Walking through Architectural Spaces: The Impact of Interior Forms on Human Brain Dynamics.

Imaging of Eating Disorders: Multiple Techniques to Demonstrate the Dynamic Brain

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

The cingulate gyrus is a major part of the "anatomical limbic system" and, according to classic accounts, is involved in emotion. This view is oversimplified in light of recent clinical and experimental findings that cingulate cortex participates not only in emotion but also in sensory, motor, and cognitive processes. Anterior cingulate cortex, consisting of areas 25 and 24, has been implicated in visceromotor, skeletomotor, and endocrine outflow. These processes include responses to painful stimuli, maternal behavior, vocalization, and attention to action. Since all of these activities have an affective component, it is likely that connections with the amygdala are critical for them. In contrast, posterior cingulate cortex, consisting of areas 29, 30, 23, and 31, contains neurons that monitor eye movements and respond to sensory stimuli. Ablation studies suggest that this region is involved in spatial orientation and memory. It is likely that connections between posterior cingulate and parahippocampal cortices contribute to these processes. We conclude that there is a fundamental dichotomy between the functions of anterior and posterior cingulate cortices. The anterior cortex subserves primarily executive functions related to the emotional control of visceral, skeletal, and endocrine outflow. The posterior cortex subserves evaluative functions such as monitoring sensory events and the organism's own behavior in the service of spatial orientation and memory.

Recent studies have revealed a marked degree of variation in the pyramidal cell phenotype in visual, somatosensory, motor and prefrontal cortical areas in the brain of different primates, which are believed to subserve specialized cortical function. In the present study we carried out comparisons of dendritic structure of layer III pyramidal cells in the anterior and posterior cingulate cortex and compared their structure with those sampled from inferotemporal cortex (IT) and the primary visual area (V1) in macaque monkeys. Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors was determined, and somal areas measured. We found that pyramidal cells in anterior cingulate cortex were more branched and more spinous than those in posterior cingulate cortex, and cells in both anterior and posterior cingulate were considerably larger, more branched, and more spinous than those in area V1. These data show that pyramidal cell structure differs between posterior dysgranular and anterior granular cingulate cortex, and that pyramidal neurons in cingulate cortex have different structure to those in many other cortical areas. These results provide further evidence for a parallel between structural and functional specialization in cortex.

Auditory verbal hallucinations (AVHs) are a hallmark of schizophrenia and can significantly impair patients’ emotional, social, and occupational functioning. Despite progress in psychopharmacology, over 25% of schizophrenia patients suffer from treatment-resistant hallucinations. In the search for alternative treatment methods, neurofeedback (NF) emerges as a promising therapy tool. NF based on real-time functional magnetic resonance imaging (rt-fMRI) allows voluntarily change of the activity in a selected brain region – even in patients with schizophrenia. This study explored effects of NF on ongoing AVHs. The selected participants were trained in the self-regulation of activity in the anterior cingulate cortex (ACC), a key monitoring region involved in generation and intensity modulation of AVHs. Using rt-fMRI, three right-handed patients, suffering from schizophrenia and ongoing, treatment-resistant AVHs, learned control over ACC activity on three separate days. The effect of NF training on hallucinations’ severity was assessed with the Auditory Vocal Hallucination Rating Scale (AVHRS) and on the affective state – with the Positive and Negative Affect Schedule (PANAS). All patients yielded significant upregulation of the ACC and reported subjective improvement in some aspects of AVHs (AVHRS) such as disturbance and suffering from the voices. In general, mood (PANAS) improved during NF training, though two patients reported worse mood after NF on the third day. ACC and reward system activity during NF learning and specific effects on mood and symptoms varied across the participants. None of them profited from the last training set in the prolonged three-session training. Moreover, individual differences emerged in brain networks activated with NF and in symptom changes, which were related to the patients’ symptomatology and disease history. NF based on rt-fMRI seems a promising tool in therapy of AVHs. The patients, who suffered from continuous hallucinations for years, experienced symptom changes that may be attributed to the NF training. In order to assess the effectiveness of NF as a therapeutic method, this effect has to be studied systematically in larger groups; further, long-term effects need to be assessed. Particularly in schizophrenia, future NF studies should take into account the individual differences in reward processing, fatigue, and motivation to develop individualized training protocols.

To compare the glutamate dehydrogenase (GDH) activity and amounts of GDHI, GDHII, and GDHIII immunoreactive forms in prefrontal, anterior and posterior cingulate cortex and cerebellar cortex of patients with schizophrenia and control subjects. GDH enzymatic activity was measured and levels of GDH immunoreactive forms were determined in extracts of autopsied samples of prefrontal, anterior and posterior cingulate cortex (areas 10, 24, and 23 by Brodmann), and cerebellar cortex of patients with schizophrenia (n=8) and controls (n=9). GDH enzymatic activity was significantly increased in the prefrontal cortex (area 10) (p<0.004), the posterior cingulate cortex (area 23) (p<0.05) and the cerebellar cortex (p<0.002) and was unchanged in the anterior cingulate cortex (area 24) in patients with schizophrenia compared to controls. The levels of immunoreactive GDH I, GDH II and GDH III were significantly higher in the prefrontal cortex of patients with schizophrenia than in controls (p<0.008, p<0.003, and p<0.0001, respectively). Levels of all three immunoreactive GDH forms were unchanged in the anterior cingulate cortex (area 24), but they were increased in the posterior cingulate cortex (area 23) (p<0.004, p<0.001 and p<0.02, respectively). The levels of immunoreactive GDH II and GDH III, but not GDH I, were significantly increased in the cerebellar cortex of patients with schizophrenia compared with the control group (p<0.02 and p<0.001, respectively). The alteration in the levels of GDH immunoreactive forms in the brain of patients with schizophrenia is one of the causes of impaired brain glutamate metabolism and an important aspect of schizophrenia pathogenesis.

The anterior cingulate cortex (AC) as a part of prefrontal cortex plays a crucial role in behavioural regulation, which is profoundly disturbed in suicide. Citrate synthase (CS) is a key enzyme of tricarboxylic acid cycle fundamental for brain energetics and neurotransmitter synthesis, which are deteriorated in suicidal behaviour. However, CS activity has not been yet studied in brain structures of suicide victims. CS activity assay was performed bilaterally on frozen samples of the rostral part of the AC of 24 violent suicide completers (21 males and 3 females) with unknown psychiatric diagnosis and 24 non-suicidal controls (20 males and 4 females). Compared to controls, suicide victims revealed decreased CS activity in the right AC, however, insignificant. Further statistical analysis of laterality index revealed the left-lateralisation of CS activity in the AC in male suicides compared to male controls (U-test P = 0.0003, corrected for multiple comparisons). The results were not confounded by postmortem interval, blood alcohol concentration, age, and brain weight. Our findings suggest that disturbed CS activity in the AC plays a role in suicide pathogenesis and correspond with our previous morphological and molecular studies of prefrontal regions in suicide.

Chapter 11 - Cingulate role in Tourette syndrome

Anxiety involves the anticipation of aversive outcomes and can impair neurocognitive processes, such as the ability to recall faces encoded during the anxious state. It is important to precisely delineate and determine the replicability of these effects using causal state anxiety inductions in the general population. This study therefore aimed to replicate prior research on the distinct impacts of threat-of-shock-induced anxiety on the encoding and recognition stage of emotional face processing, in a large asymptomatic sample (n = 92). We successfully replicated previous results demonstrating impaired recognition of faces encoded under threat-of-shock. This was supported by a mega-analysis across three independent studies using the same paradigm (n = 211). Underlying this, a whole-brain fMRI analysis revealed enhanced activation in the posterior cingulate cortex (PCC), alongside previously seen activity in the anterior cingulate cortex (ACC) when combined in a mega-analysis with the fMRI findings we aimed to replicate. We further found replications of hippocampus activation when the retrieval and encoding states were congruent. Our results support the notion that state anxiety disrupts face recognition, potentially due to attentional demands of anxious arousal competing with affective stimuli processing during encoding and suggest that regions of the cingulate cortex play pivotal roles in this.

Objective The aim of the present work was to observe the activation/deactivation of cerebral functional regions after electroacupuncture (EA) at Yintang (EX-HN3) and GV20 by functional MRI (fMRI). Design A total of 12 healthy volunteers were stimulated by EA at Yintang and GV20 for 30 min. Resting-state fMRI scans were performed before EA, and at 5 and 15 min after needle removal. Statistical parametric mapping was used to preprocess initial data, and regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) were analysed. Results ReHo at 5 min post stimulation showed increases in the left temporal lobe and cerebellum and decreases in the left parietal lobe, occipital lobe and right precuneus. At 15 min post stimulation, ReHo showed increases in the left fusiform gyrus; lingual gyrus; middle temporal gyrus; postcentral gyrus; limbic lobe; cingulate gyrus; paracentral lobule; cerebellum, posterior lobe, declive; right cuneus and cerebellum, anterior lobe, culmen. It also showed decreases in the left frontal lobe, parietal lobe, right temporal lobe, frontal lobe, parietal lobe and right cingulate gyrus. ALFF at 5 min post stimulation showed increases in the right temporal lobe, but decreases in the right limbic lobe and posterior cingulate gyrus. At 15 min post stimulation ALFF showed increases in the left frontal lobe, parietal lobe, occipital lobe, right temporal lobe, parietal lobe, occipital lobe and cerebellum, but decreases in the left frontal lobe, anterior cingulate gyrus, right frontal lobe and posterior cingulate gyrus. Conclusions After EA stimulation at Yintang and GV20, which are associated with psychiatric disorder treatments, changes were localised in the frontal lobe, cingulate gyrus and cerebellum. Changes were higher in number and intensity at 15 min than at 5 min after needle removal, demonstrating lasting and strong after-effects of EA on cerebral functional regions.

The Ernst triadic model: A good start?

Objective To provide a new approach to further elucidate the underlying pathogenesis of major depressive disorder by using resting-state functional connectivity strengths(FCS) in unmedicated patients with major depressive disorder(MDD). Methods Thirty-three unmedicated patients with MDD and thirty-three normal controls underwent the resting-state functional magnetic resonance imaging(rs-fMRI).After preprocessing of rs-fMRI, the whole brain FCS values were constructed. Two-sample t-test was used to compare the FCS values of both groups to locate the regions with significant change. And correlation analysis was performed between the FCS values extracted from significantly different brain regions and Hamilton Depression Scale (HAMD24) scores. Results One sample t test had shown that high FCS values brain areas (hubs) of MDD patients and normal controls were mainly located in the default mode network (the prefrontal cortex, anterior cingulate gyrus, posterior cingulate gyrus, precuneus/cuneus, angular gyrus) and parietal cortex, lateral temporal cortex as well as occipital cortex. In comparison to the normal controls, the MDD patients had FCS values significantly decreased in the bilateral posterior cerebellar lobe (right posterior cerebellar t=-4.57, P<0.05; left posterior cerebellar t=-3.40,P<0.05), and FCS values increased in the right superior temporal gyrus (t=3.71,P<0.05) and left anterior insular lobe (t=3.91, P<0.05). There were no significant correlations between the HAMD24 scores and the FCS values in right/left posterior cerebellar (r=0.081, P=0.654; r=-0.028, P=0.877), right superior temporal gyrus (r=0.211, P=0.239) and left anterior insular lobe (r=-0.017,P=0.924). Conclusions These findings suggest abnormal functional connectivity in the bilateral posterior cerebellar lobe, right temporal lobe and left insular lobe in MDD. The FCS analysis may be used as a new research method to explore the pathogenesis of MDD. Key words: Depressive disorder; Resting state; Functional connectivity strengths

Hypothyroidism is frequently associated with subtle behavioral and psychiatric symptoms. The consequences of inadequate thyroid hormone availability to brain metabolism are poorly understood. This study assessed the relationships between neuropsychiatric symptoms and changes in relative regional cerebral glucose metabolism in hypothyroid patients undergoing thyroid hormone replacement therapy. DESIGN, SETTING, AND OUTCOME MEASURE: Relative regional cerebral glucose metabolism was compared in 13 previously untreated hypothyroid patients and 10 healthy control participants. Effects of thyroid hormone replacement therapy (levothyroxine, 3 months) were assessed using neuropsychiatric measures and positron emission tomography with [(18)F]fluorodeoxyglucose. Before treatment, hypothyroid patients exhibited lower regional activity than control subjects in the bilateral amygdala, hippocampus, and perigenual anterior cingulate cortex (ACC), left subgenual ACC, and right posterior cingulate cortex. Severity of depressive symptoms covaried negatively with pretreatment activity in the bilateral middle frontal gyrus and right subgenual and dorsal ACC. Thyroid hormone replacement therapy abolished pretreatment group differences in regional activity, robustly increased activity in the ventral ACC, and significantly reduced both clinician-rated and self-rated behavioral and psychiatric symptoms. Increased activity within the ventral ACC was associated with reduced somatic complaints, whereas increased activity within the dorsal ACC was associated with reduced depressive symptoms. Reduction of the behavioral complaints during thyroid hormone therapy is associated with a restoration of metabolic activity in brain areas that are integral to the regulation of affect and cognition. The findings suggest that thyroid hormone modulates regional glucose metabolism and psychiatric symptoms in the mature brain.

Whiplash injury (WHI) is characterised by a forced neck flexion/extension, which frequently occurs after motor vehicle collisions. Previous studies characterising differences in brain metabolite concentrations and correlations with neuropathic pain (NP) components with chronic whiplash-associated disorders (WAD) have been demonstrated in affective pain-processing areas such as the anterior cingulate cortex (ACC). However, the detection of a difference in metabolite concentrations within these cortical areas with chronic WAD pain has been elusive. In this study, single-voxel magnetic resonance spectroscopy (MRS), following the latest MRSinMRS consensus group guidelines, was performed in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and occipital cortex (OCC) to quantify differences in metabolite concentrations in individuals with chronic WAD with or without neuropathic pain (NP) components. Healthy individuals (n = 29) and participants with chronic WAD (n = 29) were screened with the Douleur Neuropathique 4 Questionnaire (DN4) and divided into groups without (WAD-noNP, n = 15) or with NP components (WAD-NP, n = 14). Metabolites were quantified with LCModel following a single session in a 3 T MRI scanner within the ACC, DLPFC, and OCC. Participants with WAD-NP presented moderate pain intensity and interference compared with the WAD-noNP group. Single-voxel MRS analysis demonstrated a higher glutamate concentration in the ACC and lower total choline (tCho) in the DLPFC in the WAD-NP versus WAD-noNP group, with no intergroup metabolite difference detected in the OCC. Best fit and stepwise multiple regression revealed that the normalised ACC glutamate/total creatine (tCr) (p = 0.01), DLPFC n-acetyl-aspartate (NAA)/tCr (p = 0.001), and DLPFC tCho/tCr levels (p = 0.02) predicted NP components in the WAD-NP group (ACC r 2 = 0.26, α = 0.81; DLPFC r 2 = 0.62, α = 0.98). The normalised Glu/tCr concentration was higher in the healthy than the WAD-noNP group within the ACC (p < 0.05), but not in the DLPFC or OCC. Neither sex nor age affected key normalised metabolite concentrations related to WAD-NP components when compared to the WAD-noNP group. This study demonstrates that elevated glutamate concentrations within the ACC are related to chronic WAD-NP components, while higher NAA and lower tCho metabolite levels suggest a role for increased neuronal-glial signalling and cell membrane dysfunction in individuals with chronic WAD-NP components.

Joyful growth vs. compulsive hedonism: A meta-analysis of brain activation on romantic love and addictive disorders