Functional connectivity analysis for resting state fMRI data revealed disorder specific abnormality of functional connections. Artificial intelligence techniques enabled development of disorder specific classifier or biomarker that can generalize to external validation datasets. By combining such biomarkers and decoding techniques with fMRI real-time neurofeedback methods, sophisticated neurofeedback interventions can be developed as future generation therapies for mental and developmental disorders.

Reading and writing is one of the most important invension in the history of mankind, and has played a central role in the dissemination of culture and the development of civilization. Therefore, an influence of aquired reading and writing disorders (i.e., alexia and agrapihia) has become more serious in the modern society. It is well known that the patient with the lesion that involves the posterior part of the left middle frontal gyrus, tradittionally known as the "Exner's area", sometimes develops pure agraphia, and this brain lesion has been described as a major "writing center". Although the role of this region is still unknown, recent clinical and neuroimaging studies suggested that this area should have a crucial roles in writing processes, e.g., the conversion of graphemic representations to motor commands, the orthographic working-memory, or the interface between orthographic represanetation and generation of motor commands. Here, we review the historical bakground and the recent findings of reading and writing disorders due to the left frontal lobe lesions. Especially, we focus on the relationship between agraphia and Exner's area.

The literature regarding the reading and writing disorders due to the left parietal lesions was reviewed. The findings of the past as well as those from the recent studies were described as regards: 1) alexia with agraphia, 2) isolated agraphia (pure agraphia, apraxic agraphia, and constructional agraphia), 3) somesthetic alexia, and 4) dystypia. Finally, the rehabilitation of the reading and writing disorders was referred.

The left temporal lobe contains the regions crucial for language processing, such as Wernicke's area and surroundings, a part of arcuate fasciculus, and the anterior temporal lobe. The damage to one of these regions results in a specific aphasic syndrome which is accompanied by a unique type of alexia and agraphia. In addition, the left angular gyrus had been plausible candidate for critical region of pure alexia and agraphia. However, many Japanese researchers have shown that the posterior part of the left inferior temporal gyrus damage develops Kanji (morphogram) impairment. Subsequently, the researchers in English-speaking world have proposed the idea of "the visual word form area" which seems to be responsible for lexical alexia and agraphia. Dual-route cascaded model of reading and writing in Japanese has been proposed to explain the dissociated alexia and agraphia in Kanji and Kana.

In the article, occipital lobular lesions were the starting point of the discussion, and I discussed disorders of reading and writing caused by occipital lobular lesions, i.e., the failure of reading and writing systems in the occipital lobes.

I considered that agraphia caused by occipital lobular lesions was associated with the lesion, which included the boundary between occipital and parietal lobes and that between occipital and temporal lobes. The lesion expanded to the angular gyrus in a parietal lobe, and lesions expanding to the middle and inferior temporal gyri could be associated with agraphia with alexia. Lesions separated from an occipital lobe and close to a parietal or temporal lobe could be associated with agraphia without alexia. Restricted occipital lobular lesions may be associated with pure alexia, and lesions expanding to a parietal or temporal lobe may accompany agraphia. Therefore, the boundary lesion in a temporal lobe around the middle and inferior temporal gyri and that in a parietal lobe around the angular gyrus are noteworthy.

In addition, I mentioned topics concerning pure alexia: several recent reports about the visual word form area (VWFA), and the mechanisms of number and letter-by-letter reading.

Patient with brain injury at thalamus has not only the neurological symptoms such as motor paralysis or sensory impairment, but also a variety of neuropsychological symptoms such as aphasia, unilateral spatial neglect, and memory impairment. On the other hand, few cases who had reading and writing disorder without aphasia has been reported. Dorsomedial nucleus and the outer ventral nucleus, posterolateral ventral nucleus, which is projected to motor and sensory areas on the cerebral cortex, is known as the thalamus of the localized lesions caused the disorders of reading and writing. SPECT in some study shows a decrease in regional cerebral blood flow in the frontal, temporal, and parietal lobe of the same side as a function lesion.

Alexia and agraphia associated with neurodegenerative disease can be classified into two types. One is aphasic, which is accompanied with primary progressive aphasia, and another is non-aphasic, namely, pure alexia or solitary agraphia. This means that not only the language areas but also other areas including posterior inferior temporal/occipital area, angular gyrus, superior parietal lobule and premotor area are involved in reading and/or writing. It is clinically important to evaluate reading and writing abilities in patients with neurodegenerative disease. The reasons are as follows. (i) Alexia or agraphia can be an initial symptom of neurodegenerative disease. (ii) Time course of alexia and agraphia in patients with neurodegenerative disease can shed light on the disease progression processes. (iii) Communication disability in patients with neurodegenerative disease is relentlessly progressive as a rule. Thus, an analysis of retained reading and writing abilities in those patients is crucial to consider the most effective way to maintain communication with them.

In this paper, we presented two patients: one with semantic dementia and another with ALS. We administered them our institutional tests evaluating their reading and writing abilities. We then discussed the nature of their alexia and agraphia.

Object orientation agnosia involving the orientation of two-dimensional material has been studied, but little is known about problems in three-dimensional orientation. In this study, we conducted orientation identification and discrimination tasks using photographs taken from various angles of a teapot to a patient with object orientation agnosia. She showed normal performance with front/rear/top/bottom orientation, could not identify right and left sides, and performed poorly with oblique views. Discrimination of orientation change in two-dimensional linear transformation such as upright/inverted, mirror, and upright/rotated images tended to be significantly worse than orientation discrimination front/rear/top/bottom views each other, and lower than including the left/right sides are direction changes in the three dimensional space. Therefore, discrimination of orientation change in two dimensional linear transformation and in the three dimensional space show differences in difficulty or involve different processes. Based on the patient's performance, we propose the following processes of cognition orientation for normally functioning individuals: front/rear/top/bottom locations are included in the initial mental representation and described adequately by language. Right/left orientations are (1) first described as side locations and then (2) calculated to distinguish between them as necessary. Oblique orientation is (1) usually described only vaguely, and then (2) calculated from axes as necessary. In discriminating orientations in two dimensional linear transformation, (1) axes are extracted, (2) redefined to another coordinate system, and (3) compared with each other. The patient showed normal performance in the first steps of all these processes, but showed impairment in later steps which require more advanced spatial information processing for additional computation as well as a detailed description and redefinition of the coordinates. In addition, the level of the morphological similarity of views was considered a factor affecting the orientation judgment.

We report a patient with progressive word deafness and foreign accent syndrome. The patient is 70-years-old right-handed female. Although pure tone audiometry is normal, speech audiometry is impaired. Her speech occasionally shows sound errors and omission or misuse of postpositional particles, and is perceived by listeners as foreign. There are not any other cognitive deterioration and aphasia including comprehension of sentences with complex syntax. The most prominent feature of her speech is abnormality of prosody, although abnormality of accent and segmentation of sounds are also apparent. MRI of the brain revealed atrophy of the right superior temporal gyrus and Heschl's gyrus. IMP-SPECT showed bilateral frontotemporoparietal hypoperfusion, particuraly in the right hemisphere. The responsible lesions may be bilateral peri-Sylvius region with an emphasis on the right hemisphere. There would be cases with progressive word deafness and speech disorders as a subtype of progressive aphasia.