Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and target being manipulated. Study 1 demonstrated automatic semantic priming in the left mid-fusiform gyrus (mid-FFG) and strategic semantic priming in five regions: left middle temporal gyrus (MTG), bilateral anterior cingulate, anterior left inferior...

Background: Head injuries are very common in children, accounting for substantial cognitive and motor deficits in this age category. Persistent deficits in motor control have been documented following traumatic brain injury (TBI) by using standardized t...

Functional magnetic resonance imaging is increasingly used as a tool to elucidate the neural substrates of olfaction. However, it is possible that the magnetic field used in functional imaging may itself affect olfaction. It is known that the direction and strength of a magnetic field have an effect on visual perception tasks. Likewise, the strong magnetic field of an MRI scanner can induce phantom gustatory perception. Anecdotal observations in our laboratory suggested that olfactory intensity perception was enhanced under a strong magnetic field. To address this possibility, the University of Pennsylvania Smell Identification Task (UPSIT) was administered to 9 subjects both in the MRI scanner (4 Tesla Varian) and out of the magnetic field in a mock scanner. In addition to identification, subjects rated stimulus intensity and pleasantness on a visual analog scale. The order of field strength conditions (IN/OUT of the magnet) and UPSIT booklets (1 through 4) were counterbalanced across subjects. There was ...

Using magnetic resonance imaging (MRI), one can view the internal structure of the brain where traditional procedures of embedding, sectioning, staining, mounting, and microscopically examining thousands of sections are not practicable. Structures can be analyzed in their precise quantitative spatial interrelationships, which is difficult to do after the distortions often accompanying histological processing. For these reasons, images of the brain of a bottle-nose dolphin Tursiops truncatus were scanned in the coronal plane at 136 antero-posterior levels. From these MRI scans, a 3-dimensional digital model was constructed using the programs VoxelView and VoxelMath (Vital Images, Inc.) This model, wherein details of internal and external morphology are represented in 3-dimensional space, was then resectioned in orthogonal planes to produce correlated series of virtual sections, 122 in the horizontal plane and 176 in the sagittal plane. These MRI sections were compared with stained sections for identificatio...

Anxiety disorders are common and debilitating conditions with higher prevalence in women. However, factors that predispose women to anxiety phenotypes are not clarified. Here we investigated potential contribution of the single nucleotide polymorphism rs2236418 in GAD2 gene to changes in regional inhibition/excitation balance, anxiety-like traits, and related neural activity in both sexes. One hundred and five healthy individuals were examined with high-field (7T) multimodal magnetic resonance imaging (MRI); including resting-state functional MRI in combination with assessment of GABA and glutamate (Glu) levels via MR spectroscopy. Regional GABA/Glu levels in anterior cingulate cortex (ACC) subregions were assessed as mediators of gene–personality interaction for the trait harm avoidance and moderation by sex was tested. In AA homozygotes, with putatively lower GAD2 promoter activity, we observed increased intrinsic neuronal activity and higher inhibition/excitation balance in pregenual ACC (pgACC) compare...

Putative therapeutic agents to treat Alzheimer’s disease (AD) will require validation in the clinic. All diagnostic imaging techniques would benefit, if not require a plaque/tangle specific probe to not only definitively diagnose AD, but also monitor the efficacy of those therapeutic agents. Magnetic resonance imaging (MRI) is the only imaging technique with resolution high enough to potentially image individual plaques. We have previously reported that radiolabeled polyamine modified Aβ40 with increased BBB permeability not only labels plaques in vivo in APP, PS1 transgenic mice, but that the gadolinium (Gd) labeled form of the peptide produces plaque selective contrast enhancement on T1-weighted MRI in ex vivo brains following IV injection. We have developed a second generation, totally synthetic peptide, Gd[N-4ab/Q-4ab] Aβ30. The purpose of the present study was to optimize time of injection and dose of Gd[N-4ab/Q-4ab] Aβ30 using 125-I radiolabeled peptide and autoradiographic techniques. APP, PS1 trans...

Evidence from both human and animal studies has demonstrated a key role for brainstem centers in the control of ascending nociceptive input. Nuclei such as the rostral ventromedial medulla and periaqueductal gray (PAG) are able to both inhibit and facilitate the nociceptive response. It has been proposed that altered descending modulation may underlie many of the chronic pain syndromes (both somatic and visceral). We used functional magnetic resonance imaging to image the neural correlates of visceral and somatic pain within the brainstem. Ten healthy subjects were scanned twice at 3 tesla, during which they received matched, moderately painful, electrical stimuli to either the midline lower abdomen or rectum. Significant activation was observed in regions consistent with the PAG, nucleus cuneiformis (NCF), ventral tegmental area/substantia nigra, parabrachial nuclei/nucleus ceruleus, and red nucleus bilaterally to both stimuli. Marked spatial similarities in activation were observed for visceral and somat...

Serotonin is involved in motor control. Serotonin re-uptake inhibitors would facilitate motor recovery in post-stroke patients undergoing rehabilitation (Dam M, Stroke, 1996;27:1211-14). Fluoxetine, an inhibitor of serotonin reuptake, was shown to enhance brain motor activation in executive motor areas of healthy subjects (Loubinoux I., JCBF, 1999;19:1365-75). Effects on cerebral motor activity of a single dose (20 or 60 mg against placebo) of paroxetine (Deroxat®) were assessed in 6 healthy subjects. Either 20 mg, or 60 mg or placebo were given in 3 sessions 8 days apart, in a within subject counterbalanced, double-blinded study. 1.5T MRI scanner was used for BOLD imaging. 16 axial images, 5-mm-thick, were acquired every 3 seconds using a T2*-weighted single-shot EPI sequence. 3 runs were acquired during one session. One run consisted of eight 30-second epochs alternating between rest and activation. During activation, subjects were instructed to perform, with the right hand, the auditory 1 Hz-paced task ...

The Bezold-Jarisch depressor reflex, implicated in myocardial ischemia and aortic stenosis, and possibly in shock sequences, elicits a profound fall in arterial pressure (AP), heart rate (HR) and apnea. The sites and patterning of central neural substrates involved in mediating this reflex remain unclear. Using functional magnetic resonance imaging procedures to examine brain activity, we elicited the Bezold-Jarish reflex via i.v. 5-hydroxytryptamine (5HT) in 9 isofluorane-anaesthetized adult cats (4.7T, TR=8 secs, TE=25 ms, FOV=8 cm, flip angle=90 degrees, voxel dimensions=0.625 x 0.625x2 mm). Intravenous 5HT (10-30mg/kg) evoked a rapid onset fall in AP (mean=20%), HR decline (mean=18%) and a prolonged apnea (mean=25secs). Signal intensity (SI) fell in brainstem cardiovascular regions (nucleus tractus solitarius, caudal and rostral ventrolateral medulla), and also in the caudal midline medulla, multiple regions of the cerebellum (deep nuclei, vermis) and the dorsolateral pons. In contrast, rostral brain s...

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HCs; 18 women). In neuromelanin-sensitive structural magnetic resonance imaging (MRI), PD patients showed smaller SNs than HCs. In a digit-ordering task with functional MRI (fMRI), participants either recalled sequential digits in the original order (pure recall) or rearranged the digits and recalled the new sequence (reorder and recall). PD patients performed less accurately than HCs, accompanied by the caudate and pallidal hypoactivation, subthalamic hyperactivation, and weakened functional connectivity between the bilateral SN and all three basal g...