Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Respons... more Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction. Another possible consequence of reduced affective discrimination between error and correct responses is that it might interfere with the reinforcement of responses that optimize outcomes. Furthermore, dysconnection of the ACC, as suggested by reduced FA, to regions involved in behavioural control might impair on-line modulations of response speed to optimize performance (i.e. speed-accuracy trade-off) and increase error likelihood. These findings suggest that in ASD, structural and functional abnormalities of the ACC compromise response monitoring and thereby contribute to behaviour that is rigid and repetitive rather than flexible and responsive to contingencies. Illuminating the mechanisms and clinical significance of abnormal response monitoring in ASD represents a fruitful avenue for further research.
Background-Longitudinal studies of illness progression in Major Depressive Disorder (MDD) indicat... more Background-Longitudinal studies of illness progression in Major Depressive Disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in MDD-especially in medial prefrontal cortex (mPFC) and the hippocampus-but few studies have investigated whether these changes are exacerbated by prior episodes.
Commentators interested in the societal implications of automated decision-making often overlook ... more Commentators interested in the societal implications of automated decision-making often overlook how decisions are made in the technology's absence. For example, the benefits of ML and big data are often summarized as efficiency, objectivity, and consistency; the risks, meanwhile, include replicating historical discrimination and oversimplifying nuanced situations. While this perspective tracks when technology replaces capricious human judgements, it is ill-suited to contexts where standardized assessments already exist. In spaces like employment selection, the relevant question is how an ML model compares to a manually built test. In this paper, we explain that since the Civil Rights Act, industrial and organizational (I/O) psychologists have struggled to produce assessments without disparate impact. By examining the utility of ML for conducting exploratory analyses, coupled with the back-testing capability offered by advances in data science, we explain modern technology's utility for hiring. We then empirically investigate a commercial hiring platform that applies several oft-cited benefits of ML to build custom job models for corporate employers. We focus on the disparate impact observed when models are deployed to evaluate real-world job candidates. Across a sample of 60 jobs built for 26 employers and used to evaluate approximately 400,00 candidates, minority-weighted impact ratios of 0.93 (Black-White), 0.97 (Hispanic-White), and 0.98 (Female-Male) are observed. We find similar results for candidates selecting disability-related accommodations within the platform versus unaccommodated users. We conclude by describing limitations, anticipating criticisms, and outlining further research.
Saccadic latencies are influenced by what occurred during the previous trial. When the previous t... more Saccadic latencies are influenced by what occurred during the previous trial. When the previous trial is an antisaccade, the latencies of both prosaccades and antisaccades are prolonged. The aim of this study was to identify neural correlates of this intertrial effect of antisaccades. Specifically, based on both monkey electrophysiology and human neuroimaging findings, we expected trials preceded by antisaccades to be associated with reduced frontal eye field (FEF) activity relative to those preceded by prosaccades. Twenty-one healthy participants performed pseudorandom sequences of prosaccade and antisaccade trials during functional magnetic resonance imaging (fMRI) with concurrent monitoring of eye position. We compared activity in trials preceded by an antisaccade with activity in trials preceded by a prosaccade. The primary result was that a previous antisaccade prolonged saccadic latency and reduced fMRI activity in the FEF and other regions. No regions showed increased activity. We interpret the reduced FEF activity and slower saccadic responses to reflect inhibitory influences on the response system as a consequence of performing an antisaccade in the previous trial. This demonstrates that neural activity is modulated by trial history, consistent with a rapid, dynamic form of learning. More generally, these results highlight the importance of trial history as a source of variability in both behavioral and neuroimaging studies.
The assumption that the deployment of executive processes invariably improves task performance is... more The assumption that the deployment of executive processes invariably improves task performance is implicit to cognitive theory. In particular, working memory can be used to retain and update historical information about predictable trial sequences (foreknowledge) so that subjects can anticipate and prepare for the upcoming trial more effectively. We review the effects of different types of foreknowledge on response accuracy and latency, particularly in relation to experiments investigating saccadic eye movements in humans. While it is possible to make all aspects of an impending trial predictable, varying the predictability of different components of the trial independently can reveal which cognitive operations are potentially modifiable by foreknowledge. These operations include stimulus processing, retrieval of task-set rules, and response preparation, among others. The available data suggest that, while response preparation can be completed and the response even executed before the stimulus appears (i.e. anticipation) when the subject possesses complete taskforeknowledge (knowing both the stimulus to appear and the response required), foreknowledge of the task-set alone does not permit advance configuration of the task-set rules. A taxonomy for foreknowledge is proposed, including foreknowledge for timing, stimulus, set, response, and task. Work on differentiating these effects in neurophysiology, neuroimaging, and neuropsychology is still in the early stages.
The amygdala detects aversive events and coordinates with rostral anterior cingulate cortex to ad... more The amygdala detects aversive events and coordinates with rostral anterior cingulate cortex to adapt behavior. We assessed error-related activation in these regions and its relation to task performance using functional MRI and a saccadic paradigm. Both amygdalae showed increased activation during error versus correct antisaccade trials that was correlated with error-related activation in the corresponding rostral anterior cingulate cortex. Together, activation in right amygdala and right rostral anterior cingulate cortex predicted greater accuracy. In contrast, left amygdala activation predicted a higher error rate. These findings support a role for amygdala in response monitoring. Consistent with proposed specializations of right and left amygdala in aversive conditioning, we hypothesize that right amygdala-rostral anterior cingulate cortex interactions mediate learning to avoid errors, while left error-related amygdala activation underpins detrimental negative affect.
Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder ... more Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective: To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design: Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting: Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients: Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions: Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures: Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results: Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions: The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient.
Objective: Schizophrenia patients consistently show impairments on tasks requiring inhibition suc... more Objective: Schizophrenia patients consistently show impairments on tasks requiring inhibition such as the antisaccade task. Deficits in performance monitoring including the detection of errors and subsequent adjustments to performance may contribute to such impairments. We examined whether immediate error-related performance adjustments during the antisaccade task were intact in schizophrenia. Method: We compared 21 schizophrenia patients and 14 healthy control subjects on the following measures: 1) error-related, trial-by-trial adjustments in reaction time (pre-error speeding, faster errors and post-error slowing); 2) the speed-accuracy tradeoff (SATO) function; and 3) the frequency and type of error self-correction. Results: Although antisaccade performance in schizophrenia was characterized by increased errors and latency of correct responses, measures of immediate error-related performance adjustments were intact. Conclusion: Schizophrenia is characterized by intact immediate error-related performance adjustments, even in the context of impaired antisaccade performance. It is possible that deficiencies in other aspects of error processing, indexed by electrophysiological and hemodynamic markers, contribute to antisaccade and other cognitive deficits in schizophrenia.
Academics, activists, and regulators are increasingly urging companies to develop and deploy soci... more Academics, activists, and regulators are increasingly urging companies to develop and deploy sociotechnical systems that are fair and unbiased. Achieving this goal, however, is complex: the developer must (1) deeply engage with social and legal facets of "fairness" in a given context, (2) develop software that concretizes these values, and (3) undergo an independent algorithm audit to ensure technical correctness and social accountability of their algorithms. To date, there are few examples of companies that have transparently undertaken all three steps. In this paper we outline a framework for algorithmic auditing by way of a case-study of pymetrics, a startup that uses machine learning to recommend job candidates to their clients. We discuss how pymetrics approaches the question of fairness given the constraints of ethical, regulatory, and client demands, and how pymetrics' software implements adverse impact testing. We also present the results of an independent audit of pymetrics' candidate screening tool. We conclude with recommendations on how to structure audits to be practical, independent, and constructive, so that companies have better incentive to participate in third party audits, and that watchdog groups can be better prepared to investigate companies. CCS CONCEPTS • Social and professional topics → Gender; Race and ethnicity; Employment issues; Codes of ethics.
This article was published in an Elsevier journal. The attached copy is furnished to the author f... more This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and education use, including for instruction at the author's institution, sharing with colleagues and providing to institution administration. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
To perform a saccadic response to a visual stimulus, a 'sensorimotor transformation' is required ... more To perform a saccadic response to a visual stimulus, a 'sensorimotor transformation' is required (i.e., transforming stimulus location into a motor command). Where in the brain is this accomplished? While previous monkey neurophysiology and human fMRI studies examined either parietal cortex or frontal eye field, we studied both of these regions simultaneously using magnetoencephalography (MEG). Nineteen healthy participants performed a pseudorandom series of prosaccades and antisaccades during MEG. Antisaccades require a saccade in the direction opposite a suddenly appearing stimulus. We exploited this dissociation between stimulus and saccadic direction to identify cortical regions that show early activity for a contralateral stimulus and late activity for a contralateral saccade. We found that in the left hemisphere both the intraparietal sulcus and the frontal eye field showed a pattern of activity consistent with sensorimotor transformation-a transition from activity reflecting the direction of the stimulus to that representing the saccadic goal. These findings suggest that sensorimotor transformation is the product of coordinated activity across the intraparietal sulcus and frontal eye field, key components of a cortical network for saccadic generation.
Supplementary material used in the analysis of data for submitted paper.Context: Current behavior... more Supplementary material used in the analysis of data for submitted paper.Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). This is the first study to examine neuroimaging-based treatment prediction in SAD. Objective: To measure brain activation in patients affected by SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design: Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting: Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at MIT. Patients: Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of social anxiety disorder. Interventions: Brain responses to angry versus neutral faces or emotional versus neutral scenes were examined with fMRI prior to initiation of CBT. Main outcome measures: Whole-brain regression analyses with differential fMRI responses for angry versus neutral faces and changes on the Liebowitz Social Anxiety Scale as the treatment outcome measure. Results: Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than forty percent of the variance in treatment response, and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusion: The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions, and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient. Clinical trial registration at www.clinicaltrials.gov (Identifier: NCT00515879): http://clinicaltrials.gov/ct2/show/NCT00515879?term=Hofmann&rank=1Oliver Doehrmann is supported by a postdoctoral fellowship by the Deutsche Forschungsgemeinschaft (DO-1469/1-1). Neuroimaging was supported by the Poitras Center for Affective Disorders Research. The authors gratefully acknowledge the Athinoula A. Martinos Imaging Center at McGovern Institute for Brain Research for providing an excellent neuroimaging environment. Dr. Hofmann is a paid consultant by Merck/Schering-Plough and supported by NIMH grant MH078308. Dr. Pollack also supported by NIMH grant MH078308. He additionally is a member of the advisory boards of or a consultant for Brain Cells, Eli Lilly, Johnson and Johnson, Medavante, Labopharm, Mindsite, Otsuka, Targia Pharmaceuticals, Pfizer. He has received research grants from Bristol Myers Squibb, Euthymics, Forest Laboratories, GlaxoSmithKline, Eli Lilly, NCCAM, NIDA, NIMH. CME supported activities of Dr. Pollack were sponsored by Astra-Zeneca, Sepracor, Pfizer. He holds equity in Medavante, Mensante Corporation, Mindsite, Targia Pharmaceuticals and receives royalties for SIGH-A, SAFER interviews
S.25. Biological predictors of psychotherapy outcome genetic information (a) as predictors of tre... more S.25. Biological predictors of psychotherapy outcome genetic information (a) as predictors of treatment response and (b) as mechanisms of change. Method: DNA was collected from~1800 children with anxiety disorders undergoing CBT. First, we attempted to replicate our previous association between the serotonin transporter promoter polymorphism (5HTTLPR) and outcome. Second, we examined change in methylation at the 5HTTLPR during treatment. Third we undertook a genome-wide association analysis of treatment response. Outcome was measured using structured diagnostic interview post-treatment and was considered both as (a) remission from primary anxiety disorder and (b) change in severity from pre-treatment. Results: First, we observed modest evidence for greater rates of remission and reduction in severity in S carriers than other genotypes (p < 0.05). Second, we found that children who responded well showed significantly greater (p < 0.002) increases in methylation during this period. Third, our genome-wide analyses revealed several markers that reached nominal significance (p < 10 −6). Genome-wide complex trait analyses (GCTA) indicate that approximately 30% of variance in change in severity scores from pre-to post-treatment was accounted for by the SNPs on the array. Conclusion: Genetic factors will become useful predictors of treatment response. Next steps include identifying variants associated with differential treatment response and elucidating the mechanisms of change including biomarkers such as DNA methylation.
Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Respons... more Autism spectrum disorders (ASD) are characterized by inflexible and repetitive behaviour. Response monitoring involves evaluating the consequences of behaviour and making adjustments to optimize outcomes. Deficiencies in this function, and abnormalities in the anterior cingulate cortex (ACC) on which it relies, have been reported as contributing factors to autistic disorders. We investigated whether ACC structure and function during response monitoring were associated with repetitive behaviour in ASD. We compared ACC activation to correct and erroneous antisaccades using rapid presentation event-related functional MRI in 14 control and ten ASD participants. Because response monitoring is the product of coordinated activity in ACC networks, we also examined the microstructural integrity of the white matter (WM) underlying this brain region using diffusion tensor imaging (DTI) measures of fractional anisotropy (FA) in 12 control and 12 adult ASD participants. ACC activation and FA were examined in relation to Autism Diagnostic Interview-Revised ratings of restricted and repetitive behaviour. Relative to controls, ASD participants: (i) made more antisaccade errors and responded more quickly on correct trials; (ii) showed reduced discrimination between error and correct responses in rostral ACC (rACC), which was primarily due to (iii) abnormally increased activation on correct trials and (iv) showed reduced FA in WM underlying ACC. Finally, in ASD (v) increased activation on correct trials and reduced FA in rACC WM were related to higher ratings of repetitive behaviour. These findings demonstrate functional and structural abnormalities of the ACC in ASD that may contribute to repetitive behaviour. rACC activity following errors is thought to reflect affective appraisal of the error. Thus, the hyperactive rACC response to correct trials can be interpreted as a misleading affective signal that something is awry, which may trigger repetitive attempts at correction. Another possible consequence of reduced affective discrimination between error and correct responses is that it might interfere with the reinforcement of responses that optimize outcomes. Furthermore, dysconnection of the ACC, as suggested by reduced FA, to regions involved in behavioural control might impair on-line modulations of response speed to optimize performance (i.e. speed-accuracy trade-off) and increase error likelihood. These findings suggest that in ASD, structural and functional abnormalities of the ACC compromise response monitoring and thereby contribute to behaviour that is rigid and repetitive rather than flexible and responsive to contingencies. Illuminating the mechanisms and clinical significance of abnormal response monitoring in ASD represents a fruitful avenue for further research.
Background-Longitudinal studies of illness progression in Major Depressive Disorder (MDD) indicat... more Background-Longitudinal studies of illness progression in Major Depressive Disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in MDD-especially in medial prefrontal cortex (mPFC) and the hippocampus-but few studies have investigated whether these changes are exacerbated by prior episodes.
Commentators interested in the societal implications of automated decision-making often overlook ... more Commentators interested in the societal implications of automated decision-making often overlook how decisions are made in the technology's absence. For example, the benefits of ML and big data are often summarized as efficiency, objectivity, and consistency; the risks, meanwhile, include replicating historical discrimination and oversimplifying nuanced situations. While this perspective tracks when technology replaces capricious human judgements, it is ill-suited to contexts where standardized assessments already exist. In spaces like employment selection, the relevant question is how an ML model compares to a manually built test. In this paper, we explain that since the Civil Rights Act, industrial and organizational (I/O) psychologists have struggled to produce assessments without disparate impact. By examining the utility of ML for conducting exploratory analyses, coupled with the back-testing capability offered by advances in data science, we explain modern technology's utility for hiring. We then empirically investigate a commercial hiring platform that applies several oft-cited benefits of ML to build custom job models for corporate employers. We focus on the disparate impact observed when models are deployed to evaluate real-world job candidates. Across a sample of 60 jobs built for 26 employers and used to evaluate approximately 400,00 candidates, minority-weighted impact ratios of 0.93 (Black-White), 0.97 (Hispanic-White), and 0.98 (Female-Male) are observed. We find similar results for candidates selecting disability-related accommodations within the platform versus unaccommodated users. We conclude by describing limitations, anticipating criticisms, and outlining further research.
Saccadic latencies are influenced by what occurred during the previous trial. When the previous t... more Saccadic latencies are influenced by what occurred during the previous trial. When the previous trial is an antisaccade, the latencies of both prosaccades and antisaccades are prolonged. The aim of this study was to identify neural correlates of this intertrial effect of antisaccades. Specifically, based on both monkey electrophysiology and human neuroimaging findings, we expected trials preceded by antisaccades to be associated with reduced frontal eye field (FEF) activity relative to those preceded by prosaccades. Twenty-one healthy participants performed pseudorandom sequences of prosaccade and antisaccade trials during functional magnetic resonance imaging (fMRI) with concurrent monitoring of eye position. We compared activity in trials preceded by an antisaccade with activity in trials preceded by a prosaccade. The primary result was that a previous antisaccade prolonged saccadic latency and reduced fMRI activity in the FEF and other regions. No regions showed increased activity. We interpret the reduced FEF activity and slower saccadic responses to reflect inhibitory influences on the response system as a consequence of performing an antisaccade in the previous trial. This demonstrates that neural activity is modulated by trial history, consistent with a rapid, dynamic form of learning. More generally, these results highlight the importance of trial history as a source of variability in both behavioral and neuroimaging studies.
The assumption that the deployment of executive processes invariably improves task performance is... more The assumption that the deployment of executive processes invariably improves task performance is implicit to cognitive theory. In particular, working memory can be used to retain and update historical information about predictable trial sequences (foreknowledge) so that subjects can anticipate and prepare for the upcoming trial more effectively. We review the effects of different types of foreknowledge on response accuracy and latency, particularly in relation to experiments investigating saccadic eye movements in humans. While it is possible to make all aspects of an impending trial predictable, varying the predictability of different components of the trial independently can reveal which cognitive operations are potentially modifiable by foreknowledge. These operations include stimulus processing, retrieval of task-set rules, and response preparation, among others. The available data suggest that, while response preparation can be completed and the response even executed before the stimulus appears (i.e. anticipation) when the subject possesses complete taskforeknowledge (knowing both the stimulus to appear and the response required), foreknowledge of the task-set alone does not permit advance configuration of the task-set rules. A taxonomy for foreknowledge is proposed, including foreknowledge for timing, stimulus, set, response, and task. Work on differentiating these effects in neurophysiology, neuroimaging, and neuropsychology is still in the early stages.
The amygdala detects aversive events and coordinates with rostral anterior cingulate cortex to ad... more The amygdala detects aversive events and coordinates with rostral anterior cingulate cortex to adapt behavior. We assessed error-related activation in these regions and its relation to task performance using functional MRI and a saccadic paradigm. Both amygdalae showed increased activation during error versus correct antisaccade trials that was correlated with error-related activation in the corresponding rostral anterior cingulate cortex. Together, activation in right amygdala and right rostral anterior cingulate cortex predicted greater accuracy. In contrast, left amygdala activation predicted a higher error rate. These findings support a role for amygdala in response monitoring. Consistent with proposed specializations of right and left amygdala in aversive conditioning, we hypothesize that right amygdala-rostral anterior cingulate cortex interactions mediate learning to avoid errors, while left error-related amygdala activation underpins detrimental negative affect.
Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder ... more Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective: To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design: Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting: Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients: Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions: Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures: Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results: Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions: The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient.
Objective: Schizophrenia patients consistently show impairments on tasks requiring inhibition suc... more Objective: Schizophrenia patients consistently show impairments on tasks requiring inhibition such as the antisaccade task. Deficits in performance monitoring including the detection of errors and subsequent adjustments to performance may contribute to such impairments. We examined whether immediate error-related performance adjustments during the antisaccade task were intact in schizophrenia. Method: We compared 21 schizophrenia patients and 14 healthy control subjects on the following measures: 1) error-related, trial-by-trial adjustments in reaction time (pre-error speeding, faster errors and post-error slowing); 2) the speed-accuracy tradeoff (SATO) function; and 3) the frequency and type of error self-correction. Results: Although antisaccade performance in schizophrenia was characterized by increased errors and latency of correct responses, measures of immediate error-related performance adjustments were intact. Conclusion: Schizophrenia is characterized by intact immediate error-related performance adjustments, even in the context of impaired antisaccade performance. It is possible that deficiencies in other aspects of error processing, indexed by electrophysiological and hemodynamic markers, contribute to antisaccade and other cognitive deficits in schizophrenia.
Academics, activists, and regulators are increasingly urging companies to develop and deploy soci... more Academics, activists, and regulators are increasingly urging companies to develop and deploy sociotechnical systems that are fair and unbiased. Achieving this goal, however, is complex: the developer must (1) deeply engage with social and legal facets of "fairness" in a given context, (2) develop software that concretizes these values, and (3) undergo an independent algorithm audit to ensure technical correctness and social accountability of their algorithms. To date, there are few examples of companies that have transparently undertaken all three steps. In this paper we outline a framework for algorithmic auditing by way of a case-study of pymetrics, a startup that uses machine learning to recommend job candidates to their clients. We discuss how pymetrics approaches the question of fairness given the constraints of ethical, regulatory, and client demands, and how pymetrics' software implements adverse impact testing. We also present the results of an independent audit of pymetrics' candidate screening tool. We conclude with recommendations on how to structure audits to be practical, independent, and constructive, so that companies have better incentive to participate in third party audits, and that watchdog groups can be better prepared to investigate companies. CCS CONCEPTS • Social and professional topics → Gender; Race and ethnicity; Employment issues; Codes of ethics.
This article was published in an Elsevier journal. The attached copy is furnished to the author f... more This article was published in an Elsevier journal. The attached copy is furnished to the author for non-commercial research and education use, including for instruction at the author's institution, sharing with colleagues and providing to institution administration. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
To perform a saccadic response to a visual stimulus, a 'sensorimotor transformation' is required ... more To perform a saccadic response to a visual stimulus, a 'sensorimotor transformation' is required (i.e., transforming stimulus location into a motor command). Where in the brain is this accomplished? While previous monkey neurophysiology and human fMRI studies examined either parietal cortex or frontal eye field, we studied both of these regions simultaneously using magnetoencephalography (MEG). Nineteen healthy participants performed a pseudorandom series of prosaccades and antisaccades during MEG. Antisaccades require a saccade in the direction opposite a suddenly appearing stimulus. We exploited this dissociation between stimulus and saccadic direction to identify cortical regions that show early activity for a contralateral stimulus and late activity for a contralateral saccade. We found that in the left hemisphere both the intraparietal sulcus and the frontal eye field showed a pattern of activity consistent with sensorimotor transformation-a transition from activity reflecting the direction of the stimulus to that representing the saccadic goal. These findings suggest that sensorimotor transformation is the product of coordinated activity across the intraparietal sulcus and frontal eye field, key components of a cortical network for saccadic generation.
Supplementary material used in the analysis of data for submitted paper.Context: Current behavior... more Supplementary material used in the analysis of data for submitted paper.Context: Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). This is the first study to examine neuroimaging-based treatment prediction in SAD. Objective: To measure brain activation in patients affected by SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design: Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting: Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at MIT. Patients: Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of social anxiety disorder. Interventions: Brain responses to angry versus neutral faces or emotional versus neutral scenes were examined with fMRI prior to initiation of CBT. Main outcome measures: Whole-brain regression analyses with differential fMRI responses for angry versus neutral faces and changes on the Liebowitz Social Anxiety Scale as the treatment outcome measure. Results: Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than forty percent of the variance in treatment response, and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusion: The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions, and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient. Clinical trial registration at www.clinicaltrials.gov (Identifier: NCT00515879): http://clinicaltrials.gov/ct2/show/NCT00515879?term=Hofmann&rank=1Oliver Doehrmann is supported by a postdoctoral fellowship by the Deutsche Forschungsgemeinschaft (DO-1469/1-1). Neuroimaging was supported by the Poitras Center for Affective Disorders Research. The authors gratefully acknowledge the Athinoula A. Martinos Imaging Center at McGovern Institute for Brain Research for providing an excellent neuroimaging environment. Dr. Hofmann is a paid consultant by Merck/Schering-Plough and supported by NIMH grant MH078308. Dr. Pollack also supported by NIMH grant MH078308. He additionally is a member of the advisory boards of or a consultant for Brain Cells, Eli Lilly, Johnson and Johnson, Medavante, Labopharm, Mindsite, Otsuka, Targia Pharmaceuticals, Pfizer. He has received research grants from Bristol Myers Squibb, Euthymics, Forest Laboratories, GlaxoSmithKline, Eli Lilly, NCCAM, NIDA, NIMH. CME supported activities of Dr. Pollack were sponsored by Astra-Zeneca, Sepracor, Pfizer. He holds equity in Medavante, Mensante Corporation, Mindsite, Targia Pharmaceuticals and receives royalties for SIGH-A, SAFER interviews
S.25. Biological predictors of psychotherapy outcome genetic information (a) as predictors of tre... more S.25. Biological predictors of psychotherapy outcome genetic information (a) as predictors of treatment response and (b) as mechanisms of change. Method: DNA was collected from~1800 children with anxiety disorders undergoing CBT. First, we attempted to replicate our previous association between the serotonin transporter promoter polymorphism (5HTTLPR) and outcome. Second, we examined change in methylation at the 5HTTLPR during treatment. Third we undertook a genome-wide association analysis of treatment response. Outcome was measured using structured diagnostic interview post-treatment and was considered both as (a) remission from primary anxiety disorder and (b) change in severity from pre-treatment. Results: First, we observed modest evidence for greater rates of remission and reduction in severity in S carriers than other genotypes (p < 0.05). Second, we found that children who responded well showed significantly greater (p < 0.002) increases in methylation during this period. Third, our genome-wide analyses revealed several markers that reached nominal significance (p < 10 −6). Genome-wide complex trait analyses (GCTA) indicate that approximately 30% of variance in change in severity scores from pre-to post-treatment was accounted for by the SNPs on the array. Conclusion: Genetic factors will become useful predictors of treatment response. Next steps include identifying variants associated with differential treatment response and elucidating the mechanisms of change including biomarkers such as DNA methylation.
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