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.

Background-Some studies have suggested that in stroke patients, spatial inattention on the cancellation test is closely related to disorganized visual search. However, methods to assess spatial aspects of search organization on cancellation tests have not been well developed. In this study the authors design and evaluate new methods to quantify strategies of spatial exploration on the cancellation test in stroke patients who showed a broad range of spatial attentional abilities, and test whether disorganization and inattention are related.Methods-Twenty stroke patients were videotaped while they performed a cancellation test. Several variables that reflect spatial aspects of search organization were measured through subsequent video playback. Two patients with severe neglect were excluded from further analysis to avoid constraining the spatial expression of search organization. Spearman correlations were used to assess whether severity of spatial inattention correlated with the individual search organization measures.Results-Of the 18 remaining patients, 10 had mild-moderate spatial neglect (pathologic inattention), while the other 8 omitted at most one target (normal performance). There were no significant correlations between the number of targets omitted and any of the search organization measures.Conclusions-Spatial inattention on cancellation due to neglect following stroke is not closely related to the organization of visual search. Instead, search disorganization during cancellation may reflect disturbance of an unspecified executive control mechanism.The cancellation test has long been used in stroke patients to assess spatial inattention or neglect (pathologic inattention), partly because it is easy to reproduce and administer. The test presents numerous printed images (targets) on a conventionally sized sheet of paper that are to be marked once and individually with a pen or pencil; they are thus "canceled" as if they are postage stamps. Spatial inattention is measured by the amount of targets left unmarked after the patient indicates test completion. Cancellation neglect is highly

Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked with heightened rates of conversion to Alzheimer's disease. Improving apathy may slow the neurodegenerative process. The objective was to establish the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross-over study was conducted in nine subjects (66 ± 9 years) with apathy and MCI. Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks following which they underwent a 4-week treatment-free period. Subjects then crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES-C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B), and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6, and 8 weeks. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS compared to the sham treatment. This study establishes that rTMS is efficacious in improving apathy in subjects with MCI.

rTMS is a promising treatment modality that can transiently diminish tinnitus in some individuals, but further trials are needed to determine the optimal techniques required to achieve a lasting response. It is unclear whether the improved reaction times were caused by tinnitus reduction or a general effect of rTMS. PET/CT scans immediately after treatment suggest that improvement may be related to reduction of cortical asymmetry associated with tinnitus.

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 and 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 (20Hz, 10Hz, 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.