Decreased interhemispheric connectivity and increased cortical excitability in unmedicated schizophrenia: A prefrontal interleaved TMS fMRI study.

BACKGROUND: Prefrontal abnormalities in schizophrenia have consistently emerged from resting state and cognitive neuroimaging studies. However, these correlative findings require causal verification via combined imaging/stimulation approaches. To date, no interleaved transcranial magnetic stimulation and functional magnetic resonance imaging study (TMS fMRI) has probed putative prefrontal cortex abnormalities in schizophrenia. OBJECTIVE: /Hypothesis: We hypothesized that subjects with schizophrenia would show significant hyperexcitability at the site of stimulation (BA9) and decreased interhemispheric functional connectivity. METHODS: We enrolled 19 unmedicated subjects with schizophrenia and 22 controls. All subjects underwent brain imaging using a 3T MRI scanner with a SENSE coil. They also underwent a single TMS fMRI session involving motor threshold (rMT) determination, structural imaging, and a parametric TMS fMRI protocol with 10 Hz triplet pulses at 0, 80, 100 and 120% rMT. Scanning involved a surface MR coil optimized for bilateral prefrontal cortex image acquisition. RESULTS: Of the original 41 enrolled subjects, 8 subjects with schizophrenia and 11 controls met full criteria for final data analyses. At equal TMS intensity, subjects with schizophrenia showed hyperexcitability in left BA9 (p = 0.0157; max z-score = 4.7) and neighboring BA46 (p = 0.019; max z-score = 4.47). Controls showed more contralateral functional connectivity between left BA9 and right BA9 through increased activation in right BA9 (p = 0.02; max z-score = 3.4). GM density in subjects with schizophrenia positively correlated with normalized prefrontal to motor cortex ratio of the corresponding distance from skull to cortex ratio (S-BA9/S-MC) (r = 0.83, p = 0.004). CONCLUSIONS: Subjects with schizophrenia showed hyperexcitability in left BA9 and impaired interhemispheric functional connectivity compared to controls. Interleaved TMS fMRI is a promising tool to investigate prefrontal dysfunction in schizophrenia.

Imaging the neural mechanisms of TMS neglect-like bias in healthy volunteers with the interleaved TMS/fMRI technique: preliminary evidence.

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.

Reduced parietal activation in cervical dystonia after parietal TMS interleaved with fMRI.

OBJECTIVE: Clinically normal hand movement with altered cerebral activation patterns in cervical dystonia (CD) may imply cerebral adaptation. Since impaired sensorimotor integration appears to play a role in dystonia, left superior parietal cortex modulation with repetitive transcranial magnetic stimulation (TMS) was employed to further challenge adaptation mechanisms reflected by changes in cerebral activation. METHODS: Seven CD patients and ten healthy controls were scanned on a 3T magnetic resonance imaging (MRI) scanner with 1 Hz inhibitory interleaved TMS. They executed and imagined right wrist flexion/extension movements. Each task was preceded by a 10-s period with or without TMS. RESULTS: The activations of both tasks after TMS in controls showed a similar pattern as found in CD without TMS, i.e. activation increases in bilateral prefrontal and posterior parietal regions during both tasks and decreases in right anterior parietal cortex during imagery (P<0.001). the activations of both tasks after TMS in CD were weaker but with a similar trend in activation changes. Only in the right angular gyrus, TMS significantly failed to induce an activation increase in CD as was seen in the controls (P<0.001). CONCLUSION: The similarity between TMS effects on the distribution of cerebral activations in controls and the pattern seen in CD may support the concept that CD make use of compensatory circuitry enabling clinically normal hand movement. The fact that a similar but weaker TMS effect occurred in CD could suggest that the capacity of compensation is reduced. Particularly for the right angular gyrus, this reduction was statistically significant.

Using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (fMRI) and dynamic causal modeling to understand the discrete circuit specific changes of medications: lamotrigine and valproic acid changes in motor or prefrontal effective connectivity.

The purpose of this study was to use interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) to investigate the effects of lamotrigine (LTG) and valproic acid (VPA) on effective connectivity within motor and corticolimbic circuits. In this randomized, double-blind, crossover trial, 30 healthy volunteers received either drug or placebo 3.5 h prior to interleaved TMS/fMRI. We utilized dynamic causal modeling (DCM) to assess changes in the endogenous effective connectivity of bidirectional networks in the motor-sensory system and corticolimbic circuit. Results indicate that both LTG and VPA have network-specific effects. When TMS was applied over the motor cortex, both LTG and VPA reduced TMS-specific effective connectivity between primary motor (M1) and pre-motor cortex (PMd), and between M1 and the supplementary area motor (SMA). When TMS was applied over prefrontal cortex, however, LTG alone increased TMS-specific effective connectivity between the left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulate cortex (ACC). In summary, LTG and VPA inhibited effective connectivity in motor circuits, but LTG alone increased effective connectivity in prefrontal circuits. These results suggest that interleaved TMS/fMRI can assess region- and circuit-specific effects of medications or interventions.

Interleaved transcranial magnetic stimulation and fMRI suggests that lamotrigine and valproic acid have different effects on corticolimbic activity.

RATIONALE: Combined transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) can be used to study anticonvulsant drugs. A previous study showed that lamotrigine (LTG) inhibited brain activation induced when TMS was applied over motor cortex, whereas it increased activation induced by TMS applied over prefrontal cortex. OBJECTIVES: The present double-blind, placebo-controlled, crossover study in 30 healthy subjects again combined TMS and fMRI to test whether the effects seen previously with LTG would be confirmed and to compare these with a second anticonvulsant drug, valproic acid (VPA). RESULTS: Statistical parametric mapping analysis showed that both LTG and VPA, compared to placebo, inhibited TMS-induced activation of the motor cortex. In contrast, when TMS was applied over prefrontal cortex, LTG increased the activation of limbic regions, confirming previous results; VPA had no effect. CONCLUSION: We conclude that LTG and VPA have similar inhibitory effects on motor circuits, but differing effects on the prefrontal corticolimbic system. The study demonstrates that a combination of TMS and fMRI techniques may be useful in the study of the effects of neuroactive drugs on specific brain circuits.

Changes in cerebral activations during movement execution and imagery after parietal cortex TMS interleaved with 3T MRI.

The left parietal cortex contributes to goal-directed hand movement. In this study, we targeted this region with transcranial magnetic stimulation (TMS) to assess the effects on a wider distributed circuitry related to motor control. Ten healthy subjects underwent 3 Tesla functional magnetic resonance imaging (fMRI) with interleaved TMS. They either executed or imagined right wrist flexion/extension movements, which was preceded by a 10-second period either with or without TMS. This was applied to the left superior parietal cortex in 10 stimuli of 1 Hz at 115% motor threshold intensity. TMS preceding the movement execution condition resulted in significantly increased activation in the bilateral prefrontal, right temporo-parietal and left posterior parietal cortices, when compared to movement without such intervention (P<0.001 voxel-level; P<0.05, volume corrected). Movement imagery after TMS showed significantly increased activation in the left medial prefrontal cortex, right lateral prefrontal cortex, left supramarginal gyrus and right occipital cortex, while a decrease was present in bilateral anterior parietal cortex (P<0.01 voxel-level; P<0.05 volume corrected). Activation changes after TMS of left superior parietal cortex thus appears to increase prefrontal and posterior parietal cortex activation, associated with a reduced function of the anterior parietal cortex, including S2. These changes are thought to reflect an impaired ability to estimate the proprioceptive consequences of movement during its preparation, which is compensated by the increased contribution of more remote parietal and prefrontal cortical regions.

Motor threshold in transcranial magnetic stimulation: the impact of white matter fiber orientation and skull-to-cortex distance.

The electrophysiology of transcranial magnetic stimulation (TMS) of motor cortex is not well understood. In this study, we investigate several structural parameters of the corticospinal tract and their relation to the TMS motor threshold (MT) in 17 subjects, with and without schizophrenia. We obtained structural and diffusion tensor MRI scans and measured the fractional anisotropy and principal diffusion direction for regions of interest in the corticospinal tract. We also measured the skull-to-cortex distance over the left motor region. The anterior-posterior trajectory of principle diffusion direction of the corticospinal tract and skull-to-cortex distance were both found to be highly correlated with MT, while fractional anisotropy, age and schizophrenia status were not. Two parameters-skull-to-cortex distance and the anterior component of the principle diffusion direction of the corticospinal tract as it passes the internal capsule-are highly predictive of MT in a linear regression model, and account for 82% of the variance observed (R2 = 0.82, F = 20.27, P < 0.0001) in measurements of MT. The corticospinal tract's anterior-posterior direction alone contributes 13% of the variance explained.

Consensus paper: combining transcranial stimulation with neuroimaging.

In the last decade, combined transcranial magnetic stimulation (TMS)-neuroimaging studies have greatly stimulated research in the field of TMS and neuroimaging. Here, we review how TMS can be combined with various neuroimaging techniques to investigate human brain function. When applied during neuroimaging (online approach), TMS can be used to test how focal cortex stimulation acutely modifies the activity and connectivity in the stimulated neuronal circuits. TMS and neuroimaging can also be separated in time (offline approach). A conditioning session of repetitive TMS (rTMS) may be used to induce rapid reorganization in functional brain networks. The temporospatial patterns of TMS-induced reorganization can be subsequently mapped by using neuroimaging methods. Alternatively, neuroimaging may be performed first to localize brain areas that are involved in a given task. The temporospatial information obtained by neuroimaging can be used to define the optimal site and time point of stimulation in a subsequent experiment in which TMS is used to probe the functional contribution of the stimulated area to a specific task. In this review, we first address some general methodologic issues that need to be taken into account when using TMS in the context of neuroimaging. We then discuss the use of specific brain mapping techniques in conjunction with TMS. We emphasize that the various neuroimaging techniques offer complementary information and have different methodologic strengths and weaknesses.

Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects.

The study aimed to analyze the effects of a short-term very low-calorie diet (VLCD) on intramyocellular lipid (IMCL), total body fat, and insulin sensitivity in a group of obese nondiabetic and type 2 diabetic subjects. Seven untreated type 2 diabetic and 5 obese nondiabetic individuals were studied before and after a 6-day VLCD using proton magnetic resonance spectroscopy to quantify IMCL, dual-energy x-ray absorptiometry to assess body fat, and hyperinsulinemic-euglycemic clamps to measure peripheral insulin sensitivity. In both groups, decrements in total body fat mass and body mass index were small but statistically significant. In contrast, the diet resulted in a pronounced reduction in IMCL compared with baseline values in nondiabetic subjects (56% decrease) and type 2 diabetic subjects (40% decrease) (P < .05), and this was accompanied by an overall 9.3% increase in maximally stimulated glucose disposal rate (P < .01). Intramyocellular lipid was significantly correlated with insulin sensitivity (r = -0.69, P < .01) and waist circumference (r = 0.72 and 0.83, baseline and postdiet, respectively; both P < .01), but neither IMCL nor insulin sensitivity was related to measures of general adiposity such as body mass index, percentage of body fat, or total body fat (P = not significant). In conclusion, short-term VLCD is accompanied by small decrements in general adiposity, marked decrease in IMCL, and an increase in insulin sensitivity in nondiabetic and type 2 diabetic subjects. Therefore, rapid amelioration of insulin resistance by VLCD can be partially explained by loss of IMCL both in nondiabetic and type 2 diabetic subjects in the absence of substantial changes in total body fat. These observations are consistent with the idea that insulin resistance is more directly related to IMCL rather than to body fat per se.

Changed patterns of cerebral activation related to clinically normal hand movement in cervical dystonia.

OBJECTIVES: The relief of cervical dystonia by sensory tricks points at complex sensorimotor interaction. The relation between such stimulus-induced normalization of posture and parietal activation [Naumann M, Magyar-Lehmann S, Reiners K, Erbguth F, Leenders KL. Sensory tricks in cervical dystonia: perceptual dysbalance of parietal cortex modulates frontal motor programming. Ann Neurol 2000;47:322-8] further supports the idea of disturbed higher-order motor control and suggests that the organization of movement is affected beyond the level of a local output channel. Dysbalance beyond a restricted output channel is also supported by the spread of focal dystonia to adjacent body parts. In this fMRI study, we aimed to determine whether cervical dystonia patients have indeed different patterns of cerebral activation during clinically normal hand performance. PATIENTS AND METHODS: By means of statistical parametric mapping (SPM) of 3T fMRI results, task-related cerebral activations measured in eight cervical dystonia patients were compared to data of nine healthy volunteers. RESULTS: Compared to controls, the patient group showed a relative reduction of activations in bilateral parietal, left premotor and cingulate cortex regions during imagining of movement, while activation of right (ipsilateral) putamen, insula and cingulate cortex was impaired during movement execution. CONCLUSION: Cervical dystonia appears to concern a general disorganization of cerebral motor control, which indicates a pre-dystonic state of clinically normal hand movements. The latter may imply an increased vulnerability for deteriorating triggers such as minor accidents.

Cerebral activation patterns related to initiation and inhibition of hand movement.

Sequential ordering of purposeful movements includes distinct transitions between muscle contraction and relaxation. To explore cerebral activation patterns underlying such movement initiation and inhibition, we applied functional magnetic resonance imaging to test the effects of (1) ballistic movement (dominated by initiation), (2) movement with stepwise interruption (dominated by inhibition) and (3) smooth movements. Right-hand movements were performed by 21 healthy participants. In the basal ganglia, ballistic movements evoked putamen activation, indicating its specific contribution to initiation. Stepwise interrupted movement induced increased activation of the caudate nucleus, globus pallidus and subthalamic nucleus whereas, at the cortical level, supplementary motor area activation increased. This indicates a specific basal ganglia-thalamocortical circuit involved in motor inhibition.

Serial vagus nerve stimulation functional MRI in treatment-resistant depression.

Vagus nerve stimulation (VNS) therapy has shown antidepressant effects in open acute and long-term studies of treatment-resistant major depression. Mechanisms of action are not fully understood, although clinical data suggest slower onset therapeutic benefit than conventional psychotropic interventions. We set out to map brain systems activated by VNS and to identify serial brain functional correlates of antidepressant treatment and symptomatic response. Nine adults, satisfying DSM-IV criteria for unipolar or bipolar disorder, severe depressed type, were implanted with adjunctive VNS therapy (MRI-compatible technique) and enrolled in a 3-month, double-blind, placebo-controlled, serial-interleaved VNS/functional MRI (fMRI) study and open 20-month follow-up. A multiple regression mixed model with blood oxygenation level dependent (BOLD) signal as the dependent variable revealed that over time, VNS therapy was associated with ventro-medial prefrontal cortex deactivation. Controlling for other variables, acute VNS produced greater right insula activation among the participants with a greater degree of depression. These results suggest that similar to other antidepressant treatments, BOLD deactivation in the ventro-medial prefrontal cortex correlates with the antidepressant response to VNS therapy. The increased acute VNS insula effects among actively depressed participants may also account for the lower dosing observed in VNS clinical trials of depression compared with epilepsy. Future interleaved VNS/fMRI studies to confirm these findings and further clarify the regional neurobiological effects of VNS.

Decreased brain activation during a working memory task at rested baseline is associated with vulnerability to sleep deprivation.

STUDY OBJECTIVE: To examine whether differences in patterns of brain activation under baseline conditions relate to the differences in sleep-deprivation vulnerability. DESIGN: Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging, we scanned 33 healthy young men while they performed the Sternberg working memory task following a normal night of sleep and again following 30 hours of sleep deprivation. From this initial group, based on their Sternberg working memory task performance, we found 10 subjects resilient to sleep deprivation (sleep deprivation-resilient group) and then selected 10 age- and education-matched subjects vulnerable to sleep deprivation (sleep deprivation-vulnerable group). SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Data from 10 young men (mean age 27.8 +/- 1.7 years) in the sleep deprivation-resilient group and 10 young men (mean age 28.2 +/- 1.9 years) in the sleep deprivation-vulnerable group were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared functional magnetic resonance imaging BOLD signal at rested baseline and sleep deprivation states in the 2 groups. As hypothesized, following sleep deprivation, both groups showed significant decreases in global brain activation compared to their rested group baseline. At rested baseline and in the sleep-deprivation state, the sleep deprivation-resilient group had significantly more brain activation than did the sleep deprivation-vulnerable group. There were also differences in functional circuits within and between groups in response to sleep deprivation. CONCLUSIONS: These preliminary data suggest that patterns of brain activation during the Sternberg working memory task at the rested baseline and the sleep-deprivation state, differ across individuals as a function of their sleep-deprivation vulnerability.

An increased precision comparison of TMS-induced motor cortex BOLD fMRI response for image-guided versus function-guided coil placement.

OBJECTIVE: To examine with high precision the differences between function-guided and image-guided transcranial magnetic stimulation (TMS). METHOD: Using a calibrated TMS coil holder/positioner, interleaved TMS/functional magnetic resonance imaging (fMRI), and individualized anatomy-based regional normalization, we conducted a two-phase study of TMS coil positioning guided by either function (elicited thumb motion) or image-based targeting of the "hand knob," the anatomy associated with fMRI activation during thumb motion. RESULTS: In every case, image-guided TMS coil placement produced a thumb movement response at thresholds similar to those found under function guidance. Unexpectedly, function-guided coil locations clustered bimodally over central and precentral sulci. Image-guided locations clustered as anticipated toward the targeted gyral crown. Despite these differences, blood oxygenation level-dependent (BOLD) activation locations and magnitude for the two methods displayed no consistent differences in mean or variance between or within subjects. Image guidance produced more consistent coil placement from subject to subject relative to targeted anatomy. Surprisingly, BOLD time courses from image-guided experiments showed significantly slower return to baseline after TMS than was observed under function guidance. CONCLUSIONS: The results demonstrate the effectiveness and precision of image-guided positioning of TMS coils combined with a precisely adjustable holder/positioner and regional normalization. Image guidance provides an accurate TMS placement relative to individual anatomy when no external sign is available.

Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: an interleaved TMS/functional magnetic resonance imaging study.

BACKGROUND: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. METHODS: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. RESULTS: Both TMS (110% motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected post-task "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant differences between TMS- and volition-induced effects. Differences were detectable, however, in primary data time-intensity profiles. CONCLUSIONS: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation.

Decreased cortical response to verbal working memory following sleep deprivation.

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.

Neural correlates of speech anticipatory anxiety in generalized social phobia.

Patients with generalized social phobia fear embarrassment in most social situations. Little is known about its functional neuroanatomy. We studied BOLD-fMRI brain activity while generalized social phobics and healthy controls anticipated making public speeches. With anticipation minus rest, 8 phobics compared to 6 controls showed greater subcortical, limbic, and lateral paralimbic activity (pons, striatum, amygdala/uncus/anterior parahippocampus, insula, temporal pole)--regions important in automatic emotional processing--and less cortical activity (dorsal anterior cingulate/prefrontal cortex)--regions important in cognitive processing. Phobics may become so anxious, they cannot think clearly or vice versa.

Regional brain activity in women grieving a romantic relationship breakup.

OBJECTIVE: Separation from loved ones commonly leads to grief reactions. In some individuals, grief can evolve into a major depressive episode. The brain regions involved in grief have not been specifically studied. The authors studied brain activity in women actively grieving a recent romantic relationship breakup. It was hypothesized that while remembering their ex-partner, subjects would have altered brain activity in regions identified in sadness imaging studies: the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex. METHOD: Nine right-handed women whose romantic relationship ended within the preceding 4 months were studied. Subjects were scanned using blood-oxygen-level-dependent functional magnetic resonance imaging while they alternated between recalling a sad, ruminative thought about their loved one (grief state) and a neutral thought about a different person they knew an equally long time. RESULTS: Acute grief (grief minus neutral state) was associated with increased group activity in posterior brain regions, including the cerebellum, posterior brainstem, and posterior temporoparietal and occipital brain regions. Decreased activity was more prominent anteriorly and on the left and included the anterior brainstem, thalamus, striatum, temporal cortex, insula, and dorsal and ventral anterior cingulate/prefrontal cortex. When a more lenient statistical threshold for regions of interest was used, additional increases were found in the lateral temporal cortex, supragenual anterior cingulate/medial prefrontal cortex, and right inferomedial dorsolateral prefrontal cortex, all of which were adjacent to spatially more prominent decreases. In nearly all brain regions showing brain activity decreases with acute grief, activity decreases were greater in women reporting higher grief levels over the past 2 weeks. CONCLUSIONS: During acute grief, subjects showed brain activity changes in the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex, consistent with the hypothesis. Subjects with greater baseline grief showed greater decreases in all these regions except for the cerebellum. Further imaging studies are needed to understand the relationship between normal sadness, grief, and depression.

A high resolution assessment of the repeatability of relative location and intensity of transcranial magnetic stimulation-induced and volitionally induced blood oxygen level-dependent response in the motor cortex.

OBJECTIVE: Using functional magnetic resonance imaging, we assessed variation in location and intensity of blood oxygen level-dependent contrast associated with movements induced by transcranial magnetic stimulation or volition. BACKGROUND: Anatomic location and within-subject repeatability of blood oxygen level-dependent responses induced by transcranial magnetic stimulation comprise critical information to the use of interleaved transcranial magnetic stimulation/functional magnetic resonance imaging as a neuroscience tool. METHODS: Eleven healthy adults were scanned 3 times each at 1.5 T. Interleaved with functional magnetic resonance imaging, 1-Hz transcranial magnetic stimulation was applied over motor cortex. VOL was alternated with transcranial magnetic stimulation over the scans. RESULTS: Intra-subject standard deviations in blood oxygen level-dependent locations ranged between 3 and 6 millimeters, allowing localization to subregions of the motor strip. Coil placement relative to blood oxygen level-dependent location varied more than blood oxygen level-dependent location (sdx = 9.5mm, sdy = 8.7 mm, sdz = 9.0mm) with consistent anterior displacement (dy = 21.8 mm, P = <0.025). Analysis of variance did not detect significant differences between transcranial magnetic stimulation and VOL blood oxygen level-dependent locations or intensities, in contrast to significant intensity differences detected in auditory blood oxygen level dependence. CONCLUSION: The high repeatability of location of transcranial magnetic stimulation-induced blood oxygen level-dependent activation suggests that transcranial magnetic stimulation/functional magnetic resonance imaging stimulation can be used as a precise tool in investigation of cortical mechanisms. The similarity between VOL and transcranial magnetic stimulation suggests that transcranial magnetic stimulation may act through natural brain movement circuits.

A pilot study of functional magnetic resonance imaging brain correlates of deception in healthy young men.

We hypothesized that specific brain regions would activate during deception, and these areas would correlate with changes in electrodermal activity (EDA). Eight men were asked to find money hidden under various objects. While functional MRI images were acquired and EDA was recorded, the subjects gave both truthful and deceptive answers regarding the money's location. The group analysis revealed significant activation during deception in the orbitofrontal cortex (OFCx) and anterior cingulate (AC), but individual results were not consistent. Individually and as a group, EDA correlated with blood flow changes in the OFCx and AC. Specific brain regions were activated during deception, but the present technique lacks good predictive power for individuals.