Mark Mennemeier

Repetitive Transcranial Magnetic Stimulation for Tinnitus: A Case Study

Objectives/Hypothesis: Correlate subjective improvements in tinnitus severity with restoration of cortical symmetry and sustained attention after neuronavigated low‐frequency, repetitive transcranial magnetic stimulation (rTMS).

Methodological aspects of clinical trials in tinnitus: A proposal for an international standard

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus.

Contributions of the parietal and frontal lobes to sustained attention and habituation.

The parietal cortex may be important in sustaining attention toward visual stimuli in peripheral space whereas the frontal cortex may mediate selective attention through habituation to peripheral stimuli. To test this hypothesis, patients with focal lesions of either the parietal or frontal cortex or both and normal controls were studied using a paradigm known as Troxler fading. Accordingly, if one fixates on a centrally located stimulus and attends to a stationary stimulus in peripheral vision, the peripheral stimulus quickly fades from awareness (i.e. Troxler fading: Troxler [Verschwinden, unseres, Opthal, Vol. 2, pp. 51-53. Fromann, Jena, 1804]). Movement of the peripheral stimulus on the retina normally prevents Troxler fading. Results indicated that patients with parietal lesions not only reported accelerated Troxler fading but also reported fading of moving peripheral stimuli contralateral to their brain lesion. In contrast, patients with frontal lesions rarely reported Troxler fading. In one patient with a left parietal and a right frontal lobe lesion fading was hemi-spatially dissociated, being accelerated in right hemispace but absent in left hemispace. These observations suggest that the parietal and frontal cortices play complementary roles in attentional processing.

Contributions of the left and right cerebral hemispheres to line bisection

Thirty-one right-hemisphere lesioned (RHL) patients, 11 left-hemisphere lesioned patients (LHL) and 10 normal controls (NC) bisected lines in three spatial location and four directional cuing conditions. The error direction and error size were analyzed as separate and combined variables. Seventy-seven percent of RHL patients and 45% of LHL patients made abnormally large errors in line bisection. Right-hemisphere lesioned patients were more sensitive to spatial location and directional cuing than NC subjects. In contrast, LHL patients were less sensitive to either condition than NCs. The error direction and error size emerged as dissociable components of line bisection. Right-hemisphere lesioned patients and NC subjects bisected lines consistently to one side of the true center. Left-hemisphere lesioned patients bisected lines equally often on both sides of the true center. Both RHL and LHL patients made larger absolute bisection errors than NC subjects, but the RHL patients errors were larger than those of the LHL patients. We propose that the greater sensitivity of RHL patients to spatial location and directional cues and the directional consistency of their bisection errors represent contributions of the intact left cerebral hemisphere to line bisection. In contrast, the LHL patients unrestrained ability to orient to both ends of the line reflects a contribution of the intact right cerebral hemisphere to line bisection. The failure of both groups to accurately bisect lines reflects a common visuospatial processing deficit that is more pronounced following RHLs than LHLs.

Sham transcranial magnetic stimulation using electrical stimulation of the scalp

BACKGROUND: Most methods of sham, repetitive transcranial magnetic stimulation (rTMS) fail to replicate the look, sound, and feel of active stimulation in the absence of a significant magnetic field. OBJECTIVE/HYPOTHESIS: To develop and validate a new method of sham rTMS appropriate for a double-blind, placebo-controlled study with subject crossover. METHODS: The look and sound of active rTMS was replicated using a matched, air-cooled sham TMS coil. Scalp muscle stimulation associated with rTMS was replicated using large rubber electrodes placed over selected muscles. The intensity and pulse width of electrical stimulation necessary to match 1-Hz rTMS was developed in one sample of normal subjects. The sham technique was validated in back-to-back comparisons with active rTMS in new samples of normal subjects who were either naïve or experienced with rTMS. RESULTS: Subjects naïve to TMS could not tell which type of stimulation was active or sham or which was electrical or magnetic. Naïve subjects incorrectly picked sham stimulation as active, when forced to choose, because electrical stimulation felt more focused than magnetic stimulation. Subjects experienced with TMS could correctly identify sham and active stimulation. Experimenters could detect subtle differences between conditions. CONCLUSIONS: This method of sham rTMS closely mimics the look, sound, and feel of active stimulation at 1Hz without creating a significant magnetic field. It is valid for use with naïve subjects and in crossover studies. It can accommodate differences in scalp muscle recruitment at different sites of stimulation, and it could potentially be used with higher frequency stimulation.

Memory, mood and measurement in hypothyroidism

A 63-year-old female exhibited primary hypothyroidism, both upon clinical examination and laboratory tests. A full neuropsychological exam and repeated, multiple measures of affect, memory, concentration, and problem solving were used to establish baselines prior to treatment and to assess change during the first 7 months of thyroid hormone replacement therapy. Additionally, thyroid hormone and metabolites T3, T4, TSH, and T3 (resin uptake) were regularly assessed. Results indicated that establishing stable baselines before treatment, long-term repeated assessments during treatment, and the use of control subjects are crucial to understanding the neuropsychological changes associated with hypothyroidism. Certain measures of depression, anxiety, attention, and concentration changed from severely impaired to normal levels following an explanation of the diagnosis but before actual treatment. Baseline memory functions were impaired before treatment and remained impaired relative to normals during replacement therapy in spite of improvement with repeated testing. However, replacement therapy may have arrested the progression of memory deterioration as no further decline was evident at a 7-month follow-up. Our data suggest that the memory changes associated with primary hypothyroidism may not be reversed by thyroid hormone replacement therapy.

Useful field of view after traumatic brain injury

Background:Traumatic brain injury (TBI) survivors often have sensory and cognitive impairments that may interfere with driving ability. The Useful Field of View (UFOV) is a measure of visual information processing that is a good predictor of vehicle crash risk in older adults. Objective:The objective of this study was to explore the possibility that UFOV is compromised after TBI. Design:UFOV performance of 23 TBI survivors and 18 young adults without neurological impairment were compared. Conclusion:TBI survivors had higher UFOV scores than young adults, which indicated a greater functional loss of peripheral vision. The results suggest that the UFOV may be a valuable instrument for assessing driving readiness in TBI survivors.

Neuromodulation of delay discounting, the reflection effect, and cigarette consumption

Cigarette smokers and substance users discount the value of delayed outcomes more steeply than non-users. Higher discounting rates are associated with relapse and poorer treatment outcomes. The left dorsolateral prefontal cortex (DLPFC) exerts an inhibitory influence on impulsive or seductive choices. Greater activity in the prefrontal cortex is associated with lower discounting rates. We hypothesized that increasing activity in the left DLPFC with high frequency repetitive transcranial magnetic stimulation (HF rTMS) would decrease delay discounting and decrease impulsive decision-making in a gambling task as well as decrease cigarette consumption, similar to other studies. In this single-blind, within-subjects design, smokers with no intention to quit (n = 47) and nonsmokers (n = 19) underwent three counterbalanced sessions of HF rTMS (20 Hz, 10 Hz, sham) delivered over the left DLPFC. Tasks were administered at baseline and after each stimulation session. Stimulation decreased discounting of monetary gains (F([3,250]) = 4.46, p < .01), but increased discounting of monetary losses (F([3,246]) = 4.30, p < .01), producing a reflection effect, normally absent in delay discounting. Stimulation had no effect on cigarette consumption. These findings provide new insights into cognitive processes involved with decision-making and cigarette consumption and suggest that like all medications for substance dependence, HF rTMS is likely to be most effective when paired with cognitive-behavioral interventions.

Search patterns and neglect: A case study ☆

An irregular and unsystematic search pattern may contribute to unilateral neglect. We examined the sequence of cancellations performed by a patient with unilateral neglect and found that she followed a systematic and stereotypic vertical search pattern. To overcome this vertical search pattern, foils were placed in rows. These foils induced slightly more horizontal movements, but did not alter her neglect. In another attempt to overcome her vertical search and tendency to cancel on the right, she was explicitly instructed to cancel targets alternating to and from the right and left sides of the array. This strategy overcame her vertical search, but, instead of modifying the severity of her neglect, this task only changed its spatial distribution. The altered spatial distribution of neglect is difficult to reconcile with current theories of neglect. We suggest that this patient demonstrates a limited capacity to sequentially be aware of or act upon stimuli.

Biases in Attentional Orientation and Magnitude Estimation Explain Crossover: Neglect is a Disorder of Both

Crossover refers to a pattern of performance on the line bisection test in which short lines are bisected on the side opposite the true center of long lines. Although most patients with spatial neglect demonstrate crossover, contemporary theories of neglect cannot explain it. In contrast, we show that blending the psychophysical construct of magnitude estimation with neglect theory not only explains crossover, but also addresses a quantitative feature of neglect that is independent of spatial deficits. We report a prospective validation study of the orientation/estimation hypothesis of crossover. Forty subjects (17 patients with and without neglect following unilateral brain injury and 23 normal controls) completed four experiments that examined crossover using line bisection, line bisection with cueing, and reproducing line lengths from both memory and a standard. Replicating earlier findings, all except one subject group exhibited crossover on the standard line bisection test, all groups showed a spontaneous preference to orient attention to one end of the lines, and all groups overestimated the length of short lines and underestimated long lines. Biases in attentional orientation and magnitude estimation are exaggerated in patients with neglect. The truly novel finding of this study occurred when, after removing the line from the bisection task, the direction of crossover was completely reversed in all subject groups depending on where attention was oriented. These findings are consistent with our hypothesis of crossover: (1) crossover is a normal component of performance on line bisection; (2) crossover results from the interplay of biases in attentional orientation and magnitude estimation; and (3) attentional orientation predicts the direction of crossover, whereas a disorder of magnitude estimation, not previously emphasized in neglect, accounts for the quantitative changes in length estimation that make crossover more obvious in neglect subjects. Paradoxically, we observed that the traditional line bisection test is suboptimal for exploring crossover because lines elicit spontaneous orientation responses from subjects that confound experimental manipulations of attention. We conclude that attentional orientation and magnitude estimation are necessary and sufficient to explain crossover and that bias in magnitude estimation is a core component of neglect.