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Biomedical subjects

John C Gore

Publications and source records attributed to John C Gore.

At least 55 records · Page 3Linked to original sources

A common parieto-frontal network is recruited under both low visibility and high perceptual interference conditions.

A fundamental property of visual attention is to select targets from interfering distractors. However, attention can also facilitate the detectability of near-threshold items presented in isolation. The extent to which these two perceptually challenging conditions are resolved by the same neural mechanisms is not well known. In the present event-related fMRI experiment, subjects performed a letter identification task under two perceptually challenging conditions; when the luminance contrast of a target letter was reduced (perceptual visibility manipulation) and when the target letter was flanked by distractors (perceptual interference manipulation). Perceptual interference recruited the right parietal and mid-lateral frontal cortex, while perceptual visibility activated these regions bilaterally. The overlap of activated areas between the two perceptual manipulations suggests that a single parieto-frontal network is summoned under both perceptual visibility and interference conditions.

Attention↗

The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder.

OBJECTIVE: Recent studies have suggested that attention deficit hyperactivity disorder (ADHD) is associated with abnormalities in basal ganglia and prefrontal cortical functioning. However, these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms. METHOD: The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a randomized, double-blind, placebo-controlled pharmacological challenge with methylphenidate in 15 adolescents with ADHD (ages 14-17), eight adolescents with reading disorder (ages 12-17), and four adolescents with both reading disorder and ADHD (ages 14-18) who were scanned during both a methylphenidate and a placebo session. Fourteen healthy comparison subjects (ages 12-20) who were not given methylphenidate served as the primary comparison group. RESULTS: During the divided attention task, unmedicated subjects with ADHD or reading disorder recruited the left ventral basal ganglia significantly less than the healthy comparison subjects. Methylphenidate led to an increase in activation in this region but had no effect on task performance. Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects, but methylphenidate did not have a direct effect on activation in this region. CONCLUSIONS: These results suggest that ADHD is associated with abnormal processing in attentional networks, with specific dysfunction in striatal circuitry. Methylphenidate may act to normalize activity within this network.

Adolescent↗

The effect of memory load on cortical activity in the spatial working memory circuit.

Accumulating evidence from electrophysiology and neuroimaging studies suggests that spatial working memory is subserved by a network of frontal and parietal regions. In the present study, we parametrically varied the memory set size (one to four spatial locations) of a delayed-response task and applied time-resolved fMRI to study the influence of memory load upon the spatial working memory circuit. Our behavioral results showed that performance deteriorates (lower accuracy and longer reaction time) as memory load increases. Memory load influenced cortical activity during the cue, delay, and response phases of the delayed-response task. Although delay-related activity in many regions increased with increasing memory load, it also was significantly reduced in the middle frontal gyrus and frontal eye fields and leveled off in the parietal areas when memory load increased further. Delay-related activity in the left posterior parietal cortex was also lower during the error trials, in comparison with the correct trials. Our findings indicate that the delay period activity in the spatial working memory circuit is load sensitive and that the attenuation of this signal is the neural manifestation of performance limitation in the face of excessive memory load.

Adolescent↗

Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Adult↗

A quantitative study of magnetization transfer in MAGIC gels.

Magnetization transfer (MT) has been measured quantitatively as a function of radiation dose in MAGIC polymer gels. The MT rates between the free and immobile macromolecular proton pools (kmr and kfm), and the ratio of the sizes of these coupled proton pools (Pm/Pf), were measured by analysing the response to an inversion recovery sequence. While pm/pf increases linearly with dose, the fast MT rate kmf also increases with dose, unlike previous measurements in BANG gels. This dependence of kmf on dose suggests there are additional factors that modify spin exchange in MAGIC gels as irradiation occurs.

Ascorbic Acid↗

Neural systems for compensation and persistence: young adult outcome of childhood reading disability.

BACKGROUND: This study examined whether and how two groups of young adults who were poor readers as children (a relatively compensated group and a group with persistent reading difficulties) differed from nonimpaired readers and if there were any factors distinguishing the compensated from persistently poor readers that might account for their different outcomes. METHODS: Using functional magnetic resonance imaging, we studied three groups of young adults, ages 18.5-22.5 years, as they read pseudowords and real words: 1) persistently poor readers (PPR; n = 24); 2) accuracy improved (compensated) readers (AIR; n = 19); and 3) nonimpaired readers (NI, n = 27). RESULTS: Compensated readers, who are accurate but not fluent, demonstrate a relative underactivation in posterior neural systems for reading located in left parietotemporal and occipitotemporal regions. Persistently poor readers, who are both not fluent and less accurate, activate posterior reading systems but engage them differently from nonimpaired readers, appearing to rely more on memory-based rather than analytic word identification strategies. CONCLUSIONS: These findings of divergent neural outcomes as young adults are both new and unexpected and suggest a neural basis for reading outcomes of compensation and persistence in adults with childhood dyslexia.

Adult↗

Cluster analysis of muscle functional MRI data.

Muscle functional magnetic resonance imaging (mfMRI) is frequently used to determine spatial patterns of muscle involvement in exercising humans. A frequent finding in mfMRI is that, even within synergistic muscle groups, signal intensity (SI) data from individual voxels can be quite heterogeneous. The purpose of this study was to develop a novel method for organizing heterogeneous mfMRI data into clusters whose members behave similarly to each other but distinctly from members of other clusters and apply it in studies of functional compartmentalization in the anterior compartment of the leg. An algorithm was developed that compared the SI time courses of adjacent voxels and grouped together voxels that were sufficiently similar. The algorithm's performance was verified by using simulated data sets with known regional differences in SI time courses that were then applied to experimental mfMRI data acquired from six male subjects (age 22.6 +/- 0.9 yr, mean +/- SE) who sustained isometric contractions of the dorsiflexors at 40% of maximum voluntary contraction. The experimental data were also characterized by using a traditional analysis (user-specified regions of interest from a single image), in which the relative change in SI and the contrast-to-noise ratio [CNR; 100%x(SI(RESTING) - SI(ACTIVE)/(noise standard deviation)] were measured. In general, clusters were found in areas in which the CNR exceeded 5. Cluster analysis made functional distinctions between regions of muscle that were not seen with traditional analysis. In conclusion, cluster analysis's use of the full SI time course provides more sensitivity to muscle functional compartmentation than traditional analysis.

Adult↗

Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder.

BACKGROUND: The purported functions of medial temporal lobe structures suggest their involvement in the pathophysiology of bipolar disorder (BD). Previous reports of abnormalities in the volume of the amygdala and hippocampus in patients with BD have been inconsistent in their findings and limited to adult samples. Appreciation of whether volumetric abnormalities are early features of BD or whether the abnormalities represent neurodegenerative changes associated with illness duration is limited by the paucity of data in juvenile samples. OBJECTIVE: To investigate amygdala and hippocampal volume in adults and adolescents with BD. SETTING AND PARTICIPANTS: Subjects included 36 individuals (14 adolescents and 22 adults) in outpatient treatment for BD type I at a university hospital or Veterans Affairs medical center or in the surrounding community, and 56 healthy comparison subjects (23 adolescents and 33 adults). DESIGN AND MAIN OUTCOME MEASURES: Amygdala and hippocampal volumes were defined and measured on high-resolution anatomic magnetic resonance imaging scans. We used a mixed-model, repeated-measures statistical analysis to compare amygdala and hippocampal volumes across groups while covarying for total brain volume, age, and sex. Potential effects of illness features were explored, including rapid cycling, medication, alcohol or other substance dependence, duration, and mood state. RESULTS: For both the amygdala and hippocampal regions, we found an overall significant volume reduction in the BD compared with the control group (P<.0001). Amygdala volume reductions (15.6%) were highly significant (P<.0001). We observed a nonsignificant trend (P =.054) toward reductions in hippocampal volumes of lesser magnitude (5.3%). Effects of illness features were not detected. CONCLUSIONS: These results suggest that BD is associated with decreased volumes of medial temporal lobe structures, with greater effect sizes in the amygdala than in the hippocampus. These abnormalities are likely manifested early in the course of illness, as they affected adolescent and adult subjects similarly in this sample.

Adolescent↗

A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices.

BACKGROUND: Abnormalities in prefrontal and anterior cingulate cortices are implicated in disturbances of attention, cognition, and impulse regulation in bipolar disorder. Acute episodes have been associated with dysfunction in these brain regions, and more enduring trait-related dysfunction has been implicated by volumetric and cellular abnormalities in these regions. The relative contributions of prefrontal regions to state and trait disturbances in bipolar disorder, however, have not been defined. We sought to characterize state- and trait-related functional impairment in frontal systems in bipolar disorder. METHODS: Thirty-six individuals with bipolar disorder I (11 with elevated, 10 with depressed, and 15 with euthymic mood states) and 20 healthy control subjects matched for handedness and sex participated in an event-related functional magnetic resonance imaging study of the color-word Stroop to determine mean percentage of regional task-related signal change. RESULTS: Signal increased during the Stroop task similarly across diagnostic groups in a distribution that included dorsal anterior cingulate and prefrontal cortices, consistent with previously reported activations in this task. Signal changes associated with specific mood states in bipolar disorder were detected in ventral prefrontal cortex, with a blunted increase in signal on the right side in the elevated mood group (P =.005) and an exaggerated increase in signal on the left side in the depressed group (P =.02) compared with the euthymic group. Patients (vs healthy controls) demonstrated blunted activation in a spatially distinct, rostral region of left ventral prefrontal cortex that was independent of mood state (P<.005). CONCLUSIONS: Bipolar disorder is associated with a trait abnormality in left ventral prefrontal cortex. Additional ventral prefrontal abnormalities may be associated with specific acute mood states. The hemispheric laterality of the abnormality and the directions of signal change may relate to the valence of the mood episode.

Adult↗

Gambling urges in pathological gambling: a functional magnetic resonance imaging study.

BACKGROUND: Gambling urges in pathological gambling (PG) often immediately precede engagement in self-destructive gambling behavior. An improved understanding of the neural correlates of gambling urges in PG would advance our understanding of the brain mechanisms underlying PG and would help direct research into effective treatments. METHODS: Echoplanar functional magnetic resonance imaging was used to assess brain function during viewing of videotaped scenarios with gambling, happy, or sad content. Participants rated the quality and magnitude of their emotional and motivational responses. RESULTS: Men with PG (n = 10) reported mean +/- SD greater gambling urges after viewing gambling scenarios vs control subjects (n = 11) (5.20 +/- 3.43 vs 0.32 +/- 0.60; chi21,19 = 21.71; P<.001). The groups did not differ significantly in their subjective responses to the happy (P =.56) or sad (P =.81) videotapes. The most pronounced between-group differences in neural activities were observed during the initial period of viewing of the gambling scenarios: PG subjects displayed relatively decreased activity in frontal and orbitofrontal cortex, caudate/basal ganglia, and thalamus compared with controls. Distinct patterns of regional brain activity were observed in specific temporal epochs of videotape viewing. For example, differences localized to the ventral anterior cingulate during the final period of gambling videotape viewing, corresponding to the presentation of the most provocative gambling stimuli. Although group differences in brain activity were observed during viewing of the sad and happy scenarios, they were distinct from those corresponding to the gambling scenarios. CONCLUSIONS: In men with PG, gambling cue presentation elicits gambling urges and leads to a temporally dynamic pattern of brain activity changes in frontal, paralimbic, and limbic brain structures. When viewing gambling cues, PG subjects demonstrate relatively decreased activity in brain regions implicated in impulse regulation compared with controls.

Adolescent↗

Oscillating gradient measurements of water diffusion in normal and globally ischemic rat brain.

Oscillating gradients were used to probe the diffusion-time/frequency dependence of water diffusion in the gray matter of normal and globally ischemic rat brain. In terms of a conventional definition of diffusion time, the oscillating gradient measurements provided the apparent diffusion coefficient (ADC) of water with diffusion times between 9.75 ms and 375 micros, an order of magnitude shorter than previously studied in vivo. Over this range, ADCs increased as much as 24% in vivo and 50% postmortem, depending on the nature of the oscillating gradient waveform used. Novel waveforms were employed to sample narrow frequency bands of the so-called diffusion spectrum. This spectral description of ADC includes the effects of restriction and/or flow, and is independent of experimental parameters, such as diffusion time. The results in rat brain were found to be consistent with restricted diffusion and the known micro-anatomy of gray matter. Differences between normal and postmortem data were consistent with an increase in water restriction and/or a decrease in flow, and tentatively suggest that physical changes following the onset of ischemia occur on a scale of about 2 microm, similar to a typical cellular dimension in gray matter.

Animals↗

Quantitative imaging of magnetization transfer using an inversion recovery sequence.

A new imaging method has been developed for quantitatively measuring magnetization transfer (MT). It uses a simple inversion recovery sequence, although one with very short (milliseconds) inversion times, and thus can be implemented on clinical imaging systems with little modification to existing pulse sequences. The sequence requires an inversion pulse with a length much longer than T(2m) (typically 10 micros) and much shorter than T(2f) (typically tens of ms) and 1/k(mf) (typically tens of ms), where T(2m) and T(2f) are the transverse relaxation times of the immobile macromolecular and free water protons, respectively, and k(mf) is the rate of MT between these populations. The resultant NMR signal is sensitive to MT when this inversion pulse affects the mobile and immobile proton pools to different degrees and by appropriate analysis of the signals obtained for different inversion times, quantitative information can be derived on the macromolecular content and exchange rates within the sample. The method has been used in conjunction with echo planar imaging to produce maps of the spatial distribution of the macromolecular content and MT rate in cross-linked bovine serum albumin. Comparisons between this method and other quantitative MT techniques are discussed.

Echo-Planar Imaging↗

Classification and quantification of neuronal fiber pathways using diffusion tensor MRI.

Quantitative characterization of neuronal fiber pathways in vivo is of significant neurological and clinical interest. Using the capability of MR diffusion tensor imaging to determine the local orientations of neuronal fibers, novel algorithms were developed to bundle neuronal fiber pathways reconstructed in vivo with diffusion tensor images and to quantify various physical and geometric properties of fiber bundles. The reliability of the algorithms was examined with reproducibility tests. Illustrative results show that consistent physical and geometric measurements of novel properties of neuronal tissue can be obtained, which offer considerable potential for the quantitative study of fiber pathways in vivo.

Algorithms↗

Cortical plasticity in an early blind musician: an fMRl study.

Many studies have examined tactile perception and simple auditory perception in the blind, but none have previously investigated the neural basis of musical ability in this group. This topic is of particular interest because it has been suggested that early blind individuals may possess advanced musical skills (such as absolute pitch). Presumably, these skills could be the result of neural plasticity. It has been hard to empirically assess this claim because of the difficulty in recruiting an adequate number of subjects for use in a conventional paradigm. In the present paper, we report data from a congenitally blind musician, subject ML. Behavioral tests show that she possessed absolute pitch abilities that were similar to those of a reference group of AP musicians with normal vision. To examine the neural basis of her abilities we then tested subject ML and five control subjects using an fMRI paradigm. A regions-of-interest analysis found that similar areas (the right secondary auditory cortex, left IFG, left SMG) were activated in ML and the control subjects, to a similar degree, in response to music processing. However, ML showed additional activations in left parietal association cortices and extrastriate regions of the occipital lobe. Subject ML's data are consistent with a vast body of literature on blindness-induced plasticity. They extend these findings by demonstrating that cortical plasticity may underlie special musical skills as well. These data illustrate the potential value of case studies to investigate particularly rare phenotypes.

Adolescent↗

Comparison of MRI with EMG to study muscle activity associated with dynamic plantar flexion.

This study compared magnetic resonance imaging (MRI) and surface electromyography (EMG) to evaluate the effect of knee angle upon plantar flexion activity in the triceps surae muscles [medial & lateral gastrocnemius (MG, LG) and the soleus (SOL)]. Two weight & height matched groups performed identical protocols, twelve (6M, 6F) in the MRI group, twelve (8M, 4F) in the EMG group. Subjects plantar flexed dynamically for 2 min at 25% of 1-repetition maximum voluntary contraction (1-RM). Exercise was performed with the knee extended (0 degrees flexion), flexed (90 degrees ), and partially flexed (45 degrees ). In the MRI group spin-echo images were acquired before and immediately following each exercise session. T(2) times, calculated at rest and after exercise by fitting the echoes to a monoexponential decay pattern with a least-squares algorithm, were compared with EMG data. In the EMG group a bipolar electrode was used to collect samples were from the MG, LG, SOL, and anterior tibialis (TA) during exercise at each knee angle, MRI also examined the peroneus (PER). At 0 degrees flexion MRI demonstrated a significant post-exercise T(2) increase in the MG (p < or = 0.001), LG (p < or = 0.001), and PER (p < or = 0.01), with no T(2) change in the SOL or TA. At 90 degrees flexion there was a significant T(2) increase in the SOL (p < or = 0.001) with no significant T(2) change in the MG, LG, PER, or TA. At 45 degrees T(2) increased significantly in the SOL (p < or = 0.001) and LG (p < or = 0.05), but not the MG, PER, or TA. EMG produced similar results with the exception that there was significant activity in the TA during the relaxation cycle of the 90 degrees protocol. We conclude that: 1) Soleus activity is measurable by MRI; and 2) MRI and EMG produce similar results from different physiological sources, and are therefore complementary tools for evaluating muscle activity.

Adult↗

Neural components of social evaluation.

Evaluative responses appear to involve 2 seemingly distinct sets of processes: those that are automatically activated and others that are more consciously controlled. Using functional magnetic resonance imaging, the authors investigated the brain systems associated with automatic and controlled evaluative processing. Participants made either evaluative (good-bad) or nonevaluative (past-present) judgments about famous names. Greater amygdala activity was observed for names rated as "bad" relative to those rated as "good," regardless of whether the task directly involved an evaluative judgment (good-bad) or not (past-present). Good-bad judgments resulted in greater medial and ventrolateral prefrontal cortex (PFC) activity than past-present judgments. Furthermore, there was greater ventrolateral PFC activity in good-bad judgments marked by greater ambivalence. Together, these findings indicate a neural distinction between processes engaged for automatic and controlled evaluation. Whereas automatic processes are sensitive to simple valence, controlled processes are sensitive to attitudinal complexity.

Adult↗