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Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD) 1 . However, achieving stable recovery is unpredictable 2 , typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting 3 . We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment., (© 2023. The Author(s).)

It remains elusive what language markers derived from psychotherapy sessions are indicative of therapeutic alliance, limiting our capacity to assess and provide feedback on the trusting quality of the patient-clinician relationship. To address this critical knowledge gap, we leveraged feature extraction methods from natural language processing (NLP), a subfield of artificial intelligence, to quantify pronoun and non-fluency language markers that are relevant for communicative and emotional aspects of therapeutic relationships. From twenty-eight transcripts of non-manualized psychotherapy sessions recorded in outpatient clinics, we identified therapists' first-person pronoun usage frequency and patients' speech transition marking relaxed interaction style as potential metrics of alliance. Behavioral data from patients who played an economic game that measures social exchange (i.e. trust game) suggested that therapists' first-person pronoun usage may influence alliance ratings through their diminished trusting behavior toward therapists. Together, this work supports that communicative language features in patient-therapist dialogues could be markers of alliance., Competing Interests: H.S.M. receives consulting and IP licensing fees from Abbott Labs., (© 2023 The Author(s).)

DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury., Competing Interests: RR was employed by Medtronic, Inc. HBo was employed by Boston Scientific Neuromodulation Corporation. DG was employed by the NeuroPace, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wong, Deuschl, Wolke, Bergman, Muthuraman, Groppa, Sheth, Bronte-Stewart, Wilkins, Petrucci, Lambert, Kehnemouyi, Starr, Little, Anso, Gilron, Poree, Kalamangalam, Worrell, Miller, Schiff, Butson, Henderson, Judy, Ramirez-Zamora, Foote, Silburn, Li, Oyama, Kamo, Sekimoto, Hattori, Giordano, DiEuliis, Shook, Doughtery, Widge, Mayberg, Cha, Choi, Heisig, Obatusin, Opri, Kaufman, Shirvalkar, Rozell, Alagapan, Raike, Bokil, Green and Okun.)

Background: In contrast to all other areas of medicine, psychiatry is still nearly entirely reliant on subjective assessments such as patient self-report and clinical observation. The lack of objective information on which to base clinical decisions can contribute to reduced quality of care. Behavioral health clinicians need objective and reliable patient data to support effective targeted interventions., Objective: We aimed to investigate whether reliable inferences-psychiatric signs, symptoms, and diagnoses-can be extracted from audiovisual patterns in recorded evaluation interviews of participants with schizophrenia spectrum disorders and bipolar disorder., Methods: We obtained audiovisual data from 89 participants (mean age 25.3 years; male: 48/89, 53.9%; female: 41/89, 46.1%): individuals with schizophrenia spectrum disorders (n=41), individuals with bipolar disorder (n=21), and healthy volunteers (n=27). We developed machine learning models based on acoustic and facial movement features extracted from participant interviews to predict diagnoses and detect clinician-coded neuropsychiatric symptoms, and we assessed model performance using area under the receiver operating characteristic curve (AUROC) in 5-fold cross-validation., Results: The model successfully differentiated between schizophrenia spectrum disorders and bipolar disorder (AUROC 0.73) when aggregating face and voice features. Facial action units including cheek-raising muscle (AUROC 0.64) and chin-raising muscle (AUROC 0.74) provided the strongest signal for men. Vocal features, such as energy in the frequency band 1 to 4 kHz (AUROC 0.80) and spectral harmonicity (AUROC 0.78), provided the strongest signal for women. Lip corner-pulling muscle signal discriminated between diagnoses for both men (AUROC 0.61) and women (AUROC 0.62). Several psychiatric signs and symptoms were successfully inferred: blunted affect (AUROC 0.81), avolition (AUROC 0.72), lack of vocal inflection (AUROC 0.71), asociality (AUROC 0.63), and worthlessness (AUROC 0.61)., Conclusions: This study represents advancement in efforts to capitalize on digital data to improve diagnostic assessment and supports the development of a new generation of innovative clinical tools by employing acoustic and facial data analysis., (©Michael L Birnbaum, Avner Abrami, Stephen Heisig, Asra Ali, Elizabeth Arenare, Carla Agurto, Nathaniel Lu, John M Kane, Guillermo Cecchi. Originally published in JMIR Mental Health (https://mental.jmir.org), 24.01.2022.)

We conducted a feasibility analysis to determine the quality of data that could be collected ambiently during routine clinical conversations. We used inexpensive, consumer-grade hardware to record unstructured dialogue and open-source software tools to quantify and model face, voice (acoustic and language) and movement features. We used an external validation set to perform proof-of-concept predictive analyses and show that clinically relevant measures can be produced without a restrictive protocol., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Why is psychiatry unable to define clinically useful biomarkers? We explore this question from the vantage of data and decision science and consider biomarkers as a form of phenotypic data that resolves a well-defined clinical decision. We introduce a framework that systematizes different forms of phenotypic data and further introduce the concept of decision model to describe the strategies a clinician uses to seek out, combine, and act on clinical data. Though many medical specialties rely on quantitative clinical data and operationalized decision models, we observe that, in psychiatry, clinical data are gathered and used in idiosyncratic decision models that exist solely in the clinician's mind and therefore are outside empirical evaluation. This, we argue, is a fundamental reason why psychiatry is unable to define clinically useful biomarkers: because psychiatry does not currently quantify clinical data, decision models cannot be operationalized and, in the absence of an operationalized decision model, it is impossible to define how a biomarker might be of use. Here, psychiatry might benefit from digital technologies that have recently emerged specifically to quantify clinically relevant facets of human behavior. We propose that digital tools might help psychiatry in two ways: first, by quantifying data already present in the standard clinical interaction and by allowing decision models to be operationalized and evaluated; second, by testing whether new forms of data might have value within an operationalized decision model. We reference successes from other medical specialties to illustrate how quantitative data and operationalized decision models improve patient care., Competing Interests: SH was employed by company T. J. Watson IBM Research Laboratory. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Barron, Baker, Budde, Bzdok, Eickhoff, Friston, Fox, Geha, Heisig, Holmes, Onnela, Powers, Silbersweig and Krystal.)

Walking is a complex motor function requiring coordination of all body parts. Parkinson's disease (PD) motor signs such as rigidity, bradykinesia, and impaired balance affect movements including walking. Here, we propose a computational method to objectively assess the effects of Parkinson's disease pathology on coordination between trunk, shoulder and limbs during the gait cycle to assess medication state and disease severity. Movements during a scripted walking task were extracted from wearable devices placed at six different body locations in participants with PD and healthy participants. Three-axis accelerometer data from each device was synchronized at the beginning of either left or right steps. Canonical templates of movements were then extracted from each body location. Movements projected on those templates created a reduced dimensionality space, where complex movements are represented as discrete values. These projections enabled us to relate the body coordination in people with PD to disease severity. Our results show that the velocity profile of the right wrist and right foot during right steps correlated with the participant's total score on the gold standard Unified Parkinson's Disease Rating Scale (UPRDS) with an r2 up to 0.46. Left-right symmetry of feet, trunk and wrists also correlated with the total UPDRS score with an r2 up to 0.3. In addition, we demonstrate that binary dopamine replacement therapy medication states (self-reported 'ON' or 'OFF') can be discriminated in PD participants. In conclusion, we showed that during walking, the movement of body parts individually and in coordination with one another changes in predictable ways that vary with disease severity and medication state., Competing Interests: C. Agurto, S. Heisig, A. Abrami, V. Caggiano, disclose that their employer, IBM Research, is the research branch of IBM Corporation. B.K. Ho is employed by the Department of Neurology, Tufts University School of Medicine and Tufts Medical Center. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aberrant pauses are characteristic of schizophrenia and are robustly associated with its negative symptoms. Here, we found that pause behavior was associated with negative symptoms in individuals at clinical high risk (CHR) for psychosis, and with measures of syntactic complexity-phrase length and usage of determiners that introduce clauses-that we previously showed in this same CHR cohort to help comprise a classifier that predicted psychosis. These findings suggest a common impairment in discourse planning and verbal self-monitoring that affects both speech and language, and which is detected in clinical ratings of negative symptoms.

Unconstrained human movement can be broken down into a series of stereotyped motifs or 'syllables' in an unsupervised fashion. Sequences of these syllables can be represented by symbols and characterized by a statistical grammar which varies with external situational context and internal neurological state. By first constructing a Markov chain from the transitions between these syllables then calculating the stationary distribution of this chain, we estimate the overall severity of Parkinson's symptoms by capturing the increasingly disorganized transitions between syllables as motor impairment increases. Comparing stationary distributions of movement syllables has several advantages over traditional neurologist administered in-clinic assessments. This technique can be used on unconstrained at-home behavior as well as scripted in-clinic exercises, it avoids differences across human evaluators, and can be used continuously without requiring scripted tasks be performed. We demonstrate the effectiveness of this technique using movement data captured with commercially available wrist worn sensors in 35 participants with Parkinson's disease in-clinic and 25 participants monitored at home.