James C. Eliassen

An Event-Related fMRI Investigation of Implicit Semantic Priming

The neural basis underlying implicit semantic priming was investigated using event-related fMRI. Prime-target pairs were presented auditorily for lexical decision (LD) on the target stimulus, which was either semantically related or unrelated to the prime, or was a nonword. A tone task was also administered as a control. Behaviorally, all participants demonstrated semantic priming in the LD task. fMRI results showed that for all three conditions of the LD task, activation was seen in the superior temporal gyrus (STG), the middle temporal gyrus (MTG), and the inferior parietal lobe, with greater activation in the unrelated and nonword conditions than in the related condition. Direct comparisons of the related and unrelated conditions revealed foci in the left STG, left precentral gyrus, left and right MTGs, and right caudate, exhibiting significantly lower activation levels in the related condition. The reduced activity in the temporal lobe suggests that the perception of the prime word activates a lexical semantic network that shares common elements with the target word, and, thus, the target can be recognized with enhanced neural efficiency. The frontal lobe reductions most likely reflect the increased efficiency in monitoring the activation of lexical representations in the temporal lobe, making a decision, and planning the appropriate motor response.

Dissociation of Spatial and Temporal Coupling in the Bimanual Movements of Callosotomy Patients

The neural mechanisms of limb coordination were investigated by testing callosotomy patients and normal control subjects on bimanual movements Normal subjects produced deviations in the trajectories when spatial demands for the two hands were different, despite temporal synchrony in the onset of bimanual movements Callosotomy patients did not produce spatial deviations, although their hands moved with normal temporal synchrony Normal subjects but not callosotomy patients exhibited large increases in planning and execution time for movements with different spatial demands for the two hands relative to movements with identical spatial demands for the two hands This neural dissociation indicates that spatial interference in movements results from callosal connections, whereas temporal synchrony in movement onset does not rely on the corpus callosum

Docosahexaenoic acid supplementation increases prefrontal cortex activation during sustained attention in healthy boys: a placebo-controlled, dose-ranging, functional magnetic resonance imaging study

BACKGROUND Emerging evidence suggests that docosahexaenoic acid (DHA, 22:6n-3), the principal omega-3 (n-3) fatty acid in brain gray matter, positively regulates cortical metabolic function and cognitive development. However, the effects of DHA supplementation on functional cortical activity in human subjects are unknown. OBJECTIVE The objective was to determine the effects of DHA supplementation on functional cortical activity during sustained attention in human subjects. DESIGN Healthy boys aged 8-10 y (n = 33) were randomly assigned to receive placebo or 1 of 2 doses of DHA (400 or 1200 mg/d) for 8 wk. Relative changes in cortical activation patterns during sustained attention at baseline and endpoint were determined by functional magnetic resonance imaging. RESULTS At 8 wk, erythrocyte membrane DHA composition increased significantly from baseline in subjects who received low-dose (by 47%) or high-dose (by 70%) DHA but not in those who received placebo (-11%). During sustained attention, both DHA dose groups had significantly greater changes from baseline in activation of the dorsolateral prefrontal cortex than did the placebo group, and the low-dose and high-dose DHA groups had greater decreases in the occipital cortex and cerebellar cortex, respectively. Relative to low-dose DHA, high-dose DHA resulted in greater decreases in activation of bilateral cerebellum. The erythrocyte DHA composition was positively correlated with dorsolateral prefrontal cortex activation and was inversely correlated with reaction time, at baseline and endpoint. CONCLUSION Dietary DHA intake and associated elevations in erythrocyte DHA composition are associated with alterations in functional activity in cortical attention networks during sustained attention in healthy boys. This trial was registered at clinicaltrials.gov as NCT00662142.

Cortical Plasticity Following Motor Skill Learning During Mental Practice in Stroke

Background and purpose. Mental practice (MP), which involves cognitive rehearsal of physical movements, is a noninvasive, inexpensive method of enabling repetitive, task-specific practice (RTP). Recent, randomized controlled data suggest that MP, when combined with an RTP therapy program, increases affected arm use and function significantly more than RTP only. As a next step, this 10-subject case series examined the possibility that cortical plasticity is a mechanism underlying the treatment effect of MP when combined with RTP. Method. Ten chronic stroke patients (mean = 36.7 months) exhibiting stable, moderate motor deficits received 30-minute therapy sessions for their affected arms, occurring 3 days/week for 10 weeks, and emphasizing valued activities of daily living (ADLs). Directly after therapy, subjects received 30-minute MP sessions, which required MP of the ADLs performed during therapy. Behavioral outcomes were blindly evaluated using the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment (FM). Functional magnetic resonance imaging (fMRI) was administered before and after intervention to assess cortical changes. Results. Before intervention, subjects exhibited stable motor deficits. After intervention, subjects exhibited ARAT and FM score increases (+5.3 and +4.2, respectively) and clinically significant gains in ADLs. Postintervention fMRI revealed significant increases in activation to wrist flexion and extension of the affected hand in the premotor area and primary motor cortex ipsilateral and contralateral to the affected hand, as well as in superior parietal cortex ipsilateral to the affected hand. Decreased activation was noted in parietal cortex of the hemisphere ipsilateral to the affected hand. These changes correlated with anatomical regions in which behavioral changes were observed in the ARAT and FM. Conclusions. MP is an easy to use, cost-effective strategy that was again shown to improve affected arm outcomes after stroke. This is the first study to demonstrate alteration in the cortical map in response to MP training.

Neuroimaging evidence for the emotional potency of odor-evoked memory

To assess past behavioral reports of the emotional distinctiveness of odor-evoked memories, functional magnetic resonance imaging (fMRI) was used to compare regions of activation during recall triggered by olfactory and visual cues that were connected to a personally meaningful memory and a comparable control cue presented in olfactory and visual form. Five healthy right-handed females experienced both behavioral and fMRI memory testing. fMRI analyses indicated significantly greater activation in the amygdala and hippocampal regions during recall to the personally significant odor than any other cue, and behavioral responses confirmed that emotional responses were greatest to the personally meaningful odor. These findings provide convincing neurobiological evidence that the subjective experience of the emotional potency of odor-evoked memory is correlated with specific activation in the amygdala during recall and offers new insights into the affective organization of memory.

Identification and molecular cloning of a neuropeptide Y homolog that produces prolonged inhibition in aplysia neurons

The neuroendocrine bag cell neurons of the marine mollusk Aplysia produce prolonged inhibition that lasts for more than 2 hr. We purified a peptide from the abdominal ganglion that mimics this inhibition. Mass spectrometry and microsequence analysis indicate that the peptide is 40 aa long and is amidated at its carboxyl terminus. It is highly homologous to vertebrate neuropeptide Y (NPY) and other members of the pancreatic polypeptide family. As determined from cloned cDNA, the gene coding for the precursor protein shares a common structural organization with genes encoding precursors of the vertebrate family. The peptides may therefore have arisen from a common ancestral gene. Bag cell neurons are immunoreactive for Aplysia NPY, and Northern blot analysis indicates that as with its vertebrate counterparts, the peptide is abundantly expressed in the CNS. This suggests that peptides related to NPY may have important functions in the nervous system of Aplysia as well as in other invertebrates.

Direction information coordinated via the posterior third of the corpus callosum during bimanual movements

Abstract We examined bimanual coordination in a patient before and after each stage of callosotomy surgery. We tested how well the patient coordinated movement direction between the hands. The patient drew symmetrical or asymmetrical figures simultaneously with both hands. Before surgery, symmetrical figures were drawn well and asymmetrical figures were drawn poorly. Following anterior callosotomy, the drawings improved slightly. Symmetrical figures were still drawn well, and asymmetrical ones were still drawn poorly. Thus, spatial integration remained intact despite the loss of interhemispheric communication between frontal cortical sites. After posterior callosotomy, spatial coordination deteriorated significantly. Mirror-image drawings became less symmetrical, while asymmetrical drawings improved. These data indicate that the posterior callosum mediates the coordination of direction information between the hands during bimanual movements. Given the topographical organization of the corpus callosum, this integration is likely carried out by parietal cortex.

Functional magnetic resonance imaging brain activation in bipolar mania: evidence for disruption of the ventrolateral prefrontal-amygdala emotional pathway.

BACKGROUND Bipolar I disorder is defined by the occurrence of mania. The presence of mania, coupled with a course of illness characterized by waxing and waning of affective symptoms, suggests that bipolar disorder arises from dysfunction of neural systems that maintain emotional arousal and homeostasis. We used functional magnetic resonance imaging (fMRI) to study manic bipolar subjects as they performed a cognitive task designed to examine the ventrolateral prefrontal emotional arousal network. METHODS We used fMRI to study regional brain activation in 40 DSM-IV manic bipolar I patients and 36 healthy subjects while they performed a continuous performance task with emotional and neutral distracters. Event-related region-of-interest analyses were performed to test the primary hypothesis. Voxelwise analyses were also completed. RESULTS Compared with healthy subjects, the manic subjects exhibited blunted activation to emotional and neutral images, but not targets, across most of the predefined regions of interest. Several additional brain regions identified in the voxelwise analysis also exhibited similar differences between groups, including right parahippocampus, right lingual gyrus, and medial thalamus. In addition to these primary findings, the manic subjects also exhibited increased activation in response to targets in a number of brain regions that were primarily associated with managing affective stimuli. Group differences did not appear to be secondary to medication exposure or other confounds. CONCLUSIONS Bipolar manic subjects exhibit blunted brain fMRI response to emotional cues throughout the ventrolateral prefrontal emotional arousal network. Disruption of this emotional network may contribute to the mood dysregulation of bipolar disorder.

Inferior Frontal Regions Underlie the Perception of Phonetic Category Invariance

The problem of mapping differing sensory stimuli onto a common category is fundamental to human cognition. Listeners perceive stable phonetic categories despite many sources of acoustic variability. What are the neural mechanisms that underlie this perceptual stability? In this functional magnetic resonance imaging study, a short-interval habituation paradigm was used to investigate neural sensitivity to acoustic changes within and between phonetic categories. A region in the left inferior frontal sulcus showed a pattern of activation consistent with phonetic invariance: insensitivity to acoustic changes within a phonetic category and sensitivity to changes between phonetic categories. Left superior temporal regions, in contrast, showed graded sensitivity to both within- and between-category changes. These results suggest that perceptual insensitivity to changes within a phonetic category may arise from decision-related mechanisms in the left prefrontal cortex and add to a growing body of literature suggesting that the inferior prefrontal cortex plays a domain-general role in computing category representations.

Human brain activation accompanying explicitly directed movement sequence learning

Abstract. We examined brain activation patterns occurring during the production and encoding of a motor sequence. Participants performed a variant of the serial reaction-time task under two conditions. The first condition was designed to foster the engagement of explicit mechanisms of knowledge acquisition. The second condition was intended to encourage the engagement of implicit learning mechanisms that would be more typical of the standard serial reaction-time task. In the first condition, the acquisition of explicit knowledge about an 8-element ordered sequence led to a significant and rapid decline in reaction time. By contrast, the second condition, the task in which a sequence was presented unbeknownst to participants, did not yield changes in reaction time. Several brain regions, including prefrontal cortex, superior and inferior parietal lobules, and cerebellum, exhibited explicit learning-related activation. The prefrontal cortex and inferior parietal lobules increased their levels of activation between the beginning and end of the experiment, while primary motor, primary sensory, and cerebellar cortex decreased their levels of activation from the beginning to the end of the experiment. We propose a model in which two processes, a learning-related increase and a habituation process might interact to produce the activation patterns observed during movement sequence acquisition. In short, the prefrontal cortex and inferior parietal lobule together direct and recruit superior parietal lobule and cerebellum to encode and perform the sequence. The increased activation in prefrontal cortex and inferior parietal lobule may represent the activity of a working memory circuit that functions in the acquisition and recall of sequence information.