The acceptability of lifestyle medicine for the treatment of mental illness: perspectives of people with and without lived experience of mental illness.

OBJECTIVE: While lifestyle medicine can be highly effective for treating a range of mental illnesses these approaches are grossly underutilised and have not been systematically implemented into health care systems. Understanding the acceptability of lifestyle medicine is a critical first step to remediate this. This study evaluated the acceptability of lifestyle medicine relative to pharmacotherapy and psychotherapy, and explore perspectives of people with and without lived experience of mental illness. METHODS: Six hundred and forty-nine adult Australian residents (62.6% female; 53.6% with a lifetime diagnosis of mental illness) completed an online survey based on the Theoretical Framework of Acceptability assessing the acceptability of lifestyle medicine, pharmacotherapy and psychotherapy for treating mental illness. RESULTS: Most participants felt positive about lifestyle medicine (76.9%) and felt that such approaches aligned with their personal values (74.9%). They understood how lifestyle medicine worked (86.4%) and believed it would be effective (69.6%). Lived experience of mental illness was associated with greater perceived burden and lower self-efficacy to engage in lifestyle medicine activities (both p < 0.001). While there was a clear preference for psychotherapy and lifestyle medicine over pharmacotherapy, pharmacotherapy was perceived as least effortful (p < .001) and participants were least confident in their ability to engage in lifestyle medicine (p < 0.05). CONCLUSION: The findings indicate strong acceptability of lifestyle medicine for mental illness, a preference for non-pharmacological treatment approaches, and an understanding of the challenges associated with making long-term healthy lifestyle modifications amongst people who have lived experience of mental illness.

Key influences on university students' physical activity: a systematic review using the Theoretical Domains Framework and the COM-B model of human behaviour.

BACKGROUND: Physical activity is important for all aspects of health, yet most university students are not active enough to reap these benefits. Understanding the factors that influence physical activity in the context of behaviour change theory is valuable to inform the development of effective evidence-based interventions to increase university students' physical activity. The current systematic review a) identified barriers and facilitators to university students' physical activity, b) mapped these factors to the Theoretical Domains Framework (TDF) and COM-B model, and c) ranked the relative importance of TDF domains. METHODS: Data synthesis included qualitative, quantitative, and mixed-methods research published between 01.01.2010-15.03.2023. Four databases (MEDLINE, PsycINFO, SPORTDiscus, and Scopus) were searched to identify publications on the barriers/facilitators to university students' physical activity. Data regarding study design and key findings (i.e., participant quotes, qualitative theme descriptions, and survey results) were extracted. Framework analysis was used to code barriers/facilitators to the TDF and COM-B model. Within each TDF domain, thematic analysis was used to group similar barriers/facilitators into descriptive theme labels. TDF domains were ranked by relative importance based on frequency, elaboration, and evidence of mixed barriers/facilitators. RESULTS: Thirty-nine studies involving 17,771 participants met the inclusion criteria. Fifty-six barriers and facilitators mapping to twelve TDF domains and the COM-B model were identified as relevant to students' physical activity. Three TDF domains, environmental context and resources (e.g., time constraints), social influences (e.g., exercising with others), and goals (e.g., prioritisation of physical activity) were judged to be of greatest relative importance (identified in > 50% of studies). TDF domains of lower relative importance were intentions, reinforcement, emotion, beliefs about consequences, knowledge, physical skills, beliefs about capabilities, cognitive and interpersonal skills, social/professional role and identity, and behavioural regulation. No barriers/facilitators relating to the TDF domains of memory, attention and decision process, or optimism were identified. CONCLUSIONS: The current findings provide a foundation to enhance the development of theory and evidence informed interventions to support university students' engagement in physical activity. Interventions that include a focus on the TDF domains 'environmental context and resources,' 'social influences,' and 'goals,' hold particular promise for promoting active student lifestyles. TRIAL REGISTRATION: Prospero ID-CRD42021242170.

Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Lifestyle risk factors for obsessive-compulsive symptoms and related phenomena: What should lifestyle interventions target?

OBJECTIVE: Understanding the impact of lifestyle on mental illness symptoms is important for informing psycho-education and developing interventions which target mental and physical comorbidities. Obsessive-compulsive and related disorders can have a significant impact on health-related quality of life and physical health. However, our understanding of the impact of lifestyle on obsessive-compulsive symptoms and broader compulsive and impulsive problematic repetitive behaviours is limited. AIMS: We investigated whether lifestyle factors predicted change in obsessive-compulsive symptoms and problematic repetitive behaviours in a general population sample over a 3-month period. METHODS: Eight hundred thirty-five participants completed an online questionnaire battery assessing lifestyle and mental health. Of these, 538 participants completed the same battery 3 months later. We conducted negative binomial regressions to analyse the association of lifestyle factors at baseline with future (1) obsessive-compulsive symptoms, (2) compulsive problematic repetitive behaviours and (3) impulsive problematic repetitive behaviours, adjusting for baseline obsessive-compulsive symptoms and problematic repetitive behaviours. RESULTS: Lower vegetable (p = 0.020) and oily fish (p = 0.040) intake and lower moderate intensity physical activity (p = 0.008) predicted higher obsessive-compulsive symptoms at follow-up. Higher intake of high-fat foods (p < 0.001) predicted higher compulsive problematic repetitive behaviours at follow-up. No lifestyle factors significantly predicted impulsive problematic repetitive behaviours at follow-up. CONCLUSION: Our results speak to the potential importance of lifestyle quality screening, education and lifestyle interventions (e.g. an anti-inflammatory diet) for individuals experiencing compulsivity-related behaviours and/or symptoms. Further research into potential mechanisms of action will allow for more targeted approaches to lifestyle interventions for transdiagnostic compulsive behaviours.

The role of psychological distress in the relationship between lifestyle and compulsivity: An analysis of independent, bi-national samples.

BACKGROUND: Poor mental health is a state of psychological distress that is influenced by lifestyle factors such as sleep, diet, and physical activity. Compulsivity is a transdiagnostic phenotype cutting across a range of mental illnesses including obsessive-compulsive disorder, substance-related and addictive disorders, and is also influenced by lifestyle. Yet, how lifestyle relates to compulsivity is presently unknown, but important to understand to gain insights into individual differences in mental health. We assessed (a) the relationships between compulsivity and diet quality, sleep quality, and physical activity, and (b) whether psychological distress statistically contributes to these relationships. METHODS: We collected harmonized data on compulsivity, psychological distress, and lifestyle from two independent samples (Australian n = 880 and US n = 829). We used mediation analyses to investigate bidirectional relationships between compulsivity and lifestyle factors, and the role of psychological distress. RESULTS: Higher compulsivity was significantly related to poorer diet and sleep. Psychological distress statistically mediated the relationship between poorer sleep quality and higher compulsivity, and partially statistically mediated the relationship between poorer diet and higher compulsivity. CONCLUSIONS: Lifestyle interventions in compulsivity may target psychological distress in the first instance, followed by sleep and diet quality. As psychological distress links aspects of lifestyle and compulsivity, focusing on mitigating and managing distress may offer a useful therapeutic approach to improve physical and mental health. Future research may focus on the specific sleep and diet patterns which may alter compulsivity over time to inform lifestyle targets for prevention and treatment of functionally impairing compulsive behaviors.

Contrasting patterns of cortical input to architectural subdivisions of the area 8 complex: a retrograde tracing study in marmoset monkeys.

Contemporary studies recognize 3 distinct cytoarchitectural and functional areas within the Brodmann area 8 complex, in the caudal prefrontal cortex: 8b, 8aD, and 8aV. Here, we report on the quantitative characteristics of the cortical projections to these areas, using injections of fluorescent tracers in marmoset monkeys. Area 8b was distinct from both 8aD and 8aV due to its connections with medial prefrontal, anterior cingulate, superior temporal polysensory, and ventral midline/retrosplenial areas. In contrast, areas 8aD and 8aV received the bulk of the projections from posterior parietal cortex and dorsal midline areas. In the frontal lobe, area 8aV received projections primarily from ventrolateral areas, while both 8aD and 8b received dense inputs from areas on the dorsolateral surface. Whereas area 8aD received the most significant auditory projections, these were relatively sparse, in comparison with those previously reported in macaques. Finally, area 8aV was distinct from both 8aD and 8b by virtue of its widespread input from the extrastriate visual areas. These results are compatible with a homologous organization of the prefrontal cortex in New and Old World monkeys, and suggest significant parallels between the present pathways, revealed by tract-tracing, and networks revealed by functional connectivity analysis in Old World monkeys and humans.

No Consistent Antidepressant Effects of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis.

BACKGROUND: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target. OBJECTIVE: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression. METHOD: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation. RESULTS: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters. CONCLUSIONS: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location.

PEAK Mood, Mind, and Marks: a pilot study of an intervention to support university students' mental and cognitive health through physical exercise.

Introduction: Regular exercise has the potential to enhance university students' mental and cognitive health. The PEAK Mood, Mind and Marks program (i.e., PEAK) is a neuroscience-informed intervention developed using the Behaviour Change Wheel to support students to exercise three or more times per week to benefit their mental and cognitive health. This pilot study assessed the impact of PEAK on exercise, mental and cognitive health, and implementation outcomes. Methods: PEAK was delivered to 115 undergraduate university students throughout a 12-week university semester. The primary outcome was weekly exercise frequency. Secondary outcomes were: time spent engaged in moderate-vigorous exercise, sedentary behaviour and perceived mental health and cognitive health. All were measured via online self-report questionnaires. Qualitative interviews with 15 students investigated influences on engagement, the acceptability and appropriateness of PEAK, and its mechanisms of behaviour change. Paired t-tests, Wilcoxon Signed-Rank tests and template analysis were used to analyse quantitative and qualitative data, respectively. Results: On average, 48.4% of students engaged in the recommended frequency of three or more exercise sessions per week. This proportion decreased towards the end of PEAK. Sedentary behaviour significantly decreased from baseline to end-point, and moderate-vigorous exercise significantly increased among students' who were non-exercisers. Mental wellbeing, stress, loneliness, and sense of belonging to the university significantly improved. There were no significant changes in psychological distress. Concentration, memory, and productivity significantly improved. Sixty-eight percent of students remained engaged in one or more components of PEAK at end-point. Qualitative data indicated students found PEAK to be acceptable and appropriate, and that it improved aspects of their capability, opportunity, and motivation to exercise. Conclusions: Students are receptive to an exercise-based program to support their mental and cognitive health. Students exercise frequency decreased; however, these figures are likely a conservative estimate of students exercise engagement. Students valued the neuroscience-informed approach to motivational and educational content and that the program's goals aligned with their academic goals. Students identified numerous areas PEAK's content and implementation can be optimised, including use of a single digital delivery platform, more opportunities to connect with peers and to expand the content's cultural inclusivity.

Examining the unique relationships between problematic use of the internet and impulsive and compulsive tendencies: network approach.

BACKGROUND: Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI. AIMS: The current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community. METHOD: We estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms. RESULTS: Results revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence. CONCLUSIONS: The current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.

Personal and relational changes following deep brain stimulation for treatment-resistant depression: A prospective qualitative study with patients and caregivers.

OBJECTIVE: Deep brain stimulation (DBS) and whether it alters patient personality is a much-debated topic within academic literature, yet rarely explored with those directly involved. This study qualitatively examined how DBS for treatment-resistant depression impacts patient personality, self-concept, and relationships from the perspectives of both patients and caregivers. METHODS: A prospective qualitative design was used. Eleven participants were included (six patients, five caregivers). Patients were enrolled in a clinical trial of DBS of the bed nucleus of the stria terminalis. Semi-structured interviews were conducted with participants before DBS-implantation and 9-months after stimulation-initiation. The 21 interviews were thematically analysed. RESULTS: Three primary themes were identified: (a) impact of mental illness and treatment on self-concept; (b) device acceptability and usability, and (c) relationships and connection. Severe refractory depression had profoundly impacted who patients were, how they viewed themselves, and the quality and functioning of their relationships. Patients who benefited from DBS felt reconnected with their premorbid self, yet still far from their ideal self. While reductions in depression were broadly beneficial for relationships, the process of adjusting relationship dynamics created new challenges. All patients reported recharging difficulties and challenges adapting to the device. CONCLUSIONS: Therapeutic response to DBS is a gradual and complex process that involves an evolving self-concept, adjusting relationship dynamics, and growing connection between body and device. This is the first study to provide in-depth insight into the lived experience of DBS for treatment-resistant depression. Patient and caregiver narrative accounts should be routinely collected to guide more person-centred DBS clinical interventions.

Transdiagnostic phenotypes of compulsive behavior and associations with psychological, cognitive, and neurobiological affective processing.

Compulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous sample of community-based individuals (N = 45; 18-45 years; 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled "Compulsive Non-Avoidant", "Compulsive Reactive" and "Compulsive Stressed". They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger samples are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.

Subcortical projections to the frontal pole in the marmoset monkey.

The subcortical projections to the marmoset frontal pole were mapped with the use of fluorescent tracer injections. The main thalamic projections, which originated in both the magnocellular and parvocellular subdivisions of the mediodorsal nucleus, were topographically organized. Our results suggest the existence of a third, caudal subdivision of this nucleus, which is likely to be homologous to the macaque's pars densocellularis. A substantial, but not topographically organized, projection to Brodmann's area 10 originated in the medial part of the ventral anterior nucleus. Minor thalamic projections originated in the medial pulvinar nucleus and in the midline/intralaminar nuclei. Finally, the posterior thalamic group (including the limitans and suprageniculate nuclei) sent a small projection to rostral area 10 that has not previously been documented in primates. The main extrathalamic projections stemmed from the claustrum, which contained as many as 50% of all subcortical labelled neurons. Minor connections originated in the hypothalamus (mainly in the lateral anterior and lateral tuberal regions), dorsal periaqueductal grey matter, basal forebrain (nucleus basalis of Meynert and horizontal limb of the diagonal band of Broca), and amygdala (basal, accessory basal and lateral nuclei). The present results, combined with recent data on the cortical projections to area 10, reveal the frontal pole as a region that integrates information from multiple neural processing systems, including high-level sensory, limbic and working memory-related structures. Although the pattern of subcortical projections is similar to that previously described in the macaque, suggesting a homologous organization, the present data also suggest functional distinctions between medial and lateral sectors of area 10.

"Nothing to Lose, Absolutely Everything to Gain": Patient and Caregiver Expectations and Subjective Outcomes of Deep Brain Stimulation for Treatment-Resistant Depression.

Background: How "success" is defined in clinical trials of deep brain stimulation (DBS) for refractory psychiatric conditions has come into question. Standard quantitative psychopathology measures are unable to capture all changes experienced by patients and may not reflect subjective beliefs about the benefit derived. The decision to undergo DBS for treatment-resistant depression (TRD) is often made in the context of high desperation and hopelessness that can challenge the informed consent process. Partners and family can observe important changes in DBS patients and play a key role in the recovery process. Their perspectives, however, have not been investigated in research to-date. The aim of this study was to qualitatively examine patient and caregivers' understanding of DBS for TRD, their expectations of life with DBS, and how these compare with actual experiences and outcomes. Methods: A prospective qualitative design was adopted. Semi-structured interviews were conducted with participants (six patients, five caregivers) before DBS-implantation and 9-months after stimulation initiation. All patients were enrolled in a clinical trial of DBS of the bed nucleus of the stria terminalis. Interviews were thematically analyzed with data saturation achieved at both timepoints. Results: Two primary themes identified were: (1) anticipated vs. actual outcomes, and (2) trial decision-making and knowledge. The decision to undergo DBS was driven by the intolerability of life with severe depression coupled with the exhaustion of all available treatment options. Participants had greater awareness of surgical risks compared with stimulation-related risks. With DBS, patients described cognitive, emotional, behavioral and physical experiences associated with the stimulation, some of which were unexpected. Participants felt life with DBS was like "a roller coaster ride"-with positive, yet unsustained, mood states experienced. Many were surprised by the lengthy process of establishing optimum stimulation settings and felt the intervention was still a "work in progress." Conclusion: These findings support existing recommendations for iterative informed consent procedures in clinical trials involving long-term implantation of neurotechnology. These rich and descriptive findings hold value for researchers, clinicians, and individuals and families considering DBS. Narrative accounts capture patient and family needs and should routinely be collected to guide patient-centered approaches to DBS interventions.

The Influence of Trait Compulsivity and Impulsivity on Addictive and Compulsive Behaviors During COVID-19.

Background: The COVID-19 pandemic has resulted in high levels of psychological distress worldwide, with experts expressing concern that this could result in corresponding increases in addictive behaviors as individuals seek to cope with their distress. Further, some individuals may be at greater risk than others for developing problematic addictive behaviors during times of high stress, such as individuals with high trait impulsivity and compulsivity. Despite the potential of such knowledge to inform early detection of risk, no study to date has examined the influence of trait impulsivity and compulsivity on addictive behaviors during COVID-19. Toward this aim, the current study examined the association between impulsive and compulsive traits and problematic addictive and compulsive behaviors during the first COVID-19 lockdown in Australia. Methods: Eight hundred seventy-eight adults completed a cross-sectional online survey during the first lockdown, between late May to June 2020. Participants completed scales for addictive and compulsive behaviors for the period prior to and during lockdown for problematic eating, pornography, internet use, gambling, drinking, and obsessive-compulsive behaviors. Negative binomial regressions examined the associations between impulsivity, compulsivity, and their interaction with problematic behaviors during lockdown, controlling for age, gender, sample, psychological distress, exposure to COVID-related stressors, and pre-COVID problems. Results: Greater trait compulsivity was associated with more problematic obsessive-compulsive behaviors (p < 0.001) and less problematic drinking (p = 0.038) during lockdown. Further, trait compulsivity interacted with trait impulsivity in relation to problematic eating behaviors (p = 0.014) such that greater trait compulsivity was associated with more problems among individuals with low impulsivity only (p = 0.030). Finally, psychological distress and/or exposure to COVID-related stressors were associated with greater problems across all addictive and compulsive behaviors, as was severity of pre-COVID problems. Discussion: Trait compulsivity was associated with addictive and compulsive behaviors in different ways. Further, the finding that stress-related variables (psychological distress and COVID-related stressors) were associated with greater problems across all lockdown behaviors supports the idea that stress may facilitate, or otherwise be associated with, problematic behaviors. These findings highlight the need for interventions that enhance resilience to stress, which in turn may reduce risk for addictive and compulsive disorders.

A pilot investigation of an intensive theta burst stimulation protocol for patients with treatment resistant depression.

INTRODUCTION: Accelerated or intensive forms of repetitive transcranial magnetic stimulation (rTMS) are increasingly being explored for their potential to produce more efficient and rapid treatment benefits in major depressive disorder (MDD). However, accelerated or intensive protocols using standard forms of rTMS are still quite time-consuming to apply. Theta burst stimulation (TBS) is a novel form of magnetic stimulation with the potential to produce similar anti-depressant effects but in a much abbreviated period of time. The aim of this study was to investigate the comparative efficacy of an intensive TBS protocol compared to standard rTMS treatment. METHODS: 74 outpatients (36 female, mean age 44.36 ±â€¯12.1 years) with MDD received either intensive TBS (3 intermittent TBS treatments per day for 3 days in week 1, 3 treatments a day for 2 days in week 2, and 3 treatments in 1 day in week 3 and in week 4, or standard rTMS (5 daily sessions per week for 4 weeks). Patients were assessed weekly throughout the treatment course, and at 4 weeks after treatment end. RESULTS: There were no significant differences in the degree of reduction in depressive symptoms, the rate of reduction in depressive symptoms, remission or response rates (response rates = 27.8% for intensive group, 26.3% for the standard group, p > 0.05 for all analyses) between the intensive TBS and standard rTMS treatment groups. However, the overall response and remission rates were limited in both groups. There was no difference in rates of side effects, no serious adverse events and no alterations in cognitive performance. CONCLUSION: Intensively applied TBS appears to have similar efficacy to standard rTMS when these were applied as delivered in this study but does not produce more rapid clinical benefits. The overall response rates in both groups in this study were limited, most likely by the total doses provided in both study arms. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12616000443493.

Connections of the marmoset rostrotemporal auditory area: express pathways for analysis of affective content in hearing.

The current hierarchical model of primate auditory cortical processing proposes a core of 'primary-like' areas, which is surrounded by secondary (belt) and tertiary (parabelt) regions. The rostrotemporal auditory cortical area (RT) remains the least well characterized of the three proposed core areas, and its functional organization has only recently come under scrutiny. Here we used injections of anterograde and retrograde tracers in the common marmoset (Callithrix jacchus) to examine the connectivity of RT and its adjacent areas. As expected from the current model, RT exhibited dense core-like reciprocal connectivity with the ventral division of the medial geniculate body, the rostral core area and the auditory belt, but had weaker connections with the parabelt. However, RT also projected to the ipsilateral rostromedial prefrontal cortex (area 10), the dorsal temporal pole and the ventral caudate nucleus, as well as bilaterally to the lateral nucleus of the amygdala. Thus, RT has connectivity with limbic structures previously believed to connect only with higher-order auditory association cortices, and is probably functionally distinct from the other core areas. While this view is consistent with a proposed role of RT in temporal integration, our results also indicate that RT could provide an anatomical 'shortcut' for processing affective content in auditory information.

A pilot study of bed nucleus of the stria terminalis deep brain stimulation in treatment-resistant depression.

BACKGROUND: Studies are increasingly investigating the therapeutic effects of deep brain stimulation (DBS) applied to a variety of brain regions in the treatment of patients with highly treatment refractory depression. Limited research to date has investigated the therapeutic potential of DBS applied to the Bed Nucleus Of Stria Terminalis (BNST). OBJECTIVE: The aim of this study was to explore the therapeutic potential of DBS applied to the BNST. METHOD: Five patients with highly treatment resistant depression underwent DBS to the BNST in an open label case series design. RESULTS: BNST DBS resulted in sustained remission of depression in two of the five patients, provided substantial therapeutic improvement two further patients, and had minimal antidepressant effect for the final patient. There were no operative complications and stimulation related side effects were limited and reversible with adjustment of stimulation. However, the time to achieve and complexity of programming required to achieve optimal therapeutic outcomes varied substantially between patients. CONCLUSION: DBS applied to the BNST as therapeutic potential in patients with highly refractory depression and warrants exploration in larger clinical studies.

Cortical and thalamic projections to cytoarchitectural areas 6Va and 8C of the marmoset monkey: connectionally distinct subdivisions of the lateral premotor cortex.

We studied the afferent connections of two cytoarchitectural subdivisions of the caudolateral frontal cortex, areas 6Va and 8C, in marmoset monkeys. These areas received connections from the same set of thalamic nuclei, including main inputs from the ventral lateral and ventral anterior complexes, but differed in their patterns of corticocortical connections. Areas 8C and 6Va had reciprocal interconnections, and received similar proportions of afferents from premotor areas 6M and 6DC, and from the prefrontal cortex. However, area 8C received stronger inputs from frontal areas that have been implicated in oculomotor functions, whereas area 6Va received stronger projections from the primary motor area. Somatosensory projections to area 6Va were generally stronger than those to area 8C, and originated from several areas; in contrast, only the second somatosensory area (S2) sent major inputs to area 8C. Finally, although both 6Va and 8C received major inputs from the rostral posterior parietal cortex (putative homologs of areas PE, PF, and PFG), area 8C also received a variety of smaller connections from posterior midline, caudal posterior parietal, and extrastriate areas. Statistical analyses revealed that the pattern of connections of area 8C is more akin to that characterizing a premotor area, rather than a prefrontal area. We conclude that cytoarchitectural area 6Va in the marmoset is similar to ventral premotor areas identified in other simian primates, and that area 8C corresponds to a specialized subdivision of the caudal premotor complex where visual information for the guidance of movements is likely to be emphasized.

Patterns of cortical input to the primary motor area in the marmoset monkey.

In primates the primary motor cortex (M1) forms a topographic map of the body, whereby neurons in the medial part of this area control movements involving trunk and hindlimb muscles, those in the intermediate part control movements involving forelimb muscles, and those in the lateral part control movements of facial and other head muscles. This topography is accompanied by changes in cytoarchitectural characteristics, raising the question of whether the anatomical connections also vary between different parts of M1. To address this issue, we compared the patterns of cortical afferents revealed by retrograde tracer injections in different locations within M1 of marmoset monkeys. We found that the entire extent of this area is unified by projections from the dorsocaudal and medial subdivisions of premotor cortex (areas 6DC and 6M), from somatosensory areas 3a, 3b, 1/2, and S2, and from posterior parietal area PE. While cingulate areas projected to all subdivisions, they preferentially targeted the medial part of M1. Conversely, the ventral premotor areas were preferentially connected with the lateral part of M1. Smaller but consistent inputs originated in frontal area 6DR, ventral posterior parietal cortex, the retroinsular cortex, and area TPt. Connections with intraparietal, prefrontal, and temporal areas were very sparse, and variable. Our results demonstrate that M1 is unified by a consistent pattern of major connections, but also shows regional variations in terms of minor inputs. These differences likely reflect requirements for control of voluntary movement involving different body parts.

Patterns of afferent input to the caudal and rostral areas of the dorsal premotor cortex (6DC and 6DR) in the marmoset monkey.

Corticocortical projections to the caudal and rostral areas of dorsal premotor cortex (6DC and 6DR, also known as F2 and F7) were studied in the marmoset monkey. Both areas received their main thalamic inputs from the ventral anterior and ventral lateral complexes, and received dense projections from the medial premotor cortex. However, there were marked differences in their connections with other cortical areas. While 6DR received consistent inputs from prefrontal cortex, area 6DC received few such connections. Conversely, 6DC, but not 6DR, received major projections from the primary motor and somatosensory areas. Projections from the anterior cingulate cortex preferentially targeted 6DC, while the posterior cingulate and adjacent medial wall areas preferentially targeted 6DR. Projections from the medial parietal area PE to 6DC were particularly dense, while intraparietal areas (especially the putative homolog of LIP) were more strongly labeled after 6DR injections. Finally, 6DC and 6DR were distinct in terms of inputs from the ventral parietal cortex: projections to 6DR originated preferentially from caudal areas (PG and OPt), while 6DC received input primarily from rostral areas (PF and PFG). Differences in connections suggest that area 6DR includes rostral and caudal subdivisions, with the former also involved in oculomotor control. These results suggest that area 6DC is more directly involved in the preparation and execution of motor acts, while area 6DR integrates sensory and internally driven inputs for the planning of goal-directed actions. They also provide strong evidence of a homologous organization of the dorsal premotor cortex in New and Old World monkeys.