Xiaochu Zhang

Factors underlying prefrontal and insula structural alterations in smokers

Based upon previous reports of alterations in white matter integrity and gray matter density in smokers, we examined these markers in a large, well-matched sample of smokers and non-smokers. We further investigated the effect of heavy cigarette exposure by using pack-years and the effects of two relatively stable, highly heritable traits in smokers (Fagerström Test of Nicotine Dependence (FTND), a measure of severity of nicotine dependence and Toronto Alexithymia Scale (TAS-20), a stable personality trait related to smoking). Forty-eight nicotine-dependent subjects and 48 matched controls were included in the analyses, with smokers also subdivided into high/low dependence and high/low pack-years smokers. White matter integrity (fractional anisotropy (FA)) and gray matter density (voxel-based morphometry (VBM)) were measured and compared across groups. Gray matter density was lower in left prefrontal cortex (PFC) in high pack-years smokers and was inversely related to pack-years. In contrast, left insular cortex gray matter density was higher in smokers and associated with TAS-20 total score and with difficulty-identifying-feelings factor. Further, the most highly dependent smokers showed lower prefrontal FA, which was negatively correlated with FTND. There was no correlation between pack-years and FTND in our smoker population. These data suggest chronic tobacco use is correlated with prefrontal gray matter damage , while differences in insula gray matter and PFC white matter appear to reflect stable and heritable differences between smokers and non-smokers.

Age-dependent brain activation during forward and backward digit recall revealed by fMRI

In this study, brain activation associated with forward and backward digit recall was examined in healthy old and young adults using functional MRI. A number of areas were activated during the recall. In young adults, greater activation was found in the left prefrontal cortex (BA9) and the left occipital visual cortex during backward digit recall than forward digit recall. In contrast, the activation in the right inferior frontal gyrus (BA 44/45) was more extensive in forward digit recall than in backward digit recall. In older adults, backward recall generated stronger activation than forward recall in most areas, including the frontal, the parietal, the occipital, and the temporal cortices. In the backward recall condition, the right inferior frontal gyrus (BA44/45) showed more activation in the old group than in the young group. These results suggest that different neural mechanisms may be involved in forward and backward digit recall and brain functions associated with these two types of recall are differentially affected by aging.

Anatomical differences and network characteristics underlying smoking cue reactivity.

A distributed network of brain regions is linked to drug-related cue responding. However, the relationships between smoking cue-induced phasic activity and possible underlying differences in brain structure, tonic neuronal activity and connectivity between these brain areas are as yet unclear. Twenty-two smokers and 22 controls viewed smoking-related and neutral pictures during a functional arterial spin labeling scanning session. T1, resting functional, and diffusion tensor imaging data were also collected. Six brain areas, dorsal lateral prefrontal cortex (dlPFC), dorsal medial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex/cingulate cortex, rostral anterior cingulate cortex (rACC), occipital cortex, and insula/operculum, showed significant smoking cue-elicited activity in smokers when compared with controls and were subjected to secondary analysis for resting state functional connectivity (rsFC), structural, and tonic neuronal activity. rsFC strength between rACC and dlPFC was positively correlated with the cue-elicited activity in dlPFC. Similarly, rsFC strength between dlPFC and dmPFC was positively correlated with the cue-elicited activity in dmPFC while rsFC strength between dmPFC and insula/operculum was negatively correlated with the cue-elicited activity in both dmPFC and insula/operculum, suggesting these brain circuits may facilitate the response to the salient smoking cues. Further, the gray matter density in dlPFC was decreased in smokers and correlated with cue-elicited activity in the same brain area, suggesting a neurobiological mechanism for the impaired cognitive control associated with drug use. Taken together, these results begin to address the underlying neurobiology of smoking cue salience, and may speak to novel treatment strategies and targets for therapeutic interventions.

A functional MRI study of high-level cognition

GO is a board game thought to be different from chess in many aspects, most significantly in that GO emphasizes global strategy more than local battle, a property very difficult for computer programs to emulate. To investigate the neural basis of GO, functional magnetic resonance imaging (fMRI) was used to measure brain activities of subjects engaged in playing GO. Enhanced activations were observed in many cortical areas, such as dorsal prefrontal, parietal, occipital, posterior temporal, and primary somatosensory and motor areas. Quantitative analysis indicated a modest degree of stronger activation in right parietal area than in left. This type of right hemisphere lateralization differs from the modest left hemisphere lateralization observed during chess playing.  2002 Elsevier Science B.V. All rights reserved. Theme: Neural basis of behaviour

Smoking and Schizophrenia Independently and Additively Reduce White Matter Integrity Between Striatum and Frontal Cortex

BACKGROUND Although schizophrenia patients are at high risk for tobacco use, the neurobiological basis of this comorbid association is not clear. White matter abnormalities have been described independently in schizophrenia and smoking cohorts. We sought to determine whether smoking and schizophrenia are associated with similar white matter abnormalities that could be biomarkers for the high risk of smoking in schizophrenia. METHODS Whole brain white matter integrity (fractional anisotropy) was measured in 46 schizophrenia patients (32 smokers and 14 nonsmokers) and 69 healthy age-matched control subjects (48 smokers and 21 nonsmokers). RESULTS Schizophrenia and smoking status were independently and additively associated with reduced fractional anisotropy in left anterior thalamic radiation/anterior limb of the internal capsule, and significant fractional anisotropy decreases were identified in the bilateral uncinate fasciculus/inferior fronto-occipital fasciculus in schizophrenia and the left prefrontal area in smoking status separately. CONCLUSIONS Common and distinct patterns of impaired white matter are associated with schizophrenia and smoking. Particularly, the anatomic congruence of an additive white matter abnormality in the anterior thalamic radiation/anterior limb of the internal capsule suggests that this abnormal fiber connectivity between frontal cortex and striatum/thalamus may be a biomarker for the increased comorbid smoking in schizophrenia patients.

Cross‐modal temporal order memory for auditory digits and visual locations: An fMRI study

A function of working memory is to remember the temporal sequence of events, often occurring across different sensory modalities. To study the neural correlates of this function, we conducted an event‐related functional magnetic resonance imaging (fMRI) experiment with a cross‐modal memory task. Subjects were required to recall auditory digits and visual locations either in mixed order (cross‐modality) or in separate order (within‐modality). To identify the brain regions involved in the memory of cross‐modal temporal order, we compared the blood oxygenation level‐dependent (BOLD) response between the mixed and the separate order tasks. As a control, cortical areas sensitive to the memory load were mapped by comparing the 10‐item condition with the 6‐item condition in the separate order task. Results show that the bilateral prefrontal, right premotor, temporo‐parietal junction (TPJ) and left superior parietal cortices had significantly more activation in the mixed task than in the separate task. Some of these areas were also sensitive to the memory load, whereas the right prefrontal cortex and TPJ were relatively more sensitive to the cross‐modal order but not the memory load. Our study provides potential neural correlates for the episodic buffer, a key component of working memory as proposed previously [Baddeley. Trends Cogn Sci 2000;4:417–423]. Hum. Brain Mapping 22:280–289, 2004.

Functional comparison of primacy, middle and recency retrieval in human auditory short-term memory: an event-related fMRI study

Primacy and recency effects refer to the better performance or shorter response time on the first and last items than the middle ones of a memory list. In order to investigate its neural basis in auditory short-term memory, event-related fMRI was used to measure brain activities when subject was recalling the first, the last, or the middle items. Recalling the middle item was associated with more extensive activation in the left parietal and visual cortex, basal ganglia, and dorsal cerebellum. Recalling items from different serial positions also resulted in different activation time courses in the bilateral primary auditory cortex, left prefrontal cortex and left premotor cortex. These data indicate that the auditory cortex may serve as a transient storage or the auditory input buffer, which seems to play an important role in the primacy and recency effects.

Functional magnetic resource imaging assessment of altered brain function in hypothyroidism during working memory processing

CONTEXT Hypothyroidism is related to multiple cognitive deficits including working memory dysfunction, of which the underlying neural correlates were rarely studied. In this study, the impact of hypothyroidism on neural circuits involved in working memory processing was explored by functional magnetic resource imaging (fMRI). DESIGN Using fMRI, we conducted a longitudinal study investigating alterations of brain function during a working memory task, the four-digit backward recall (BR) and forward recall (FR), in hypothyroid patients and controls. METHODS fMRI scan was used in 13 female patients at two time points: before and after having been treated with levothyroxine (L-T(4)) for ∼6 months, and 12 matched euthyroid controls were also scanned. Wechsler Memory Scale-Chinese Revision was used to assess the memory states of each participant. RESULTS The hypothyroid patients showed poorer memory states than that in controls. Furthermore, significant differences of task-induced deactivation (TID, task-dependent decreases in neural activity relative to rest) between patients and controls were found in the bilateral medial prefrontal cortices, posterior cingulate cortices, and left inferior partial lobule (P<0.05). These regions were considered as parts of a task-negative network, namely the default mode network (DMN). Concretely, relative to controls, patients showed diminished TID during BR in contrast to FR. After the L-T(4) treatment, neither the poor memory states nor the alteration of TID was detectable in patients. CONCLUSION Hypothyroidism is related to alterations of TID within DMN regions during working memory processing. These exploratory findings may imply potential neural correlates in hypothyroidism-related cognitive deficits and their recoveries.

Love-related changes in the brain: a resting-state functional magnetic resonance imaging study

Romantic love is a motivational state associated with a desire to enter or maintain a close relationship with a specific other person. Functional magnetic resonance imaging (fMRI) studies have found activation increases in brain regions involved in the processing of reward, motivation and emotion regulation, when romantic lovers view photographs of their partners. However, not much is known about whether romantic love affects the brain’s functional architecture during rest. In the present study, resting state functional magnetic resonance imaging (rsfMRI) data was collected to compare the regional homogeneity (ReHo) and functional connectivity (FC) across an “in-love” group (LG, N = 34, currently intensely in love), an “ended-love” group (ELG, N = 34, ended romantic relationship recently), and a “single” group (SG, N = 32, never fallen in love). Results show that: (1) ReHo of the left dorsal anterior cingulate cortex (dACC) was significantly increased in the LG (in comparison to the ELG and the SG); (2) ReHo of the left dACC was positively correlated with length of time in love in the LG, and negatively correlated with the lovelorn duration since breakup in the ELG; (3) FC within the reward, motivation, and emotion regulation network (dACC, insula, caudate, amygdala, and nucleus accumbens) as well as FC in the social cognition network [temporo-parietal junction (TPJ), posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal, precuneus, and temporal lobe] was significantly increased in the LG (in comparison to the ELG and SG); (4) in most regions within both networks FC was positively correlated with the duration of love in the LG but negatively correlated with the lovelorn duration of time since breakup in the ELG. This study provides first empirical evidence of love-related alterations in brain functional architecture. Furthermore, the results shed light on the underlying neural mechanisms of romantic love, and demonstrate the possibility of applying a resting-state fMRI approach for investigating romantic love.

Masked smoking-related images modulate brain activity in smokers

The questions of whether and how indiscriminate drug‐related stimuli could influence drug‐users are important to our understanding of addictive behavior, but the answers are still inconclusive. In the present preliminary functional magnetic resonance imaging study using a backward masking paradigm, the effect of indiscriminate smoking‐related stimuli on 10 smokers and 10 nonsmokers was examined. The BOLD response showed a significant reduction (P = 0.001) in the right amygdala of smokers when they viewed but did not perceive masked smoking‐related stimuli, while no significant differences were found in the nonsmoker group. More voxels in anterior cingulate cortex were negatively correlated with the amygdala during the masked smoking‐related picture condition in smokers but not in nonsmokers, whereas more positively correlated voxels were observed during the masked neutral condition. The BOLD response in drug‐users indicates the amygdala responds to drug‐related stimuli that are below the perceptual threshold. The functional connectivity data suggest a functional interaction between the amygdala and the anterior cingulate cortex when drug users view 33ms back‐masked drug‐related stimuli. This observation suggests that the amygdala plays an important role in the indiscriminate drug‐related cue process. Hum Brain Mapp, 2009.