, patients engaged other frontal structures including inferior, medial, and superior frontal areas. When counting with no auditory stimulation (C; requires components of working memory and time estimation), significant differences were observed in the level of activation of frontal and IP regions. Our naïve patients presented abnormal activation of auditory associative pathways. They failed to activate prefrontal and parietal regions at a similar level during tasks requiring increased cognitive effort, and they required a higher activation of inferior frontal regions to properly respond to cognitive demands. Hum. Brain Mapping 17:116–130, 2002. © 2002 Wiley‐Liss, Inc.     

Error-related brain activation during a Go/NoGo response inhibition task

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.     

Differences of cerebral activation between superior and inferior learners during motor sequence encoding and retrieval

Cerebral activation during memory encoding and retrieval might depend on subjects' learning capacity, either by corresponding to better performance in superior learners or by reflecting increased effort in inferior learners. To investigate these alternative hypotheses, the study compared cerebral activation during encoding and retrieval of a motor sequence in groups of subjects with superior and inferior learning performances. Ten healthy subjects underwent functional magnetic resonance imaging (fMRI) while performing a motor sequence encoding paradigm (i.e. finger tapping sequence) and a retrieval paradigm (i.e. reproduction of the learned sequence). Subjects were divided into superior and inferior learners according to the correctness of sequence reproduction during retrieval. During encoding, there was strong bilateral activation in the middle frontal gyrus, the supplementary motor area (SMA), the lateral parietal lobe and the cerebellum. During retrieval, again strong activation was found in identical areas of the prefrontal cortex, the parietal lobe and the cerebellum. During encoding, inferior learners showed more left-sided activations in the left middle frontal and inferior parietal gyri. Superior learners showed increased activation in the corresponding right-sided brain areas during encoding as well as during retrieval. Differences of cerebral activations in the prefrontal and parietal cortex during encoding and retrieval were found to be related to retrieval performance, i.e. success and effort. Further intervention studies are needed to assess whether these interindividual differences are the cause or the consequence of differences in memory performance.     

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: II. Effects of prefrontal cortex rTMS.

BACKGROUND: The changes in brain activity produced by repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) remain unclear. We examined intensity-related changes in brain activity with positron emission tomography (PET) in normal volunteers during rTMS delivered to the left PFC. METHODS: In 10 healthy volunteers, we delivered 1-Hz rTMS at randomized intensities over left PFC with a figure-eight coil. Intensities were 80, 90, 100, 110, and 120% of the right-hand muscle twitch threshold. Regional cerebral blood flow (rCBF) scans were acquired with H(2)(15)O PET during rTMS at each intensity. RESULTS: Repetitive transcranial magnetic stimulation intensity was inversely correlated with rCBF in the stimulated and contralateral PFC, ipsilateral medial temporal lobe, both parahippocampi, and posterior middle temporal gyri. Positive correlations of rCBF with intensity occurred in ipsilateral anterior cingulate, cerebellum, contralateral insula, primary auditory cortex, and somatosensory face area. CONCLUSIONS: The intensity-related inverse relationship between 1-Hz rTMS and prefrontal activity appears opposite to that seen with rTMS over the motor cortex in a companion study. Intensity-dependent increases in rCBF were seen in a number of distant cortical and subcortical areas with PFC rTMS, suggesting activation of left anterior cingulate, claustrum, and cerebellum. The regional differences in direction of rTMS effects and the greater activation of distant structures at higher intensities suggest the potential importance of higher-intensity prefrontal rTMS for therapeutic applications in neuropsychiatric patients.     

A neural network elicited by parametric manipulation of the attention load

We used a parametric experimental design to identify the rCBF variations related to a continuous variation of the attention load. The experiment involved goal-directed visual tasks. The length of time during which the subject's attention was engaged toward the external stimulus was taken as the factor of interest. The neural network revealed areas that positively (left cerebellum, bilateral MT/V5 complex and superior parietal lobule, right inferior temporal lobe and dorsolateral prefrontal cortex) or negatively (precuneus, anterior cingulate and medial superior frontal cortex) correlate with the attention load. Results demonstrate that the activity of these areas varies continuously as a function of the variation in the attention load.     

Regional brain activation changes and abnormal functional connectivity of the ventrolateral prefrontal cortex during working memory processing in adults with attention‐deficit/hyperactivity disorder

Previous studies on working memory (WM) function in adults with attention‐deficit/hyperactivity disorder (ADHD) suggested aberrant activation of the prefrontal cortex and the cerebellum. Although it has been hypothesized that activation differences in these regions most likely reflect aberrant frontocerebellar circuits, the functional coupling of these brain networks during cognitive performance has not been investigated so far. In this study, functional magnetic resonance imaging (fMRI) and both univariate and multivariate analytic techniques were used to investigate regional activation changes and functional connectivity differences during cognitive processing in healthy controls (n = 12) and ADHD adults (n = 12). Behavioral performance during a parametric verbal WM paradigm did not significantly differ between adults with ADHD and healthy controls. During the delay period of the activation task, however, ADHD patients showed significantly less activation in the left ventrolateral prefrontal cortex (VLPFC), as well as in cerebellar and occipital regions compared with healthy control subjects. In both groups, independent component analyses revealed a functional network comprising bilateral lateral prefrontal, striatal, and cingulate regions. ADHD adults had significantly lower connectivity in the bilateral VLPFC, the anterior cingulate cortex, the superior parietal lobule, and the cerebellum compared with healthy controls. Increased connectivity in ADHD adults was found in right prefrontal regions, the left dorsal cingulate cortex and the left cuneus. These findings suggest both regional brain activation deficits and functional connectivity changes of the VLPFC and the cerebellum as well as functional connectivity abnormalities of the anterior cingulate and the parietal cortex in ADHD adults during WM processing. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.