In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be... more In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
Reduced enjoyment of pleasant experiences and increased impact of negative emotions are observed ... more Reduced enjoyment of pleasant experiences and increased impact of negative emotions are observed clinically in depression and in borderline personality disorder (BPD). 1 Surprisingly, previous laboratory studies do not support a link between depression and reduced pleasantness ratings to biological rewards, such as sucrose solutions (for example see Swiecicki et al 2). However, patients with depression could be more sensitive to negative primary inputs. 3 Few studies have used aversive stimuli in the evaluation of taste in depression, and no studies have been carried out to evaluate hedonic ratings of tastes in BPD in spite of clinically observable aberrant emotional processing and increased state and trait disgust. 4 We hypothesised that patients with BPD and depression would differ from healthy controls in their pleasantness and disgust ratings to positive and especially negative taste stimuli. Method A total of 29 women with DSM-IV 5 major depressive disorder, 17 women with DSM-IV BPD and 27 female healthy controls took part in the study, which was approved by the Cambridgeshire 4 National Health Service research ethics committee; all participants provided written informed consent. Additional details, including statistical data, are provided in the online supplement. Evaluation of taste consisted of participants taking a sip, but not swallowing, from a cup with 10 ml of orange juice, quinine dihydrochloride at 0.006 mol/L or water. Participants had to maintain the liquid in the mouth for 5 s, rate the disgust and pleasantness produced using two visual scales (online Fig. DS1) and rinse their mouths with water. Order of liquids was counterbalanced across participants. Clinical evaluation was completed prior to the taste experiment. Statistical analysis (see online supplement for details) aimed to evaluate the association between taste disgust and disgust as measured using two clinical rating scales: the Self-Disgust Scale (SDS) 6 and the Disgust Scale Revised (DSR). 7 Results Overall differences between the three conditions in pleasantness and disgust ratings followed predictions across all participants. Quinine was highly unpleasant and disgusting, juice was highly pleasant and not disgusting and water was neither pleasant nor disgusting. Pleasantness and disgust ratings correlations were all significant. Regarding differences between groups, the BPD group rated both quinine and juice (but not water) as more unpleasant and disgusting than the control group, but no differences were found between the depression and control groups (all P50.05; see online Tables DS8 and DS9, and Fig. 1). Increased self-disgust was significantly correlated (Spearman's r = 0.5) with greater disgust ratings after the intake of orange juice in the BPD group (Table DS10). However, disgust propensity did not correlate with ratings in this group and all correlations were non-significant in the depression group. Discussion We found that in the BPD group there were abnormal pleasantness and disgust ratings after the intake of biological stimuli, whereas no differences between the depression and control groups were found. Our findings indicate that the hedonic experience of both positive and negative taste stimuli is negatively biased in BPD. This novel result is in line with clinical findings in the disorder, as people with BPD report more dysphoric and less positive affective cognitive states. 1 Current diagnostic criteria for the disorder include affective instability, recurrent self-threatening behaviours and chronic feelings of emptiness, all of which could be related to negative perceptions of the environment. The lack of evidence for a differential effect in the case of depression is also in line with most of the existing literature on enjoyment of pleasant tastes; 2 however, our study also shows that there were no differences between the depression group and the control group in evaluation of a disgusting taste. A limitation of our study and the prior depression studies is that sample sizes were small; hence, either there is no true difference in the ratings for chemosensory stimuli between people with depression and controls or the effect is small, suggesting that the basis of anhedonia reported in depression is complex. For example, it could be that clinically observed anhedonia in depression is primarily related to social anhedonia. Alternatively, clinical assessments of anhedonia may confound motivational, anticipatory and mnemonic aspects of enjoyment with consummatory 'in the moment' pleasure; the latter is assayed by our laboratory taste task and may be comparatively intact in depression. 8 In the BPD group, questionnaire-measured self-disgust, but not disgust propensity, correlated with laboratory-rated disgust Summary Depression and borderline personality disorder (BPD) are both thought to be accompanied by alterations in the subjective experience of environmental rewards. We evaluated responses in women to sweet, bitter and neutral tastes (juice, quinine and water): 29 with depression, 17 with BPD and 27 healthy controls. The BPD group gave lower pleasantness and higher disgust ratings for quinine and juice compared with the control group; the depression group did not differ significantly from the control group. Juice disgust ratings were related to self-disgust in BPD, suggesting close links between abnormal sensory processing and self-identity in BPD.
Decision making can be regarded as the outcome of cognitive processes leading to the selection of... more Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm.
A B S T R A C T A systematic review with meta-analyses was performed to: 1) quantify the associat... more A B S T R A C T A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents (" risk analysis "); 2) assess the effect of ADHD medications on this risk (" medication analysis "). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI = 1.40,1.67) and 1.39 (95% CI = 1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a " difference in differences " methodology)]. The pooled effect size was 0.879 (95% CI = 0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies.
Alterations in reward processes may underlie motivational and anhedonic symptoms in depression an... more Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.
Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poo... more Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms , along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiolog-ical mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.
Psychiatry and Neurosciences. Update Vol II. Springer International Publishing Switzerland., 2017
In psychiatry, as in any other medical specialty, the clinician collects information from the pat... more In psychiatry, as in any other medical specialty, the clinician collects information from the patient’s anamnesis, clinical observation and diagnostic tests, evaluates these data and makes a diagnosis. The most common manuals to assess a patient’s mental disease according to his or her symptoms are the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD). This chapter focuses on the dialogue that philosophy and psychiatry have held for decades to achieve a better understanding of dissociative identity disorder (DID). The outcome of this dialogue is the expression of the diagnostic criteria for DID, as well as other dissociative disorders, in the medical manuals. Thus, we first analyze the evolution of DID across the different versions of ICD and DSM. We then show that the characterization of DID and other dissociative disorders is a lively debate far from being settled. We demonstrate that the core of this debate is the understanding of person after John Locke’s philosophy: a person is defined by the apparent expression of consciousness and memories. This leads to what we have termed a primary conceptual dissociation: the mental qualities of the person are dissociated from the body. We propose an alternative account based on the dynamic nature of identity, and the understanding of person as a mind-body unity. We hope that our proposal, which comes up from the interdisciplinary dialogue between psychiatry and philosophy, contributes to a better understanding of this disorder and its underlying concepts.
In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be... more In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
In psychiatry, as in any other medical specialty, the clinician collects information from the pat... more In psychiatry, as in any other medical specialty, the clinician collects information from the patient’s anamnesis, clinical observation and diagnostic tests, evaluates these data and makes a diagnosis. The most common manuals to assess a patient’s mental disease according to his or her symptoms are the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD). This chapter aims to explain the dialogue that philosophy and psychiatry have held for decades to achieve a better understanding of dissociative identity disorder (DID). The outcome of this dialogue is the expression of the diagnostic criteria for DID, as well as other dissociative disorders, in the medical manuals. Thus, we first analyze the evolution of DID across the different versions of ICD and DSM. We then show that the characterization of DID and other dissociative disorders is a lively debate far from being settled. We demonstrate that the core of this debate is the understanding of person after John Locke’s philosophy: a person is defined by the apparent expression of consciousness and memories. This leads to what we have termed a primary conceptual dissociation: the mental qualities of the person are dissociated from the body. We propose an alternative account based on the dynamic nature of identity, and the understanding of person as a mind-body unity. We hope that our contribution, which comes up from the interdisciplinary dialogue between psychiatry and philosophy, contributes to a better understanding of this disorder and its underlying concepts.
Abstract
Introduction: Imaging studies help to understand the evolution of key cognitive processe... more Abstract Introduction: Imaging studies help to understand the evolution of key cognitive processes related to ageing, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to working memory processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition. Methods: We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects. Results: During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parieto network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas. Conclusions: Successful WM processes in the elderly population are accompanied by an activation pattern joint between cerebellar regions and the fronto-parietal network. 16th National Congress of the Spanish Society of Neuroscience 2015, Granada, Spain; 09/2015
In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be... more In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
Reduced enjoyment of pleasant experiences and increased impact of negative emotions are observed ... more Reduced enjoyment of pleasant experiences and increased impact of negative emotions are observed clinically in depression and in borderline personality disorder (BPD). 1 Surprisingly, previous laboratory studies do not support a link between depression and reduced pleasantness ratings to biological rewards, such as sucrose solutions (for example see Swiecicki et al 2). However, patients with depression could be more sensitive to negative primary inputs. 3 Few studies have used aversive stimuli in the evaluation of taste in depression, and no studies have been carried out to evaluate hedonic ratings of tastes in BPD in spite of clinically observable aberrant emotional processing and increased state and trait disgust. 4 We hypothesised that patients with BPD and depression would differ from healthy controls in their pleasantness and disgust ratings to positive and especially negative taste stimuli. Method A total of 29 women with DSM-IV 5 major depressive disorder, 17 women with DSM-IV BPD and 27 female healthy controls took part in the study, which was approved by the Cambridgeshire 4 National Health Service research ethics committee; all participants provided written informed consent. Additional details, including statistical data, are provided in the online supplement. Evaluation of taste consisted of participants taking a sip, but not swallowing, from a cup with 10 ml of orange juice, quinine dihydrochloride at 0.006 mol/L or water. Participants had to maintain the liquid in the mouth for 5 s, rate the disgust and pleasantness produced using two visual scales (online Fig. DS1) and rinse their mouths with water. Order of liquids was counterbalanced across participants. Clinical evaluation was completed prior to the taste experiment. Statistical analysis (see online supplement for details) aimed to evaluate the association between taste disgust and disgust as measured using two clinical rating scales: the Self-Disgust Scale (SDS) 6 and the Disgust Scale Revised (DSR). 7 Results Overall differences between the three conditions in pleasantness and disgust ratings followed predictions across all participants. Quinine was highly unpleasant and disgusting, juice was highly pleasant and not disgusting and water was neither pleasant nor disgusting. Pleasantness and disgust ratings correlations were all significant. Regarding differences between groups, the BPD group rated both quinine and juice (but not water) as more unpleasant and disgusting than the control group, but no differences were found between the depression and control groups (all P50.05; see online Tables DS8 and DS9, and Fig. 1). Increased self-disgust was significantly correlated (Spearman's r = 0.5) with greater disgust ratings after the intake of orange juice in the BPD group (Table DS10). However, disgust propensity did not correlate with ratings in this group and all correlations were non-significant in the depression group. Discussion We found that in the BPD group there were abnormal pleasantness and disgust ratings after the intake of biological stimuli, whereas no differences between the depression and control groups were found. Our findings indicate that the hedonic experience of both positive and negative taste stimuli is negatively biased in BPD. This novel result is in line with clinical findings in the disorder, as people with BPD report more dysphoric and less positive affective cognitive states. 1 Current diagnostic criteria for the disorder include affective instability, recurrent self-threatening behaviours and chronic feelings of emptiness, all of which could be related to negative perceptions of the environment. The lack of evidence for a differential effect in the case of depression is also in line with most of the existing literature on enjoyment of pleasant tastes; 2 however, our study also shows that there were no differences between the depression group and the control group in evaluation of a disgusting taste. A limitation of our study and the prior depression studies is that sample sizes were small; hence, either there is no true difference in the ratings for chemosensory stimuli between people with depression and controls or the effect is small, suggesting that the basis of anhedonia reported in depression is complex. For example, it could be that clinically observed anhedonia in depression is primarily related to social anhedonia. Alternatively, clinical assessments of anhedonia may confound motivational, anticipatory and mnemonic aspects of enjoyment with consummatory 'in the moment' pleasure; the latter is assayed by our laboratory taste task and may be comparatively intact in depression. 8 In the BPD group, questionnaire-measured self-disgust, but not disgust propensity, correlated with laboratory-rated disgust Summary Depression and borderline personality disorder (BPD) are both thought to be accompanied by alterations in the subjective experience of environmental rewards. We evaluated responses in women to sweet, bitter and neutral tastes (juice, quinine and water): 29 with depression, 17 with BPD and 27 healthy controls. The BPD group gave lower pleasantness and higher disgust ratings for quinine and juice compared with the control group; the depression group did not differ significantly from the control group. Juice disgust ratings were related to self-disgust in BPD, suggesting close links between abnormal sensory processing and self-identity in BPD.
Decision making can be regarded as the outcome of cognitive processes leading to the selection of... more Decision making can be regarded as the outcome of cognitive processes leading to the selection of a course of action among several alternatives. Borrowing a central measurement from information theory, Shannon entropy, we quantified the uncertainties produced by decisions of participants within an economic decision task under different configurations of reward probability and time. These descriptors were used to obtain blood oxygen level-dependent (BOLD) signal correlates of uncertainty and two clusters codifying the Shannon entropy of task configurations were identified: a large cluster including parts of the right middle cingulate cortex (MCC) and left and right pre-supplementary motor areas (pre-SMA) and a small cluster at the left anterior thalamus. Subsequent functional connectivity analyses using the psycho-physiological interactions model identified areas involved in the functional integration of uncertainty. Results indicate that clusters mostly located at frontal and temporal cortices experienced an increased connectivity with the right MCC and left and right pre-SMA as the uncertainty was higher. Furthermore, pre-SMA was also functionally connected to a rich set of areas, most of them associative areas located at occipital and parietal lobes. This study provides a map of the human brain segregation and integration (i.e., neural substrate and functional connectivity respectively) of the uncertainty associated to an economic decision making paradigm.
A B S T R A C T A systematic review with meta-analyses was performed to: 1) quantify the associat... more A B S T R A C T A systematic review with meta-analyses was performed to: 1) quantify the association between ADHD and risk of unintentional physical injuries in children/adolescents (" risk analysis "); 2) assess the effect of ADHD medications on this risk (" medication analysis "). We searched 114 databases through June 2017. For the risk analysis, studies reporting sex-controlled odds ratios (ORs) or hazard ratios (HRs) estimating the association between ADHD and injuries were combined. Pooled ORs (28 studies, 4,055,620 individuals without and 350,938 with ADHD) and HRs (4 studies, 901,891 individuals without and 20,363 with ADHD) were 1.53 (95% CI = 1.40,1.67) and 1.39 (95% CI = 1.06,1.83), respectively. For the medication analysis, we meta-analysed studies that avoided the confounding-by-indication bias [four studies with a self-controlled methodology and another comparing risk over time and groups (a " difference in differences " methodology)]. The pooled effect size was 0.879 (95% CI = 0.838,0.922) (13,254 individuals with ADHD). ADHD is significantly associated with an increased risk of unintentional injuries and ADHD medications have a protective effect, at least in the short term, as indicated by self-controlled studies.
Alterations in reward processes may underlie motivational and anhedonic symptoms in depression an... more Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.
Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poo... more Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia. This theory has received empirical support in the study of schizophrenia spectrum disorders and preclinical models of psychosis, but has not been tested in the psychosis associated with PD. We, therefore, investigated brain responses associated with reward expectation and prediction error signaling during reinforcement learning in PD-associated psychosis. An instrumental learning task with monetary gains and losses was conducted during an fMRI study in PD patients with (n = 12), or without (n = 17), a history of psychotic symptoms , along with a sample of healthy controls (n = 24). We conducted region of interest analyses in the ventral striatum (VS), ventromedial prefrontal and posterior cingulate cortices, and whole-brain analyses. There was reduced activation in PD patients with a history of psychosis, compared to those without, in the posterior cingulate cortex and the VS during reward anticipation (p < 0.05 small volume corrected). The results suggest that cortical and striatal abnormalities in reward processing, a putative pathophysiolog-ical mechanism of psychosis in schizophrenia, may also contribute to the pathogenesis of psychotic symptoms in PD. The finding of posterior cingulate dysfunction is in keeping with prior results highlighting cortical dysfunction in the pathogenesis of PD psychosis.
Psychiatry and Neurosciences. Update Vol II. Springer International Publishing Switzerland., 2017
In psychiatry, as in any other medical specialty, the clinician collects information from the pat... more In psychiatry, as in any other medical specialty, the clinician collects information from the patient’s anamnesis, clinical observation and diagnostic tests, evaluates these data and makes a diagnosis. The most common manuals to assess a patient’s mental disease according to his or her symptoms are the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD). This chapter focuses on the dialogue that philosophy and psychiatry have held for decades to achieve a better understanding of dissociative identity disorder (DID). The outcome of this dialogue is the expression of the diagnostic criteria for DID, as well as other dissociative disorders, in the medical manuals. Thus, we first analyze the evolution of DID across the different versions of ICD and DSM. We then show that the characterization of DID and other dissociative disorders is a lively debate far from being settled. We demonstrate that the core of this debate is the understanding of person after John Locke’s philosophy: a person is defined by the apparent expression of consciousness and memories. This leads to what we have termed a primary conceptual dissociation: the mental qualities of the person are dissociated from the body. We propose an alternative account based on the dynamic nature of identity, and the understanding of person as a mind-body unity. We hope that our proposal, which comes up from the interdisciplinary dialogue between psychiatry and philosophy, contributes to a better understanding of this disorder and its underlying concepts.
In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be... more In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.
In psychiatry, as in any other medical specialty, the clinician collects information from the pat... more In psychiatry, as in any other medical specialty, the clinician collects information from the patient’s anamnesis, clinical observation and diagnostic tests, evaluates these data and makes a diagnosis. The most common manuals to assess a patient’s mental disease according to his or her symptoms are the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD). This chapter aims to explain the dialogue that philosophy and psychiatry have held for decades to achieve a better understanding of dissociative identity disorder (DID). The outcome of this dialogue is the expression of the diagnostic criteria for DID, as well as other dissociative disorders, in the medical manuals. Thus, we first analyze the evolution of DID across the different versions of ICD and DSM. We then show that the characterization of DID and other dissociative disorders is a lively debate far from being settled. We demonstrate that the core of this debate is the understanding of person after John Locke’s philosophy: a person is defined by the apparent expression of consciousness and memories. This leads to what we have termed a primary conceptual dissociation: the mental qualities of the person are dissociated from the body. We propose an alternative account based on the dynamic nature of identity, and the understanding of person as a mind-body unity. We hope that our contribution, which comes up from the interdisciplinary dialogue between psychiatry and philosophy, contributes to a better understanding of this disorder and its underlying concepts.
Abstract
Introduction: Imaging studies help to understand the evolution of key cognitive processe... more Abstract Introduction: Imaging studies help to understand the evolution of key cognitive processes related to ageing, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to working memory processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition. Methods: We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects. Results: During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parieto network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas. Conclusions: Successful WM processes in the elderly population are accompanied by an activation pattern joint between cerebellar regions and the fronto-parietal network. 16th National Congress of the Spanish Society of Neuroscience 2015, Granada, Spain; 09/2015
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Papers by Gonzalo Arrondo
Introduction: Imaging studies help to understand the evolution of key cognitive processes related to ageing, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to working memory processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition. Methods: We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects. Results: During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parieto network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas. Conclusions: Successful WM processes in the elderly population are accompanied by an activation pattern joint between cerebellar regions and the fronto-parietal network.
16th National Congress of the Spanish Society of Neuroscience 2015, Granada, Spain; 09/2015
Introduction: Imaging studies help to understand the evolution of key cognitive processes related to ageing, such as working memory (WM). This study aimed to test three hypotheses in older adults. First, that the brain activation pattern associated to working memory processes in elderly during successful low load tasks is located in posterior sensory and associative areas; second, that the prefrontal and parietal cortex and basal ganglia should be more active during high-demand tasks; third, that cerebellar activations are related to high-demand cognitive tasks and have a specific lateralization depending on the condition. Methods: We used a neuropsychological assessment with functional magnetic resonance imaging and a core N-back paradigm design that was maintained across the combination of four conditions of stimuli and two memory loads in a sample of twenty elderly subjects. Results: During low-loads, activations were located in the visual ventral network. In high loads, there was an involvement of the basal ganglia and cerebellum in addition to the frontal and parietal cortices. Moreover, we detected an executive control role of the cerebellum in a relatively symmetric fronto-parieto network. Nevertheless, this network showed a predominantly left lateralization in parietal regions associated presumably with an overuse of verbal storage strategies. The differential activations between conditions were stimuli-dependent and were located in sensory areas. Conclusions: Successful WM processes in the elderly population are accompanied by an activation pattern joint between cerebellar regions and the fronto-parietal network.
16th National Congress of the Spanish Society of Neuroscience 2015, Granada, Spain; 09/2015