[Show abstract][Hide abstract] ABSTRACT: Previous research in non-human primates has shown that the superior longitudinal fascicle (SLF), a major intrahemispheric fiber tract, is actually composed of four separate components. In humans, only post-mortem investigations have been available to examine the trajectory of this tract. This study evaluates the hypothesis that the four subcomponents observed in non-human primates can also be found in the human brain using in vivo diffusion tensor magnetic resonance imaging (DT-MRI). The results of our study demonstrated that the four subdivisions could indeed be identified and segmented in humans. SLF I is located in the white matter of the superior parietal and superior frontal lobes and extends to the dorsal premotor and dorsolateral prefrontal regions. SLF II occupies the central core of the white matter above the insula. It extends from the angular gyrus to the caudal-lateral prefrontal regions. SLF III is situated in the white matter of the parietal and frontal opercula and extends from the supramarginal gyrus to the ventral premotor and prefrontal regions. The fourth subdivision of the SLF, the arcuate fascicle, stems from the caudal part of the superior temporal gyrus arches around the caudal end of the Sylvian fissure and extends to the lateral prefrontal cortex along with the SLF II fibers. Since DT-MRI allows the precise definition of only the stem portion of each fiber pathway, the origin and termination of the subdivisions of SLF are extrapolated from the available data in experimental material from non-human primates.
[Show abstract][Hide abstract] ABSTRACT: We present an MRI-based anatomic analysis of a series of seven human brains with the semilobar form of holoprosencephaly. The analysis defines a set of common descriptors for a pattern of topological anomaly which is uniform for the set of seven brains. The core of the anomaly is a rostro-caudally aligned midline gray matter 'seam' that extends from the telencephalic-suprachiasmatic junctional region to abut the posterior aspect of the callosal commissure. The seam forms the ventricular roof throughout its extent. Rostrally it is formed by the conjoined heads of caudate/accumbens nuclei. It continues caudally as a gray matter bridge in the fundus of the interhemispheric fissure, where it bridges right and left neocortex. Fornix, septal nuclei and septal limb of the choroid plexus are absent, and the telencephalic ventricles communicate with the diencephalic via open septal limbs of the choroid fissures. By contrast, the temporal limb of hippocampal formation and the choroid plexus are normal and the temporal limb of the choroid fissure is closed. This topological anomaly of conjoined left and right cortical and nuclear gray matter into a midline seam and absent septal structures is thus confined to the region of the midline telencephalic hemisphere evagination. Total telencephalic growth is strongly correlated with the length of this topologically abnormal midline telencephalic segment. The set of findings is consistent with graded failure of induction of rostral to caudal specification in the midline rostral telencephalic zone.
[Show abstract][Hide abstract] ABSTRACT: We present an MRI-based anatomic analysis of a series of 9 human brains, representing lobar, semilobar and alobar forms of holoprosencephaly. The analysis of these variable forms of the malformation is based upon a topologic systematics established in a prior analysis of a homogeneous set of semilobar malformations. This systematics has the dual advantage that it serves both as a uniform reference for qualitative description and as a quantitative descriptive base for mathematical correlations between parameters of topology and of growth and development. Within this systematics, the prosencephalic midline is divided from caudal to rostral into diencephalic (DD—right and left, subthalamus through suprachiasmatic junction with telencephalon), telencephalic (TT—right and left, suprachiasmatic border of telencephalon midline to hippocampal commissure) and diencephalic—telencephalic (DT—right and left—hippocampal commissure through temporal limb of choroid fissure) segments. The topologic abnormality of the initial semilobar series was expressed in an orderly rostral to caudal gradient along the TT segment. In each malformation, normal midline topology began with a small posterior corpus callosum. Although the topologic anomaly in the present series invariably also involved the TT segment, this involvement was not continuous and was variably associated with anomalies of the DD in 6 and unilaterally of the DT in 1 brain. In the present as well as with the earlier series of HPE malformations but not in “normative brains,” total telencephalic growth is strongly correlated with the length of the midline telencephalic segment. We propose that this system of analysis will be sensitive to the developmental stage and locus of expression of genetic and non-genetic determinants of the formal origin of HPE. For all of the present series, karyotype anlyses were normal. Mutations in the Shh and Zic2 genes were excluded in 2 cases.
Journal of Neurocytology 01/2004; 33(1). · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The neuroinformatics landscape in which human brain morphometry occurs has advanced dramatically over the past few years. Rapid advancement in image acquisition methods, image analysis tools and interpretation of morphometric results make the study of in vivo anatomic analysis both challenging and rewarding. This has revolutionized our expectations for current and future diagnostic and investigative work with the developing brain. This paper will briefly cover the methods of morphometric analysis available for neuroanatomic analysis, and tour some sample results from a prototype retrospective database of neuroanatomic volumetric information. From these observations, issues regarding the anatomic variability of developmental maturation of neuroanatomic structures in both typically and atypically developing populations can be discussed.
Mental Retardation and Developmental Disabilities Research Reviews 02/2003; 9(3):155-60. · 3.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Central nervous system habituation in humans was studied using functional magnetic resonance imaging and repeated presentations of single fearful and neutral faces. Habituation of blood-oxygenation-level-dependent (BOLD) signal during exposure to face stimuli, collapsed over fearful and neutral expressions, was evident in the right amygdala and hippocampus, as well as in the medial/inferior temporal cortex bilaterally. In the hippocampus, significantly greater habituation was evident on the right as compared to the left side, which could reflect the visual nature of the stimuli. There were no time by expression interaction effects in these regions, suggesting similar neural attenuation rates to fearful and neutral face stimuli. These results indicate that brain regions involved in novelty detection and memory processing habituate at similar rates regardless of whether the face in focus displays an aversive emotional expression or not.
Brain Research Bulletin 02/2003; 59(5):387-92. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several recent neuroimaging studies have provided data consistent with functional abnormalities in anterior cingulate cortex in posttraumatic stress disorder (PTSD). In our study, we implemented a cognitive activation paradigm to test the functional integrity of anterior cingulate cortex in PTSD.
Eight Vietnam combat veterans with PTSD (PTSD Group) and eight Vietnam combat veterans without PTSD (non-PTSD Group) underwent functional magnetic resonance imaging (fMRI) while performing the Emotional Counting Stroop. In separate conditions, subjects counted the number of combat-related (Combat), generally negative (General Negative), and neutral (Neutral) words presented on a screen and pressed a button indicating their response.
In the Combat versus General Negative comparison, the non-PTSD group exhibited significant fMRI blood oxygenation level-dependent signal increases in rostral anterior cingulate cortex, but the PTSD group did not.
These findings suggest a diminished response in rostral anterior cingulate cortex in the presence of emotionally relevant stimuli in PTSD. We speculate that diminished recruitment of this region in PTSD may, in part, mediate symptoms such as distress and arousal upon exposure to reminders of trauma.
[Show abstract][Hide abstract] ABSTRACT: Functional magnetic resonance imaging (fMRI) of the human brain was used to compare changes in amygdala activity associated with viewing facial expressions of fear and anger. Pictures of human faces bearing expressions of fear or anger, as well as faces with neutral expressions, were presented to 8 healthy participants. The blood oxygen-level dependent (BOLD) fMRI signal within the dorsal amygdala was significantly greater to Fear versus Anger, in a direct contrast. Significant BOLD signal changes in the ventral amygdala were observed in contrasts of Fear versus Neutral expressions and, in a more spatially circumscribed region, to Anger versus Neutral expressions. Thus, activity in the amygdala is greater to fearful facial expressions when contrasted with either neutral or angry faces. Furthermore, directly contrasting fear with angry faces highlighted involvement of the dorsal amygdaloid region.
[Show abstract][Hide abstract] ABSTRACT: Repeated presentations of emotional facial expressions were used to assess habituation in the human brain using fMRI. Significant fMRI signal decrement was present in the left dorsolateral prefrontal and premotor cortex, and right amygdala. Within the left prefrontal cortex greater habituation to happy vs fearful stimuli was evident, suggesting devotion of sustained neural resources for processing of threat vs safety signals. In the amygdala, significantly greater habituation was observed on the right compared to the left. In contrast, the left amygdala was significantly more activated than the right to the contrast of fear vs happy. We speculate that the right amygdala is part of a dynamic emotional stimulus detection system, while the left is specialized for sustained stimulus evaluations.
[Show abstract][Hide abstract] ABSTRACT: In summary, contemporary pathophysiological models of OCD and related disorders implicate CSTC circuitry. In this chapter, we have reviewed relevant concepts related to implicit learning and more specifically, the use of an implicit sequence learning paradigm as a probe of striato-thalamic function. An initial PET investigation of patients with OCD confirmed a priori hypotheses of failure to recruit right striatum, despite the absence of a performance deficit (22). A modified version of the SRT was studied in conjunction with fMRI and yielded reliable right-lateralized striatal activation in a cohort of 10 male subjects, with clear spatial dissociation of caudate and putamen activation foci (119). Subsequent studies in our laboratory suggest that this paradigm also yields a reliable temporal window of thalamic deactivation, and hence a means for assessing thalamic gating in human subjects (120). Finally, as presented in this chapter, preliminary data from the fMRI-SRT in patients with OCD and TS as well as normal control subjects appear to replicate and extend the findings from our original PET-SRT study in OCD. Future investigations in our laboratory will seek to elaborate upon these preliminary results. In particular, we intend to study psychiatric comparison groups to establish the generalizability and/or specificity of these findings across disorders. Within OCD, we hope to explore the relationship between abnormal brain-activation patterns and symptom dimensions (34). Further, by studying subjects with remitted OCD who have been successfully treated, we hope to determine whether the observed brain-activation abnormalities represent state or trait markers. Finally, we have already begun to test a hypothesis of parallel processing deficiency in OCD by using a dual-task version of the SRT that makes simultaneous demands on implicit and explicit information processing systems (128). It is our hope that this program of research will yield new insights about OCD and related disorders, including TS. Most importantly, as other teams of investigators pursue complementary lines of inquiry, it is our wish that collective efforts in this field will lead to improved diagnosis and treatment, if not cure or prevention, for those who are afflicted with these illnesses.
[Show abstract][Hide abstract] ABSTRACT: Here we describe response in the human amygdala to the presentation of racial outgroup vs ingroup faces. Functional magnetic resonance imaging (fMRI) measures of brain activity were acquired while subjects who identified themselves as White or Black viewed photographs of both White and Black faces. Across all subjects, we observed significantly greater blood oxygen-level-dependent (BOLD) signal in the amygdala to outgroup vs ingroup faces, but only during later stimulus presentations. A region of interest (ROI)-based analysis of these voxels revealed a significant interaction between amygdala response to outgroup and ingroup faces over time. Specifically, the greater amygdala activation to outgroup faces during later stimulus presentations was the result of amygdala response habituation to repeated presentations of ingroup faces with sustained responses to outgroup faces. The present results suggest that amygdala responses to human face stimuli are affected by the relationship between the perceived race of the stimulus face and that of the subject. Results are discussed as consistent with a role for the amygdala in encoding socially and/or biologically relevant information. We conclude that researchers seeking to study brain responses to face stimuli in human subjects should consider the relationship between the race of subjects and stimuli as a significant potential source of variance. Moreover, these data provide a foundation for future related studies in the neuroscience of social cognition and race.
[Show abstract][Hide abstract] ABSTRACT: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli.
We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD.
The findings indicate that patients with PTSD exhibit exaggerated amygdala responses to masked-fearful versus masked-happy faces.
Although some previous neuroimaging studies of PTSD have demonstrated amygdala recruitment in response to reminders of traumatic events, this represents the first evidence for exaggerated amygdala responses to general negative stimuli in PTSD. Furthermore, by using a probe that emphasizes automaticity, we provide initial evidence of amygdala hyperresponsivity dissociated from the "top-down" influences of medial frontal cortex.
[Show abstract][Hide abstract] ABSTRACT: Psychomotor stimulant drugs engender intense euphoria as well as anxiogenic effects, both potentially involving the mesolimbic dopamine system.
(1) Do animals that discriminate a psychomotor stimulant drug from saline generalize to a non-pharmacological stressful event such as social defeat? (2) How does the generalization from d-amphetamine to social defeat stress relate to dopamine overflow in the mesocorticolimbic system in response to this stress?
Adult male Long-Evans rats were trained to discriminate either 1.0 mg/kg d-amphetamine or 10 mg/kg cocaine from saline in a two-lever drug discrimination task; each injection-appropriate tenth lever press was reinforced by milk presentation (fixed ratio, FR10). After confirming systematic cocaine and d-amphetamine dose-effect curves, additional discrimination tests involved exposure to several stress conditions; (1) brief confrontations with an aggressive resident rat that resulted in the intruder's defeat. Rats were administered saline, then exposed to aggressive threats behind a protective screen for 15 min, and subsequently performed the two-lever discrimination task; (2) exposure for 15 min to aggressive threats without prior defeat; (3) exposure to a novel cage for 15 min. A subgroup of rats was prepared for in vivo microdialysis after they generalized the social stress response to the d-amphetamine cue.
Nine of 35 d-amphetamine-trained and six of 18 cocaine-trained animals responded at least 80% at the drug-appropriate lever after social defeat stress. Social defeat stress increased dopamine in nucleus accumbens, with a closely similar dopamine response in amphetamine-discriminating rats that were behaviorally sensitized versus those that were not sensitized by amphetamine.
Generalization from social stress to the stimulant "cue" differs among individuals, which may be relevant to the anxiety-like effects of stimulants. By contrast, mesolimbic DA activity and motor activity was increased in response to social defeat stress or a d-amphetamine challenge, regardless of the qualitatively different stimulant-stress generalization. Mesolimbic DA in response to stress or amphetamine appears significant in behavioral activation, but not in the qualitatively divergent internal stimulus properties.
[Show abstract][Hide abstract] ABSTRACT: The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad).
Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired.
We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words.
In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.
[Show abstract][Hide abstract] ABSTRACT: Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.
[Show abstract][Hide abstract] ABSTRACT: Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, healthy subjects by using a backward masking procedure that resulted in 8 of 10 subjects reporting that they had not seen these facial expressions. The backward masking procedure consisted of 33 msec presentations of fearful or happy facial expressions, their offset coincident with the onset of 167 msec presentations of neutral facial expressions. Although subjects reported seeing only neutral faces, blood oxygen level-dependent (BOLD) fMRI signal in the amygdala was significantly higher during viewing of masked fearful faces than during the viewing of masked happy faces. This difference was composed of significant signal increases in the amygdala to masked fearful faces as well as significant signal decreases to masked happy faces, consistent with the notion that the level of amygdala activation is affected differentially by the emotional valence of external stimuli. In addition, these facial expressions activated the sublenticular substantia innominata (SI), where signal increases were observed to both fearful and happy faces--suggesting a spatial dissociation of territories that respond to emotional valence versus salience or arousal value. This study, using fMRI in conjunction with masked stimulus presentations, represents an initial step toward determining the role of the amygdala in nonconscious processing.
Journal of Neuroscience 02/1998; 18(1):411-8. · 6.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed "Counting Stroop" to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., "two" written three times), while neutral trials contain single semantic category common animals (e.g., "bird"). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P < or = 10(-4) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories.
Human Brain Mapping 01/1998; 6(4):270-82. · 6.88 Impact Factor