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Childhood trauma is a vulnerability factor for the development of obsessive–compulsive disorder (OCD). Empirical findings suggest that trauma-related alterations in brain networks, especially in thalamus-related regions, have been observed in OCD patients. However, the relationship between childhood trauma and thalamic connectivity in patients with OCD remains unclear. The present study aimed to examine the impact of childhood trauma on thalamic functional connectivity in OCD patients.
Magnetic resonance imaging resting-state scans were acquired in 79 patients with OCD, including 22 patients with a high level of childhood trauma (OCD_HCT), 57 patients with a low level of childhood trauma (OCD_LCT) and 47 healthy controls. Seven thalamic subdivisions were chosen as regions of interest (ROIs) to examine the group difference in thalamic ROIs and whole-brain resting-state functional connectivity (rsFC).
We found significantly decreased caudate-thalamic rsFC in OCD patients as a whole group and also in OCD_LCT patients, compared with healthy controls. However, OCD_HCT patients exhibited increased thalamic rsFC with the prefrontal cortex when compared with both OCD_LCT patients and healthy controls.
Taken together, OCD patients with high and low levels of childhood trauma exhibit different pathological alterations in thalamic rsFC, suggesting that childhood trauma may be a predisposing factor for some OCD patients.
Uncertainty exists about what causes brain structure alterations associated with schizophrenia (SZ) and bipolar disorder (BD). Whether a history of asphyxia-related obstetric complication (ASP) – a common but harmful condition for neural tissue – contributes to variations in adult brain structure is unclear. We investigated ASP and its relationship to intracranial (ICV), global brain volumes and regional cortical and subcortical structures.
A total of 311 patients on the SZ – BD spectrum and 218 healthy control (HC) participants underwent structural magnetic resonance imaging. They were evaluated for ASP using prospective information obtained from the Medical Birth Registry of Norway.
In all groups, ASP was related to smaller ICV, total brain, white and gray matter volumes and total surface area, but not to cortical thickness. Smaller cortical surface areas were found across frontal, parietal, occipital, temporal and insular regions. Smaller hippocampal, amygdala, thalamus, caudate and putamen volumes were reported for all ASP subgroups. ASP effects did not survive ICV correction, except in the caudate, which remained significantly smaller in both patient ASP subgroups, but not in the HC.
Since ASP was associated with smaller brain volumes in all groups, the genetic risk of developing a severe mental illness, alone, cannot easily explain the smaller ICV. Only the smaller caudate volumes of ASP patients specifically suggest that injury from ASP can be related to disease development. Our findings give support for the ICV as a marker of aberrant neurodevelopment and ASP in the etiology of brain development in BD and SZ.
Bilingualism has been said to improve cognition and even delay the onset of Alzheimer's disease (AD). This research aimed to investigate whether bilingualism leaves a neurophysiological trace even when people are highly educated. We expected bilinguals to present better preserved brain functional networks, which could be a trace of higher cognitive reserve. With this purpose, we conducted a magnetoencephalographic study with a group of healthy older adults. We estimated functional connectivity using phase-locking value and found five clusters in parieto-occipital regions in which bilinguals exhibited greater functional connectivity than monolinguals. These clusters included brain regions typically implicated in language processing. Furthermore, these functional changes correlated with caudate volumes (a key region in language shifting and control) in the bilingual sample. Interestingly, decreased Functional Connectivity between posterior brain regions had already been identified as an indicator of aging/preclinical AD but, according to our study, bilingualism seems to exert the opposite effect.
Objectives: Apathy is a debilitating symptom of Huntington’s disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington’s disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. Methods: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. Results: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. Conclusions: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. (JINS, 2019, 25, 462–469)
Commonly observed distortions in decision-making among patients with major depressive disorder (MDD) may emerge from impaired reward processing and cognitive biases toward negative events. There is substantial theoretical support for the hypothesis that MDD patients overweight potential losses compared with gains, though the neurobiological underpinnings of this bias are uncertain.
Twenty-one unmedicated patients with MDD were compared with 25 healthy controls (HC) using functional magnetic resonance imaging (fMRI) together with an economic decision-making task over mixed lotteries involving probabilistic gains and losses. Region-of-interest analyses evaluated neural signatures of gain and loss coding within a core network of brain areas known to be involved in valuation (anterior insula, caudate nucleus, ventromedial prefrontal cortex).
Usable fMRI data were available for 19 MDD and 23 HC subjects. Anterior insula signal showed negative coding of losses (gain > loss) in HC subjects consistent with previous findings, whereas MDD subjects demonstrated significant reversals in these associations (loss > gain). Moreover, depression severity further enhanced the positive coding of losses in anterior insula, ventromedial prefrontal cortex, and caudate nucleus. The hyper-responsivity to losses displayed by the anterior insula of MDD patients was paralleled by a reduced influence of gain, but not loss, stake size on choice latencies.
Patients with MDD demonstrate a significant shift from negative to positive coding of losses in the anterior insula, revealing the importance of this structure in value-based decision-making in the context of emotional disturbances.
Objectives: Huntington’s disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis. Methods: The dataset includes 34 cognitive, motor, psychiatric, and functional variables and five subcortical brain volumes from 984 prodromal HD individuals enrolled in the PREDICT HD study. Using cluster analyses, seven distinct clusters encompassing cognitive, motor, psychiatric, and functional domains were identified. Individual cluster scores were then regressed against the subcortical brain volumetric measurements. Results: Accounting for site and genetic burden (the interaction of age and CAG repeat length) smaller caudate and putamen volumes were related to clusters reflecting motor symptom severity, cognitive control, and verbal learning. Conclusions: Variable reduction of the HD phenotype using cluster analysis revealed biologically related domains of HD and are suitable for future research with this population. Our cognitive control cluster scores show sensitivity to changes in basal ganglia both within and outside the striatum that may not be captured by examining only motor scores. (JINS, 2017, 23, 159–170)
Obsessive compulsive disorder (OCD) and social anxiety disorder (SAD) are characterized by biased perception and processing of potentially threatening stimuli. A hyper-reactivity of the fear-circuit [e.g. amygdala, anterior cingulate (ACC)] has been consistently reported using functional magnetic resonance imaging (fMRI) in SAD in comparison with healthy controls (HCs). Studies investigating the processing of specific emotional stimuli in OCD reported mainly orbitofrontal-striatal abnormalities. The goal of this study was to examine similar/common and differential neurobiological responses in OCD and SAD using unspecific emotional stimuli.
Fifty-four subjects participated: two groups (each n = 18) of outpatients with a current diagnosis of OCD or SAD, and 18 HCs. All subjects underwent fMRI while anticipating and perceiving unspecific visual stimuli with prior announced emotional valence (e.g. positive).
Compared to HCs, the combined patient group showed increased activation in amygdala, caudate and prefrontal/orbitofrontal cortex while anticipating unspecific emotional stimuli. Caudate was more active in the combined patient group during perception. A comparison between the OCD and the SAD samples revealed increased amygdala and decreased rostral ACC activation in OCD patients during perception, but no differences in the anticipation phase.
Overall, we could identify common fronto-subcortical hyper-reactivity in OCD and SAD while anticipating and perceiving unspecific emotional stimuli. While differential neurobiological responses between OCD and SAD when processing specific stimuli are evident from the literature, differences were less pronounced using unspecific stimuli. This could indicate a disturbance of emotion regulation common to both OCD and SAD.
Progressive enlargement of basal ganglia volume has been observed in schizophrenia individuals, potentially being sustained by chronic administration of antipsychotic drugs. Here we briefly summarise the state of the art of the role of antipsychotic in leading to increased basal ganglia in schizophrenia, particularly focusing on the caudate nucleus.
Individuals with major depressive disorder (MDD) are characterized by maladaptive responses to both positive and negative outcomes, which have been linked to localized abnormal activations in cortical and striatal brain regions. However, the exact neural circuitry implicated in such abnormalities remains largely unexplored.
In this study 26 unmedicated adults with MDD and 29 matched healthy controls (HCs) completed a monetary incentive delay task during functional magnetic resonance imaging (fMRI). Psychophysiological interaction (PPI) analyses probed group differences in connectivity separately in response to positive and negative outcomes (i.e. monetary gains and penalties).
Relative to HCs, MDD subjects displayed decreased connectivity between the caudate and dorsal anterior cingulate cortex (dACC) in response to monetary gains, yet increased connectivity between the caudate and a different, more rostral, dACC subregion in response to monetary penalties. Moreover, exploratory analyses of 14 MDD patients who completed a 12-week, double-blind, placebo-controlled clinical trial after the baseline fMRI scans indicated that a more normative pattern of cortico-striatal connectivity pre-treatment was associated with greater improvement in symptoms 12 weeks later.
These results identify the caudate as a region with dissociable incentive-dependent dACC connectivity abnormalities in MDD, and provide initial evidence that cortico-striatal circuitry may play a role in MDD treatment response. Given the role of cortico-striatal circuitry in encoding action–outcome contingencies, such dysregulated connectivity may relate to the prominent disruptions in goal-directed behavior that characterize MDD.
Psychosis is characterized by a profound lack of trust and disturbed social interactions. Investigating the neural basis of these deficits is difficult because of medication effects but first-degree relatives show qualitatively similar abnormalities to patients with psychosis on various tasks. This study aimed to investigate neural activation in siblings of patients in response to an interactive task. We hypothesized that, compared to controls, siblings would show (i) less basic trust at the beginning of the task and (ii) reduced activation of the brain reward and mentalizing systems.
Functional magnetic resonance imaging (fMRI) data were acquired on 50 healthy siblings of patients with psychosis and 33 healthy controls during a multi-round trust game with a cooperative counterpart. An a priori region-of-interest (ROI) analysis of the caudate, temporoparietal junction (TPJ), superior temporal sulcus (STS), insula and medial prefrontal cortex (mPFC) was performed focusing on the investment and repayment phases. An exploratory whole-brain analysis was run to test for group-wise differences outside these ROIs.
The siblings’ behaviour during the trust game did not differ significantly from that of the controls. At the neural level, siblings showed reduced activation of the right caudate during investments, and the left insula during repayments. In addition, the whole-brain analysis revealed reduced putamen activation in siblings during investments.
The findings suggest that siblings show aberrant functioning of regions traditionally involved in reward processing in response to cooperation, which may be associated with the social reward deficits observed in psychosis.
Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Participants were genetically confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on four cognitive measures and three brain volumes over approximately 6 years. Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals. (JINS, 2013, 19, 1–12).
Behaviorally spontaneous confabulation is characterized by a confusion of reality evident in currently inappropriate acts that patients justify with confabulations and in disorientation. Here, we describe a 38-year-old woman lawyer hospitalized because of non-herpetic, presumably autoimmune, limbic encephalitis. For months, she considered herself at work and desperately tried to respect her falsely believed professional obligations. In contrast to a completely erroneous concept of reality, she did not confabulate about her remote personal past. In tasks proposed to test strategic retrieval monitoring, she produced no confabulations. As expected, she failed in tasks of reality filtering, previously shown to have high sensitivity and specificity for behaviorally spontaneous confabulation and disorientation: she failed to suppress the interference of currently irrelevant memories and she had deficient extinction capacity. The observation underscores the special status of behaviorally spontaneous confabulation among confabulatory phenomena and of reality filtering as a thought control mechanism. We suggest that different processes may underlie the generation of false memories and their verbal expression. We also emphasize the need to present theories of confabulation together with experimental tasks that allow one to empirically verify the theories and to explore underlying physiological mechanisms. (JINS, 2010, 16, 995–1005.)
To investigate the subcortical connections of the object vision and spatial vision cortical processing pathways, we injected the inferior temporal and posterior parietal cortex of six Rhesus monkeys with retrograde or anterograde tracers. The temporal injections included area TE on the lateral surface of the hemisphere and adjacent portions of area TEO. The parietal injections covered the posterior bank of the intraparietal sulcus, including areas VIP and LIP. Our results indicate that several structures project to both the temporal and parietal cortex, including the medial and lateral pulvinar, claustrum, and nucleus basalis. However, the cells in both the pulvinar and claustrum that project to the two systems are mainly located in different parts of those structures, as are the terminals which arise from the temporal and parietal cortex. Likewise, the projections from the temporal and parietal cortex to the caudate nucleus and putamen are largely segregated. Finally, we found projections to the pons and superior colliculus from parietal but not temporal cortex, whereas we found the lateral basal and medial basal nuclei of the amygdala to be reciprocally connected with temporal but not parietal cortex. Thus, the results show that, like the cortical connections of the two visual processing systems, the subcortical connections are remarkably segregated.
Individuals with Down's syndrome (DS) are at high risk of developing Alzheimer's disease (AD). However, few studies have investigated brain anatomy in DS individuals with AD.
We compared whole brain anatomy, as measured by volumetric magnetic resonance imaging (MRI), in DS individuals with and without AD. We also investigated whether volumetric differences could reliably classify DS individuals according to AD status. We used volumetric MRI and manual tracing to examine regional brain anatomy in 19 DS adults with AD and 39 DS adults without AD.
DS individuals with AD had significantly smaller corrected volumes bilaterally of the hippocampus and caudate, and right amygdala and putamen, and a significantly larger corrected volume of left peripheral cerebrospinal fluid (CSF), compared to DS individuals without AD. The volume of the hippocampus and caudate nucleus correctly categorized 92% and 92% respectively of DS individuals without AD, and 75% and 80% respectively of DS individuals with AD.
DS individuals with AD have significant medial temporal and striatal volume reductions, and these may provide markers of clinical AD.
Production of complex discourse—lengthy, open-ended utterances
and narratives—requires intact basic language operations, but it
also requires a series of learned procedures for construction of complex,
goal-directed communications. The progression of clinical disorders from
transcortical motor aphasia to dynamic aphasia to discourse impairments
represents a progression of procedural deficits from basic morpho-syntax
to complex grammatical structures to narrative and a progression of
lesions from posterior frontal to polar and/or lateral frontal to
medial frontal. Two cases of impaired utilization of language exemplify
the range of impairments from clearly aphasic agrammatic, nonfluency to
less and less “aphasic” and more and more executive
impairments from transcortical motor aphasia to dynamic aphasia to
narrative discourse disorder. The clinical phenomenology of these
disorders gradually comes to be more accurately defined in the terminology
of executive deficits than that of aphasia. The executive deficits are, in
turn, based on impairments in various components of attention. Specific
impairments in energizing attention and setting response criteria
associated, respectively, with lesions in superior medial and left
ventrolateral frontal regions may cause defective recruitment of the
procedures of complex language assembly. (JINS, 2006,
HIV infection often results in MRI-detectable brain
atrophy and white matter signal hyperintensities (WMSHs).
Magnetic resonance images were obtained from 31 HIV+ male
patients and 10 high-risk controls. Variation within the
HIV+ group on neuropsychological (NP) impairment and stage
of systemic disease were relatively independent, allowing
examination of the relative association of MRI measures
with NP impairment versus with systemic stage
of disease. HIV+ patients compared to high-risk controls
evidenced global atrophy, reduced caudate nuclei volume,
and a trend to gray matter volume loss but no difference
in white matter volume or in WMSHs. These effects were
progressive with CDC clinical stage such that patients
at CDC stage A had values very close to those of controls,
while patients at CDC stage C had the most abnormal values.
In contrast, the relationship between these MRI variables
and severity of NP impairment was much less dramatic, with
the mildly to moderately impaired HIV+ subjects showing
MRI volume effects greater than or equal to those of the
severely impaired HIV+ subjects. These results suggest
that MRI-detectable brain atrophy secondary to HIV infection
is not the primary substrate underlying the progressive
NP impairment in HIV disease. (JINS, 1997, 3,
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