Glutamate is down-regulated and tinnitus loudness-levels decreased following rTMS over auditory cortex of the left hemisphere: A prospective randomized single-blinded sham-controlled cross-over study.

Using a prospective randomized single-blinded sham-controlled cross-over design, we studied the efficacy of low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) over auditory cortex of the left temporal lobe as an experimental treatment modality for noise-induced tinnitus. Pre/post outcome measures for sham vs. active rTMS conditions included differential changes in tinnitus loudness, self-perceived changes in the Tinnitus Handicap Questionnaire (THQ), and neurochemical changes of brain metabolite concentrations using single voxel proton magnetic resonance spectroscopy (1H-MRS) obtained from left and right auditory cortical areas. While no subject in our sample had complete abatement of their tinnitus percept, active but not sham rTMS significantly reduced the loudness level of the tinnitus perception on the order of 4.5 dB; improved subscales in several content areas on the THQ, and down regulated (reduced) glutamate concentrations specific to the auditory cortex of the left temporal lobe that was stimulated. In addition, significant pair-wise correlations were observed among questionnaire variables, metabolite variables, questionnaire-metabolite variables, and metabolite-loudness variables. As part of this correlation analysis, we demonstrate for the first time that active rTMS produced a down regulation in the excitatory neurotransmitter glutamate that was highly correlated (r = 0.77, p < 0.05) with a reduction in tinnitus loudness levels measured psychoacoustically with a magnitude estimation procedure. Overall, this study provides unique information on neurochemical, psychoacoustic, and questionnaire-related profiles which emphasizes the emerging fields of perceptual and cognitive MRS and provides a perspective on a new frontier in auditory and tinnitus-related research.

Electrophysiological markers of skill-related neuroplasticity.

Neuroplasticity involved in acquiring a new cognitive skill was investigated with standard time domain event-related potentials (ERPs) of scalp-recorded electroencephalographic (EEG) activity and frequency domain analysis of EEG oscillations looking at the event-related synchronization (ERS) and desynchronization (ERD) of neural activity. Electroencephalographic activity was recorded before and after practice, while participants performed alphabet addition (i.e., E+3=G, true or false?). Participant's performance became automated with practice through a switch in cognitive strategy from mentally counting-up in the alphabet to retrieving the answer from memory. Time domain analysis of the ERPs revealed a prominent positive peak at approximately 300 ms that was not reactive to problem attributes but was reduced with practice. A second prominent positive peak observed at approximately 500 ms was found to be larger after practice, mainly for problems presented with correct answers. Frequency domain spectral analyses yielded two distinct findings: (1) a frontal midline ERS of theta activity that was greater after practice, and (2) a beta band ERD that increased with problem difficulty before, but not after practice. Because the EEG oscillations were not phase locked to the stimulus, they were viewed as being independent of the time domain results. Consequently, use of time and frequency domain analyses provides a more comprehensive account of the underlying electrophysiological data than either method alone. When used in combination with a well-defined cognitive/behavioral paradigm, this approach serves to constrain the interpretations of EEG data and sets a new standard for studying the neuroplasticity involved in skill acquisition.

Verification of multiplication facts: an investigation using retrospective protocols.

Retrospective verbal protocols collected throughout participants' performance of a multiplication verification task (e.g., "7 x 3 = 28, true or false?") documented a number of different strategies and changes in strategy use across different problem categories used for this common experimental task. Correct answer retrieval and comparison to the candidate answer was the modal but not the only strategy reported. Experiment 1 results supported the use of a calculation algorithm on some trials and the use of the difference between the candidate and correct answers (i.e., split) on others. Experiment 2 clearly demonstrated that participants sometimes bypassed retrieval by relying on the split information. Implications for mental arithmetic theories and the general efficacy of retrospective protocols are discussed.

Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus.

It has been proposed that behavior is influenced by representations of different types of knowledge: action representations, event knowledge, attitudes and stereotypes. Attitudes (representations of a concept or object and its emotional evaluation) allow us to respond quickly to a given stimulus. In this study, we explored the representation and inhibition of attitudes. We show that right dorsolateral prefrontal cortex mediates negative attitudes whereas left ventrolateral prefrontal cortex mediates positive attitudes. Parahippocampal regions and amygdala mediate evaluative processing. Furthermore, anxiety modulates right dorsolateral prefrontal activation during negative attitude processing. Inhibition of negative attitudes activates left orbitofrontal cortex: a region that when damaged is associated with socially inappropriate behavior in patients. Inhibition of positive attitudes activates a brain system involving right inferior frontal gyrus and bilateral anterior cingulate. Thus, we show that there are dissociable networks for the representation and inhibition of attitudes.