Neurobiological and clinical effects of fNIRS-controlled rTMS in patients with panic disorder/agoraphobia during cognitive-behavioural therapy.

BACKGROUND: A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD. METHODS: In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls. RESULTS: In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group. LIMITATIONS: Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT. CONCLUSION: Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.

Does rTMS alter neurocognitive functioning in patients with panic disorder/agoraphobia? An fNIRS-based investigation of prefrontal activation during a cognitive task and its modulation via sham-controlled rTMS.

OBJECTIVES: Neurobiologically, panic disorder (PD) is supposed to be characterised by cerebral hypofrontality. Via functional near-infrared spectroscopy (fNIRS), we investigated whether prefrontal hypoactivity during cognitive tasks in PD-patients compared to healthy controls (HC) could be replicated. As intermittent theta burst stimulation (iTBS) modulates cortical activity, we furthermore investigated its ability to normalise prefrontal activation. METHODS: Forty-four PD-patients, randomised to sham or verum group, received 15 iTBS-sessions above the left dorsolateral prefrontal cortex (DLPFC) in addition to psychoeducation. Before first and after last iTBS-treatment, cortical activity during a verbal fluency task was assessed via fNIRS and compared to the results of 23 HC. RESULTS: At baseline, PD-patients showed hypofrontality including the DLPFC, which differed significantly from activation patterns of HC. However, verum iTBS did not augment prefrontal fNIRS activation. Solely after sham iTBS, a significant increase of measured fNIRS activation in the left inferior frontal gyrus (IFG) during the phonological task was found. CONCLUSION: Our results support findings that PD is characterised by prefrontal hypoactivation during cognitive performance. However, verum iTBS as an "add-on" to psychoeducation did not augment prefrontal activity. Instead we only found increased fNIRS activation in the left IFG after sham iTBS application. Possible reasons including task-related psychophysiological arousal are discussed.

Neurocognitive effects of atypical and conventional antipsychotic drugs in schizophrenia: a naturalistic 6-month follow-up study.

The present study aimed to assess the neurocognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions. Eighty-two patients with schizophrenia underwent a comprehensive neuropsychological assessment both at baseline during inpatient treatment and 6 months after discharge from hospital (follow-up). From this sample, we selected two subgroups of patients, which had either a continuous atypical (n=33) or conventional (n=16) antipsychotic medication. Twenty-seven out of 40 healthy controls were also retested to control for practice effects. Both patient groups showed a moderate and significant improvement in global cognitive functioning. The repeated measurement ANOVAs revealed no differential treatment effects for all neuropsychological domains. These results remained after controlling for potential confounders between groups. Administering antipsychotic medications in an individually optimized manner seems to have the potential to improve some aspects of neurocognition in schizophrenia, regardless of the kind of antipsychotic medication.

Course of cognitive functioning during the stabilization phase of schizophrenia.

The present study aimed at examining the longitudinal course of neuropsychological impairments in schizophrenia patients during the stabilization phase of the illness. Cognitive functioning of 151 schizophrenia patients was assessed at baseline, 9-month, and 15-month follow-up with a comprehensive battery of cognitive tests. Cognitive performance of 40 matched controls was also examined at baseline and follow-up in order to control for effects of repeated testing. We found significant improvements in memory, attention, and global cognitive functioning from baseline to 9-month follow-up. Abstraction was stable at a relatively normal level. Global cognitive functioning remained at 9-month follow-up one standard deviation below normative level. Improvements in patients' cognitive performance between the 9-month and the 15-month follow-up were fewer and less pronounced. The present study implies that schizophrenia is a static encephalopathy with trait and state dependent cognitive components particularly in the attention and memory domain. The statistically and clinically significant cognitive improvements should be ground for clinical optimism.