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Background: Case reports and open trials have reported beneficial effects of divalproex in the treatment of posttraumatic stress disorder (PTSD). The objective of this study was to conduct a placebo-controlled study of the efficacy and tolerability of divalproex in chronic PTSD patients., Methods: Patients were randomized to receive placebo or divalproex. The primary outcome measure was the Clinician Administered PTSD Scale (CAPS)., Results: Of 29 patients randomized, 16 received divalproex and 13 placebo. There were no significant differences between groups in mean change from baseline to end point (last observation carried forward) on the CAPS total score or subscales except for a significant decrease in avoidance/numbing scores with placebo. The only significant difference in secondary outcomes was a greater improvement in Clinical Global Impression Scale-Severity favoring placebo., Conclusions: Divalproex was not superior to placebo in this study. This could be due to lack of efficacy of divalproex in this population, inadequate sample size to detect differences, or other factors. Further study of divalproex is needed to better clarify the role of this agent in PTSD.

Parenting behavior critically shapes human infants' current and future behavior. The parent-infant relationship provides infants with their first social experiences, forming templates of what they can expect from others and how to best meet others' expectations. In this review, we focus on the neurobiology of parenting behavior, including our own functional magnetic resonance imaging (fMRI) brain imaging experiments of parents. We begin with a discussion of background, perspectives and caveats for considering the neurobiology of parent-infant relationships. Then, we discuss aspects of the psychology of parenting that are significantly motivating some of the more basic neuroscience research. Following that, we discuss some of the neurohormones that are important for the regulation of social bonding, and the dysregulation of parenting with cocaine abuse. Then, we review the brain circuitry underlying parenting, proceeding from relevant rodent and nonhuman primate research to human work. Finally, we focus on a study-by-study review of functional neuroimaging studies in humans. Taken together, this research suggests that networks of highly conserved hypothalamic-midbrain-limbic-paralimbic-cortical circuits act in concert to support aspects of parent response to infants, including the emotion, attention, motivation, empathy, decision-making and other thinking that are required to navigate the complexities of parenting. Specifically, infant stimuli activate basal forebrain regions, which regulate brain circuits that handle specific nurturing and caregiving responses and activate the brain's more general circuitry for handling emotions, motivation, attention, and empathy--all of which are crucial for effective parenting. We argue that an integrated understanding of the brain basis of parenting has profound implications for mental health.

Background: Posttraumatic stress disorder (PTSD) is a highly prevalent, disabling illness. Selective serotonin reuptake inhibitors (SSRIs) are considered first-line medication treatment, with sertraline, paroxetine, and fluoxetine being the most studied. More limited but favorable data suggest that citalopram, an SSRI, may also have a role in the treatment of PTSD. Its S-enantiomer escitalopram, which may have faster onset and greater magnitude of effect than citalopram in other conditions, has not yet been investigated in PTSD., Objective: To assess the efficacy, safety, and tolerability of escitalopram in the treatment of PTSD., Method: A 12-week, prospective, open-label trial of escitalopram was conducted from January 2003 through August 2004 in military veterans with PTSD. Escitalopram was initiated at 10 mg daily for 4 weeks, then increased to 20 mg daily for the remainder of the study. Concomitant psychiatric medications were discontinued at least 2 weeks prior to enrollment. The primary outcome variable was the change from baseline to endpoint in global Clinician-Administered PTSD Scale-Symptom version (CAPS-SX) score. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, the Hamilton Rating Scale for Depression (HAM-D), and the Davidson Trauma Scale (DTS). Posttraumatic stress disorder and comorbid diagnoses were established using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition., Results: Twenty-four of 25 patients were evaluated for efficacy. The mean global CAPS-SX score decreased from 79.4 (SD = 15.7) at baseline to 61.2 (SD = 24.7) at the end of the study (p = .0002). The CAPS-C avoidance/numbing and CAPS-D hyper-arousal subscale scores decreased significantly from baseline to endpoint (CAPS-C, p = .0171; CAPS-D, p = .0001), with trend-level reductions observed in CAPS-B reexperiencing subscale scores (p = .0593). Forty-five percent of patients (9/20) were much or very much improved at the end of the study (CGI-I of 1 or 2). The HAM-D and DTS also significantly improved (p = .0063 and p = .0004, respectively). Mild to moderate gastrointestinal disturbances were the most common side effects. Only 4 patients discontinued early because of adverse effects., Conclusions: This preliminary open-label study suggests that escitalopram is both efficacious and well tolerated in PTSD patients. However, randomized controlled studies are needed to confirm these results and to further define its potential role in the treatment of PTSD.

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.

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.

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.

Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS.

Cognitive impairments are cardinal features of schizophrenia and predictors of poor vocational and social outcome. Imaging studies with verbal fluency tasks (VFT) lead some to suggest that in schizophrenia, the combination of a failure to deactivate the left temporal lobe and a hypoactive frontal lobe reflects a functional disconnectivity between the left prefrontal cortex and temporal lobe. Others have theorized that an abnormal cingulate gyrus modulates such fronto-temporal connectivity. Thus addition of a cognitive enhancing medication to current antipsychotic therapy might improve functionality of networks necessary in working memory and internal concept generation. To test this hypothesis, we serially measured brain activity in 6 subjects on stable atypical antipsychotics performing a VFT, using BOLD fMRI. Measurements were made at baseline and again after groups were randomized to receive 12 weeks of donepezil (an acetylcholinesterase inhibitor) and placebo in a blind cross-over design. Donepezil addition provided a functional normalization with an increase in left frontal lobe and cingulate activity when compared to placebo and from baseline scans. This pilot study supports the cingulate's role in modulating cognition and neuronal connectivity in schizophrenia.

Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge. Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.

Purpose: To measure motor and auditory cortex blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) response to impulse-like transcranial magnetic stimulation (TMS) pulses as a function of train length., Materials and Methods: Interleaved with fMRI at 1.5 T, TMS pulses 0.3-msec long were applied at 1 Hz to the motor cortex area for thumb. Six subjects were studied in a TR = 1 second session administering trains of 1, 2, 4, 8, and 16 pulses, and a TR = 3 seconds session administering trains of 1, 2, 4, 8, 16, and 24 pulses. A simple hemodynamic model with finite recovery and saturation was used to quantitatively characterize the BOLD-fMRI response as a function of train length., Results: In both the activations directly induced in motor cortex by TMS and the indirect activations in auditory cortex caused by the sound of the TMS coil firing, the BOLD-fMRI responses to multiple pulses were well described by a summation of single-pulse impulse functions., Conclusion: Up to 24 discrete pulses, BOLD-fMRI response to 1 Hz TMS in both motor cortex and auditory cortex were consistent with a linear increase in amplitude and length with train length, possibly suggesting that stimuli of 1 to 2 seconds may be too long to represent impulses., (Copyright 2003 Wiley-Liss, Inc.)

In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraumatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PTSD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100+/-70 mg/d. There was significant improvement in CAPS scores, from 89.8+/-15.7 to 67.5+/-21.0 (t=4.863, df=18, <0.005), and composite PANSS ratings from baseline to endpoint. General psychopathology (PANSS) and depressive symptoms (HRSD) were also reduced at the 6-week end point. There were no serious adverse events and no clinically significant changes in vital signs or neurologic ratings. This preliminary open trial suggests that quetiapine is well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications. Studies utilizing a randomized, controlled trial design and larger sample sizes are needed to better define the potential role of quetiapine and other atypical antipsychotics in the treatment of PTSD.

Background: Little is known about the regional brain basis of human maternal behavior. To understand this better, we have been examining brain activity in mothers listening to infant cries., Methods: We measured functional Magnetic Resonance Imaging brain activity in healthy, breastfeeding first-time mothers with young infants while they listened to infant cries, white noise control sounds, and a rest condition. Based on the thalamocingulate theory of maternal behavior and pilot work, we hypothesized that the cingulate, medial thalamus, medial prefrontal cortex, and right orbitofrontal cortex would display more activity with infant cries than with white noise (comparison 1) and would uniquely activate with the cries, meaning that these regions would display activity with cry minus rest but not with white noise minus rest (comparison 2)., Results: In hypothesized regions, the group displayed more activity in the medial thalamus, medial prefrontal and right orbitofrontal cortices with both comparisons. The anterior and posterior cingulate cortex displayed more activity only with comparison 1. In non-hypothesized brain regions, several other structures thought important in rodent maternal behavior displayed activity with both comparisons including the midbrain, hypothalamus, dorsal and ventral striatum, and vicinity of the lateral septal region., Conclusions: Our results partially support our hypotheses and are generally consistent with neuroanatomical studies of rodent maternal behavior.

The evolutionary form of the iterated prisoner's dilemma (IPD) is a repeated game where players strategically choose whether to cooperate with or exploit opponents and reproduce in proportion to game success. It has been widely used to study the evolution of cooperation among selfish agents. In the past 15 years, researchers proved over a series of papers that there is no evolutionarily stable strategy (ESS) in the IPD when players maintain long-term relationships. This makes it difficult to make predictions about what strategies can actually persist as prevalent in a population over time. Here, we show that this no ESS finding may be a mathematical technicality, relying on implausible players who are "too perfect" in that their probability of cooperating on any move is arbitrarily close to either 0 or 1. Specifically, in the no ESS proof, all strategies were allowed, meaning that after a strategy X experiences any history H, X cooperates with an unrestricted probability p (X, H) where 0< or =p (X, H)< or =1. Here, we restrict strategies to the set S in which X is a member of S [corrected] if after any H, X cooperates with a restricted probability p (X, H) where e< or =p (X, H)< or =1-e and 0

Transcranial magnetic stimulation (TMS) administered over the prefrontal cortex has been shown to subtly influence neuropsychological tasks, and has antidepressant effects when applied daily for several weeks. Prefrontal TMS does not, however, produce an immediate easily observable effect, making it hard to determine if one has stimulated the cortex. Most prefrontal TMS studies have stimulated using intensity relative to the more easily determined motor threshold (MT) over motor cortex. Five healthy adults were studied in a 1.5 T MRI scanner during short trains of 1 Hz TMS delivered with a figure eight MR compatible TMS coil followed by rest epochs. In a randomized manner, left prefrontal TMS was delivered at 80%, 100% and 120% of MT interleaved with BOLD fMRI acquisition. Compared to rest, all TMS epochs activated auditory cortex, with 80% MT having no other areas of significant activation. 100% MT showed contralateral activation and 120% MT showed bilateral prefrontal activation. Higher intensity TMS, compared to lower, in general produced more activity both under the coil and contralaterally. Higher prefrontal TMS stimulation intensity produces greater local and contralateral activation. Importantly, unilateral prefrontal TMS produces bilateral effects, and TMS at 80% MT produces only minimal prefrontal cortex activation.

Background: Functional imaging studies have recently demonstrated that specific brain regions become active in cocaine addicts when they are exposed to cocaine stimuli. To test whether there are regional brain activity differences during alcohol cue exposure between alcoholic subjects and social drinkers, we designed a functional magnetic resonance imaging (fMRI) protocol involving alcohol-specific cues., Methods: Ten non-treatment-seeking adult alcoholic subjects (2 women) (mean [SD] age, 29.9 [9.9] years) as well as 10 healthy social drinking controls of similar age (2 women) (mean [SD] age, 29.4 [8.9] years) were recruited, screened, and scanned. In the 1.5-T magnetic resonance imaging scanner, subjects were serially rated for alcohol craving before and after a sip of alcohol, and after a 9-minute randomized presentation of pictures of alcoholic beverages, control nonalcoholic beverages, and 2 different visual control tasks. During picture presentation, changes in regional brain activity were measured with the blood oxygen level-dependent technique., Results: Alcoholic subjects, compared with the social drinking subjects, reported higher overall craving ratings for alcohol. After a sip of alcohol, while viewing alcohol cues compared with viewing other beverage cues, only the alcoholic subjects had increased activity in the left dorsolateral prefrontal cortex and the anterior thalamus. The social drinkers exhibited specific activation only while viewing the control beverage pictures., Conclusions: When exposed to alcohol cues, alcoholic subjects have increased brain activity in the prefrontal cortex and anterior thalamus-brain regions associated with emotion regulation, attention, and appetitive behavior.

Using transcranial magnetic stimulation (TMS), a handheld electrified copper coil against the scalp produces a powerful and rapidly oscillating magnetic field, which in turn induces electrical currents in the brain. The amount of electrical energy needed for TMS to induce motor movement (called the motor threshold [MT]), varies widely across individuals. The intensity of TMS is dosed relative to the MT. Kozel et al observed in a depressed cohort that MT increases as a function of distance from coil to cortex. This article examines this relationship in a healthy cohort and compares the two methods of assessing distance to cortex. Seventeen healthy adults had their TMS MT determined and marked with a fiducial. Magnetic resonance images showed the fiducials marking motor cortex, allowing researchers to measure distance from scalp to motor and prefontal cortex using two methods: 1) measuring a line from scalp to the nearest cortex and 2) sampling the distance from scalp to cortex of two 18-mm-square areas. Confirming Kozel's previous finding, we observe that motor threshold increases as distance to motor cortex increased for both methods of measuring distance and that no significant correlation exists between MT and prefontal cortex distance. Distance from TMS coil to motor cortex is an important determinant of MT in healthy and depressed adults. Distance to prefontal cortex is not correlated with MT, raising questions about the common practice of dosing prefontal stimulation using MT determined over motor cortex.

Repetitive transcranial magnetic stimulation (rTMS) is a new technology for exploring brain function. With this method, a small electromagnet is placed on the scalp; by activating and deactivating it, nerve cells in the underlying superficial cortex are depolarized. Several studies have found that prefrontal rTMS has potential efficacy in treating depression, and this technology, in addition to being a research tool, may soon play a role in psychiatric practice. Thus, establishing the safety of this technology is important and has been studied insufficiently. The authors performed T1-weighted three-dimensional volumetric magnetic resonance (MR) imaging on 22 depressed adults (15 active, 7 control) before and after they participated in a 2-week double-blinded, placebo-controlled trial of daily left prefrontal rTMS for the treatment of depression (a total of 16,000 stimuli). Seventeen patients also had paired T2-weighted scans. In a blinded manner, MR scans were qualitatively and quantitatively assessed for structural changes. No qualitative structural differences were observed before and after treatment. In addition, volumetric analysis of the prefrontal lobe showed no changes in the 2 weeks of the study. In conclusion, 10 days of daily prefrontal rTMS at these intensities and frequencies does not cause observable structural changes on MR scans in depressed adults.

Rationale and Objectives: The relatively high temporal and spatial resolution of functional MR imaging was used to compare the blood oxygenation level dependent (BOLD) response associated with movement induced by transcranial magnetic stimulation (TMS) with that for a similar movement executed volitionally (VOL)., Methods: Seven healthy adults were studied in a 1.5-T MR scanner. One hertz TMS at 110% of motor threshold was applied over the motor cortex for the thumb in 21-pulse trains in alternation with VOL every 63 seconds and interleaved with functional MR imaging., Results: BOLD increases in motor cortex associated with TMS and VOL movement were similar (2%-3%). Mean separation of their centers of activity was 3.7 + 1.9 mm (mean displacement: left/right = 0.3 +/- 4.1 mm; superior/inferior = 0.7 +/- 1.9 mm). There was no indication of supraphysiological brain activity., Conclusions: Motor cortex BOLD response associated with thumb movement induced by 1-Hz TMS at 110% motor threshold is similar in both location and level to that caused by a similar movement executed volitionally.

Five healthy volunteers were studied using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) and an averaged single trial (AST) protocol. Blood oxygenation level-dependent (BOLD)-fMRI response to single TMS pulses over the motor cortex was detectable in both the ipsilateral motor cortex under the TMS coil and the contralateral motor cortex, as well as bilaterally in the auditory cortex. The associated BOLD signal increase showed the typical fMRI hemodynamic response time course. The brain's response to a single TMS pulse over the motor cortex at 120% of the level required to induce thumb movement (1.0%-1.5% signal increase) was comparable in both level and duration to the auditory cortex response to the sound accompanying the TMS pulse (1.5% -2.0% signal increase).

Repetitive transcranial magnetic stimulation (rTMS) is a tool with antidepressant potential that uses a coil placed on the scalp to produce a powerful magnetic field that directly stimulates only the outermost cortex. MRI scans were obtained in 29 depressed adults involved in an rTMS antidepressant clinical treatment. These scans were analyzed to investigate the effect of distance from coil to cortex on clinical parameters. Longer motor cortex distance, but not prefrontal distance, strongly correlated with increased motor threshold (P<0.01). Clinical antidepressant response did not correlate with either distance. The rTMS antidepressant responders, however, were significantly younger (t=-2.430, P<0.05), and there appears to be a maximum threshold of age and distance to prefrontal cortex for response.

A 12-week, open label flexible dosing study was conducted to evaluate the efficacy of bupropion-SR in the treatment of generalized social phobia. The primary outcome measures include the Clinical Global Impression of Improvement (CGI-I) and the Brief Social Phobia Rating Scale (BSPS). A total of 18 subjects were enrolled. Five of the ten subjects who completed all 12 weeks were considered as responders. Response to treatment was defined as a CGI-I score of 1 or 2, ("much improved" or "very much improved," respectively) and a > 50% decrease in BSPS score. The final doses for the completers ranged between 200 and 400 mg/day (mean 366 +/- 68 mg/day). The medication was generally well tolerated. Findings from this open-label trial suggest that bupropion-SR may be useful in treating generalized social phobia.

Background: Transcranial magnetic stimulation (TMS) allows noninvasive stimulation of neurons using time-varying magnetic fields. Researchers have begun combining TMS with functional imaging to simultaneously stimulate and image brain activity. Recently, the feasibility of interleaving TMS with functional magnetic resonance imaging (fMRI) was demonstrated. This study tests this new method to determine if TMS at different intensities shows different local and remote activation., Methods: Within a 1.5 Tesla (T) MRI scanner, seven adults were stimulated with a figure-eight TMS coil over the left motor cortex for thumb, while continuously acquiring blood oxygen level dependent (BOLD) echoplanar images. TMS was applied at 1 Hz in 18-second long trains delivered alternately at 110% and 80% of motor threshold separated by rest periods., Results: Though the TMS coil caused some artifacts and reduced the signal to noise ratio (SNR), higher intensity TMS caused greater activation than lower, both locally and remotely. The magnitude (approximately 3% increase) and temporal onset (2 to 5 sec) of TMS induced blood flow changes appear similar to those induced using other motor and cognitive tasks., Conclusions: Though work remains in refining this potentially powerful method, combined TMS/fMRI is both technically feasible and produces measurable dose-dependent changes in brain activity.

While parenting is a universal human behavior, its neuroanatomic basis is currently unknown. Animal data suggest that the cingulate may play an important function in mammalian parenting behavior. For example, in rodents cingulate lesions impair maternal behavior. Here, in an attempt to understand the brain basis of human maternal behavior, we had mothers listen to recorded infant cries and white noise control sounds while they underwent functional MRI (fMRI) of the brain. We hypothesized that mothers would show significantly greater cingulate activity during the cries compared to the control sounds. Of 7 subjects scanned, 4 had fMRI data suitable for analysis. When fMRI data were averaged for these 4 subjects, the anterior cingulate and right medial prefrontal cortex were the only brain regions showing statistically increased activity with the cries compared to white noise control sounds (cluster analysis with one-tailed z-map threshold of P < 0.001 and spatial extent threshold of P < 0.05). These results demonstrate the feasibility of using fMRI to study brain activity in mothers listening to infant cries and that the anterior cingulate may be involved in mothers listening to crying babies. We are currently replicating this study in a larger group of mothers. Future work in this area may help (1) unravel the functional neuroanatomy of the parent-infant bond and (2) examine whether markers of this bond, such as maternal brain response to infant crying, can predict maternal style (i.e., child neglect), offspring temperament, or offspring depression or anxiety.

Many symptoms of PTSD represent conditioned responses to stimuli associated with a traumatic experiences. In this review, we propose that the anterior cingulate--a brain region that appears to be involved in fear-conditioning--is dysfunctional in PTSD, thus facilitating exaggerated emotional and behavioral responses (hyperarousal) to conditioned stimuli. Preclinical studies suggest that the anterior cingulate may serve a critical gating function in modulating conditioned fear responses. As such, this region would be a key component of a neural circuit involved in the pathophysiology of PTSD. An amygdala-locus coeruleus-anterior cingulate circuit may be consistent with evidence for chronic noradrenergic activation documented in PTSD patients. According to this model, efferent noradrenergic projections from the locus coeruleus may dampen anterior cingulate function. This in turn would allow myriad external or internally driven stimuli to produce the exaggerated emotional and behavioral responses characteristic of PTSD. If confirmed in future research, cingulate dysfunction would have important theoretical and treatment implications.

Rationale and Objectives: The authors demonstrate the feasibility of combining transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) inside an MR scanner to noninvasively stimulate and image regional brain activity., Methods: Echoplanar blood oxygen level dependent (BOLD)-based fMRI studies of TMS response were performed on three human volunteers inside a standard 1.5 T MR scanner using independent computer control to interleave echoplanar image acquisition and stimulation of right thumb primary motor cortex with a nonferromagnetic TMS coil., Results: Significant (P< 0.001) response was observed in motor cortex under the TMS coil during stimulation compared to rest, as well in auditory cortex, the latter presumably due to the loud "snap" when the coil was pulsed., Conclusions: Concurrent TMS stimulation and echoplanar BOLD fMRI imaging is possible. This method has potential for tracing neural circuits with brain imaging, as well as investigating the effects of TMS.